{"id":3693,"date":"2019-08-03T12:53:46","date_gmt":"2019-08-03T10:53:46","guid":{"rendered":"https:\/\/aa-pnh.pe-dev.de\/diseases\/pnh\/"},"modified":"2025-03-10T18:24:29","modified_gmt":"2025-03-10T17:24:29","slug":"pnh","status":"publish","type":"page","link":"https:\/\/aa-pnh.org\/en\/diseases\/pnh\/","title":{"rendered":"PNH"},"content":{"rendered":"<h2><span style=\"color: #f9a801;\">Paroxysmal Nocturnal Haemoglobinuria (PNH)<\/span><\/h2>\n<p>&nbsp;<\/p>\n<input type=\"hidden\" bg_collapse_expand_pro=\"69e60b5ac11083039197766\" value=\"69e60b5ac11083039197766\"><input type=\"hidden\" id=\"bg-show-more-text-69e60b5ac11083039197766\" value=\"  1 What is PNH?\"><input type=\"hidden\" id=\"bg-show-less-text-69e60b5ac11083039197766\" value=\"  1 What is PNH?\"><input type=\"hidden\" id=\"bg-icon-bg-color-69e60b5ac11083039197766\" value=\"\"><a id=\"bg-showmore-action-69e60b5ac11083039197766\" class=\"bg-showmore-plg-link bg-arrow  \" style=\"color:#f9a801;;font-weight:bold; font-size:24px; line-height: 150%\" href=\"#\">  1 What is PNH?<\/a><ul class=\"bg-showmore-no-padding-no-margin bg-showmore-closed\" id=\"bg-showmore-pro-hidden-69e60b5ac11083039197766\">\n<h4><span style=\"color: #f9a801;\">1.1 General<\/span><\/h4>\n<p>Paroxysmal nocturnal <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;haemoglobinuria&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Excretion of haemoglobin in the urine, resulting in darkened urine; may lead to acute kidney failure if severe &lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/haemoglobinuria\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">haemoglobinuria<\/a> (PNH), like <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;aplastic&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Condition of the non-functional bone marrow that cannot develop blood cells&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/aplastic\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">aplastic<\/a> anaemia (AA), is not <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;malignant&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Characterises abnormal cell growth&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/malignant\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">malignant<\/a>, but is a very rare, acquired and life-threatening disease. It is due to a defect in the blood-developing stem cells of the bone marrow, and is not inherited.<\/p>\n<h4><span style=\"color: #f9a801;\">1.2 Occurrence (epidemiology)<\/span><\/h4>\n<p>The disease frequency (<a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;incidence&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Frequency of new cases per 100,000 inhabitants per year&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/incidence\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">incidence<\/a>) is 1-2 occurrences per million people per year. However, due to the diversity of its symptoms, PNH is rarely recognised and is therefore underdiagnosed. The disease is usually diagnosed in people between the ages of 25 and 45. The frequency of diagnosis is about the same for men and women. There is no familial predisposition.<\/p>\n<h4><span style=\"color: #f9a801;\">1.3 Origin (pathogenesis)<\/span><\/h4>\n<p>PNH is caused by a <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;mutation&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Alteration of genetic material (gene)&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/mutation\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">mutation<\/a> (genetic modification) of blood-developing stem cells in the bone marrow. This modification is not present from birth, but only occurs in later life <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;somatic&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Involving the body&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/somatic\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">somatic<\/a> gene <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;mutation&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Alteration of genetic material (gene)&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/mutation\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">mutation<\/a> and cannot be passed on to children. Healthy and sick cells can be present together at the same time (mosaic).<\/p>\n<p>This gene <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;mutation&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Alteration of genetic material (gene)&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/mutation\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">mutation<\/a> is typically found in a particular section of the genome, the PIG-a gene, and affects one or more types of blood-developing stem cells in the bone marrow. The gene produces an <a class=\"glossaryLink\"  aria-describedby=\"tt\"  data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;enzyme&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Biocatalyst; a protein that mediates all chemical transformations that occur in living organisms (metabolism). The cells of an organism have a specific enzyme for nearly every chemical reaction. &lt;\/div&gt;\"  href=\"https:\/\/aa-pnh.org\/en\/glossar\/enzyme\/\"  data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]'  tabindex='0' role='link'>enzyme<\/a> (a biological catalyst) that is normally required for production of a special anchor system, the glycosylphosphatidylinositol anchor GPI-anchor). This is located on the cell membrane and serves to attach numerous <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;protein&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Macromolecule consisting of one or more long chains of amino acids&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/protein\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">protein<\/a>s to the cell membrane; these <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;protein&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Macromolecule consisting of one or more long chains of amino acids&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/protein\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">protein<\/a>s are involved in regulation of the <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;immune system&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Defence system; system that enables the body to fight off infections and to distinguish between its own and foreign tissues. In humans, the immune system consists of specialised proteins (antibodies), immune cells (white blood cells) and immune organs. It is responsible for our body&amp;#039;s defences(...)&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/immune-system\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">immune system<\/a>. In this way, they protect the cells from an attack by a certain part of the <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;immune system&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Defence system; system that enables the body to fight off infections and to distinguish between its own and foreign tissues. In humans, the immune system consists of specialised proteins (antibodies), immune cells (white blood cells) and immune organs. It is responsible for our body&amp;#039;s defences(...)&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/immune-system\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">immune system<\/a>, the <span style=\"color: #000080;\"><a style=\"color: #000080;\" href=\"#komplsys\">&rdquo;complement system&rsquo;<\/a><\/span>, by marking the cells as &lsquo;self&rsquo; or non-foreign.<\/p>\n<p>Two of these <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;protein&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Macromolecule consisting of one or more long chains of amino acids&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/protein\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">protein<\/a>s play a particularly important role:<\/p>\n<ul>\n<li>Complement Decay Accelerating Factor (DAF, CD55)<\/li>\n<li>Protectin (MAC-IP: Membrane Attack Complex Inhibitory Protein, MIRL: Membrane Inhibitor of Reactive Lysis, CD59)<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<p>Loss or complete absence of GPI-anchored <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;protein&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Macromolecule consisting of one or more long chains of amino acids&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/protein\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">protein<\/a>s on the cell membrane of <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;erythrocyte&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Red blood cell; erythrocytes make up the majority of cellular blood components. They are formed in the bone marrow, contain haemoglobin (the red pigment in blood ) and have a life expectancy of about 120 days in healthy people. The haemoglobin content of the blood is an important measurement(...)&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/erythrocyte\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">erythrocyte<\/a>s, <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;leukocytes&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;White blood cell. Cells with a wide variety of forms and functions. The leukocytes are responsible for defending against pathogens and removing debris due to decaying cells.  &lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/leukocytes\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">leukocytes<\/a> and platelets makes these cells more susceptible to destruction by the <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;complement system&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;A group of plasma proteins for immune defence against microorganisms&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/complement-system\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">complement system<\/a>. This leads to a rupture of the <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;erythrocyte&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Red blood cell; erythrocytes make up the majority of cellular blood components. They are formed in the bone marrow, contain haemoglobin (the red pigment in blood ) and have a life expectancy of about 120 days in healthy people. The haemoglobin content of the blood is an important measurement(...)&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/erythrocyte\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">erythrocyte<\/a>s in the blood vessels (<a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;intravascular haemolysis&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Breakdown of red blood cells inside the blood vessels&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/intravascular-haemolysis\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">intravascular haemolysis<\/a>) and activation of the platelets, which can lead to <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;thrombosis&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Vascular disease in which a clot forms in a blood vessel; can occur in any vessel, most commonly in veins, especially in the deep veins of the legs&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/thrombosis\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">thrombosis<\/a>.<\/p>\n<p><a id=\"komplsys\"><\/a><strong>The <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;complement system&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;A group of plasma proteins for immune defence against microorganisms&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/complement-system\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">complement system<\/a> serves to defend the body against infectious agents, parasites, foreign molecules, etc. Once activated, a progressive cascade-like process (<a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;complement cascade&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Once the complement system has been activated, a cascade-like process takes place for immune defence&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/complement-cascade\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">complement cascade<\/a>) starts, which can end with destruction of the target cell.<\/strong><\/p>\n<p><\/p><\/ul><ul style=\"margin-top:0;margin-bottom:0\"><style type=\"text\/css\">a.bg-showmore-plg-link:hover,a.bg-showmore-plg-link:active,a.bg-showmore-plg-link:focus{color:#0071bb;}<\/style>\n<input type=\"hidden\" bg_collapse_expand_pro=\"69e60b5ac12205014768219\" value=\"69e60b5ac12205014768219\"><input type=\"hidden\" id=\"bg-show-more-text-69e60b5ac12205014768219\" value=\"  2 Symptoms\"><input type=\"hidden\" id=\"bg-show-less-text-69e60b5ac12205014768219\" value=\"  2 Symptoms\"><input type=\"hidden\" id=\"bg-icon-bg-color-69e60b5ac12205014768219\" value=\"\"><a id=\"bg-showmore-action-69e60b5ac12205014768219\" class=\"bg-showmore-plg-link bg-arrow  \" style=\"color:#f9a801;;font-weight:bold; font-size:24px; line-height: 150%\" href=\"#\">  2 Symptoms<\/a><\/ul><ul class=\"bg-showmore-no-padding-no-margin bg-showmore-closed\" id=\"bg-showmore-pro-hidden-69e60b5ac12205014768219\">\n<h4><span style=\"color: #f9a801;\">2.1 Low cell counts (Cytopenia)<\/span><\/h4>\n<p>&nbsp;<\/p>\n<h5><span style=\"color: #f9a801;\">Anaemia<\/span><\/h5>\n<p>Destruction of red blood cells (<a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;haemolysis&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Breakdown of red blood cells&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/haemolysis\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">haemolysis<\/a>) can lead to anaemia and the loss of oxygen carriers (<a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;haemoglobin&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Hb; red blood cell pigment consisting of haem (an iron-containing component) and globin (a protein). Binds, transports and releases oxygen and carbon dioxide. Reference values: women 12-16 g\/dl or 7.5-9.9 mmol\/l, men 14-18 g\/dl or 8.7-11.2 mmol\/l &lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/haemoglobin\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">haemoglobin<\/a>).<\/p>\n<p><strong>Symptoms include:<\/strong><\/p>\n<ul>\n<li>Pale skin (non-specific sign)<\/li>\n<li>Loss of stamina, lack of concentration, depression, <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;fatigue&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Severe tiredness, exhaustion or increased need for rest; a symptom that often accompanies various chronic diseasesitet&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/fatigue\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">fatigue<\/a>, heavy legs and rapid <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;fatigue&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Severe tiredness, exhaustion or increased need for rest; a symptom that often accompanies various chronic diseasesitet&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/fatigue\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">fatigue<\/a><\/li>\n<li>Shortness of breath (<a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;dyspnoea&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Shortness of breath&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/dyspnoea\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">dyspnoea<\/a>) under load due to a smaller number of oxygen carriers<\/li>\n<li>Dizziness, ringing in the ears, increased heart rate (<a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;tachycardia&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Accelerated heartbeat (over 100 beats per minute in adults)&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/tachycardia\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">tachycardia<\/a>), chest pain (angina pectoris), visual disturbances<\/li>\n<\/ul>\n<p><strong><a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;Anaemia&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Reduction of red blood cells or their content of (blood pigment); as a result of blood loss, reduced haemoglobin production, reduced blood cell development due to bone marrow diseases, increased blood cell decay due to poisoning and metabolic disorders. Anaemia leads to reduced physical capacity. &lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/anaemia\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">Anaemia<\/a> may be so severe that <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;transfusion&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Transfer of blood or blood components&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/transfusion\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">transfusion<\/a> of red blood cells (<a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;erythrocyte&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Red blood cell; erythrocytes make up the majority of cellular blood components. They are formed in the bone marrow, contain haemoglobin (the red pigment in blood ) and have a life expectancy of about 120 days in healthy people. The haemoglobin content of the blood is an important measurement(...)&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/erythrocyte\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">erythrocyte<\/a> concentrates) becomes necessary.<\/strong><\/p>\n<h5><span style=\"color: #f9a801;\">Further loss of cell lines<\/span><\/h5>\n<p>In addition to the red blood cell line, other blood cell lines may be reduced (<a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;cytopenia&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Reduction in the number of cells in the blood, e.g. erythro-, leuko-, granulo-, lympho- or thrombocytopenia&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/cytopenia\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">cytopenia<\/a>), such as platelets (<a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;thrombocytopenia&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Platelet deficiency&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/thrombocytopenia\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">thrombocytopenia<\/a>) or <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;granulocytes&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;subgroup of white blood cells They destroy invading bacteria that can cause diseases. &lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/granulocytes\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">granulocytes<\/a> (<a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;neutropenia&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Deficiency of neutrophils&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/neutropenia\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">neutropenia<\/a>).<\/p>\n<p>&nbsp;<\/p>\n<h4><span style=\"color: #f9a801;\">2.2 Effects of haemolysis<\/span><\/h4>\n<p>Destruction of red blood cells leads to increased levels of bilirubin (a bile pigment) in the blood. This may cause the skin and the <a class=\"glossaryLink\"  aria-describedby=\"tt\"  data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;sclera&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;White outer layer of the eyeball that surrounds and protects it.&lt;\/div&gt;\"  href=\"https:\/\/aa-pnh.org\/en\/glossar\/sclera\/\"  data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]'  tabindex='0' role='link'>sclera<\/a> (white outer layer of the eyeball) to turn yellow. This is also referred to as jaundice.<\/p>\n<p>Haemoglobin is also released when the red blood cells break down. If the levels of free <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;haemoglobin&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Hb; red blood cell pigment consisting of haem (an iron-containing component) and globin (a protein). Binds, transports and releases oxygen and carbon dioxide. Reference values: women 12-16 g\/dl or 7.5-9.9 mmol\/l, men 14-18 g\/dl or 8.7-11.2 mmol\/l &lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/haemoglobin\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">haemoglobin<\/a> become excessive, some can be eliminated via the kidney, resulting in dark, red-brown urine (<a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;haemoglobinuria&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Excretion of haemoglobin in the urine, resulting in darkened urine; may lead to acute kidney failure if severe &lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/haemoglobinuria\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">haemoglobinuria<\/a>). <\/p>\n<p>Free <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;haemoglobin&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Hb; red blood cell pigment consisting of haem (an iron-containing component) and globin (a protein). Binds, transports and releases oxygen and carbon dioxide. Reference values: women 12-16 g\/dl or 7.5-9.9 mmol\/l, men 14-18 g\/dl or 8.7-11.2 mmol\/l &lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/haemoglobin\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">haemoglobin<\/a> leads to reduced availablity of nitric oxide (NO) via various intermediate steps. Nitric oxide is required for relaxation of smooth muscle (located e.g. in the gastrointestinal tract and lungs); insufficient levels of NO result in increased tension of the smooth muscles, e.g. spasms and constriction of vessels.<\/p>\n<p>This explains many of the clinical symptoms of PNH:<\/p>\n<ul>\n<li>Severe, often crisis-type abdominal pain<\/li>\n<li>Cramping of the oesophagus with swallowing disorders (<a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;dysphagia&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Problems with swallowing&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/dysphagia\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">dysphagia<\/a>)<\/li>\n<li>High blood pressure (Hypertension)<\/li>\n<li>High blood pressure in the lung circulation (<a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;pulmonary hypertension&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Pulmonary hypertension. A disease characterised by an increase in blood pressure in the pulmonary circulation and often by an increasing rise in vascular resistance in the pulmonary arteries. Patients suffer from severely restricted physical performance, circulatory disorders and fatigue. &lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/pulmonary-hypertension\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">pulmonary hypertension<\/a>) with shortness of breath Renal insufficiency Erectile dysfunction<\/li>\n<li>Renal insufficiency<\/li>\n<li>Erectile dysfunction<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<h4><span style=\"color: #f9a801;\">2.3 Fatigue<\/span><\/h4>\n<p>Fatigue is unusually persistant tiredness or exhaustion that may significantly impair physical and mental performance. It is characterised by the fact that increased rest or sleep results in little or no improvement. <\/p>\n<p>Potential causes of <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;fatigue&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Severe tiredness, exhaustion or increased need for rest; a symptom that often accompanies various chronic diseasesitet&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/fatigue\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">fatigue<\/a> are anaemia and destruction of red blood cells with the resulting lack of nitric oxide (NO), as well as disorders of the <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;immune system&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Defence system; system that enables the body to fight off infections and to distinguish between its own and foreign tissues. In humans, the immune system consists of specialised proteins (antibodies), immune cells (white blood cells) and immune organs. It is responsible for our body&amp;#039;s defences(...)&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/immune-system\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">immune system<\/a> and\/or metabolism.<\/p>\n<p>&nbsp;<\/p>\n<h4><span style=\"color: #f9a801;\">2.4 Thrombosis tendency (Thrombophilia)<\/span><\/h4>\n<p>One of the most dangerous consequences of the lack of nitric oxide is formation of blood clots (<a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;thrombosis&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Vascular disease in which a clot forms in a blood vessel; can occur in any vessel, most commonly in veins, especially in the deep veins of the legs&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/thrombosis\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">thrombosis<\/a>). The platelets are presumably activated by the NO deficiency, and this causes abnormal clots. These can occur in various parts of the body, including the liver or brain and both arteries and <a class=\"glossaryLink\"  aria-describedby=\"tt\"  data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;vein&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Blood vessel that leads to the heart and transports oxygen-poor blood (exception: pulmonary vein)&lt;\/div&gt;\"  href=\"https:\/\/aa-pnh.org\/en\/glossar\/vein\/\"  data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]'  tabindex='0' role='link'>vein<\/a>s. The symptoms and complaints associated with PNH may be permanent. In addition, activation of the <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;complement system&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;A group of plasma proteins for immune defence against microorganisms&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/complement-system\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">complement system<\/a> by infections, pregnancy or stress may lead to further exacerbation of the symptoms, including greatly increased destruction of red blood cells (<a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;haemolytic crisis&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Sudden massive haemolysis. Possible signs are fever, chills, circulatory problems up to and including collapse, abdominal pain, backache, headache, dark urine and later yellowing of the skin. &lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/haemolytic-crisis\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">haemolytic crisis<\/a>). This condition may be life-threatening if not treated. Blood clots can clog the small blood vessels in the kidneys, which can lead to <a class=\"glossaryLink\"  aria-describedby=\"tt\"  data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;acute&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Sudden onset, rapidly progressing&lt;\/div&gt;\"  href=\"https:\/\/aa-pnh.org\/en\/glossar\/acute\/\"  data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]'  tabindex='0' role='link'>acute<\/a> kidney failure. There is also an increased risk of <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;thrombosis&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Vascular disease in which a clot forms in a blood vessel; can occur in any vessel, most commonly in veins, especially in the deep veins of the legs&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/thrombosis\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">thrombosis<\/a> during these <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;haemolytic&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Breakdown of red blood cells&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/haemolytic\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">haemolytic<\/a> crises. In these situations <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;packed RBCs&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;packed RBCs; blood with concentrated red blood cells (erythrocytes), which are collected from donors &lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/packed-rbcs\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">packed RBCs<\/a> (<a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;erythrocyte&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Red blood cell; erythrocytes make up the majority of cellular blood components. They are formed in the bone marrow, contain haemoglobin (the red pigment in blood ) and have a life expectancy of about 120 days in healthy people. The haemoglobin content of the blood is an important measurement(...)&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/erythrocyte\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">erythrocyte<\/a> concentrates) are often required.  <\/p>\n<p><\/p><\/ul><ul style=\"margin-top:0;margin-bottom:0\"><style type=\"text\/css\">a.bg-showmore-plg-link:hover,a.bg-showmore-plg-link:active,a.bg-showmore-plg-link:focus{color:#0071bb;}<\/style>\n<input type=\"hidden\" bg_collapse_expand_pro=\"69e60b5ac12c91008667996\" value=\"69e60b5ac12c91008667996\"><input type=\"hidden\" id=\"bg-show-more-text-69e60b5ac12c91008667996\" value=\"  3 Diagnosis\"><input type=\"hidden\" id=\"bg-show-less-text-69e60b5ac12c91008667996\" value=\"  3 Diagnosis\"><input type=\"hidden\" id=\"bg-icon-bg-color-69e60b5ac12c91008667996\" value=\"\"><a id=\"bg-showmore-action-69e60b5ac12c91008667996\" class=\"bg-showmore-plg-link bg-arrow  \" style=\"color:#f9a801;;font-weight:bold; font-size:24px; line-height: 150%\" href=\"#\">  3 Diagnosis<\/a><\/ul><ul class=\"bg-showmore-no-padding-no-margin bg-showmore-closed\" id=\"bg-showmore-pro-hidden-69e60b5ac12c91008667996\">\n<p>The method used to diagnose PNH is <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;flow cytometry&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Measurement method that enables the analysis of cells that each pass an electric voltage or a light beam at high speed. Depending on the shape, structure and\/or colouring of the cells, different effects are produced, from which the properties of the cells can be recorded. Used in the diagnosis(...)&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/flow-cytometry\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">flow cytometry<\/a>. This method is very sensitive and can detect a very small number of cells that have been altered as a result of the disease. In addition, the proportion of affected cells (the <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;PNH clone&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;All blood cells affected by the mutation typical of PNH; the size of the PNH clone is a measure of the severity of the disease&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/pnh-clone\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">PNH clone<\/a> size) and the affected cell types (e.g. <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;erythrocyte&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Red blood cell; erythrocytes make up the majority of cellular blood components. They are formed in the bone marrow, contain haemoglobin (the red pigment in blood ) and have a life expectancy of about 120 days in healthy people. The haemoglobin content of the blood is an important measurement(...)&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/erythrocyte\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">erythrocyte<\/a>s or <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;granulocytes&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;subgroup of white blood cells They destroy invading bacteria that can cause diseases. &lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/granulocytes\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">granulocytes<\/a>) are determined very accurately. Venous (<a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;peripheral&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Area outside a centre or origin; peripheral blood is blood in the peripheral circulation&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/peripheral\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">peripheral<\/a> blood) is used for this test.   <\/p>\n<p><strong>Additional tests are usually carried out during the initial diagnosis:<\/strong><\/p>\n<ul>\n<li>The patient&rsquo;s (and family&rsquo;s) medical history (<a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;anamnesis&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Medical history, development of symptoms&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/anamnesis\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">anamnesis<\/a>) are taken, including a targeted survey of symptoms typical of PNH (see Section <span style=\"color: #000080;\"><a style=\"color: #000080;\" href=\"#symptome\">2 Symptoms<\/a><\/span><\/li>\n<li>Physical examination with regard to the special aspects mentioned above: signs of anaemia or jaundice, <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;indication&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Reason to perform a medical procedure&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/indication\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">indication<\/a>s of <a class=\"glossaryLink\"  aria-describedby=\"tt\"  data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;acute&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Sudden onset, rapidly progressing&lt;\/div&gt;\"  href=\"https:\/\/aa-pnh.org\/en\/glossar\/acute\/\"  data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]'  tabindex='0' role='link'>acute<\/a> or previous <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;thrombosis&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Vascular disease in which a clot forms in a blood vessel; can occur in any vessel, most commonly in veins, especially in the deep veins of the legs&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/thrombosis\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">thrombosis<\/a>, evidence of bleeding, constitutional abnormalities such as congenital <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;aplastic&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Condition of the non-functional bone marrow that cannot develop blood cells&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/aplastic\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">aplastic<\/a> anaemia (see Chapter 3 AA), and enlargement of the spleen (<a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;splenomegaly&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Enlargement of the spleen e.g. in leukaemia and lymphoma, infection with bacteria or viruses, rheumatic disease, (lysosomal) storage disease. An enlarged spleen may store blood cells and cause a general lack of blood cells (pancytopenia). The underlying disease needs to be treated, and in rare(...)&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/splenomegaly\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">splenomegaly<\/a>)<\/li>\n<li>Cell investigations\n<ul>\n<li style=\"list-style-type: none;\">\n<ul>\n<li style=\"list-style-type: none;\">\n<ul>\n<li>Microscopic differential haemogram<\/li>\n<li>Reticulocytes<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<\/li>\n<li>Clinical chemistry\n<ul>\n<li style=\"list-style-type: none;\">\n<ul>\n<li style=\"list-style-type: none;\">\n<ul>\n<li>Haemolysis parameters: in particular <a class=\"glossaryLink\"  aria-describedby=\"tt\"  data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;LDH&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;lactate dehydrogenase; marker in the blood indicating cell damage&lt;\/div&gt;\"  href=\"https:\/\/aa-pnh.org\/en\/glossar\/ldh\/\"  data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]'  tabindex='0' role='link'>LDH<\/a>, haptoglobin, bilirubin<\/li>\n<li>Renal function parameters: <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;creatinine&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Nitrogenous metabolic end product that is excreted via the kidneys. An elevated creatinine level in the blood indicates impaired kidney function &lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/creatinine\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">creatinine<\/a>, urea<\/li>\n<li>Levels of vitamin B12 and folic acid<\/li>\n<li>Iron status: <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;ferritin&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Protein that stores iron; if ECs are given frequently, the ferritin level should be monitored in case chelation therapy becomes necessary.&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/ferritin\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">ferritin<\/a>, transferrin, transferrin saturation, <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;reticulocyte&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Young, immature red blood cell; precursor of erythrocyte&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/reticulocyte\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">reticulocyte<\/a> <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;haemoglobin&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Hb; red blood cell pigment consisting of haem (an iron-containing component) and globin (a protein). Binds, transports and releases oxygen and carbon dioxide. Reference values: women 12-16 g\/dl or 7.5-9.9 mmol\/l, men 14-18 g\/dl or 8.7-11.2 mmol\/l &lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/haemoglobin\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">haemoglobin<\/a>. With <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;ferritin&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Protein that stores iron; if ECs are given frequently, the ferritin level should be monitored in case chelation therapy becomes necessary.&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/ferritin\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">ferritin<\/a> values&gt; &gt; 1000 &micro;g\/l, further clarification of possible organ damage due to possible iron overload <\/li>\n<li><a class=\"glossaryLink\"  aria-describedby=\"tt\"  data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;BNP&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Brain (Ventricular) Natriuretic Peptide; hormone produced in the heart that stimulates the kidneys to excrete sodium and fluids&lt;\/div&gt;\"  href=\"https:\/\/aa-pnh.org\/en\/glossar\/bnp\/\"  data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]'  tabindex='0' role='link'>BNP<\/a> (B-type natriueretic peptide) value in the blood serum to assess function of the right heart<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<\/li>\n<li>Functional diagnostics\n<ul>\n<li style=\"list-style-type: none;\">\n<ul>\n<li style=\"list-style-type: none;\">\n<ul>\n<li>Ultrasound of abdomen<\/li>\n<li>Lung function<\/li>\n<li>ECG<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<p>Diagnostic tests of bone marrow with <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;cytology&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;The field of general biology that covers the structure and function of cells&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/cytology\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">cytology<\/a>, <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;cytogenetics&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;A branch of genetics in which the number and structure of the chromosomes of a dividing cell are examined under a microscope&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/cytogenetics\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">cytogenetics<\/a>, and <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;histology&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Science of tissues: the branch of medicine that involves tissues at the microscopic level&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/histology\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">histology<\/a> should be performed at the time of the initial diagnosis. This is particularly important if there is also <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;cytopenia&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Reduction in the number of cells in the blood, e.g. erythro-, leuko-, granulo-, lympho- or thrombocytopenia&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/cytopenia\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">cytopenia<\/a> severe enough that PNH in connection with another haematological disease (e.g. <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;aplastic&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Condition of the non-functional bone marrow that cannot develop blood cells&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/aplastic\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">aplastic<\/a> anaemia or myelodysplastic syndrome (MDS)) must be suspected. With evidence of PNH cells (<a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;PNH clone&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;All blood cells affected by the mutation typical of PNH; the size of the PNH clone is a measure of the severity of the disease&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/pnh-clone\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">PNH clone<\/a>) or diagnosis of a <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;bone marrow insufficiency&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Reduced production of blood cells in the bone marrow&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/bone-marrow-insufficiency\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">bone marrow insufficiency<\/a> syndrome, check-ups should be carried out every 6 months, especially in the first two years after initial diagnosis and in the case of new symptoms. It is important to measure the extent of the <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;PNH clone&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;All blood cells affected by the mutation typical of PNH; the size of the PNH clone is a measure of the severity of the disease&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/pnh-clone\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">PNH clone<\/a> as a proportion of the total number of bone marrow cells. This parameter is useful for estimating the prognosis and managing treatment of the disease. <\/p>\n<p><\/p><\/ul><ul style=\"margin-top:0;margin-bottom:0\"><style type=\"text\/css\">a.bg-showmore-plg-link:hover,a.bg-showmore-plg-link:active,a.bg-showmore-plg-link:focus{color:#0071bb;}<\/style>\n<input type=\"hidden\" bg_collapse_expand_pro=\"69e60b5ac13687028274701\" value=\"69e60b5ac13687028274701\"><input type=\"hidden\" id=\"bg-show-more-text-69e60b5ac13687028274701\" value=\"  4 Clinical course\"><input type=\"hidden\" id=\"bg-show-less-text-69e60b5ac13687028274701\" value=\"  4 Clinical course\"><input type=\"hidden\" id=\"bg-icon-bg-color-69e60b5ac13687028274701\" value=\"\"><a id=\"bg-showmore-action-69e60b5ac13687028274701\" class=\"bg-showmore-plg-link bg-arrow  \" style=\"color:#f9a801;;font-weight:bold; font-size:24px; line-height: 150%\" href=\"#\">  4 Clinical course<\/a><\/ul><ul class=\"bg-showmore-no-padding-no-margin bg-showmore-closed\" id=\"bg-showmore-pro-hidden-69e60b5ac13687028274701\">\n<h4><span style=\"color: #f9a801;\">4.1 General<\/span><\/h4>\n<p>The symptoms and handicaps associated with PNH can vary widely and may lead to deterioration of the quality of life.<\/p>\n<p>Due to the mechanisms of the disease (mentioned above), arterial and <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;pulmonary hypertension&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Pulmonary hypertension. A disease characterised by an increase in blood pressure in the pulmonary circulation and often by an increasing rise in vascular resistance in the pulmonary arteries. Patients suffer from severely restricted physical performance, circulatory disorders and fatigue. &lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/pulmonary-hypertension\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">pulmonary hypertension<\/a> (high blood pressure in the body and lungs) as well as kidney dysfunction can occur. These problems can lead to permanent damage and require continuous follow-up. <\/p>\n<h4><span style=\"color: #f9a801;\">4.2 Blood Clots (Thrombosis\/Thromboembolism)<\/span><\/h4>\n<p>The most feared complication of PNH is formation of blood clots (<a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;thrombosis&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Vascular disease in which a clot forms in a blood vessel; can occur in any vessel, most commonly in veins, especially in the deep veins of the legs&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/thrombosis\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">thrombosis<\/a>\/<a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;thromboembolism&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;A blood clot that is carried into the bloodstream and leads to closure of the affected blood vessel, which is then unable to supply the corresponding organs &lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/thromboembolism\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">thromboembolism<\/a>), which can block blood vessels. According to trials, the probability of <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;thrombosis&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Vascular disease in which a clot forms in a blood vessel; can occur in any vessel, most commonly in veins, especially in the deep veins of the legs&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/thrombosis\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">thrombosis<\/a> occurring without specific PNH therapy was over 30% within 10 years. Approximately 30-50% of all PNH patients develop <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;thrombosis&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Vascular disease in which a clot forms in a blood vessel; can occur in any vessel, most commonly in veins, especially in the deep veins of the legs&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/thrombosis\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">thrombosis<\/a> in the course of their disease without specific treatment measures. Complications of <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;thromboembolism&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;A blood clot that is carried into the bloodstream and leads to closure of the affected blood vessel, which is then unable to supply the corresponding organs &lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/thromboembolism\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">thromboembolism<\/a> are responsible for up to 67% of all deaths due to PNH. The probability of <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;thrombosis&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Vascular disease in which a clot forms in a blood vessel; can occur in any vessel, most commonly in veins, especially in the deep veins of the legs&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/thrombosis\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">thrombosis<\/a> may also depend on the number of PNH cells, although even patients with only a few PNH cells have an increased risk of <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;thrombosis&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Vascular disease in which a clot forms in a blood vessel; can occur in any vessel, most commonly in veins, especially in the deep veins of the legs&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/thrombosis\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">thrombosis<\/a>.    <\/p>\n<p><\/p><div id=\"attachment_3516\" style=\"width: 672px\" class=\"wp-caption alignnone\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-3516\" class=\"wp-image-3516\" src=\"https:\/\/aa-pnh.org\/wp-content\/uploads\/2019\/08\/pnh_thrombose_web.gif\" alt=\"Diagnosis of PNH: potential locations of thromboses\" width=\"662\" height=\"347\"\/><p id=\"caption-attachment-3516\" class=\"wp-caption-text\"><em>Thrombosis in PNH patients occurs in several areas, both typical and atypical:<\/em><\/p><\/div>\n<p>&nbsp;<\/p>\n<h4><span style=\"color: #f9a801;\">4.3 Kidney disease<\/span><\/h4>\n<p>Two-thirds of all patients with PNH have kidney disease. This is usually due to impairment of the filtering function of the kidney, and therefore its ability to purify the blood plasma. The parameter for plasma purification is <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;creatinine&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Nitrogenous metabolic end product that is excreted via the kidneys. An elevated creatinine level in the blood indicates impaired kidney function &lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/creatinine\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">creatinine<\/a> clearance, which is a measure of how long it takes for <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;creatinine&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Nitrogenous metabolic end product that is excreted via the kidneys. An elevated creatinine level in the blood indicates impaired kidney function &lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/creatinine\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">creatinine<\/a> (a product of muscle degradation) to be cleared from the blood plasma. The filter function and <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;creatinine&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Nitrogenous metabolic end product that is excreted via the kidneys. An elevated creatinine level in the blood indicates impaired kidney function &lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/creatinine\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">creatinine<\/a> clearance may both deteriorate during the course of the disease.   <\/p>\n<h4><span style=\"color: #f9a801;\">4.4 Reduced cell numbers (Cytopenias)<\/span><\/h4>\n<p>Significant diminution of blood cell numbers due to concomitant bone marrow disease is the second-most common cause of serious complications (20%). In the course of PNH, approximately 15% of patients develop <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;aplastic&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Condition of the non-functional bone marrow that cannot develop blood cells&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/aplastic\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">aplastic<\/a> anaemia with the absence of all three blood cell lines (<a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;pancytopenia&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Tricytopenia; deficiency of blood cells of all three cell lines (erythrocytes, leukocytes, platelets)&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/pancytopenia\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">pancytopenia<\/a>). Conversely, <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;aplastic&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Condition of the non-functional bone marrow that cannot develop blood cells&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/aplastic\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">aplastic<\/a> anaemia can develop first and be followed by PNH.  <\/p>\n<p><\/p><\/ul><ul style=\"margin-top:0;margin-bottom:0\"><style type=\"text\/css\">a.bg-showmore-plg-link:hover,a.bg-showmore-plg-link:active,a.bg-showmore-plg-link:focus{color:#0071bb;}<\/style>\n<input type=\"hidden\" bg_collapse_expand_pro=\"69e60b5ac154c0047109663\" value=\"69e60b5ac154c0047109663\"><input type=\"hidden\" id=\"bg-show-more-text-69e60b5ac154c0047109663\" value=\"  5 Treatment\"><input type=\"hidden\" id=\"bg-show-less-text-69e60b5ac154c0047109663\" value=\"  5 Treatment\"><input type=\"hidden\" id=\"bg-icon-bg-color-69e60b5ac154c0047109663\" value=\"\"><a id=\"bg-showmore-action-69e60b5ac154c0047109663\" class=\"bg-showmore-plg-link bg-arrow  \" style=\"color:#f9a801;;font-weight:bold; font-size:24px; line-height: 150%\" href=\"#\">  5 Treatment<\/a><\/ul><ul class=\"bg-showmore-no-padding-no-margin bg-showmore-closed\" id=\"bg-showmore-pro-hidden-69e60b5ac154c0047109663\">\n<h4><span style=\"color: #f9a801;\">5.1 Overview<\/span><\/h4>\n<p>How PNH is treated depends on the patient&rsquo;s symptoms. In the absence of relevant symptoms, only detailed check-ups are justified. Supportive measures and medication to inhibit blood clotting (anticoagulation), incorrectly referred to as &lsquo;blood thinning&rsquo;, may be considered. With symptomatic PNH, the type of treatment depends, among other things, on the severity of blood cell destruction (<a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;haemolysis&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Breakdown of red blood cells&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/haemolysis\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">haemolysis<\/a>) and the presence of blood clots.   <\/p>\n<p>The following diagram illustrates the treatment concept used for <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;haemolytic&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Breakdown of red blood cells&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/haemolytic\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">haemolytic<\/a> PNH.<\/p>\n<p><\/p><div id=\"attachment_3517\" style=\"width: 749px\" class=\"wp-caption alignnone\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-3517\" class=\"wp-image-3517\" src=\"https:\/\/aa-pnh.org\/wp-content\/uploads\/PNHalgorithmEN2024.png\" alt=\"Simplified presentation of the therapy algorithm.\" width=\"739\" height=\"658\"\/><p id=\"caption-attachment-3517\" class=\"wp-caption-text\"><em>Simplified presentation of the therapy algorithm. For the complete algorithm, please visit <\/em> <a href=\"https:\/\/www.onkopedia.com\/de\/onkopedia\/guidelines\/paroxysmale-naechtliche-haemoglobinurie-pnh\/@@guideline\/html\/index.html\" target=\"_blank\" rel=\"noopener noreferrer\">Onkopedia <\/a> (German).<\/p><\/div>\n<p>&nbsp;<\/p>\n<h4><span style=\"color: #f9a801;\">5.2 Specific treatment<\/span><\/h4>\n<p>Since the <span style=\"color: #000080;\"><a style=\"color: #000080;\" href=\"#komplsys\">complement system<\/a><\/span> attacks the diseased red blood cells, partial inhibition of the system can suppress such destruction.<\/p>\n<p>Since 2007, the only treatment available for PNH therapy has been the eculizumab <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;antibody&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;A protein normally produced by the immune system to defend against a pathogen that has entered the body or another threat; an antibody binds specifically to certain surface structures of the intruder, and triggers a series of further immune reactions that ultimately lead to the killing and(...)&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/antibody\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">antibody<\/a>, which must be infused every two weeks. In July 2019, ravulizumab (a development of eculizumab) was authorised in the EU. The new <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;antibody&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;A protein normally produced by the immune system to defend against a pathogen that has entered the body or another threat; an antibody binds specifically to certain surface structures of the intruder, and triggers a series of further immune reactions that ultimately lead to the killing and(...)&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/antibody\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">antibody<\/a> is administered as an <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;infusion&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Injection of a liquid into a vein&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/infusion\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">infusion<\/a> every eight weeks, and according to one trial it is not less effective than and and compatble with the previous standard therapy.  <\/p>\n<p>The following description relates to eculizumab, for which data is available for a much longer timespan. <strong>The information on function, precautions and behavioural recommendations is analogous to that for treatment with ravulizumab.<\/strong><\/p>\n<p>Eculizumab blocks activity of the C5 <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;protein&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Macromolecule consisting of one or more long chains of amino acids&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/protein\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">protein<\/a>, part of the <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;complement system&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;A group of plasma proteins for immune defence against microorganisms&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/complement-system\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">complement system<\/a>. Various studies have shown that with this blockade, eculizumab greatly reduces the destruction of red blood cells in the blood vessels (<a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;intravascular haemolysis&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Breakdown of red blood cells inside the blood vessels&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/intravascular-haemolysis\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">intravascular haemolysis<\/a>). There was a significant improvement in the quality of life for PNH patients treated with eculizumab. This improvement was even observed in patients who did not experience normalisation of <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;haemoglobin&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Hb; red blood cell pigment consisting of haem (an iron-containing component) and globin (a protein). Binds, transports and releases oxygen and carbon dioxide. Reference values: women 12-16 g\/dl or 7.5-9.9 mmol\/l, men 14-18 g\/dl or 8.7-11.2 mmol\/l &lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/haemoglobin\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">haemoglobin<\/a> levels. This suggests that, in addition to improving anaemia, part of the effect is due to blockage of the blood destruction (<a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;haemolysis&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Breakdown of red blood cells&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/haemolysis\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">haemolysis<\/a>) itself. As a further consequence of the reduced destruction of the red blood cells, there was a significant decrease in the <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;transfusion&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Transfer of blood or blood components&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/transfusion\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">transfusion<\/a> requirement, anaemia, <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;fatigue&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Severe tiredness, exhaustion or increased need for rest; a symptom that often accompanies various chronic diseasesitet&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/fatigue\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">fatigue<\/a>, crisis-type abdominal pain, as well as a reduction in high blood pressure (<a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;arterial hypertension&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Arterial hypertension. A clinical picture in which blood pressure in the arterial system is chronically elevated. A systolic blood pressure of more than 140 mmHg and\/or a diastolic blood pressure of more than 90 mmHg is regarded as hypertension. Temporary increases in blood pressure due to(...)&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/arterial-hypertension\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">arterial hypertension<\/a>) and <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;pulmonary hypertension&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Pulmonary hypertension. A disease characterised by an increase in blood pressure in the pulmonary circulation and often by an increasing rise in vascular resistance in the pulmonary arteries. Patients suffer from severely restricted physical performance, circulatory disorders and fatigue. &lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/pulmonary-hypertension\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">pulmonary hypertension<\/a>. In addition, clinical trials showed improvement or even normalisation of kidney function after a previous <a class=\"glossaryLink\"  aria-describedby=\"tt\"  data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;renal&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Involving the kidney&lt;\/div&gt;\"  href=\"https:\/\/aa-pnh.org\/en\/glossar\/renal\/\"  data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]'  tabindex='0' role='link'>renal<\/a> impairment. <\/p>\n<p><\/p><div id=\"attachment_3515\" style=\"width: 554px\" class=\"wp-caption alignnone\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-3515\" class=\"wp-image-3515\" src=\"https:\/\/aa-pnh.org\/wp-content\/uploads\/2019\/08\/ecu_verb_web-e1564826894856.gif\" alt=\"Eculizumab treatment in PNH: Improvement of symptoms\" width=\"544\" height=\"319\"\/><p id=\"caption-attachment-3515\" class=\"wp-caption-text\"><em>Effect of eculizumab with treatment of PNH<\/em><\/p><\/div>\n<p><strong>Medical reasons for treatment with eculizumab include<\/strong><\/p>\n<ul>\n<li>Blood clots<\/li>\n<li>Crisis-type abdominal pain<\/li>\n<li>Haemolytic crises<\/li>\n<li>PNH-related impairment of kidney function<\/li>\n<li>Need for <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;transfusion&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Transfer of blood or blood components&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/transfusion\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">transfusion<\/a><\/li>\n<li>Pulmonary hypertension associated with PNH<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<ul>\n<li style=\"list-style-type: none;\">\n<ul>\n<li style=\"list-style-type: none;\">\n<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p><strong>The aim of treatment is to prevent serious, life-threatening complications and resulting damage to the affected organs.<\/strong> Eculizumab is administered as an <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;infusion&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Injection of a liquid into a vein&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/infusion\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">infusion<\/a> into a <a class=\"glossaryLink\"  aria-describedby=\"tt\"  data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;vein&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Blood vessel that leads to the heart and transports oxygen-poor blood (exception: pulmonary vein)&lt;\/div&gt;\"  href=\"https:\/\/aa-pnh.org\/en\/glossar\/vein\/\"  data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]'  tabindex='0' role='link'>vein<\/a> (<a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;intravenous&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;i.v.; injection of a medication into a vein&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/intravenous\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">intravenous<\/a>) and can be administered on an outpatient basis. The <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;infusion&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Injection of a liquid into a vein&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/infusion\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">infusion<\/a> is usually given once a week for saturation in the first four weeks, and then every two weeks as maintenance therapy. The data from authorisation studies and current evaluations of long-term therapy show that this therapy is very well tolerated. Headaches are a very common side effect at the start of therapy. Infections, changes in blood count, insomnia, gastrointestinal symptoms, skin problems, flu-like symptoms and <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;fatigue&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Severe tiredness, exhaustion or increased need for rest; a symptom that often accompanies various chronic diseasesitet&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/fatigue\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">fatigue<\/a> are among the common side effects. Due to inhibition of the <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;complement system&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;A group of plasma proteins for immune defence against microorganisms&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/complement-system\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">complement system<\/a>, the body cannot provide sufficient protection against certain bacteria (<a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;meningococci&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Bacteria that colonise the nasopharynx and can lead to serious diseases, e.g. meningitis. They are transmitted from person to person by droplet infection, for example when coughing, sneezing or kissing. There are 13 known meningococcal groups (A, B, C, D, 29E, H, I, K, L, W-135, X, Y and Z).(...)&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/meningococci\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">meningococci<\/a>), which can cause blood poisoning or bacterial meningitis. Vaccination against meningococcal disease is therefore absolutely necessary during treatment with eculizumab. Two different vaccines are recommended (Menveo&reg;\/Nimenrix&reg; and Bexsero&reg;\/Trumenba&reg;) to cover as many of the meningococcal strains as possible (a, C, W135, Y at the start of therapy and B during ongoing therapy), although 100% protection is not achieved. Booster vaccinations should be given every three years. <\/p>\n<p><strong>In case of fever ( &gt; 38,0 &deg;C), rash, strong feeling of illness or neck stiffness, it is crucial that &ldquo;stand-by therapy&rdquo; (e.g. ciprofloxacin 750 mg) is provided as soon as possible and a doctor is consulted immediately to initiate further diagnosis and, if necessary, extended antibiotic therapy. If ciprofloxacin cannot be given, amoxicillin or clavulanic acid 1000 mg are stand-by options.<\/strong><\/p>\n<p>Clinical trials showed that PNH patients complained more of headaches after the initial doses of eculizumab. This is a sign of the effectiveness of the medication. By decreasing the destruction of the red blood cells, more nitric oxide (NO) is available and the blood vessels can expand, but the body needs to get used to this normal condition. However, eculizumab therapy does not reduce the number of damaged cells or cure the disease. On the contrary, the <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;antibody&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;A protein normally produced by the immune system to defend against a pathogen that has entered the body or another threat; an antibody binds specifically to certain surface structures of the intruder, and triggers a series of further immune reactions that ultimately lead to the killing and(...)&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/antibody\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">antibody<\/a> protection means that fewer of the diseased red blood cells disintegrate, so that more of them remain. An increase in the number of these <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;erythrocyte&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Red blood cell; erythrocytes make up the majority of cellular blood components. They are formed in the bone marrow, contain haemoglobin (the red pigment in blood ) and have a life expectancy of about 120 days in healthy people. The haemoglobin content of the blood is an important measurement(...)&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/erythrocyte\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">erythrocyte<\/a>s is therefore a sign of effective therapy. Adherence to regular treatment intervals (every 14 +\/- 2 days) is essential to ensure continuous protection of the injured cells and to avoid the complications of PNH (<a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;breakthrough haemolysis&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Severe haemolysis with severe symptoms; requires treatment&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/breakthrough-haemolysis\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">breakthrough haemolysis<\/a>). Due to the reduced destruction of the damaged red blood cells, little or no <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;haemoglobin&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Hb; red blood cell pigment consisting of haem (an iron-containing component) and globin (a protein). Binds, transports and releases oxygen and carbon dioxide. Reference values: women 12-16 g\/dl or 7.5-9.9 mmol\/l, men 14-18 g\/dl or 8.7-11.2 mmol\/l &lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/haemoglobin\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">haemoglobin<\/a> (and thus iron) is excreted in the urine. Due to the elimination of this <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;chronic&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Over a long period of time and persistent&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/chronic\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">chronic<\/a> loss of iron via the kidney, increased iron storage is observed in some PNH patients receiving eculizumab therapy. These patients should therefore be monitored regularly (especially if they have concomitant <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;aplastic&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Condition of the non-functional bone marrow that cannot develop blood cells&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/aplastic\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">aplastic<\/a> anaemia), to ensure that they discontinue any ongoing treatment with iron tablets at an early stage and, if necessary, that they remove excess iron with chelate therapy. Despite the successful suppression of cell destruction in the blood vessels (<a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;intravascular haemolysis&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Breakdown of red blood cells inside the blood vessels&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/intravascular-haemolysis\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">intravascular haemolysis<\/a>) by eculizumab, a minor degradation of the diseased red blood cells does take place outside the vessels .<a id=\"extravashaem\"><\/a> (<a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;extravascular haemolysis&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Breakdown of red blood cells outside blood vessels&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/extravascular-haemolysis\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">extravascular haemolysis<\/a>). This can be detected with a special blood test (<a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;Coombs test&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Test for the detection of certain antibodies against red blood cells&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/coombs-test\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">Coombs test<\/a>)  <\/p>\n<p>&nbsp;<\/p>\n<h4><span style=\"color: #f9a801;\">5.3 Symptomatic treatment<\/span><\/h4>\n<p>In addition to specific treatment of PNH with eculizumab, there are other options for treating the symptoms. Symptoms of anaemia can be treated with <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;packed RBCs&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;packed RBCs; blood with concentrated red blood cells (erythrocytes), which are collected from donors &lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/packed-rbcs\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">packed RBCs<\/a>. Although small amounts of complement factors are added by <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;transfusion&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Transfer of blood or blood components&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/transfusion\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">transfusion<\/a>, there is no increase in complement-mediated <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;haemolysis&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Breakdown of red blood cells&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/haemolysis\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">haemolysis<\/a>. This also applies to the use of platelet concentrates, see Chapter <a href=\"https:\/\/aa-pnh.org\/en\/diseases\/aplastic-anaemia\/#tx\">Aplastic Anaemia, 5.5 Supportive therapy &gt; Blood transfusions<\/a>.<\/p>\n<p>If affection with PNH is not directly related to bone marrow failure, it is referred to as &ldquo;classical PNH&rdquo;. If PNH is not treated, iron deficiency often develops due to the ongoing loss of <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;haemoglobin&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Hb; red blood cell pigment consisting of haem (an iron-containing component) and globin (a protein). Binds, transports and releases oxygen and carbon dioxide. Reference values: women 12-16 g\/dl or 7.5-9.9 mmol\/l, men 14-18 g\/dl or 8.7-11.2 mmol\/l &lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/haemoglobin\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">haemoglobin<\/a> via the kidneys. As iron is necessary for the development of red blood cells, it must be supplemented in such situations. Iron can be administered in the form of tablets or a venous <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;infusion&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Injection of a liquid into a vein&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/infusion\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">infusion<\/a>. Oral preparations should be taken daily or every other day on an empty stomach. Iron should not be taken simultaneously with antibiotics or medications for neutralising stomach acid (antacids). If appropriate iron treatment is started, the decision to take iron supplements must be reviewed regularly. For this purpose, <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;ferritin&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Protein that stores iron; if ECs are given frequently, the ferritin level should be monitored in case chelation therapy becomes necessary.&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/ferritin\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">ferritin<\/a> levels should be monitored as part of the regular medical check-ups. Due to the increased (compensatory) development of red blood cells, there is an increased need for folic acid and possibly vitamin B12. Supplementation should generally be in the form of e.g. 5 mg folic acid per day. Vitamin B12 should be taken according to current levels. In previous studies, it was found that the risk of <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;thrombosis&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Vascular disease in which a clot forms in a blood vessel; can occur in any vessel, most commonly in veins, especially in the deep veins of the legs&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/thrombosis\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">thrombosis<\/a> is associated with the quantity of PNH cells and the severity of <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;haemolytic&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Breakdown of red blood cells&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/haemolytic\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">haemolytic<\/a> activity. The occurrence of <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;thrombosis&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Vascular disease in which a clot forms in a blood vessel; can occur in any vessel, most commonly in veins, especially in the deep veins of the legs&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/thrombosis\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">thrombosis<\/a> increases significantly if the proportion of GPI-deficient <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;granulocytes&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;subgroup of white blood cells They destroy invading bacteria that can cause diseases. &lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/granulocytes\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">granulocytes<\/a> is more than 50% and\/or the <a class=\"glossaryLink\"  aria-describedby=\"tt\"  data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;LDH&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;lactate dehydrogenase; marker in the blood indicating cell damage&lt;\/div&gt;\"  href=\"https:\/\/aa-pnh.org\/en\/glossar\/ldh\/\"  data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]'  tabindex='0' role='link'>LDH<\/a> value is more than 1.5 times the upper limit. If such patients are given <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;prophylactic&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Prevention or precaution&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/prophylactic\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">prophylactic<\/a> clotting inhibitors, they develop significantly less <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;thrombosis&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Vascular disease in which a clot forms in a blood vessel; can occur in any vessel, most commonly in veins, especially in the deep veins of the legs&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/thrombosis\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">thrombosis<\/a>.       <\/p>\n<p><strong>The following recommendations therefore apply:<\/strong><\/p>\n<ul>\n<li>The use of anticoagulant medication should be decided on an individual basis for each patient.<\/li>\n<li>Prophylactic clotting inhibitors are not necessary with eculizumab therapy.<\/li>\n<li>If <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;prophylactic&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Prevention or precaution&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/prophylactic\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">prophylactic<\/a> clotting inhibition has been initiated prior to eculizumab therapy, one should consider discontinuing it once <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;haemolytic&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Breakdown of red blood cells&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/haemolytic\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">haemolytic<\/a> activity has normalised during eculizumab therapy. However, patients should under no circumstances discontinue treatment without consulting their doctor. However, patients should under no circumstances discontinue treatment without consulting their doctor.<\/li>\n<li><a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;Anticoagulation&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Inhibition of blood clotting&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/anticoagulation\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">Anticoagulation<\/a> should be applied if <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;thrombosis&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Vascular disease in which a clot forms in a blood vessel; can occur in any vessel, most commonly in veins, especially in the deep veins of the legs&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/thrombosis\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">thrombosis<\/a> has already occurred. The duration depends on the location of the <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;thrombosis&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Vascular disease in which a clot forms in a blood vessel; can occur in any vessel, most commonly in veins, especially in the deep veins of the legs&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/thrombosis\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">thrombosis<\/a> and its clinical course.<\/li>\n<li>In the case of risk situations such as being bed-bound, long-term restriction of movement (plaster cast), surgery or long trips &gt; (&gt; 4 hours in a bus or aeroplane), clotting inhibitors should be taken as a <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;prophylactic&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Prevention or precaution&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/prophylactic\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">prophylactic<\/a> measure according to the current platelet values.<\/li>\n<li>Bacterial infections need to be detected at an early stage and treated appropriately with an antibiotic, since infection can lead to <a class=\"glossaryLink\"  aria-describedby=\"tt\"  data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;acute&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Sudden onset, rapidly progressing&lt;\/div&gt;\"  href=\"https:\/\/aa-pnh.org\/en\/glossar\/acute\/\"  data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]'  tabindex='0' role='link'>acute<\/a> deterioration of PNH and even a <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;haemolytic crisis&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Sudden massive haemolysis. Possible signs are fever, chills, circulatory problems up to and including collapse, abdominal pain, backache, headache, dark urine and later yellowing of the skin. &lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/haemolytic-crisis\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">haemolytic crisis<\/a>.<\/li>\n<li>Adequate fluid intake (<a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;hydration&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Therapeutic replacement of body fluid deficiency, e.g. in cases of high blood loss or massive diarrhoea. In order to compensate quickly for fluid loss, supplementation is usually carried out as an infusion. &lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/hydration\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">hydration<\/a>) should be ensured in the event of a <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;haemolytic crisis&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Sudden massive haemolysis. Possible signs are fever, chills, circulatory problems up to and including collapse, abdominal pain, backache, headache, dark urine and later yellowing of the skin. &lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/haemolytic-crisis\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">haemolytic crisis<\/a>. Anti-infection therapy, <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;transfusion&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Transfer of blood or blood components&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/transfusion\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">transfusion<\/a>s and eculizumab may be required; if the kidneys are endangered, purification (<a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;dialysis&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Blood purification in case of reduced or failed kidney function&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/dialysis\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">dialysis<\/a>) may be necessary.<\/li>\n<li>In exceptional cases of concomitant bone marrow disorder (<a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;bone marrow insufficiency&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Reduced production of blood cells in the bone marrow&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/bone-marrow-insufficiency\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">bone marrow insufficiency<\/a>) or after the development of kidney-related (<a class=\"glossaryLink\"  aria-describedby=\"tt\"  data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;renal&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Involving the kidney&lt;\/div&gt;\"  href=\"https:\/\/aa-pnh.org\/en\/glossar\/renal\/\"  data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]'  tabindex='0' role='link'>renal<\/a>) anaemia, administration of haematopoietic (blood-forming) growth factors, e.g. erythropoietin or <a class=\"glossaryLink\"  aria-describedby=\"tt\"  data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;G-CSF&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;G-CSF; genetically engineered drug that promotes the development of granulocytes and leads to washout of stem cells from the bone marrow into the blood. It is tolerated quite well, but may cause temporary fever and limb pain in a small proportion of patients. &lt;\/div&gt;\"  href=\"https:\/\/aa-pnh.org\/en\/glossar\/g-csf\/\"  data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]'  tabindex='0' role='link'>G-CSF<\/a>, may be useful.<\/li>\n<li>If bone marrow deficiency (<a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;aplasia&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Condition of the non-functional bone marrow that cannot develop blood cells&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/aplasia\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">aplasia<\/a>) is a greater concern than PNH, <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;immunosuppressive&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Suppression of the immune system&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/immunosuppressive\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">immunosuppressive<\/a> therapy, stem cell or bone marrow transplantation should be performed (see .<a href=\"https:\/\/aa-pnh.org\/en\/diseases\/aplastic-anaemia\/#therapie\">3.5 Aplastic Anaemia, 5 Treatment<\/a>.<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<ul>\n<li style=\"list-style-type: none;\">\n<ul>\n<li style=\"list-style-type: none;\">\n<ul>\n<li style=\"list-style-type: none;\">\n<ul>\n<li style=\"list-style-type: none;\">\n<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>In addition, the current vaccination status should be discussed with the treating haematologist, especially with regard to vaccination against pneumococcal pneumonia and influenza viruses.<\/p>\n<p>&nbsp;<\/p>\n<h4><span style=\"color: #f9a801;\">5.4 Healing<\/span><\/h4>\n<p>The only treatment of PNH with the prospect of a cure (<a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;curative&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Healing, focused on healing&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/curative\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">curative<\/a> approach) is transplantation of allogeneic bone marrow or stem cells. However, this is accompanied by a significant rate of complications (<a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;morbidity&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Frequency of illness; complaints and complications caused by an illness or during therapy&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/morbidity\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">morbidity<\/a>) and <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;mortality&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Death rate&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/mortality\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">mortality<\/a>. Therefore, the <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;indication&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Reason to perform a medical procedure&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/indication\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">indication<\/a> (therapeutic decision) for a transplant should be considered very carefully, especially since <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;antibody&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;A protein normally produced by the immune system to defend against a pathogen that has entered the body or another threat; an antibody binds specifically to certain surface structures of the intruder, and triggers a series of further immune reactions that ultimately lead to the killing and(...)&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/antibody\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">antibody<\/a> therapy with eculizumab is now an option.  <\/p>\n<p><strong>Medical reasons for a stem cell transplant are:<\/strong><\/p>\n<ul>\n<li>Recurrent, life-threatening <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;thromboembolic&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;A blood clot that is carried into the bloodstream and leads to closure of the affected blood vessel, which is then unable to supply the corresponding organs &lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/thromboembolic\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">thromboembolic<\/a> complications that do not respond to any other therapy<\/li>\n<li>Very severe (<a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;refractory&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;A disease is refractory if it does not respond to therapy.&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/refractory\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">refractory<\/a>) <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;haemolytic anaemia&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Form of anaemia caused by increased breakdown or decay of red blood cells. This leads to shortening of the life span of the erythrocytes. Depending on the site affected, a distinction can be made between haemolysis inside the blood vessels (intravascular) and outside the blood vessels(...)&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/haemolytic-anaemia\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">haemolytic anaemia<\/a> that is not affected by therapy and requires <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;transfusion&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Transfer of blood or blood components&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/transfusion\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">transfusion<\/a>s<\/li>\n<li>Presence of PNH in addition to <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;aplastic&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Condition of the non-functional bone marrow that cannot develop blood cells&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/aplastic\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">aplastic<\/a> anaemia (AA) or myelodysplastic syndrome (MDS), if AA or MDS already justify a transplant<\/li>\n<li>Transition to <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;aplastic&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;Condition of the non-functional bone marrow that cannot develop blood cells&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/aplastic\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">aplastic<\/a> anaemia or myelodysplastic syndrome<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<h4><span style=\"color: #f9a801;\">5.5 Prospects<\/span><\/h4>\n<p>Several new substances that inhibit the <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;complement system&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;A group of plasma proteins for immune defence against microorganisms&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/complement-system\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">complement system<\/a> are currently being investigated in<a href=\"https:\/\/aa-pnh.org\/en\/diseases\/clinical-trials\/\">Clinical trials<\/a>. Ravulizumab which received admission in the EU on 2 July 2019 is being tested for subcutaneous application in clinical trials.<\/p>\n<p><\/p><\/ul><ul style=\"margin-top:0;margin-bottom:0\"><style type=\"text\/css\">a.bg-showmore-plg-link:hover,a.bg-showmore-plg-link:active,a.bg-showmore-plg-link:focus{color:#0071bb;}<\/style>\n<input type=\"hidden\" bg_collapse_expand_pro=\"69e60b5ac16d92019193109\" value=\"69e60b5ac16d92019193109\"><input type=\"hidden\" id=\"bg-show-more-text-69e60b5ac16d92019193109\" value=\"  6 Prognosis\"><input type=\"hidden\" id=\"bg-show-less-text-69e60b5ac16d92019193109\" value=\"  6 Prognosis\"><input type=\"hidden\" id=\"bg-icon-bg-color-69e60b5ac16d92019193109\" value=\"\"><a id=\"bg-showmore-action-69e60b5ac16d92019193109\" class=\"bg-showmore-plg-link bg-arrow  \" style=\"color:#f9a801;;font-weight:bold; font-size:24px; line-height: 150%\" href=\"#\">  6 Prognosis<\/a><\/ul><ul class=\"bg-showmore-no-padding-no-margin bg-showmore-closed\" id=\"bg-showmore-pro-hidden-69e60b5ac16d92019193109\">\n<p>PNH patients now have approximately the same life expectancy as the normal population, since eculizumab therapy significantly reduces the occurrence of <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;thromboembolic&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;A blood clot that is carried into the bloodstream and leads to closure of the affected blood vessel, which is then unable to supply the corresponding organs &lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/thromboembolic\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">thromboembolic<\/a> events.<\/p>\n<p><\/p><\/ul><ul style=\"margin-top:0;margin-bottom:0\"><style type=\"text\/css\">a.bg-showmore-plg-link:hover,a.bg-showmore-plg-link:active,a.bg-showmore-plg-link:focus{color:#0071bb;}<\/style>\n<input type=\"hidden\" bg_collapse_expand_pro=\"69e60b5ac175e0014240191\" value=\"69e60b5ac175e0014240191\"><input type=\"hidden\" id=\"bg-show-more-text-69e60b5ac175e0014240191\" value=\"  7 Wish to have children\/pregnancy \"><input type=\"hidden\" id=\"bg-show-less-text-69e60b5ac175e0014240191\" value=\"  7 Wish to have children\/pregnancy \"><input type=\"hidden\" id=\"bg-icon-bg-color-69e60b5ac175e0014240191\" value=\"\"><a id=\"bg-showmore-action-69e60b5ac175e0014240191\" class=\"bg-showmore-plg-link bg-arrow  \" style=\"color:#f9a801;;font-weight:bold; font-size:24px; line-height: 150%\" href=\"#\">  7 Wish to have children\/pregnancy <\/a><\/ul><ul class=\"bg-showmore-no-padding-no-margin bg-showmore-closed\" id=\"bg-showmore-pro-hidden-69e60b5ac175e0014240191\">\n<p>Until a few years ago, PNH patients were advised not to become pregnant, because life-threatening complications were often observed in the mother and child. This risk has been significantly reduced with <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemTitle&gt;antibody&lt;\/div&gt;&lt;div class=glossaryItemBody&gt;A protein normally produced by the immune system to defend against a pathogen that has entered the body or another threat; an antibody binds specifically to certain surface structures of the intruder, and triggers a series of further immune reactions that ultimately lead to the killing and(...)&lt;\/div&gt;\" href=\"https:\/\/aa-pnh.org\/en\/glossar\/antibody\/\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">antibody<\/a> therapy, so the issue of family planning arises again. Meanwhile, reports of pregnancies during eculizumab treatment are available and show very encouraging results, although the number of cases is limited. These pregnancies were basically without complications, and all the children have been healthy. However, if women wish to become (or already are) pregnant, they should seek support from a specialised centre with haematological and gynaecological expertise in order to clarify the individual risk profile of the patient and, if necessary, to adjust the dose of eculizumab.    <\/p>\n<p><\/p><\/ul><ul style=\"margin-top:0;margin-bottom:0\"><style type=\"text\/css\">a.bg-showmore-plg-link:hover,a.bg-showmore-plg-link:active,a.bg-showmore-plg-link:focus{color:#0071bb;}<\/style>\n<input type=\"hidden\" bg_collapse_expand_pro=\"69e60b5ac17de8085640191\" value=\"69e60b5ac17de8085640191\"><input type=\"hidden\" id=\"bg-show-more-text-69e60b5ac17de8085640191\" value=\"  8 Registry\"><input type=\"hidden\" id=\"bg-show-less-text-69e60b5ac17de8085640191\" value=\"  8 Registry\"><input type=\"hidden\" id=\"bg-icon-bg-color-69e60b5ac17de8085640191\" value=\"\"><a id=\"bg-showmore-action-69e60b5ac17de8085640191\" class=\"bg-showmore-plg-link bg-arrow  \" style=\"color:#f9a801;;font-weight:bold; font-size:24px; line-height: 150%\" href=\"#\">  8 Registry<\/a><\/ul><ul class=\"bg-showmore-no-padding-no-margin bg-showmore-closed\" id=\"bg-showmore-pro-hidden-69e60b5ac17de8085640191\">\n<p>Since PNH is an extremely rare disease, relevant information on the disease and its treatment can only be obtained by analysing the data of as many PNH patients as possible at an international level.<\/p>\n<p>The International PNH Patient Registry was established for this purpose. It documents data on the course of the disease and the quality of life in anonymised form every six months after receiving patient approval. Since new knowledge of the disease and further improvement of the therapy can only be achieved on the basis of such information, as many PNH patients as possible should make their data available to the Registry.  <\/p>\n<p><strong>PLEASE HELP!<\/strong><\/p>\n<p>If you would like to help or have any questions, please email Prof Dr Alexander R&ouml;th (<a href=\"mailto:alexander.roeth@ukessen.de\">alexander.roeth(at)ukessen.de<\/a>) or Prof Dr Hubert Schrezenmeier (<a href=\"mailto:h.schrezenmeier@blutspende.de\">h.schrezenmeier(at)blutspende.de<\/a>).<\/p>\n<p><\/p><\/ul><ul style=\"margin-top:0;margin-bottom:0\"><style type=\"text\/css\">a.bg-showmore-plg-link:hover,a.bg-showmore-plg-link:active,a.bg-showmore-plg-link:focus{color:#0071bb;}<\/style>\n<\/ul>","protected":false},"excerpt":{"rendered":"<p>Paroxysmal Nocturnal Haemoglobinuria (PNH) &nbsp;<\/p>\n","protected":false},"author":7,"featured_media":0,"parent":3689,"menu_order":20,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-3693","page","type-page","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/aa-pnh.org\/en\/wp-json\/wp\/v2\/pages\/3693","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/aa-pnh.org\/en\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/aa-pnh.org\/en\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/aa-pnh.org\/en\/wp-json\/wp\/v2\/users\/7"}],"replies":[{"embeddable":true,"href":"https:\/\/aa-pnh.org\/en\/wp-json\/wp\/v2\/comments?post=3693"}],"version-history":[{"count":2,"href":"https:\/\/aa-pnh.org\/en\/wp-json\/wp\/v2\/pages\/3693\/revisions"}],"predecessor-version":[{"id":7668,"href":"https:\/\/aa-pnh.org\/en\/wp-json\/wp\/v2\/pages\/3693\/revisions\/7668"}],"up":[{"embeddable":true,"href":"https:\/\/aa-pnh.org\/en\/wp-json\/wp\/v2\/pages\/3689"}],"wp:attachment":[{"href":"https:\/\/aa-pnh.org\/en\/wp-json\/wp\/v2\/media?parent=3693"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}