Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease, which is characterized by an intravascular hemolysis and hemoglobinuria occurring amplified during periods of sleep. Leukopenia, thrombocytopenia, arterial and venous thrombosis and episodic hemolytic crises are frequent. The diagnosis is made by flow cytometry. Treatment is supportive and is carried out with eculizumab, a terminal complement inhibitor.
PNH is most common in men in the third decade of life, but may both sexes and patients of all ages relate.
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease, which is characterized by an intravascular hemolysis and hemoglobinuria occurring amplified during periods of sleep. Leukopenia, thrombocytopenia, arterial and venous thrombosis and episodic hemolytic crises are frequent. The diagnosis is made by flow cytometry. Treatment is supportive and is carried out with eculizumab, a terminal complement inhibitor. PNH is most common in men in the third decade of life, but may both sexes and patients of all ages relate. Etiology In PNH is an acquired genetic mutation that causes a membrane defect in the stem cells and their progeny, including red cells, white cells and platelets. This leads to an unusually high sensitivity to normal plasma C3, resulting in a continuous intravascular hemolysis of red blood cells and decreased production of leukocytes and platelets by the bone marrow result has. The defect itself is the lack of a glycosyl phosphatidylinositol anchor for membrane proteins, which is caused by a mutation in the PIG-A gene is on the X chromosome. Pathophysiology of PNH can lead to iron deficiency, a prolonged loss of hemoglobin in the urine. Patients have a strong predisposition for venous and arterial thrombi, including for the Budd-Chiari syndrome. This thrombosis often fatal. Some patients with PNH develop aplastic anemia, and conversely, some patients develop aplastic anemia PNH. Symptoms crises by infection, the administration of iron, vaccinations or menstrual bleeding caused. A strong hemoglobinuria and splenomegaly are common. It can abdominal and lumbar pain and symptoms of severe anemia can occur. Diagnostic flow cytometry may Säurehämolysetest (Ham test) The suspected PNH, patients with typical anemia symptoms (eg. As pallor, fatigue, dizziness, possible hypotension) or unexplained normozytärer anemia with intravascular hemolysis, especially when leucopenia and thrombocytopenia available. Formerly a sugar water test is usually carried out in suspected PNH first. The test is based on an increased C3-dependent hemolysis in isotonic solutions with low ionic strength, is easy to carry out and sensitive. However, it is not specific. Positive results require confirmation by further tests. The most sensitive and specific examination is performed by flow cytometry. In this case, the lack of specific membrane proteins (CD59 and CD55) is determined on erythrocytes or leukocytes. Alternatively, a Säurehämolysetest (Ham-test) can be performed. Hemolysis usually occurs when blood acidified with hydrochloric acid, incubated for 1 hour and is then centrifuged. If a bone marrow examination, which is not necessary is done to rule out other diseases that may show hypoplasia is here. A strong hemoglobinuria is often during a crisis, and the urine may contain hemosiderin. Supportive treatment measures may Eculizumab Therapy is largely symptomatic. However, a new monoclonal antibody, eculizumab, which acts as a terminal complement the disease process changed significantly and reduces Notwendigeit a transfusion, the Thromboemboliehäufigkeit and the symptoms. Eculizumab increases the risk of meningococcal meningitis, which is why patients should receive the meningococcal vaccine at least 14 days before the start of eculizumab administration. Among the supportive measures include oral iron and folic acid substitution and possibly transfusions. Through the empirical use of corticosteroids (prednisone 20 to 40 mg po once daily) the symptoms are controlled and stabilized the erythrocytes values> 50% of patients. Transfusions should be generally used only in times of crisis. , Plasma (and therefore C3) include transfusions should be avoided. The washing of erythrocytes in a saline solution before transfusion is no longer required. Heparin followed by warfarin may be necessary in thrombosis, but should be used cautiously. Most patients can be treated for years or decades with these supportive measures.