Paroxysmal nocturnal hemoglobinuria

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Abstract
Paroxysmal nocturnal hemoglobinuria, first described in the late 19th century, is an acquired disorder characterized by hemoglobinemia and hemoglobinuria. The major clinical manifestation of PNH is chronic intravascular hemolysis of various severity. Patients-mostly young adults — may also present with episodes of abdominal or back pain. Common cause of death is thrombosis especially of the hepatic veins. Granulocytopenia and thrombocytopenia may be the initial manifestation of PNH, indicating that the disorder is a primary bone-marrow disease, affecting not only the erythrocytes but also other peripheral blood cells and the haematopoietic stem cell. The course of the disease is variable. Partial complete recovery was described, but also fatal thrombosis. The major phenotypic expression of PNH is an increased susceptibility of the erythrocytes to the lytic action of complement in vitro. The enhanced complement susceptibility is most probably due to membrane defects: two membrane proteins regulating the complement cascade in PNH cells were missing, the decay-accelerating factor, DAF, inhibiting the activation of the lytic complement complex and the C8 binding protein, C8bp, which interferes with the lytic process. Aside from the lack of the complement regulators also other membrane defects have been described (e.g. of acetylcholinesterase or alkaline phosphatase). The proteins as well as DAF and C8bp are linked to the cell membrane via a phosphatidylinositol (PI) anchor, leading to the speculation that the disease results from a deficiency in the posttranslational PI anchoring mechanism. The diagnosis of PNH is based on the Hamtest, but will be extended to the quantitation of the above described membrane proteins. Therapy of PNH is restricted to treatment of symptoms: Transfusion of washed erythrocytesnecessary when the hemoglobin level is critically low, iron supplementation, or in cases of thrombosis anticoagulans. Ideal treatment of PNH would be a replacement of the abnormal stem cells by bone-marrow transplantation. Due to its limitations bone-marrow transplantation have been done only in a few cases.