cyclic-gmp and Hemoglobinuria--Paroxysmal

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disorder of hematopoietic stem cells. Somatic mutation in the phosphatidylinositol glycan class A (PIG-A), X-linked gene, is responsible for a deficiency in glycosphosphatidylinositol-anchored proteins (GPI-AP). The lack of one of the GPI-AP complement regulatory proteins (CD55, CD59) leads to hemolysis. The disease is diagnosed with hemolytic anemia, marrow failure and thrombosis. Thromboembolic complication occurs in 30% of patient after 10 years of follow-up and is the first event in one out of 10 patients. The two most common sites are hepatic and cerebral veins. These locations are correlated with high risk of death. Currently, these data are balanced with the use of a monoclonal antibody (Eculizumab), which has significantly improved the prognosis with a survival similar to general population after 36 months of follow-up. Anticoagulant treatment is recommended after a thromboembolic event but has no place in primary prophylaxis.

Topics: Antibodies, Monoclonal, Humanized; Anticoagulants; Bone Marrow Transplantation; CD55 Antigens; CD59 Antigens; Complement Membrane Attack Complex; Cyclic GMP; Disease Management; Endothelium, Vascular; Female; Follow-Up Studies; Glycosylphosphatidylinositols; Hemoglobinuria, Paroxysmal; Humans; Male; Membrane Proteins; Nitric Oxide; Practice Guidelines as Topic; Thrombophilia; Thrombosis