Free hemoglobin, in turn, can cause various toxic effects, including hypercoagulability, changes in vascular tone from reduction of circulating nitric oxide and renal damage.Įxtravascular hemolysis also occurs in patients with PNH because C3 fragments that are not destroyed by the membrane attack complex (MAC) intravascularly can accumulate on the GPI-negative red blood cell (lacking CD55) surface and these fragments opsonize the RBCs, causing reticuloendothelial destruction in the liver and spleen. 1, 9, 10, 11 Intravascular hemolysis leads to release of free hemoglobin (Hb) into the blood. These patients manifest with chronic intravascular hemolysis, paroxysmal flares of hemolysis and a propensity for thrombosis. Lack of the complement inhibitor CD59 on the RBCs surface is mostly responsible for the clinical manifestations in PNH. The mechanism of the PIGA mutation is unknown, but the close association between PNH and acquired aplastic anemia (AA) suggests that the immune attack on hematopoietic stem cells provides a conditional survival advantage to the PNH clone. The acquired mutation in PNH occurs in the phosphatidylinositol glycan class A (PIGA) gene, which is responsible for the first step in the synthesis of the glycosylphosphatidylinositol (GPI) anchor, a glycolipid that links dozens of cell-surface proteins to the plasma membrane on hematopoietic cells, including blood group antigens, adhesion molecules and complement regulatory proteins. 3, 4, 5, 6Ī multistep process seems necessary for PNH to develop. In this consensus, we want to emphasize the diagnosis and treatment of the PNH patients, as well as the early recognition of its systemic complications. 3, 4, 5, 6 In the last decade, PNH has received novel and much more in-depth attention and a new kind of therapy has become available, the complement blockade by the anti-C5 monoclonal antibody eculizumab. The CD59, whose action is to inhibit the terminal complement cascade leading to the destruction of red blood cells may be more important. Two complement regulatory proteins, the CD55 (decay accelerating factor ) and CD59 (homologous restriction factor or membrane inhibitor of reactive lysis ), were found to be missing from PNH blood cells, explaining the unusual sensitivity of RBCs to the hemolytic action of complement. Granulocytes and platelets are sensitive to the complement, as well. Compared with normal RBCs, PNH RBCs lyse more readily in the presence of the activated complement. 1, 2 Hemolysis in PNH is due to the action of the complement on abnormal red blood cells (RBCs). Paroxysmal nocturnal hemoglobinuria (PNH) is a chronic, multi-systemic, progressive and life-threatening disease characterized by intravascular hemolysis, thrombotic events, serious infections and bone marrow failure. These procedures express the opinions of experts and have been based on the best available evidence and international guidelines, with the purpose of increasing benefits and reducing harm to patients. In this consensus, we are aiming to review the diagnosis and treatment of the paroxysmal nocturnal hemoglobinuria patients, as well as the early recognition of its systemic complications. The treatment that has recently become available is the complement blockade by the anti-C5 monoclonal antibody eculizumab. The traditional therapy for paroxysmal nocturnal hemoglobinuria includes blood transfusion, anti-thrombosis prophylaxis or allogeneic bone marrow transplantation. Early diagnosis, using flow cytometry performed on peripheral blood, the gold standard test to confirm the diagnosis of paroxysmal nocturnal hemoglobinuria, is essential for improved patient management and prognosis. Paroxysmal nocturnal hemoglobinuria results from the expansion of a clone of hematopoietic cells that due to an inactivating mutation of the X-linked gene PIG-A are deficient in glycosylphosphatidylinositol-linked proteins. Paroxysmal nocturnal hemoglobinuria is a chronic, multi-systemic, progressive and life-threatening disease characterized by intravascular hemolysis, thrombotic events, serious infections and bone marrow failure.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |