Racial Differences in Paroxysmal Nocturnal Hemoglobinuria Thrombosis and Glycosylphosphatidylinositol-Deficient Granulocytes
Journal Title: Journal of Hematology & Thrombosis - Year 2016, Vol 2, Issue 2
Abstract
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired glycosylphosphatidylinositol (GPI)-deficient hematopoietic stem cell disorder that is characterized by complement-mediated hemolytic anemia, thrombosis, and bone marrow failure. Eculizumab, an inhibitor of terminal complement C5, provides patients with PNH with a good quality of life by ameliorating hemolysis and thrombosis, and promotes a better understanding of the complement-mediated molecular pathophysiology of PNH [1-3]. However, the underlying reasons for distinct differences in the incidences of thrombosis and bone marrow failure between Caucasian and Asian patients with PNH are still unknown (West vs. Japan, 32% vs. 4%) [4]. Racial differences are more evident in PNH thrombosis than in other conventional arterial thromboses (PNH vs. others, 2.4 to 9.8 vs. 1.7 to 3.9-fold increase) [4,5], suggesting that the presence of thrombus formation is characteristic of PNH. Progression to thrombosis is generally attributable to synergistic interactions between hypercoagulation and hypofibrinolysis. Hypercoagulability in PNH patients may be due to chronic hemolysis, accentuated platelet aggregation, and other complement-mediated events, whereas hypofibrinolysis in PNH patients is explained by the loss of the urokinase plasminogen activator receptor (uPAR) on leukocytes and elevated soluble uPAR plasma levels [3,6]. Besides erythrocytes and platelets, leukocytes play a critical role in the progression of thrombosis. Thrombotic events often occur in patients with leukocytosis due to myeloproliferative neoplasms as well as in those treated with granulocyte macrophage colony-stimulating factor. In contrast, patients with a plastic anemia-PNH syndrome showing leukocytopenia manifest clinical thrombosis less frequently than patients with de novo PNH maintaining normal leukocyte counts [7,8]. In contrast to thrombosis, cytopenias are more common in Japanese PNH patients than in those in the United States [4]. Based on this background, we attempted to elucidate a plausible link between marrow failure-associated leukocytopenia and the infrequent complication of thrombosis in Japanese PNH patients by analyzing data obtained from our own PNH patients and previous findings [1-3,6-10]. We also investigated the reasons for racial differences using GPI-deficient (PNH) granulocyte counts in PNH thrombosis.
Authors and Affiliations
Nobuyoshi Hanaoka
Keywords
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- EP ID EP246545
- DOI 10.13188/2380-6842.1000016
- Views 131
- Downloads 0
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