Vascular complications in Chuvash polycythemia

Chuvash polycythemia is characterized by a homozygous 598C > T germline mutation in the von Hippel-Lindau gene (VHL), upregulation of hypoxia-inducible factor-1 alpha during normoxia, and resulting augmentation of erythropoietin and several other hypoxia-con trolled genes. Although endemic to the Chuvash population of Russia, this mutation occurs worldwide and usually originates from a single ancient event. Matched-cohort and case-control analyses have shown that VHL 598C > T homozygosity is associated with lower peripheral blood pressures, varicose veins, vertebral hemangiomas, lower white blood cell and platelet Counts, and elevated serum concentrations of vascular endothelial growth factor and plasminogen activator inhibitor-1. These studies have also shown associations with arterial and venous thrombosis, major bleeding episodes, cerebral vascular events, and premature mortality. Spinocerebellar hemangioblastomas, renal carcinomas, and pheochromocytomas typical of classical VHL tumor predisposition syndrome have not been found, and no increased risk of cancer has been demonstrated. Retrospective analyses among patients with Chuvash polycytherma have not shown benefit for therapy with phlebotomy or aspirin, but these and other modes of therapy should be studied prospectively. Further investigation of the vascular complications of Chuvash polycythemia may increase Our fundamental knowledge of thrombophilia, bleeding diatheses, and protection from cancer.