In Chuvash polycythemia, homozygosity for the 598 C->T mutation in the von Hippel-Lindau gene (VHL) leads to upregulation of hypoxia inducible factor-1a (HIF1a), a transcription factor that mediates cellular responses to hypoxia. This defect in the oxygen-sensing pathway causes increased expression of a broad range of hypoxia-regulated genes. Clinically, Chuvash polycythemia (CP) patients display not only erythrocytosis, but also premature mortality related to cerebrovascular and peripheral thrombotic events. As it is not clear that the thrombophilic nature of CP correlates with elevated hematocrit (
Disclosure: No relevant conflicts of interest to declare.