Abstract
In Chuvash polycythemia (CP), homozygous germline VHLR200W results in augmented hypoxia sensing, elevated erythropoietin and hemoglobin, and increased morbidity and mortality from thrombosis, but the relative risks and molecular basis have not been prospectively evaluated.1-3 We enrolled 128 CP adults and 128 controls from Russia's Chuvash Republic in an observational study from 2005-2009, in order to prospectively define the risk of complications and to provide mechanistic insights. We hypothesized that variation in the expression of hypoxia inducible factor (HIF)-regulated genes may contribute to increased thrombosis.
During a median follow up of 8.8-years, CP was associated with a 9.6-fold increase in the rate of new thrombosis compared to controls, after adjustment for significant risk factors such as age and smoking. The probability of new thrombosis in CP did not increase with higher baseline hemoglobin concentration, but it increased with age, smoking, baseline therapeutic phlebotomy and higher expressions of THBS1, CXCL2 and EREG.