Could hypoxia increase the prevalence of thrombotic complications in polycythemia vera?

Thromboses represent a major cause of morbidity and mortality in polycythemia vera but the contributing mechanisms are not fully described. To evaluate whether environmental conditions such as altitude/hypoxia could impact thrombosis history, we retrospectively analyzed thrombosis history in 71 polycythemia vera patients living at an elevation of 5000 feet or more in the Salt Lake City (SLC) area and 166 polycythemia vera patients living near sea level in the Baltimore (BLM) area. The SLC cohort was older with a longer disease duration. No significant differences in type of anticoagulation therapy or prothrombotic factors were present between the two cohorts. After adjusting for age, sex and disease duration, SLC patients experienced an estimated 3.9-fold increase in the odds of a history of thrombosis compared with BLM patients (95% confidence interval 1.8-7.6; P =  0.0004). A history of a cardiovascular event was present in 58% of the SLC patients compared with 27% of the BLM patients (P < 0.0001). Before diagnosis, thrombosis occurred in 18 and 4% of the SLC and BLM groups, respectively (P = 0.003). No correlation between the JAK2 allele burden and thrombosis was observed in this study. This retrospective study suggests that even moderate hypoxia associated with 5000 feet elevation should be considered as an independent prothrombotic risk factor. This observation needs to be confirmed by prospective studies.