Phlebotomy-Induced Iron Deficiency Increases The Expression Of Prothrombotic Genes

Thrombosis is the major cause of morbidity and mortality in Chuvash erythrocytosis (CE), caused by a hypomorphic R200W mutation of the Von Hippel-Lindau (VHL) gene, a negative regulator of hypoxia inducible factors (HIFs). This mutation augments HIF activity even in normoxia. High hematocrit associated with hyperviscosity has been considered a risk factor for thrombosis suggesting that maintaining normal hematocrit may prevent thrombosis. However, our prospective controlled study reported that phlebotomies, but not the high hematocrit, are associated with increased risk of thrombosis (PMID 289208) by a mechanism that remains to be elucidated.