In polycythemia vera (PV) thrombotic events are the major cause of morbidity and mortality. Although in PV vascular complications encompass the whole spectrum of thrombembolic events, arterial occlusions (stroke, TIA, myocardial infarction and peripheral arterial disease) play a major role. In a large retrospective analysis arterial thromboses accounted for about 75% of all thrombotic complications while venous thrombotic events were less frequent and accounted only for a quarter of vascular complications. As a preclinical sign of arterial thrombosis we observed in a previous study a significantly more pronounced endothelial dysfunction in PV compared to a sex and age matched control group with even a higher cardiovascular risk profile. So far the pathogenesis of this predisposition to endothelial dysfunction and arterial thrombosis in PV remains poorly understood and no clear association with any laboratory parameter could be established. The V617F mutation in the JAK2 kinase gene (JAK2-V617F) showed an association with thrombosis in essential thrombocythemia. Virtually all patients with PV acquire JAK2-V617F although the abundance of myeloid cells carrying the V671F mutation varies greatly among patients. Therefore, we quantified the presence of the mutated allele of JAK2 (%V617F) in granulocytes using a quantitative allele-specific PCR-assay and examined the endothelial function as a preclinical indicator for arterial vascular disease in 27 patients with PV. Endothelium-dependent flow-mediated vasodilatation (FMD) was measured using high-resolution ultrasound of the brachial artery. We did not observe a correlation between the FMD values and %V617F in our cohort of PV patients (P=0.48). A similar lack of correlation was observed when only patients with low and high %V617F were compared (P=0.60). To date the low FMD values in PV have not been associated with any laboratory or genetic parameters. Thus, a unique V617F-independent pathogenetic mechanism is likely to play a role in endothelial dysfunction in PV.
Disclosure: No relevant conflicts of interest to declare.