Platelet and coagulation activation markers in myeloproliferative diseases: relationships with JAK2 V617F status, clonality, and antiphospholipid antibodies

Background and objcctives: Patients with myeloproliferative disease (MPD) have an increased risk of thrombosis. We studied markers of platelet and coagulation activation in a large cohort of patients with MPD (n = 118) and related this to Janus Kinase 2 (JAK2) V617 F mutation status, a marker of clonality, and the presence of antiphosp-holipid antibodies (APA), all of which have been associated with thrombosis in MPD. Methods: D-dimer, thrombin-antithrombin complexes (TAT), prothrombin fragments 1 + 2 (F1 + 2), soluble E-selectin (sE-selectin), and soluble P-selectin (sP-selectin) levels were compared between patients and hypertensive controls (n = 127). Assays for lupus anticoagulant (LA), anticardiolipin antibodies (ACA), antibeta2 glycoprotein 1 antibodies (anti-P2GP1), and antiprothrombin antibodies (alpha-Pro) were also performed. The JAK2 V617F mutation status was determined in the cohort using amplification refractory mutation system (ARMS) polymerase chain reaction. Disease clonality was determined in 54 patients using the HUMARA assay. Results: sP-selectin was significantly increased in patients with MPD (P <= 0.001). sP-selectin levels were significantly elevated in JAK2 V617F-positive patients compared to wild-type (P = 0.006), or controls (P < 0.001). There was no correlation between proportion clonality and any activation marker. We found no significant difference in the incidence of APA between patients and controls (11 % vs. 14%, P = 0.46), and no significant association between APA status and any activation marker. Conclusions: The JAK2 V617F mutation is associated with platelet activation, as measured by elevated sP-selectin levels, in MPD. In contrast to previous reports, we found no excess of APA in patients with MPD.