Patients with
essential thrombocythemia (ET) have an increased frequency of
thrombosis, but the relationship of both
thrombosis and JAK2 V617F allele burden with platelet turnover, acquired
activated protein C resistance (aAPCR), and levels of
coagulation factors and soluble markers of platelet, and endothelial activation is not well known. In 53 ET patients (26 with a history of
thrombosis), reticulated platelets (RP) percentage, aAPCR, platelet
tissue factor (TF) expression, and plasma levels of TF,
coagulation factors, soluble
P-selectin (sP-
selectin), soluble
CD40 ligand (sCD40L),
von Willebrand factor antigen (VWF:Ag), soluble
thrombomodulin (sTM),
D-dimer and
prothrombin fragment 1 + 2 were compared with those in matched healthy individuals and correlated with
thrombosis occurrence and JAK2 mutational load. ET patients with
thrombosis had significantly higher values for RP percentage, aAPCR, and levels of factors V and VIII, VWF:Ag, sP-
selectin, and sCD40L than patients without
thrombosis and controls. At multivariate study, RP percentage,
factor V levels, and aAPCR were independently associated with an increased risk of
thrombosis. Patients with JAK2 mutation had significantly lower levels of free
protein S (PS) and higher levels of TF, sP-
selectin, sCD40L, VWF:Ag, and sTM than those with wild-type allele. A mutant allele dosage effect (>or= 12%) was observed for TF, sP-
selectin, sCD40L, VWF:Ag, and PS levels. These results support a role for platelet turnover,
factor V, and aAPCR in the
thrombosis of ET as well as the association between JAK2 V617F allele burden and either decreased free PS or increased TF and soluble markers of platelet and endothelial activation.