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Arellano-Rodrigo E, Alvarez-Larrán A, Reverter JC, Colomer D, Villamor N, Bellosillo B, Cervantes F

Platelet turnover, coagulation factors, and soluble markers of platelet and endothelial activation in essential thrombocythemia: relationship with thrombosis occurrence and JAK2 V617F allele burden.

Am. J. Hematol.. 2009 Feb;84(2):102-8, PMID: 19105233

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.


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