title: Platelet-induced thrombin generation by the calibrated automated thrombogram assay is increased in patients with essential thrombocythemia and polycythemia vera.
abstract: The platelet contribution to the thrombophilic state of patients with myeloproliferative neoplasms (MPNs), i.e., essential thrombocythemia (ET) and polycythemia vera (PV), remains uncertain. In this study we aimed to characterize the thrombin generation (TG) potential expressed by platelets from these subjects, compare it to normal platelets, and identify what factors might be responsible for platelet TG. In a group of 140 MPN patients (80 ET and 60 PV) and 72 healthy subjects, we measured the global procoagulant potential of platelet-rich plasma (PRP) utilizing the TG assay by the calibrated automated thrombogram (CAT). To characterize the procoagulant contribution of platelets in PRP, the TG of both isolated platelets and platelet-poor plasma was measured, and the platelet surface expression of TF was determined. Finally, the activation status of platelets was assessed by the levels of P-selectin expressed on platelet surface. MPN patients had significantly increased PRP and isolated platelet TG potential compared to controls. This was associated to the occurrence of platelet activation. Patients carriers of the JAK2V617F mutation showed the highest values of TG and platelet surface TF and P-selectin. Platelet TG potential was significantly lower in hydroxyurea(HU) compared to non-HU-treated patients and was lowest in HU-treated JAK2V617F carriers. In subjects not receiving HU, platelet TG significantly increased by JAK2V617F allele burden increment (P < 0.05).This study demonstrates a platelet-dependent form of hypercoagulability in MPN patients, particularly in those carriers of the JAK2V617F mutation. The cytoreductive therapy with HU significantly affects this prothrombotic phenotype.
authors: Division of Immunohematology and Transfusion Medicine, Ospedali Riuniti di Bergamo, Largo Barozzi 1, Bergamo, Italy.
authors: Marina
authors: M
authors: Panova-Noeva
authors: Marina
authors: M
authors: Marchetti
authors: Henri Maria
authors: HM
authors: Spronk
authors: Laura
authors: L
authors: Russo
authors: Erika
authors: E
authors: Diani
authors: Guido
authors: G
authors: Finazzi
authors: Good
authors: G
authors: Finazzi
authors: Silvia
authors: S
authors: Salmoiraghi
authors: Alessandro
authors: A
authors: Rambaldi
authors: Aueesandrd
authors: A
authors: Rambaldi
authors: Tiziano
authors: T
authors: Barbui
authors: Titiano
authors: T
authors: Barbui
authors: Hugo
authors: H
authors: Ten Cate
authors: Huao
authors: H
authors: Ten Cate
authors: Anna
authors: A
authors: Falanga
mesh_terms: D000328:Adult; D000368:Aged; D001780:Blood Coagulation Tests; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010976:Platelet Count; D053657:Platelet-Rich Plasma; D011087:Polycythemia Vera / Q000097:blood* / Q000378:metabolism; D013917:Thrombin / Q000096:biosynthesis*; D013920:Thrombocythemia, Essential / Q000097:blood* / Q000378:metabolism
chemical_list: C507924:JAK2 protein, human; D053614:Janus Kinase 2; D013917:Thrombin