title: ADP-induced platelet aggregation and thrombin generation are increased in Essential Thrombocythemia and Polycythemia Vera.
abstract: BACKGROUND
  Essential Thrombocythemia (ET) and Polycythemia Vera (PV) patients are characterized by an increased rate of thrombotic complications and by several abnormalities of platelets, more pronounced in JAK2V617F positive patients. The aim of this study was to characterize the platelet aggregation as well as the platelet procoagulant potential induced by several different agonists in ET and PV patients.
  
  
  METHODS
  Venous blood samples were obtained from 65 ET and 51 PV patients. Whole blood impedance aggregometry was utilized to characterize platelet aggregation induced by collagen, ADP, thrombin receptor activating peptide and arachidonic acid, while the Calibrated Automated Thrombogram (CAT) assay was used to determine the thrombin generation (TG) potential induced by ADP in platelet-rich plasma. CAT assay was also performed in the presence of annexin V to evaluate the contribution of platelet phospholipids to TG.
  
  
  CONCLUSIONS
  ADP-induced platelet aggregation and TG were significantly increased in ET and PV patients compared to controls. The highest values were observed in JAK2V617F positive patients and in patients on aspirin. In these subjects, annexin V was less effective in inhibiting both basal and ADP-induced TG. This study demonstrates for first time that platelets from ET and PV patients are more responsive to the ADP stimulus, in terms of both increased platelet aggregation, and enhanced TG, particularly in the JAK2V617F positive patients. Our data support the hypothesis that the use of ADP receptor inhibitors, in addition to aspirin, might be considered in the prevention of thrombosis in these conditions, by allowing a more complete inhibition of platelet functions.
authors.affiliation: Division of Immunohematology and Transfusion Medicine, Ospedale Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Panova-Noeva
authors.forename: Marina
authors.initials: M
authors.lastname: Marchetti
authors.forename: Laura
authors.initials: L
authors.lastname: Russo
authors.forename: Carmen J
authors.initials: CJ
authors.lastname: Tartari
authors.forename: Anna
authors.initials: A
authors.lastname: Leuzzi
authors.forename: Guido
authors.initials: G
authors.lastname: Finazzi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Rambaldi
authors.forename: Hugo
authors.initials: H
authors.lastname: ten Cate
authors.forename: Anna
authors.initials: A
authors.lastname: Falanga
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000627:therapeutic use; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D011087:Polycythemia Vera / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D013917:Thrombin / Q000378:metabolism*; D013920:Thrombocythemia, Essential / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D055815:Young Adult
chemical_list: D010975:Platelet Aggregation Inhibitors; D000244:Adenosine Diphosphate; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D013917:Thrombin; D001241:Aspirin
keywords: JAK2617F mutation; aspirin; myeloproliferative disorders; platelet aggregation; thrombin generation; thrombosis