title: Platelet dysfunction in thrombosis patients treated with vitamin K antagonists and recurrent bleeding.
abstract: BACKGROUND
  Recurrent bleeding can complicate the treatment of thrombosis patients with vitamin K antagonists (VKA), even at a well-regulated level of anticoagulation. In this proof-of-principle study, we investigated whether alterations in platelet function or von Willebrand factor (vWf) contribute to a bleeding phenotype in these patients.
  
  
  METHODS
  In this case-control study 33 well-regulated patients without bleeding events (controls) and 33 patients with recurrent bleeding (cases) were retrospectively included. Thrombin generation and vWf were determined in plasma. Platelet function was assessed by light transmission aggregometry and flow cytometry using a validated panel of agonists.
  
  
  RESULTS
  Thrombin generation was similarly reduced in controls and cases, in comparison to normal plasma. Plasma vWf level was above the normal range in 85% of controls and 67% of the cases. vWf activity was similarly increased in all patients in comparison to healthy volunteers. Platelet aggregation was in the normal range for almost all patients irrespective of the type of agonist. However, in response to a low collagen dose, platelets from 21% of controls and 27% of cases showed diminished responses. Agonist-induced secretion of alpha- and dense-granules or integrin αIIbβ3 activation were affected in platelets from neither controls nor cases.
  
  
  CONCLUSIONS
  Recurrent bleeding in well-controlled patients on VKA therapy is not explained by anti-hemostatic changes in platelet or vWf function.
authors.affiliation: Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center, Maastricht, The Netherlands. p.vandermeijden@maastrichtuniversity.nl
authors.forename: Paola E J
authors.initials: PE
authors.lastname: van der Meijden
authors.forename: Annemieke C
authors.initials: AC
authors.lastname: Bouman
authors.forename: Marion A H
authors.initials: MA
authors.lastname: Feijge
authors.forename: René
authors.initials: R
authors.lastname: van Oerle
authors.forename: Henri M H
authors.initials: HM
authors.lastname: Spronk
authors.forename: Karly
authors.initials: K
authors.lastname: Hamulyák
authors.forename: Arina J
authors.initials: AJ
authors.lastname: ten Cate-Hoek
authors.forename: Hugo
authors.initials: H
authors.lastname: ten Cate
authors.forename: Johan W M
authors.initials: JW
authors.lastname: Heemskerk
mesh_terms: D000368:Aged; D001791:Blood Platelet Disorders / Q000139:chemically induced*; D001792:Blood Platelets; D016022:Case-Control Studies; D005260:Female; D006470:Hemorrhage / Q000097:blood / Q000139:chemically induced*; D006801:Humans; D016023:Integrins / Q000378:metabolism; D008297:Male; D010974:Platelet Aggregation; D012008:Recurrence; D013917:Thrombin / Q000378:metabolism; D013927:Thrombosis / Q000097:blood / Q000188:drug therapy*; D014812:Vitamin K / Q000037:antagonists & inhibitors*; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D016023:Integrins; D014841:von Willebrand Factor; D014812:Vitamin K; D013917:Thrombin