title: Coagulation activation and microparticle-associated coagulant activity in cancer patients. An exploratory prospective study.
abstract: Cancer increases the risk of venous thromboembolism (VTE). Here, we investigated the contribution of microparticle (MP)-dependent procoagulant activity to the prothrombotic state in these patients. In 43 cancer patients without VTE at study entry and 22 healthy volunteers, markers of  in vivo  and MP-dependent coagulation were measured and patients were prospectively followed for six months for the development of VTE. Procoagulant activity of MPs was measured  in vitro  using a tissue factor (TF)-independent phospholipid dependent test, a factor Xa-generation assay with and without anti-TF, and a fibrin generation test (FGT) with and without anti-factor VII(a). Markers of  in vivo  coagulation activation and total number of MPs at baseline were significantly elevated in cancer patients compared to controls (F1+2 246 vs. 156 pM, thrombin-antithrombin complexes 4.1 vs. 3.0 mg/l, D-dimer 0.76 vs. 0.22 mg/l and 5.53 x 10⁶ vs. 3.37 x 10⁶ MPs/ml). Five patients (11.6%) developed VTE. Patients with VTE had comparable levels of coagulation activation markers and phospholipid-dependent MP procoagulant activity. However, median TF-mediated Xa-generation (0.82 vs. 0.21 pg/ml, p=0.016) and median VIIa-dependent FGT (13% vs. 0%, p=0.036) were higher in the VTE group compared with the non-VTE group. In this exploratory study the overall hypercoagulable state in cancer patients was not associated directly with the MP phospholipid-dependent procoagulant activity. However, in the patients who developed VTE within six months when compared to those who did not, an increased MP procoagulant activity was present already at baseline, suggesting this activity can be used to predict VTE.
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Frederiek
authors.initials: F
authors.lastname: van Doormaal
authors.forename: Ankie
authors.initials: A
authors.lastname: Kleinjan
authors.forename: René J
authors.initials: RJ
authors.lastname: Berckmans
authors.forename: Nigel
authors.initials: N
authors.lastname: Mackman
authors.forename: David
authors.initials: D
authors.lastname: Manly
authors.forename: Pieter W
authors.initials: PW
authors.lastname: Kamphuisen
authors.forename: Dick J
authors.initials: DJ
authors.lastname: Richel
authors.forename: Harry R
authors.initials: HR
authors.lastname: Büller
authors.forename: Auguste
authors.initials: A
authors.lastname: Sturk
authors.forename: Rienk
authors.initials: R
authors.lastname: Nieuwland
mesh_terms: D000368:Aged; D001780:Blood Coagulation Tests; D001792:Blood Platelets / Q000648:ultrastructure*; D055252:Cell-Derived Microparticles / Q000378:metabolism* / Q000648:ultrastructure; D015942:Factor VIIa / Q000378:metabolism; D015951:Factor Xa / Q000032:analysis; D005260:Female; D005337:Fibrin / Q000032:analysis; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications / Q000175:diagnosis* / Q000473:pathology; D010743:Phospholipids / Q000378:metabolism; D015539:Platelet Activation; D011379:Prognosis; D011446:Prospective Studies; D012306:Risk; D054556:Venous Thromboembolism / Q000175:diagnosis* / Q000209:etiology / Q000473:pathology
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; D010743:Phospholipids; C036309:fibrin fragment D; D005337:Fibrin; D015942:Factor VIIa; D015951:Factor Xa