Persistent high factor VIII activity leading to increased thrombin generation – A prospective cohort study

• Published in: Thrombosis research 2012-04, Vol.129 (4), p.447-452
• Main Authors: Ryland, J.K, Lawrie, A.S, Mackie, I.J, Machin, S.J
• Format: Article
• Language: English
• Subjects: Adult; Aged; Anticoagulants - therapeutic use; Biological and medical sciences; Biomarkers - blood; Blood and lymphatic vessels; Cardiology. Vascular system; Cohort Studies; D-dimer; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Factor VIII; Factor VIII - analysis; Female; Fundamental and applied biological sciences. Psychology; FVIII; General aspects; Hematology, Oncology and Palliative Medicine; Humans; Male; Medical sciences; Middle Aged; pathophysiology; Prevalence; Prospective Studies; Risk Assessment; Risk Factors; Thrombin - analysis; thrombin generation; United Kingdom - epidemiology; Venous Thromboembolism - blood; Venous Thromboembolism - drug therapy; Venous Thromboembolism - epidemiology; venous thrombosis; Vertebrates: cardiovascular system; Young Adult
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/j.thromres.2011.07.020

Abstract Introduction A persistently elevated level of factor VIII (FVIII) is an independent risk factor for venous thromboembolism (VTE). Although the pathophysiology of VTE is unclear, the involvement of thrombin generation (TG) has been postulated. Consequently this study was designed to (i) investigate the relationships between FVIII, Thrombin generation test (TGT) parameters and D-dimer in VTE patients, (ii) determine whether elevated levels of FVIII and increased TG in these patients are transient or sustained. Patients and Methods After an initial period of anticoagulation had been completed 91 VTE patients and 52 healthy controls were recruited. FVIII levels were determined by one-stage clotting (FVIII:C) and chromogenic (FVIII:Ch) assays. The potential to generate thrombin was measured using the Calibrated Automated Thrombogram (CAT) and D-Dimer was by immuno-turbidometric assay. Results Patients' FVIII:C levels and FVIII:Ch, exhibited good agreement (rs = 0.94; p < 0.0001), although FVIII:C exhibited a mean bias of -6%. FVIII:Ch show a significant correlation with TGT Peak Thrombin (rs = 0.30; p = 0.004) and Peak Thrombin was found to be significantly higher (p = 0.04) in patients with FVIII > 200 iu/dL. Furthermore elevated levels of FVIII and increased thrombin generation parameters appeared to be consistent over time. Conclusion Our data suggests that high FVIII leading to increased TG confers a significant risk of recurrent VTE and therefore we speculate that these patients may benefit from prolonged anticoagulation therapy.