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Persistent high factor VIII activity leading to increased thrombin generation - A prospective cohort study.
MedLine Citation:
PMID:  21849206     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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>200iu/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.
Authors:
J K Ryland; A S Lawrie; I J Mackie; S J Machin
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-8-15
Journal Detail:
Title:  Thrombosis research     Volume:  -     ISSN:  1879-2472     ISO Abbreviation:  -     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-8-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0326377     Medline TA:  Thromb Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Elsevier Ltd. All rights reserved.
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