Assessment of coagulation and fibrinolysis in families with unexplained thrombophilia

Iris M. Wichers; Michael W. T. Tanck; Joost C. M. Meijers; Ton Lisman; Pieter H. Reitsma; Frits R. Rosendaal; Harry R. Büller; Saskia Middeldorp

doi:10.1160/TH08-06-0405

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2009; 101(03): 465-470
DOI: 10.1160/TH08-06-0405

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Assessment of coagulation and fibrinolysis in families with unexplained thrombophilia

Authors

Iris M. Wichers

¹Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands
Michael W. T. Tanck

²Department of Clinical Epidemiology, Biostatics and Bioinformatics, Academic Medical Center, Amsterdam, The Netherlands
Joost C. M. Meijers

¹Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands
Ton Lisman

³Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The Netherlands
Pieter H. Reitsma

⁴Center for Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, The Netherlands
Frits R. Rosendaal

⁵Departments of Clinical Epidemiology and Haematology, Leiden University Medical Center, Leiden, The Netherlands
Harry R. Büller

¹Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands
Saskia Middeldorp

¹Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands

Abstract

Summary

Despite knowledge of various inherited risk factors associated with venous thromboembolism (VTE), no definite cause can be found in about 50% of patients. The lack of an intermediate phenotype in VTE impedes the discovery of new familial risk factors. We set out to define an intermediate phenotype for VTE by performing global coagulation analyses in unexplained thrombophilic families. Families were selected through a proband with VTE but without one of the known thrombophilic defects and at least one 1st or two 2nd degree family members with VTE. Clinical data were collected using a standardized questionnaire. Blood samples were collected for overall haemostasis assays (i.e. thrombin generation time [TGT], endogenous thrombin potential [ETP], prothrombin fragment 1+2 [F1+2] and activated protein C-sensitivity ratio [APC-sr] and clot lysis time [CLT]). Data were analysed using logistic regression. Coagulation assays were performed in 353 individuals of whom 41 (12%) had a history of VTE; these belonged to 17 thrombophilic families. Of the tested variables only the ETP was associated with VTE (odds ratio [OR] 1.03 for each % increase, 95% confidence interval [CI] 1.01–1.05). However, the relatively low number of cases does not firmly exclude the other assays as candidate intermediate phenotypes for venous thrombosis. We found that an increased ETP may serve as an intermediate phenotype for VTE and may be used to discover novel inherited risk factors by genetic linkage analysis.

Keywords

Coagulation factors - deep venous thrombosis - familial thrombosis - hypercoagulability - venous thrombosis

Full Text

References

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