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 Blood, 1 October 2005, Vol. 106, No. 7, pp. 2363-2365.
Prepublished online as a Blood First Edition Paper on June 16, 2005; DOI 10.1182/blood-2005-04-1461.

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Submitted April 11, 2005
Accepted June 2, 2005

An underestimated combination of opposites resulting in enhanced thrombotic tendency

Paolo Simioni*, Elisabetta Castoldi, Barbara Lunghi, Daniela Tormene, Jan Rosing, and Francesco Bernardi

Department of Medical and Surgical Sciences, 2nd Chair of Internal Medicine, University of Padua Medical School, Padua, Italy
Department of Biochemistry, Cardiovascular Research Institute, Maastricht University, Maastricht, The Netherlands
Department of Biochemistry and Molecular Biology, University of Ferrara, Ferrara, Italy

* Corresponding author; email: paolo.simioni{at}unipd.it.

Heterozygous carriers of Factor V (FV) Leiden who also carry FV deficiency often develop venous thromboembolism, but the thrombosis risk associated with this rare condition (pseudo-homozygous APC resistance) is still unclear. The thrombosis risk of genetically characterized pseudo-homozygotes (n=6) was compared to that of FV Leiden heterozygotes (n=683) and homozygotes (n=50) recruited within a large cohort study on familial thrombophilia. Both thrombin generation and Kaplan-Meier thrombosis-free survival analysis were performed in different FV genotype groups. Factor V Leiden pseudo-homozygotes showed significantly higher thrombosis risk than heterozygotes. The thrombin generation test in pseudo-homozygotes showed a pattern similar to homozygotes. Accordingly, early thrombotic manifestations occurred in pseudo-homozygotes at a similar rate as in homozygotes. Thus, failure to recognize FV deficiency in FV Leiden heterozygotes may result in underestimate of the thrombosis risk and inadequate management of affected patients.


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