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J Thromb Haemost. 2010 Feb;8(2):228-33. doi: 10.1111/j.1538-7836.2009.03702.x. Epub 2009 Nov 23.

Unraveling the thrombophilia paradox: from hypercoagulability to the prothrombotic state.

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Department of Haematology, Cambridge University Hospitals NHS Trust, Addenbrooke's Hospital, Cambridge, UK.


The thrombophilia paradox whereby thrombophilia testing identifies defects associated with an increased risk of a first venous thrombosis but not of a particularly high risk of recurrence is likely the result of limitations imposed by a limited dichotomous testing strategy compounded by test inaccuracy and imprecision. Consequently, the observed intermediate phenotype (defined by limited laboratory test results) is not fully concordant with the heritable genotype. The next generation of thrombophilia tests, which utilize either individual genomic analysis or global measurement of the composite plasma intermediate phenotype, may more accurately quantify the thrombophilic risk. In conjunction with clinical risk assessment a more quantitative measurement of hypercoagulability and definition of the prothrombotic state should facilitate transition of clinical management from a disease-focused to a more patient-focused strategy.

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