For a good while we’ve known about the importance of family history in the assessment of patients’ risk for VTE. In many ways the family history is more powerful than all the expensive thrombophilia tests. The more common genetic thrombophilias have low penetrance rates. Thus, when thrombophilia is expressed clinically in families, two or more genetic risks are often present in combination. This helps explain why the family history is often more helpful than laboratory testing.
Another factor is the state of the science of thrombophilia testing. Take 100 patients with familial thrombophilia and do an extensive battery of genetic and phenotypic laboratory tests. You’ll find something in only around 60 of them. The other 40 have a genetic disorder waiting to be discovered. Back in the 1980’s, when the relatively uncommon anti-thrombin, protein C and protein S deficiencies were the only hereditary thrombophilias known the number of patients with a positive test would have been around 15. The number has increased only recently with the discovery of the most common thrombophilias, factor V Leiden and the prothrombin mutation. (The more common thrombophilias tend to be discovered later because of their low penetrance).
A population-based case-control study recently published in the Archives of Internal Medicine adds to our understanding of the risk factors for VTE and their interactions. It demonstrated that family history was at least as predictive as, and correlated poorly with, known genetic risk factors. The full text, if you can access it, is well worth the read as it provides a world of background information which should be helpful to the clinician in understanding the optimal use of thrombophilia testing.