According to the results of a nearly 20-year-long study published in Blood Cells, Molecules and Disease, incidence of thrombotic events appears to be unassociated with factor XII (FXII) deficiency in heterozygous individuals compared with unaffected family members.

Past case reports have indicated that a mild FXII deficiency may be more strongly associated with increased incidence of thrombotic events and mortality than a severe deficiency. To investigate the incidence of thrombotic events in patients heterozygous for FXII deficiency, researchers followed 103 individuals with heterozygous FXII deficiency (54 male) and 103 unaffected, control family members (matched for sex and age, ±5 years) for 19.6 years. Endpoints of interest were myocardial infarction, deep vein thrombosis, and ischemic stroke.

The mean FXII level in heterozygotes was approximately half of that of the controls (48.5% [range, 35%-60%] vs 96.5% [range, 70%-155%]). Among both groups, the number of prothrombotic conditions were also similar. Five women with FXII deficiency had 7 pregnancies and 5 women in the control group had 6 pregnancies. Additionally, 4 and 5 surgical procedures were conducted in the heterozygote and control groups, respectively.

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Thrombotic events were infrequent in both groups. In heterozygotes, 1 myocardial infarction, 2 deep vein thromboses, and no ischemic stroke occurred. Similarly, in the controls, 2 myocardial infarctions, 1 deep vein thrombosis, and 1 ischemic stroke occurred.

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The authors concluded, “One should always remember that association between 2 events does not necessarily indicate the presence of a causal relation,” and that “FXII deficiency neither causes nor prevents thrombosis.”


1. Girolami A, Ferrari S, Cosi E, Randi ML. Heterozygous FXII deficiency is not associated with an increased incidence of thrombotic events: Results of a long term study [published online March 11, 2019]. Blood Cells, Mol Dis. doi:10.1016/j.bcmd.2019.03.001