Prevalence and Clinical Significance of Single and Combined Inherited Thrombophilias.

The prevalence of inherited single and combined thrombophilias were examined in 986 patients (330 males and 656 females) between 1995–2004 with venous thromboembolism (VTE).

Methods: Screening blood coagulation tests (PT, APTT, TT, FG), coagulation inhibitor activities and antigen levels (AT, PC, PS), APC-R, FV: Q506, FII 20210A, anti-phospholipoid antibodies, plasma homocystein level and circumstantial risk factors were examined. The age at first thromboembolic episode, family history for thrombosis, localization of VTE, therapies administered, recurrences, chronic venous insufficiency (CVI) and crural ulcer (CU) were registered.

Results: The mean age at the first thromboembolic episode was 34,4 +/− 11,4 y. VTE was present in the family in 416 cases (46%), the mean observation time was 9,24+/−8,81 years. We found AT deficiency in 4,3%, PC in 5,9 % (mutation in the PC gene was verified in 7 families), PS in 5,4%. APC resistence was 25,3%, FV:Q506 mutation 24%. Inherited defect was present in 459 p. (46,5%). Single inherited abnormality in 279/986 p. (28,2%), combined in 82/986 p. (8,3%), two abnormalities in 70, three in 11 and four in 1 patient. The distribution of circumstantial risk factors among patients with and without inherited coagulation abnormalities were equal, except OC usage, pregnancy and labor. These obstetrical risk factors occured significantly higher in patients having inherited abnormalities. VTE in the family, the ileofemoral localization of the VTE and the need for thrombolythic therapy was also significantly higher among patients with inherited abnormalities. We also examined and compared the occurence rate of recurrence, CVI and CU among patients with single and combined inherited abnormalities vs. those without such abnormalities. Recurrence rate was significantly higher in patients with coagulation defects vs. without defects, and between those having only one vs. more defects. It was not dependent on the type of the single coagulation defect. FVQ506+PC and FVQ506+AT defects increased, whereas the FVQ506+FII20210A and +PS defects did not increase singificantly the relapse rate. The occurance of CVI and CU in patients with coagulation defects was significantly increased independently of having one vs. more defects.

Conclusions: Inherited coagulation abnormalities predisposing to VTE are detectable in 46,5% of young Hungarian VTE patients. Among them 60,7% had single and 17,8% had combined abnormalities. Recurrence rate was significantly higher in patients with more then one vs. no inherited coagulation abnormality. CVI and CU developed significantly more frequently in patients having one or even more inherited coagulation defects. The detailed detection of coagulation abnormalities is of prognostic significance. (Supported by OTKA T026428 and ETT 124/96.)