Risk of Venous Thromboembolism in Relatives of Factor V Leiden and Factor II G20210A Carriers: A Combined Analysis of Retrospective and Prospective Studies.
Authors: Oliveira Luciana C.O. , Rizzatti Edgar G. , Inacio Rosemeire A.S. , Baggio Marcia S. , Tavella Marli H. , Franco Rendrik F. 
Published: October 2019

Abstract
There are scarce data on thrombotic risk in FVL and FII G20210A asymptomatic carriers, probably due to the requirement of a great number of observed people for a long period of time. This study evaluated retrospectively and prospectively the incidence of VTE in first-degree relatives of FVL and FII G20210A carriers and it performed combined analysis with previous similar observational studies. Retrospective combined analysis for FVL evaluated four previous studies and ours (Table 1). Of the 2016 included family members, 1065 subjects were FVL carries. 37464 and 33433 years of observation were recorded in the group of FVL carriers (car) and non-carriers (N-car), respectively. Annual incidence of VTE was 0.27% in FVL car and 0.08% in N-car (RR=3.4, CI95 2.22–5.19). For FII G20210A analysis, we added another study to the previously mentioned studies (Table 1). Of the 695 analysed family members, 210 subjects carried the mutation. 8312 and 18354 years of observation were recorded in the group of car and N-car, respectively. Annual incidence of VTE was 0.14% in car and 0.06% in N-car (RR=2.4, CI95 1.06–5.45). Prospective combined analysis for FVL evaluated two studies, including ours (Table 2). 653 family members were evaluated, being 357 FVL car. 1387 and 1145 years of observation were recorded in the group of car and N-car, respectively. Annual incidence of VTE was 0.79% in FVL car and 0.617% in N-car (RR=4.51, CI95 1–20.32). For FIIG20210A, the prospective analysis was performed only in our study. Included were 113 family members, being 64 FII G20210 carries. 194 and 151 years of observation were recorded in the group of car and N-car, respectively. Annual incidence of VTE was 1.55% in car and 0% in N-car (RR=∞). In conclusion, the incidence of VTE in asymptomatic carriers of the two most common prothrombotic mutations was found to be low in the retrospective and prospective analysis, not justifying a routine thrombophilia mutation screening in this population.
Table 1 - Results of retrospective studies with relatives of FVL and FIIG20210A carriers. Studies Mutation N Observed years VTE Annual Incidence rate VTE (%) CI 95 FV Leiden Middeldorp 1998 present 236 6524 29 0.45 (0.28–0.61) absent 201 5716 6 0.10 (0.02–0.19) FV Leiden Simioni 1999 present 224 6114 17 0.28 (0.15–0.41) absent 154 4401 4 0.09 (<0.01–0.18) FV Leiden Lensen 2000 present 122 5294 18 0.34 (0.2–0.5) absent 111 5090 5 0.10 (0.01–0.2) FV Leiden Martinelli 2000 present 447 18320 35 0.19 (0.13–0.25) absent 436 16720 11 0.07 (0.03–0.11) FV Leiden Our study 2005 present 36 1212 4 0.33 (0.10–0.88) absent 49 1506 1 0.07 (<0.01–0.42) FII G20210A Martinelli 2000 present 158 6738 9 0.13 (0.06–0.24) absent 436 16720 11 0.07 (0.03–0.11) FII G20210A Our study 2005 present 36 1574 3 0.19 (0.04–0.59) absent 49 1634 0 0 (0–0.023) Table 2 - Results of prospective studies with relatives of FVL carriers Studies Mutation N Observed years VTE Annual incidence rate VTE (%) CI 95 FV Leiden Simioni 2002 present 313 1255 8 0.67 (0.29–1.33) absent 248 984 1 0.1 (0.003–0.56) FV Leiden Our study 2005 present 44 132 3 2.27 (0.49–6.81) absent 48 161 1 0.62 (<0.01–3.83)