F5 and Rare hereditary thrombophilia: A meta-analysis of 12 case–control and three cohort studies performed in the Netherlands in the 2016 year showed that “mild” (FVL or prothrombin mutation) and “severe” (antithrombin, protein C and S deficiency, homozygosity or double heterozygosity for FVL or prothrombin mutation) thrombophilia increased the risk of VTE almost 6-fold (RR 5.89; 95% confidence interval [CI], 4.21–8.23) and 7-fold (RR, 7.15; 95% CI, 2.93–17.45), respectively, compared with COC users without genetic thrombophilia [83].