To cite this article: van Vlijmen EFW, Wiewel-Verschueren S, Monster TBM, Meijer K. Combined oral contraceptives, thrombophilia and the risk of venous thromboembolism: a systematic review and meta-analysis. J Thromb Haemost 2016; 14: 1393-403. Essentials• We performed a meta-analysis on thrombosis risk in thrombophilic oral contraceptive (COC)-users.• The results support discouraging COC-use in women with a natural anticoagulant deficiency.• Contrary, additive risk of factor V Leiden (FVL) or prothrombin-G20210A (PT) mutation is modest.• Women with a FVL/PT-mutation as single risk factor can use COCs if alternatives are not tolerated. The cohort studies showed that absolute VTE risk was far higher in COC-users with severe thrombophilia than in those with mild thrombophilia (4.3 to 4.6 vs. 0.49 to 2.0 per 100 pill-years, respectively), and these differences in absolute risks were also noted in non-affected women (0.48 to 0.7 vs. 0.19 to 0.0), but with the caveat that absolute risks were estimated in relatives of thrombophilic patients with VTE (i.e. with a positive family history). Conclusion: These results support discouraging COC-use in women with severe hereditary thrombophilia. By contrast, additive VTE risk of mild thrombophilia is modest. When no other risk factors are present, (e.g. family history) COCs can be offered to these women when reliable alternative contraceptives are not tolerated.

Women with FXI deficiency have a clearly increased risk of HMB, and of bleeding complications after miscarriage, TOP and delivery. No high quality data are available regarding prophylactic treatment.

To cite this article: Wiewel-Verschueren S, Knol HM, Lisman T, Bogchelman DH, Kluin-Nelemans JC, van der Zee AGJ, Mulder AB, Meijer K.No increased systemic fibrinolysis in women with heavy menstrual bleeding. J Thromb Haemost 2014; 12: 1488-93.Summary. Background: Bleeding disorders have been recognized as important etiologic or contributory factors in women with heavy menstrual bleeding. Fibrinolysis in the endometrium plays a role in heavy menstrual bleeding. It is unknown whether increased systemic fibrinolysis might also increase the risk of heavy menstrual bleeding. Objective: To investigate fibrinolytic parameters, including clot lysis time, in women with heavy menstrual bleeding. Methods: We included 102 patients referred for heavy menstrual bleeding (Pictorial Bleeding Assessment Chart score of > 100) in our cohort. Patients and controls (28 healthy volunteers without heavy menstrual bleeding) underwent hemostatic testing in the first week after menstruation. For 79 patients and all controls, fibrinolytic parameters (thrombin-activatable fibrinolysis inhibitor activity, and plasminogen activator inhibitor-1, tissuetype plasminogen activator and plasmin inhibitor levels) and clot lysis time were available. Results: Fibrinolytic parameters were similar between patients and controls, except for thrombin-activatable fibrinolysis inhibitor (89.4% vs. 82.5%) and plasmin inhibitor (106% vs. 96%), the levels of which which were significantly higher in patients. In women with menorrhagia without gynecologic abnormalities, we found lower thrombinactivatable fibrinolysis inhibitor and plasminogen activator inhibitor-1 levels than in women with gynecologic abnormalities (thrombin-activatable fibrinolysis inhibitor, 85.4% vs. 94.8%; plasminogen activator inhibitor-1, 16.0). Conclusion: Systemic fibrinolytic capacity is not increased in women with heavy menstrual bleeding. Overall, levels of the fibrinolytic inhibitors thrombin-activatable fibrinolysis inhibitor and plasmin inhibitor were even higher in patients than in controls. However, in a subgroup of women without gynecologic abnormalities, relatively lower levels of inhibitors may contribute to the heavy menstrual bleeding.