Management of Pregnancy in Inherited Dysfibrinogenemia after Recurrent Miscarriage

Dysfibrinogenemia can lead to bleeding or thrombosis as well as to obstetric complications. The latter include early pregnancy loss, hemorrhage, placental abruption, and thrombosis. There are only a few case reports with treatment recommendations for pregnancy in affected women. We report on a meanwhile 34-year-old woman who had four consecutive early abortions between 2013 and 2015. At the presentation in our outpatient clinic, the patient reported a tendency to bruising, but no other bleeding and no thromboembolic events. Laboratory examinations showed a reduced Quick value, a prolonged thrombin time, a largely prolonged reptilase time, and fibrinogen concentrations of 0.67 g/l (Clauss method) and 3.87 g/l (immunoturbidimetry). The patient was diagnosed with dysfibrinogenemia. The molecular biological examination revealed the mutation c.103C>T. (p.Arg35Cys) in Exon 2 of the FGA gene (synonym A alpha 16Arg -> Cys substitution). During the fifth and sixth pregnancy, the patient was treated with a low-molecular heparin using the recommended prophylaxis dose for increased risk of thrombosis. At the same time, the patient received fibrinogen concentrate three times a week (3 x 2 g per week). Both pregnancies were uneventful. Poor pregnancy outcomes were reported in many cases if functionally active fibrinogen levels were less than 0.6 g/l (Clauss method). After the diagnosis of dysfibrinogenemia in a woman without an obvious tendency to bleed and without thromboembolic events in her history, it seems to us to be the best procedure to substitute fibrinogen and to applicate low-molecular-weight heparins at the same time to prevent bleeding, thrombosis, and pregnancy loss as well.