Dysfibrinogenemia during pregnancy treated successfully with fibrinogen

Abstract

There are three types of congenital abnormalities associated with fibrinogen: afibrinogenemia, hypofibrinogenemia and dysfibrinogenemia. Of these, dysfibrinogenemia is usually clinically silent or is associated with mild to moderate bleeding tendency or defective wound healing. The obstetric complications of dysfibrinogenemia include first-trimester abortion, hemorrhage and placental abruption during pregnancy, and thrombophlebitis (1). We report a case of a dysfibrinogenemic patient with a history of recurrent fetal loss due to placental abruption, which was successfully treated with fibrinogen prophylaxis. The patient was a 38-year-old woman who had no bleeding diathesis. Her obstetric history was complicated, with two miscarriages at 8 weeks' gestation and two second-trimester fetal losses at 25 and 26 weeks' gestation because of placental abruption. After the last fetal loss at 26 weeks' gestation she was referred to Kobe University Hospital to investigate the etiological background of these episodes. Blood coagulation tests performed at that time were as follows: clottable fibrinogen (66 mg/dL; normal 170–350 mg/dL), immunologic fibrinogen (225 mg/dL; normal 170–350 mg/dL). Congenital dysfibrinogenemia was diagnosed by discrepancy between clottable and immunologic fibrinogen. Thereafter, she became pregnant and received our consultation at 8 weeks' gestation in the hope of maintaining the pregnancy. She was treated with 2 g of fibrinogen three times a week from 8 weeks' gestation to maintain a fibrinogen level of more than 100 mg/dL, as recommended in a previous report (2). At 16 weeks' gestation, she developed uterine contractions followed by moderate vaginal bleeding, when the level of fibrinogen was 138 mg/dL. Systemic tocolysis by beta- sympathomimetic drug therapy was needed during the rest of the pregnancy due to persistent uterine contractions. As pregnancy progressed, the fibrinogen requirement increased to a dose of 10–14 g/week to control the vaginal bleeding and uterine contractions. Fetal growth was normal. At 29 weeks' gestation, uterine contractions became stronger, and she developed moderate vaginal bleeding again. The fibrinogen level was 191 mg/dL. Emergency cesarean section was performed under general anesthesia and she delivered a male infant (weight 1622 g) with Apgar scores of 3 and 7 at 1 and 5 min, respectively. There were no findings of placental abruption at the time of surgery. The fibrinogen level of the newborn was 147 mg/dL. He had no episodes of bleeding and developed normally. Before and during operation 6 g of fibrinogen was infused continuously, considering the rapid consumption of fibrinogen with the operation. The estimated blood loss during operation was about 2500 mL and she received 1200 mL of blood transfusion. She had a normal puerperium with a reduced dose of fibrinogen infusion, which was stopped on the seventh day postpartum. Two cases have been reported of pregnancy associated with dysfibrinogenemia: one case diagnosed at 9 weeks' gestation was treated with subcutaneous heparin administration because of clear thromboembolic tendencies and had a third-trimester fetal loss due to placental abruption (3). The other case diagnosed at 24 weeks' gestation developed placental abruption 5 days after the diagnosis (4). These two cases had no fibrinogen replacement. The present case is unique because there are no other reported cases of dysfibrinogenemia in pregnancy with a history of recurrent fetal loss that were successfully treated with fibrinogen replacement from the early stage of gestation. Poor pregnancy outcomes were reported in all cases if fibrinogen levels were less than 60 mg/dL. Therefore, it has been suggested that the minimum level of fibrinogen to maintain pregnancy might be about 60 mg/dL (5,6). In our case, however, the fibrinogen level of 60 mg/dL was insufficient to prevent placental abruptions in the previous pregnancies. Kobayashi et al. (2) proposed that the fibrinogen level should be at least 60 mg/dL and, if possible, greater than 100 mg/dL during the pregnancy to prevent bleeding and abortion. We therefore elected to maintain our case's fibrinogen levels at quasi-physiological levels throughout her fifth pregnancy, where the development of placental abruption was prevented. Nevertheless, vaginal bleeding subsequent to uterine contractions developed at 16 weeks' gestation despite maintaining the fibrinogen level of 120 mg/dL. This implies that the fibrinogen requirement increases because of the rapid consumption of fibrinogen in the uteroplacental unit in dysfibrinogenemic women with increased uterine contractions.