WD shows abnormal copper accumulation in the liver and brain due to a decrease in ceruloplasmin, which is the transport protein bound to serum copper. ATP7B mutation on chromosome 13q14 gene has been identified as the causative gene [1, 2]. Generally, the treatment of WD is by pharmaceutical means that reduce copper absorption or promote copper excretion. Liver transplantation may also be performed in severe liver failure that is uncontrolled by pharmaceutical therapy.
Our patient had severe WD controlled with anti-copper therapy. Her liver function had rapidly deteriorated during pregnancy, and she showed severe coagulopathy, thrombocytopenia, and obstetric DIC. Intensive coagulation therapy could prevent massive peripartum hemorrhage.
Fibrinogen was reported to be the most important factor in obstetric hemorrhage [9]. It has been reported that a fibrinogen concentration ≤ 2 g/L has a positive predictive value of 100% for progression to severe postpartum hemorrhage [10]. Fibrinogen supplementation for postpartum hemorrhage has been reported [9,10,11,12]; however, prophylactic administration of fibrinogen in severe coagulopathy has not been well investigated. Our patient experienced both hypofibrinogenemia and thrombocytopenia, and was diagnosed with obstetric DIC. Her preoperative serum fibrinogen had decreased to < 1.5 g/L. Therefore, we considered the risk of massive perioperative hemorrhage to be high and that a massive blood transfusion may be required. The patient’s dramatic body weight gain had caused dyspnea and severe systemic edema. We were thus concerned about the cardiopulmonary dysfunction due to volume load caused by massive blood transfusion and fluid shift from prominent systemic edema. A large FFP transfusion can induce pulmonary edema due to volume overload [13]. Therefore, we decided to administer cryoprecipitate and fibrinogen concentrate. Additionally, we confirmed her coagulation function with ROTEM to determine the appropriate dose of fibrinogen concentrate. Although there have been reports about baseline ROTEM parameters of healthy pregnant women [14], ROTEM analysis in obstetrics has not been established. The efficacy of ROTEM-guided fibrinogen therapy for postpartum hemorrhage has been reported [15, 16]. In our case, her blood examination on the day of surgery showed thrombocytopenia, hypofibrinogenemia, and coagulation disorder. Preoperative platelet transfusion, cryoprecipitate, and fibrinogen concentrate administration improved her coagulation function and helped to avoid massive hemorrhage intraoperatively. Coagulation monitoring by ROTEM allowed us to evaluate her coagulation function just before surgery and determine the dose of supplemental fibrinogen administration.
WD exacerbation, as seen in our patient, is rare; therefore, we investigated other factors that can cause acute liver dysfunction associated with pregnancy, including the HELLP syndrome, acute fatty liver of pregnancy, and exacerbation of underlying chronic liver disease [17]. There are case reports of pregnant women with WD who had developed placenta abruption [18], preeclampsia [6], or HELLP syndrome [19, 20]. In our case, levels of total bilirubin, AST, and ALT were within normal limits. Therefore, liver function deterioration was considered to be due to WD exacerbation. However, the prominent systemic edema and significant weight gain might have also been attributed to a preeclampsia-related condition. Additionally, thrombocytopenia, decrease in urine output, and severe coagulopathy in the third trimester indicated obstetric DIC [12], which made her pregnancy difficult to continue.
Our patient had an episode of serious hepatic insufficiency at 20 years of age due to discontinuation of d-penicillamine. Discontinuation of medication in WD has been reported to exacerbate liver function and liver failure [21]. Liver biopsy revealed hepatic fibrosis, and liver function had already deteriorated severely enough to necessitate liver transplantation. Poor hepatic reserve may have been irreversible, despite copper metabolism and liver function showing improvement by treatment. She showed a remarkable decrease in liver function including albumin, AT-III, and coagulation factor levels, while AST and ALT levels remained normal. No reports show that only protein synthesis function markedly decreases in WD. Pregnancy might induce unexpected liver dysfunction in patients with WD, even when WD treatment is ongoing.