Ravulizumab Treatment during Pregnancy: A Case Report

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare chronic blood disorder associated with a significant risk of thrombosis, the leading cause of death in patients (pts) with PNH. In pregnant women, PNH is also associated with increased maternal and fetal complications. While data are available for eculizumab (ECU) for PNH during pregnancy, none exist for ravulizumab (RAV). We present a pt with PNH and polycythemia vera (PV) who required a liver transplant owing to Budd-Chiari, had dural venous sinus thrombosis (DVST), and later became pregnant while receiving RAV.

A 29-year-old pt presented with progressively severe epigastric pain, nausea, vomiting, and radiation to the right shoulder and lower abdomen in 2016. Initial findings showed mild hepatomegaly (19 cm) and positive H. pylori, requiring antibiotics. Persistent symptoms led to a HIDA scan, identifying biliary dyskinesia and sludge (EF 12%). Subsequent follow-up visits showed persistent leukocytosis (WBC 11,000-16,000/µL) with neutrophilia, elevated alkaline phosphatase (244 IU/L; 1.7×ULN), hepatomegaly (18 cm), and worsening splenomegaly (16.5 cm) with intermittent abdominal pain, nausea, fatigue, diarrhea, epigastric bloating, and dark-colored urine. Further evaluation revealed Budd-Chiari with splenomegaly, small portosystemic collaterals with portal hypertension and minimal ascites. The pt switched from enoxaparin to rivaroxaban and discontinued (d/c) oral contraception. Flow cytometry (62.0% granulocyte clone and 96.0% type 2 erythrocyte clone) and genetic testing confirmed JAK2V617F (50.0% VAF) positive PV and PNH in 2017. Spironolactone was started after worsening ascites. Head pain with asymmetric signal in the sinus and right jugular vein/sigmoid sinus enhancement raised concerns of DVST 1-week postdiagnosis. She started ECU. Over 9 months, complications of worsening liver function and erythrocytosis (Hgb=17.3 g/dL) led to initiation of hydroxyurea, later d/c due to thrombocytopenia, and intermittent therapeutic phlebotomies. Further decline of liver function in 2019 led to switching rivaroxaban to apixaban to warfarin, followed by a liver transplant and tacrolimus initiation. In 2021, she switched to RAV 3000-3300 mg IV after concerns of breakthrough hemolysis owing to dark urine and fatigue with ECU. RAV improved her PNH symptoms. After worsening splenomegaly (28 cm) in 2022, she initiated ruxolitinib (RUX).

Despite recommendations, she became pregnant in 2022 and remained on RAV and tacrolimus. RUX and apixaban were d/c and she restarted enoxaparin. Due to worsening abdominal pain and splenomegaly (30 cm) at week 20, she restarted RUX. Week 21-28 hospitalization complications included malnutrition, hemoptysis related to a mass-like consolidation in the right upper lung secondary to infection with EGD negative for varices, imaging indicating splenic infarcts, hemorrhagic pleural effusion requiring thoracentesis, acute renal failure requiring temporary dialysis, and decompensated cirrhosis requiring paracentesis. Imaging revealed near complete inferior vena cava occlusion likely due to withholding anticoagulation during complications. After 1 additional preoperative dose of RAV was administered at 28 weeks+2 days (5/17/2023), delivery of a healthy baby (1.09 kg; APGAR, 3/4/4) occurred prematurely via cesarean section; an IUD was inserted. Her organ function improved postpartum; she resumed prepregnancy medications, including apixaban after receiving heparin intermittently during pregnancy due to bleeding. On postop day 16, the pt was discharged with close follow-up. The baby remained in the NICU for ~8 weeks for nutrition and monitoring of respiratory status. The pt continues to receive RAV every 8 weeks with no thrombotic or hemolytic events.

PNH is a complex disease that can lead to complications during pregnancy, including potentially life-threatening thrombosis. This is the first report of RAV for PNH during pregnancy. Due to the case's complexity, it required collaboration among hepatology, obstetrics, hematology, pulmonary critical care, gastroenterology, and nephrology. Despite complications, her hemolysis with PNH was well-controlled with RAV during pregnancy, with limited postoperative complications. As of 6/13/2024, our pt and her baby remain healthy. This report may help guide future treatment by providing an example of treatment with RAV during pregnancy.

Patel:Alexion: Honoraria; Novartis: Honoraria; Geron: Honoraria.