Paroxysmal nocturnal hemoglobinuria (PNH) is a hematologic disorder characterized by an acquired somatic mutation in the phosphatidylinositol glycan class A gene which leads to a higher risk for increased venous and arterial thrombosis. Current treatment for PNH includes eculizumab. Pregnant patients who have PNH have higher risk for thrombosis and hemorrhage with both pregnancy and their underlying PNH. Treatment frequently poses conundrum. The safety and efficacy of eculizumab during pregnancy and breast feeding have not been extensively studied and contraception has been recommended due to potential for teratogenicity. We present a case of a patient who was safely on both eculizumab and modest prophylactic anticoagulation for 6 weeks post-partum.
Paroxysmal nocturnal hemoglobinuria (PNH) is a complex hematologic disorder characterized by an acquired somatic mutation in the phosphatidylinositol glycan (PIG-A) gene resulting in a deficiency of the glycosyl phosphatidylinositol (GPI) anchored proteins, particularly CD55 and CD59 on the cell membrane [
Current treatment for PNH includes eculizumab, a monoclonal antibody that blocks terminal complement activation. This results in the reduction in hemolysis and, for many, improvement in the quality of life [
We present the case of a nulliparous 24-year-old female with no prior past medical history of hereditary conditions predisposing to thrombosis, a body mass index of 25, no family history of thrombosis, and the only acquired and secondary risk of thrombophilia due to PNH, who was referred to our institution for consideration of hematopoietic stem cell transplant. The transplant was offered, and she declined. She was placed on eculizumab for control of her disease and to decrease blood transfusion requirements. Due to potential teratogenicity of eculizumab, she was counseled against becoming pregnant. She tolerated eculizumab treatment well and her transfusion requirements decreased; however, after six months of eculizumab, screening HCG testing revealed she was pregnant. At this time her risk factors for thrombosis were PNH and pregnancy. Due to a confirmed pregnancy, eculizumab was temporarily held for two months. After discussions with the patient regarding the potential risks, eculizumab was restarted in the 10th week of her pregnancy. With the concomitant thrombotic risk conferred by PNH as well as a newly diagnosed pregnancy, thromboprophylaxis was strongly considered. Given a clone size above 50%, anticoagulation with unfractionated heparin was administered antepartum and for six weeks post-partum. A dose of heparin, 5000 units subcutaneously twice daily, was chosen due to her ongoing thrombocytopenia with platelets in the 20,000/mcL. The patient was followed closely on weekly basis to address compliance, monitor blood counts, and evaluate thrombosis and complications of anticoagulation. The patient underwent elective induction of labor at 37 weeks’ gestation and delivered a healthy neonate. She remained transfusion independent throughout her pregnancy and experienced no bleeding or thrombotic complications. With regard to her PNH, she experienced no significant change in her granulocyte clone size during her pregnancy.
Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal blood disorder that can present with hemolytic anemia and in some cases smooth muscle dystonia, thrombosis, and bone marrow failure [
Eculizumab is a pregnancy class C medication, and animal studies showed a rare complication of retinal dysplasia and umbilical herniation [
Despite the increased risk of thrombosis and death in patients with PNH, there are currently no established guidelines for DVT prophylaxis during pregnancy and post-partum [
Our patient tolerated her pregnancy well and had no thrombotic complications. At her six-month post-partum follow-up the child had no medical complications. The patient continued eculizumab without grade 3 or 4 side effects and remains minimally transfusion dependent requiring transfusions once every three months as opposed to weekly. This case highlights the difficulty in management of PNH during pregnancy with eculizumab in the setting of severe thrombocytopenia.
The authors declare that they have no conflicts of interest.