Higher doses of eculizumab may be beneficial in paroxysmal nocturnal haemoglobinuria in pregnancy

Introduction: Paroxysmal nocturnal haemoglobinuria (PNH) is a rare bone marrow failure disorder that results in complement-mediated haemolysis (mostly intravascular), thrombosis and bone marrow suppression. Terminal complement inhibitors, such as eculizumab, have improved outcomes in pregnant and non-pregnant individuals. However, the optimal management of PNH during pregnancy has not been fully established. Case description: We describe the case of a 30-year-old Caucasian woman with classical PNH who became pregnant while on eculizumab therapy. Despite complete terminal complement blockade, as confirmed by appropriately suppressed functional C5 levels and elevated C5 antigen levels, the patient experienced recurrent breakthrough haemolysis and transfusion dependence during the first trimester. Her eculizumab dose was escalated beyond the standard recommended doses, which improved haemoglobin levels and reduced transfusion requirements, although lactate dehydrogenase (LDH) levels remained elevated. The patient delivered a healthy infant via elective caesarean section at term without complications. Postpartum, she transitioned to a combination of eculizumab and pegcetacoplan to address ongoing haemolysis, likely due to C3b mediated opsonisation. Conclusion: The case illustrates the complexity of managing PNH during pregnancy and highlights the importance of individualised therapy and close monitoring to achieve optimal foetomaternal outcomes. Our experience suggests that despite appropriately suppressed complement levels, pregnant patients with continued transfusion dependence and elevated LDH levels may benefit from higher than standard doses of eculizumab. Given the paucity of data, detailed reporting of such cases is essential to inform treatment strategies for pregnant patients.