Targeted therapy radically changed the prognosis in paroxysmal nocturnal hemoglobinuria (PNH) and made it possible not only to increase the survival rate, but also to improve the quality of life. Therefore issues of reproductive health in PNH patients are becoming very important. Recently the management of PNH during pregnancy has been challenging because of the high risk of maternal morbidity due to thrombosis and frequent pregnancy loss. The aim of our research was an evaluation the efficacy and safety of eculizumab treatment during pregnancy and analysis the pregnancy outcomes.

Since 2013 we observed 14 pregnancies in 14 PNH patients receiving eculizumab treatment. –°linical manifestations of hemolysis significantly regressed during the therapy: normalization of LDH was registered in 71,4% patients before the conceiving. The median age at the start of pregnancy was 29 years (22-37), the median of PNH granulocyte clone at that time was 74,7% (23-99). PNH diagnosed before the pregnancy in all cases. 64,3% of them had previously received immunosuppressive treatment of aplastic anemia.

92,9% of patients had been using eculizumab prior to becoming pregnant, mean duration of therapy was 21 months (4-44). All of patients remained on the treatment during pregnancy and postpartum. 42,9% of patients required a dose adjustment due to breakthrough hemolysis (a dose increase and/or more frequent use of eculizumab). Anticoagulation with low molecular weight heparin was used in 85,7% pregnancies (intermediate or therapeutic doses). Pregnancies before eculizumab therapy were registered in 28,6% patients: then from 10 pregnancy cases on supportive reatment only 2 ended with a childbirth. 28,6% patients registered venous thromboembolism before conception. No maternal death and thrombotic events during pregnancy and postpartum have been observed. Maternal complications during gestation included abortion threat, arterial hypertension, the appendicitis (successful surgical treated during the second trimester of pregnancy), placental insufficiency, placenta previa and two cases of preeclampsia. In 21,4% patients before the birth was registered an increase of transaminases in addition to LDH level rise. During 64,3% gestations patients underwent red cells and/or platelets transfusion. Transfusions rate increased in all these patients from 0.25 units per month to 1,1 units per month during pregnancy. PNH granulocyte clone size decreased during pregnancy in 42,9%, but ut it did not correlate with the clinical manifestations of hemolysis. Pregnancies resulted in the birth of infants in all of 14 cases. No miscarriages or stillbirths have been observed. Caesarean sections were performed in 78,6% of births, early surgical delivery (26-34 weeks)- in 35,7% cases due to preeclampsia, placenta previa, breakthrough hemolysis or placental insufficiency). There were no malformations in the newborns. Mean birth weight 2560 g (450-3550). One preterm infant with extremely low weight and a growth retardation syndrome due to placental insufficiency died on the second day of life due to generalized hemorrhagic complications. One newborn diagnosed with neuroblastoma in the first year of life, the therapy is continuing now. Most of newborns (85,7%) are healthy, 71,4% of them received breastfeeding without complications.

Our data demonstrate the possibility of safe therapy with eculizumab in pregnant women. Targeted therapy PNH improves the pregnancy outcomes for both the mother and fetus compared to historical controls. A dose adjustment of eculizumab is often required during pregnancy due to the increased complement activity. Pregnancy does not worsen the prognosis of PNH in the case of targeted and adequate supportive therapy. There is no difference in health between infants born by mothers with PNH and the newborns from general population.


No relevant conflicts of interest to declare.

Author notes


Asterisk with author names denotes non-ASH members.

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