Managing a pregnant patient with paroxysmal nocturnal hemoglobinuria in the era of eculizumab

Danilov, Alexey V.; Craigo, Sabrina; Smith, Hedy; Miller, Kenneth B.

doi:10.1016/j.leukres.2009.10.025

Cited by 34 publications

(26 citation statements)

References 43 publications

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“…The importance of the data is emphasized by the increasing number of pregnant women who are candidates for eculizumab treatment. PNH is the disease where most pregnant patients have been treated with eculizumab (28,29,39,40), but there are also reports for aHUS and preeclampsia (41)(42)(43). Other conditions, in which pregnancy is an option, will likely come up in the future as candidates for complement inhibition, like the antiphospholipid syndrome (44).…”

Section: Discussionmentioning

confidence: 99%

Eculizumab treatment during pregnancy does not affect the complement system activity of the newborn

et al. 2015

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Eculizumab is a humanized IgG2/4 chimeric anti-complement C5 antibody used to treat patients with paroxysmal nocturnal hemoglobinuria (PNH) or atypical hemolytic uremic syndrome. The aim of this study was to evaluate whether or not the complement activity in newborns from pregnant women who receive eculizumab is impaired. A novel eculizumab-C5 complex (E-C5) specific assay was developed and revealed that two newborns carried only 6-7% of the E-C5 detected in their eculizumab-treated PNH mothers. Serum from the pregnant women completely lacked terminal complement pathway activity, whereas the complement activity in the serum of the newborns was completely normal. Data from the pregnant women and their newborns were compared with that of healthy age-matched female controls and healthy newborns, as well as a non-treated pregnant woman with PNH and her newborn. These all showed normal complement activity without detectable E-C5 complexes. Furthermore, absence of eculizumab or E-C5 in the newborn could not be explained by lack of eculizumab binding to the neonatal Fc receptor (FcRn), as eculizumab bound strongly to the receptor in vitro. In conclusion, despite binding to FcRn neither eculizumab nor E-C5 accumulates in fetal plasma, and eculizumab treatment during pregnancy does not impair the complement function in the newborn.

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Section: Discussionmentioning

confidence: 99%

Eculizumab treatment during pregnancy does not affect the complement system activity of the newborn

et al. 2015

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“…[23][24] Pregnancy occurring in women with PNH is particularly high-risk because pregnancy itself is considered a prothrombotic state. [25][26] Among 43 pregnancies reported in the medical literature between 1965 and 2006, 8 were associated with thrombosis. Two incidents of thrombosis occurred during pregnancy 5,19 and the remaining 6 occurred during the postpartum period, 4,7,19,[21][22]27 leading to maternal death in 3 cases.…”

Section: Discussionmentioning

confidence: 99%

Paroxysmal nocturnal hemoglobinuria and pregnancy before the eculizumab era: the French experience

Guibert¹,

Latour²,

Varoqueaux³

et al. 2011

Haematologica

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The online version of this article has a Supplementary Appendix. BackgroundPregnancy in women with paroxysmal nocturnal hemoglobinuria is rare, with few reports on maternal and fetal mortality rates. Design and MethodsA specific questionnaire designed to solicit data on pregnancies in women with paroxysmal nocturnal hemoglobinuria was sent to all members of the French Society of Hematology in January 2008. ResultsWe identified 27 pregnancies in 22 women at 10 French Society of Hematology centers between 1978 and 2008. The median age was 21.5 years at diagnosis of paroxysmal nocturnal hemoglobinuria and 27 years at pregnancy. None of these women had received eculizumab during their pregnancy. Maternal complications, consisting mostly of cytopenias requiring transfusions, occurred in 95% of cases. Two cases of severe aplastic anemia (de novo in one case and relapse in the other) were recorded. No thrombotic events occurred during pregnancy, whereas 4 postpartum thromboses (16%) were recorded, 2 of which were fatal (maternal mortality rate 8%). Most patients received antithrombotic prophylaxis during pregnancy and postpartum (n=16; 64%). Delivery was preterm in 29% of cases, and birth weight was less than 3 kg in 53% of cases. Fetal mortality rate was 4%. ConclusionsPregnancy during paroxysmal nocturnal hemoglobinuria is associated with increased maternal and fetal mortality rates (8% and 4%, respectively, in this series). Maternal mortality is related to postpartum thromboses. Prophylactic anticoagulation is recommended during pregnancy and for six weeks postpartum.

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“…In addition, iron defi ciency anemia is common during pregnancy and folate defi ciency can also occur. It may sometimes be diffi cult to distinguish the manifestations of PNH from those of normal pregnancy and from other pathological conditions which can occur during pregnancy such as HELLP syndrome (Hemolysis, Elevated Liver enzymes and Low Platelets), preeclampsia, gestational thrombocytopenia and immune thrombocytopenia [ 66 ]. HELLP syndrome, in particular, is often diffi cult to distinguish from a PNH crisis during pregnancy as both conditions share common features.…”

Section: Bone Marrow Failure and Increased Hemolysis During Pregnancymentioning

confidence: 99%

“…Red cell and platelet transfusion should be administered as clinically required. In the case of signifi cant bleeding during pregnancy or at delivery, fresh frozen plasma (FFP) should be used with great caution, as it contains a large amount of complement, which markedly increases the risk of thrombosis and intravascu- [ 66 ]. If its use is essential, FFP must be covered with eculizumab [ 66 ].…”

Section: Supportive Therapy and Anticoagulationmentioning

confidence: 99%

“…In the case of signifi cant bleeding during pregnancy or at delivery, fresh frozen plasma (FFP) should be used with great caution, as it contains a large amount of complement, which markedly increases the risk of thrombosis and intravascu- [ 66 ]. If its use is essential, FFP must be covered with eculizumab [ 66 ]. Prothrombin complex concentrate may be considered but should be used with caution due to the risk of thrombosis [ 15 ].…”

Section: Supportive Therapy and Anticoagulationmentioning

confidence: 99%

See 1 more Smart Citation

Paroxysmal Nocturnal Hemoglobinuria in Pregnancy

Arachchillage

Hillmen

2015

Disorders of Thrombosis and Hemostasis in Pregnancy

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Managing a pregnant patient with paroxysmal nocturnal hemoglobinuria in the era of eculizumab

Cited by 34 publications

References 43 publications

Eculizumab treatment during pregnancy does not affect the complement system activity of the newborn

Eculizumab treatment during pregnancy does not affect the complement system activity of the newborn

Paroxysmal nocturnal hemoglobinuria and pregnancy before the eculizumab era: the French experience

Paroxysmal Nocturnal Hemoglobinuria in Pregnancy

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