The Extended Use of Eculizumab in Pregnancy and Complement Activation–Associated Diseases Affecting Maternal, Fetal and Neonatal Kidneys—The Future Is Now?
Abstract
:1. Introduction
2. Antiphospholipid Syndrome
3. Sickle-Cell Trait/Anemia/Disease
4. HELLP Syndrome
5. Paroxysmal Nocturnal Hemoglobinuria (PNH)
6. Atypical Hemolytic Uremic Syndrome (aHUS)
7. Preterm Birth and Its Influence on the Renal Development and Function in Offspring
8. Conclusions and Further Perspectives
Funding
Acknowledgments
Conflicts of Interest
References
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Disease | Subject(s) | Treatment | Key Points | Ref. |
---|---|---|---|---|
Antiphospholipid syndrome | Pregnant mice | Human IgG containing aPL antibodies | Antibodies or peptides that block C5a-C5a receptor interactions prevent pregnancy complications. | [8] |
Non-pregnant mice | IgG-APS/rEV576 (treatment group) and IgG-APS/phosphate buffer (controls) | Mice treated with IgG-APS/rEV576 [(coversin), a recombinant protein inhibitor of complement factor 5 activation] had significantly smaller thrombi than those treated with IgG-APS/phosphate buffer. This confirmed involvement of complement activation in antiphospholipid antibody-mediated thrombogenesis and suggested that this effect might be ameliorated by complement inhibition. | [9] | |
Pregnant woman (case report) | Eculizumab | Triple positive aPL. Multiple previous arterial thromboses and ongoing ischemia during pregnancy. Significant risk of catastrophic APS. Eculizumab was administered twice before cesarean section which was performed at 32+4 gestational weeks with the birth of a heathy child. Complement activity surprisingly increased to normal levels within a week after both doses of eculizumab despite the evidence of complete inhibition of complement activity after each infusion. Pregnancy may influence pharmacodynamics and pharmacokinetics of eculizumab. Individual approach suggested. | [10] | |
Pregnant woman (case report) | Eculizumab | Triple positive aPL. Abruptly developed microangiopathic hemolytic anemia, renal insufficiency, and thrombocytopenia at 30+6 weeks despite treatment with ASA, LMWH and hydroxycholoquine. Eculizumab was administered and pregnancy was safely continued for 9 days. The second eculizumab infusion was administered a week after the first treatment with rapid normalization of platelet count, renal function and hemoglobin level. | [11] | |
Sickle-cell disease | Patients with thrombotic microangiopathies | Eculizumab | Increased complement activation was demonstrated in a portion of patients, especially older patients and those with higher HbS levels. In vitro study on the efficacy of complement inhibition by eculizumab in the modified Ham test. Mixing eculizumab-containing serum with complement-activated sera abolished complement-mediated cell killing in a dose-dependent relationship that was consistent across the three patients tested. | [12] |
SCD patient who developed aHUS (case report) | Eculizumab | Respiratory and renal insufficiency unresponsible to plasmapheresis successfully treated with eculizumab. A clear evidence of complement activation was demonstrated by increased levels of sC5b-9 levels retrospectively analyzed from stored plasma prior to plasmapheresis. After eculizumab treatment and improvement of clinical symptoms and laboratory baseline, sC5b-9 levels normalized. This case demonstrated that patients with SCD may develop complement-mediated thrombotic microangiopathy i.e., aHUS, particularly when an underlying genetic defect in complement regulation is present. | [13] | |
Pregnant woman (case report) | Eculizumab | A pregnant woman with HbSS who presented with hyperhemolysis at 25 gestational weeks and worsening anemia despite methylprednisolone and immunoglobulin treatment. Eculizumab treatment resulted in resolution of the hemolysis, with safe delivery at 34 weeks of gestation. | [14] | |
HELLP syndrome | Sixteen pregnant women with HELLP | N/A | Incresed complement activation demonstration in sera. | [15] |
Pregnant women with HELLP | N/A | Increased complement activation was observed in participants with classic or atypical HELLP compared with those with normal pregnancies and nonpregnant controls. Mixing HELLP serum with eculizumab-containing serum resulted in a significant decrease in cell killing compared with HELLP serum alone. Data of this study demonstrated striking similarities between HELLP and aHUS. | [16] | |
Pregnant women with HELLP (case report) | Eculizumab | Prolongation of pregnancy from 26+3 to 28+6 (17 days) was achieved. In this case, reduction of soluble C5b-9 in plasma and urine correlated with clinical improvement, and resolution of hemolysis, thrombocytopenia and liver inflammation along with a prolonged pregnancy. | [17] |
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Stefanovic, V. The Extended Use of Eculizumab in Pregnancy and Complement Activation–Associated Diseases Affecting Maternal, Fetal and Neonatal Kidneys—The Future Is Now? J. Clin. Med. 2019, 8, 407. https://doi.org/10.3390/jcm8030407
Stefanovic V. The Extended Use of Eculizumab in Pregnancy and Complement Activation–Associated Diseases Affecting Maternal, Fetal and Neonatal Kidneys—The Future Is Now? Journal of Clinical Medicine. 2019; 8(3):407. https://doi.org/10.3390/jcm8030407
Chicago/Turabian StyleStefanovic, Vedran. 2019. "The Extended Use of Eculizumab in Pregnancy and Complement Activation–Associated Diseases Affecting Maternal, Fetal and Neonatal Kidneys—The Future Is Now?" Journal of Clinical Medicine 8, no. 3: 407. https://doi.org/10.3390/jcm8030407