Successful Pregnancies During Ongoing Eculizumab Therapy in Two Patients With Complement-Mediated Thrombotic Microangiopathy

Haninger-Vacariu, Natalja; Aigner, Christof; Kain, Renate; Prohászka, Zoltán; Gaggl, Martina; Böhmig, Georg A.; Piggott, Leah Charlotte; Sunder‐Plaßmann, Raute; Sunder‐Plassmann, Gere; Schmidt, Alice

doi:10.1016/j.xkme.2019.12.004

Cited by 8 publications

(8 citation statements)

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“…However, we excluded two other KTRs who conceived before 2010, although we have included some information on these cases in Supplementary data , Tables S1, S2, S3 and S4. Supplementary data , Tables S5 and S6 indicate the case numbers of our patients and pregnancies reported in other analyses of the Vienna TMA cohort [ 1 , 2 , 13 ].…”

Section: Resultsmentioning

confidence: 99%

“…Labour had to be induced at Week 37 + 0 of gestation because of a slight increase in blood pressure and proteinuria at the end of pregnancy. Details of complement-related analyses of the mother and the newborn were reported elsewhere [ 13 ]. A biopsy, taken 4 months after delivery because of persistent proteinuria and presence of DSA, did not show signs of humoral and cellular rejection or TMA; proteinuria improved thereafter.…”

Section: Resultsmentioning

confidence: 99%

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Pregnancies in kidney transplant recipients with complement gene variant-mediated thrombotic microangiopathy

Haninger-Vacariu

Aigner

Gaggl

et al. 2020

Clinical Kidney Journal

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Background Pregnancies in patients with complement gene variant-mediated thrombotic microangiopathy (cTMA) are challenging, and pregnancies in such patients after kidney transplantation (KTX) are even more so. Methods We identified nine pregnancies following KTX of three genetically high-risk cTMA patients enrolled in the Vienna thrombotic microangiopathy cohort. Preventive plasma therapy was used in three pregnancies, and one patient had ongoing eculizumab (ECU) therapy during two pregnancies. Results Seven out of nine pregnancies (78%) resulted in the delivery of healthy children. The other two included one early abortion at gestational Week 12 during ongoing ECU therapy and one late foetal death at gestational Week 33 + 3, most likely not related to complement dysregulation. Kidney transplant function after delivery remained stable in all but one pregnancy. In the aforementioned case, a severe cTMA flare occurred after delivery despite use of preventive plasma infusions. Kidney graft function could be rescued in this patient by ECU. As such, successful pregnancies can be accomplished in kidney transplant recipients (KTRs) with a history of cTMA. We used preemptive plasma therapy or ongoing ECU treatment in selected cases. Conclusions Thus, becoming pregnant can be encouraged in KTRs with native kidney cTMA. Extensive preconception counselling, however, is mandatory in such cases.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Pregnancies in kidney transplant recipients with complement gene variant-mediated thrombotic microangiopathy

Haninger-Vacariu

Aigner

Gaggl

et al. 2020

Clinical Kidney Journal

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“…Наиболее дискуссионным был и остается вопрос о необходимости профилактического применения экулизумаба при последующих беременностях у пациенток, ранее перенесших акушерский аГУС. Некоторые авторы предпочитают продолжить или возобновить лечение экулизумабом у пациенток с аГУС при наступлении беременности, особенно при наличии мутаций генов системы комплемента и/или неблагоприятных исходов предыдущих беременностей [19,20]. Повидимому, вопрос о профилактическом назначении экулизумаба в период гестации при полной ремиссии аГУС должен решаться в каждом случае индивидуально с учетом особенностей анамнеза, генетической предрасположенности, стадии хронической болезни почек в исходе ранее перенесенных эпизодов ТМА, наличия трансплантированной почки.…”

Section: Discussionunclassified

The favorable outcome of subsequent pregnancy in a patient with a history of obstetric atypical hemolytic uremic syndrome

Prokopenko

Guryeva

2022

Almanac of Clinical Medicine

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Atypical hemolytic uremic syndrome (aHUS) is a severe life-threatening disease associated with uncontrolled activation of alternative complement pathway. Obstetric aHUS, which develops in pregnant women and puerperas, is characterized by a particularly severe course with multiple organ failure, high death risk and end-stage renal disease. The prognosis of patients with obstetric aHUS has changed dramatically after the introduction of eculizumab, a monoclonal antibody to C5 complement component, into clinical practice. With timely initiation of the complement blocking therapy, the patients would not only survive, but also completely restore the function of the affected organs. Naturally, the question arises on the possibility of repeated pregnancies in women with previous obstetric aHUS and on the strategy of pregnancy management. The paper describes a clinical case of successful treatment with eculizumab for obstetric aHUS in the third trimester of the first pregnancy in a young and previously healthy woman, and the management of her second pregnancy. A 23-year old woman at 35-36 weeks of her first pregnancy developed the clinical picture of obstetric thrombotic microangiopathy, which was interpreted as a manifestation of severe preeclampsia and HELLP syndrome. However, after an emergency surgical delivery, the patient's condition continued to deteriorate despite the plasma exchange procedure. After exclusion of the other causes of thrombotic microangiopathy, aHUS was diagnosed and treatment with eculizumab was started, which resulted in complete recovery. No aHUS-associated mutations were identified. The complement inhibitor treatment was discontinued after 12 months. Four years after the first birth, the patient had a second pregnancy after preconception planning. During pregnancy, the patient was closely monitored for a timely identification of potential complications and had prevention of placental complications with acetylsalicylic acid and low molecular weight heparin. No aHUS recurrence and/or other complications were observed, and the patient did not require treatment with eculizumab during pregnancy. Elective caesarean section was performed at 39 week of gestation. A healthy boy was born with a bodyweight of 3370 g, a height of 50 cm, and Apgar score 8-9. In women with obstetric aHUS history, a favorable outcome of repeated pregnancies is possible, in some cases even without any prophylactic use of complement-blocking therapy, provided that with complete remission of aHUS has been achieved, with close monitoring during gestation and prevention of placenta-associated complications.

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“…110,111 Although eculizumab can be detected in cord blood, the effect of complement blockade on the fetus is unknown. 110,112,113 A pooled analysis of more than 300 pregnant individuals with live births after exposure to eculizumab have not identified any concerns for adverse fetal developmental outcomes (Eculizumab package insert, Alexion Pharmaceuticals, 2019). As for breastfeeding, limited published data showed undetectable levels of eculizumab in breast milk.…”

Section: Management Of Complement-mediated Hemolytic-uremic Syndrome ...mentioning

confidence: 99%

Differentiating and Managing Rare Thrombotic Microangiopathies During Pregnancy and Postpartum

Lim

Abou‐Ismail

Branch

2022

Obstetrics &Amp; Gynecology

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The most common thrombotic microangiopathy (TMA) of pregnancy is the well-recognized syndrome of preeclampsia with hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. However, rare TMAs, including thrombotic thrombocytopenic purpura, complement-mediated hemolytic-uremic syndrome, and catastrophic antiphospholipid syndrome, may occur during pregnancy or postpartum and present with features similar to those of preeclampsia with severe features. Early recognition and treatment of these infrequently encountered conditions are key for avoiding serious maternal morbidities with long-term sequelae and possible maternal or fetal death. Differentiating between preeclampsia with severe features and these rare TMAs is diagnostically challenging as there is significant overlap in their clinical and laboratory presentation. Given the rarity of these TMAs, high-quality evidencebased recommendations on diagnosis and management during pregnancy are lacking. Using current objective information and recommendations from working groups, this report provides practical clinical approaches to diagnose and manage these rare TMAs. This report also discusses how to manage individuals with a history of these rare TMAs who are planning to conceive. To optimize favorable outcomes, a multidisciplinary approach including obstetricians, maternalfetal medicine specialists, hematologists, and nephrologists alongside close clinical and laboratory monitoring is vital.

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Successful Pregnancies During Ongoing Eculizumab Therapy in Two Patients With Complement-Mediated Thrombotic Microangiopathy

Cited by 8 publications

References 18 publications

Pregnancies in kidney transplant recipients with complement gene variant-mediated thrombotic microangiopathy

Pregnancies in kidney transplant recipients with complement gene variant-mediated thrombotic microangiopathy

The favorable outcome of subsequent pregnancy in a patient with a history of obstetric atypical hemolytic uremic syndrome

Differentiating and Managing Rare Thrombotic Microangiopathies During Pregnancy and Postpartum

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