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Role of Soluble C5b-9 (sC5b-9) in Dosing Adjustments of Anti-complement Therapy during Pregnancy in a Patient with History of Atypical Hemolytic Uremic Syndrome (aHUS)

C. Dos Santos1, G. Greloni2, M.F. Alberto3, A. Sánchez-Luceros3

1IMEX-CONICET-ANM, Buenos Aires, Argentina, 2Hospital Italiano de Buenos Aires, Buenos Aires, Argentina, 3IIHEMA-Academia Nacional de Medicina, Buenos Aires, Argentina

Abstract Number: PB0865

Meeting: ISTH 2021 Congress

Theme: Platelet Disorders, von Willebrand Disease and Thrombotic Microangiopathies » HUS

Background: Complications of pregnancy in women with aHUS include preeclampsia. This case study is a 35-year-old carrier of genetic complement anomalies, with GMNC3 and aHUS diagnosis, currently treated with eculizumab (1200 mg/two weeks).

Aims: To monitor clinical and laboratory parameters of the patient during her second pregnancy.

Methods: Routine laboratory and complement testing (ELISA) were performed: (i) total complement activity (IMTEC, Human Diagnostics), (ii) plasmatic sC5b-9 (BD biosciences) and (iii) C5b-9 formation on endothelial cell line HMEC-1 in presence of human serum (home-made cell-based ELISA).

Results: At 24 weeks (w) of gestation, signs of hypertensive crisis included headaches and vomiting for which magnesium sulfate was administered. Between 36-37w, patient suffered nauseas, headaches and blurred vision, and delivered a healthy live birth (2.630kg) following caesarean section. Eculizumab treatment was associated with low levels of total complement activation (≤20U/mL) during pre- and post-natal period. Interestingly, plasmatic sC5b-9 increased significantly between 32w of gestation and first week puerperium (fig 1). However, eculizumab administration (900 mg) was given weekly during first month postpartum (fig 1). 

Figure 1Timeline of soluble C5b-9 levels in patient plasma during her pregnancy and postpartum. Eculizumab (ECU) dosing regimen was indicated by asterisk (*) or black arrow.

Additionally, we quantified complement activation on HMEC-1 surface induced by cell incubation with patient serum. C5b-9 formation on HMEC-1 was significantly higher in presence of serum from pregnant patient compared with serum from patient postpartum (fig 2A). Complex formation of C5b-9 during puerperium was similar to complex formed with a pooled human serum from 42 healthy donors (PS). Heat-inactivated (HI) serum at 56°C from 34w of gestation, corresponding to peak levels of plasmatic sC5b-9, showed remnant complement activation on HMEC-1, whereas HI PS demonstrated complement inhibition (fig 2B). 

Figure 2Detection of C5b-9 complex formation on endotelial cell line HMEC-1 using a cell-based ELISA assay. A. Serum from patient during her pregnancy and postpartum as well as from pooled human donors (PS) were incubated with HMEC-1 and complement membrane attack complex was detected using an anti-human C5b-9 antibody. **p<0.01 by Student's t-test. B. Serum from pooled human donors (PS) and from patient at 34 weeks gestation were heat-inactivated at 56⁰C during 1 hour before incubation on HMEC-1 for detection of C5b-9 on cell surface. w: weeks, OD: optical density. *p<0.05 and ***p<0.001 by Student's t-test.

 

Conclusions: Observations from this aHUS case study suggest that monitoring levels of sC5b-9 during pregnancy could offer insight in dose adjustment of anti-C5 therapy. Further studies are needed to explore other pathological pathway mechanisms involved in C5b-9 complex formation on cell surface during pregnancy.

To cite this abstract in AMA style:

Dos Santos C, Greloni G, Alberto MF, Sánchez-Luceros A. Role of Soluble C5b-9 (sC5b-9) in Dosing Adjustments of Anti-complement Therapy during Pregnancy in a Patient with History of Atypical Hemolytic Uremic Syndrome (aHUS) [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/role-of-soluble-c5b-9-sc5b-9-in-dosing-adjustments-of-anti-complement-therapy-during-pregnancy-in-a-patient-with-history-of-atypical-hemolytic-uremic-syndrome-ahus/. Accessed May 19, 2022.

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