#5113 THE MULTIVERSE OF PREGNANCY-ASSOCIATED AHUS: TRIGGERS, TIMING AND OUTCOMES – A SINGLE CENTER EXPERIENCE
Authors: Spasiano Andrea , Palazzetti Daniela , Petrosino Anna , Tacente Chiara , De Luca Gianmarco , Naticchia Alessandro , Bruno Francesca , Baccaro Rocco , Ferraro Pietro Manuel , Grandaliano Giuseppe 
Published: June 2023

Background and Aims

Atypical hemolytic uremic syndrome (aHUS) is a rare disease caused by dysregulation of the alternative pathway of complement, characterized by hemolytic microangiopathic anemia, thrombocytopenia and acute kidney injury. Incidence is ∼ 0.23 per year per million people and about 7% of aHUS diagnoses occur in the setting of pregnancy, determining the so-called “pregnancy associated aHUS” (PaHUS). It could occur during gestation, in the immediate postpartum period or up to 12 weeks after delivery. Maternal exposure to semiallogenic fetoplacental material represents a complement triggering condition, worsened over gestation, with a climax at the delivery. Despite the attempt of solute and membrane regulators to mitigate the immune overactivation, an exaggerated inflammatory response, a decrease in the amount of regulatory proteins or some inherited or de novo mutations in complement factors’ genes, predispose to complement dysregulation. Its diagnosis is often delayed due to a multiform manifestation and similarity with HELLP syndrome or other thrombotic microangiopathy disorders (TMA), such as thrombotic thrombocytopenic purpura. It results in a delayed treatment, consequently threatening mother and fetus life. PaHUS is linked to high rates of end stage kidney disease, nearly achieving 78% at 24 months’ postpartum without eculizumab therapy. Indeed, anti-C5 therapy is effective and universally considered the best choice to treat aHUS.

Method

In this case series, we report our experience about the management of PaHUS during the last 2 years. An internal hospital protocol points out suspected TMA patients semi-automatically, thanks to a structured teamwork among emergency department and laboratory, hematology, nephrology and intensive care units. Treatment protocol applied was standard eculizumab induction therapy for all cases. All data will be presented as mean ± SD, medians and percentages.

Results

From January 2020 to December 2022, we diagnosed 14 patients with aHUS in our hospital. Five (35.7%) of them faced this disorder during the third trimester of pregnancy. Among different possible triggers, we observed postpartum hemorrhage, intrauterine fetal death, uterine atony and abruptio placentae with spontaneous abortion. Only 1 out of 5 reported a positive genetic test, showing a heterozygous missense mutation in CD46 of uncertain significance (Table 1). Due to the outbreak of peripartum complications, all patients were diagnosed between 1 and 5 days (2.2 days ± 1.6, median 2.0 days). After the diagnosis, we started the treatment within 27.6 ± 15.2 hours (median 24.0 hours). Only one patient needed acute renal replacement therapy. All our patients gradually recovered a normal kidney function, without any further complications. Serum creatinine normalized in 16.4 ± 9.5 days (median 20.0 days) (Fig. 1A), hemoglobin values improved in 35.2 ± 7.33 days (median 34.0 days) (Fig. 1B) and platelets returned in range in 8 ± 5 days (median 7.0 days) (Fig. 1C). Moreover, LDH and haptoglobin levels, chosen as hemolysis markers, restored in an average time of 29.8 ± 5.0 (median 30.0 days) (Fig. 1D) and 19.8 ± 14.3 days (median 10.0 days), respectively.

Conclusion

Nowadays, our patients have normal kidney function, treated with C5-inhibitors twice a month in outpatient setting. Moreover, one patient suspended infusion with close monitoring. Hence, we hope that these clinical records could help to improve the awareness of this manifold syndrome and to emphasize the importance of an early diagnosis and a timely treatment with eculizumab to guarantee full pregnants’ recovery.