Pregnancy-induced atypical haemolytic uremic syndrome: A new era with eculizumab

Abstract

Pregnancy is a well-recognised trigger of atypical haemolytic syndrome (P-aHUS) and often occurs in the post-partum period. Similar to atypical haemolytic uremic syndrome, it carries a poor prognosis with high morbidity particularly in the form of renal failure. Early recognition and intervention is crucial in its management particularly with the recent availability of eculizumab, a humanized monoclonal antibody to complement component C5, which has demonstrated drastic improvement in prognosis. The issue, however, is arriving at a timely diagnosis given the considerable amount of overlap in the clinical and biochemical manifestation of P-aHUS, HELLP syndrome (haemolysis, elevated liver enzyme and low platelet count) and other hypertensive disorders of pregnancy. We present a case report and literature review that highlights the clinical conundrum of arriving at the diagnosis. We also highlight the importance of early management of P-aHUS with eculizumab and its impact on improving morbidity.

Complement in Thrombotic Microangiopathies: Unraveling Ariadne's Thread Into the Labyrinth of Complement Therapeutics

“…Clinical manifestations resemble CM-HUS, including MAHA, thrombocytopenia, hypertension and renal or neurological dysfunction. Due to these similarities, HELLP syndrome might be often characterized as pregnancy-associated HUS, according to the traditional terminology, and vice versa ( 75 ). Of note, HELLP syndrome is a cause of severe morbidity and mortality for both the mother and fetus ( 76 ).…”

Acute Kidney Injury in Pregnancy: The Need for Higher Awareness. A Pragmatic Review Focused on What Could Be Improved in the Prevention and Care of Pregnancy-Related AKI, in the Year Dedicated to Women and Kidney Diseases

“…After delivery, inflammation, the release of foetal cells in the maternal circulation, infections, and haemorrhage can lead to activation of the alternative complement pathway, which, in the absence of effective regulatory mechanisms, may induce postpartum atypical haemolytic-uremic syndrome (aHUS); complement dysregulation was also found to be associated with the HELLP syndrome, which shares several features with pregnancy-associated TMA [ 148 , 149 , 150 , 151 , 152 ]. The new frontiers of treatment with eculizumab make diagnosis of pivotal importance for allowing timely treatment [ 149 , 150 , 151 , 153 ].…”

Eculizumab, a novel potential treatment for acute kidney injury associated with preeclampsia/HELLP syndrome

“…The common genetic mutations associated with the ACP were not detected in our patient, but genetic testing is negative in 40%–50% of patients with aHUS and 20%–36% of HELLP may have mutations 11 24. HELLP and P-aHUS may be part of a spectrum 23…”

“…The differentiation between HELLP and pregnancy-associated atypical hemolytic uremic syndrome (P-aHUS) is often tricky as they share biochemical features 23. Atypical HUS is mainly characterised by microangiopathic haemolytic anaemia (MAHA) and AKI 12 23. Contrarily, this case presented with multi-organ dysfunction including non-cardiogenic pulmonary oedema, subcapsular hepatic haematoma and impaired liver functions in addition to AKI and MAHA, which is more consistent with preeclampsia with severe features/HELLP.…”

“…The differentiation between HELLP and pregnancy-associated atypical hemolytic uremic syndrome (P-aHUS) is often tricky as they share biochemical features 23. Atypical HUS is mainly characterised by microangiopathic haemolytic anaemia (MAHA) and AKI 12 23.…”