Features of Postpartum Hemorrhage-Associated Thrombotic Microangiopathy and Role of Short-Term Complement Inhibition

Abstract

BackgroundIn pregnancy-related atypical hemolytic uremic syndrome (p-aHUS), transferring recommendations for treatment decisions from non-pregnant cohorts with thrombotic microangiopathy (TMA) is difficult. Although potential causes of p-aHUS may be unrelated to inherent complement defects, peripartal complications such as postpartum hemorrhage or (pre)-eclampsia/HELLP-syndrome may be unrecognized drivers of complement activation. MethodsTo evaluate diagnostic and therapeutic decisions in the practical real-life setting, we conducted an analysis of a cohort of 40 patients from three German academic hospitals with a diagnosis of p-aHUS, stratified by the presence (n= 25) or absence (n=15) of postpartum hemorrhage. ResultsHistological signs of TMA were seen in 84.2% of all patients (100% versus 72.7% in patients without or with postpartum hemorrhage). Patients without postpartum hemorrhage had a higher likelihood (20 % versus 0 %) of pathogenic genetic abnormalities in the complement system although notably less than in other published cohorts. Four out of five patients with seen renal cortical necrosis after postpartum hemorrhage received complement inhibition and partially recovered kidney function. Patients on complement inhibition with or without postpartum hemorrhage had an increased need for kidney replacement therapy and plasma exchange. Since renal recovery was comparable among all patients treated with complement inhibition, a potential beneficial effect in this group of pregnancy-associated thrombotic microangiopathies and p-aHUS is presumed. ConclusionsBased on our findings, we suggest a pragmatic approach towards limited and short-term anti-complement therapy for patients with the clinical diagnosis of p-aHUS, which should be stopped once causes of TMA other than genetic complement abnormalities emerge.