Postsurgical Thrombotic Microangiopathy and Deregulated Complement

Abstract

Postsurgical thrombotic microangiopathy (TMA) is a complication associated with significant morbidity and mortality. Still, the pathophysiological underlying mechanism of postsurgical TMA, a diagnosis often overlooked in postoperative patients with acute kidney injury and thrombocytopenia, is largely unknown. Here, we report the case of a 56-year-old male that developed anuric acute kidney injury, Coombs-negative hemolysis, and thrombocytopenia after surgical aortic arch replacement. Massive ex vivo complement activation on the endothelium, a rare complement gene variant in C2, at-risk haplotype MCPggaac, and excellent response to therapeutic complement inhibition, points to the pivotal role of complement in the pathophysiology of disease. Moreover, the importance of a multidisciplinary team approach in (postsurgical) thrombocytopenia is emphasized.

Keywords: aortic surgery; complement activation; complement inhibition; genetic variance; hemolytic uremic syndrome; multidisciplinary approach; thrombocytopenia; thrombotic micro-angiopathy.

Figure 1

Pre- and postoperative contrast-enhanced CT scans. (A) Pre-operative CT demonstrating the 68 mm descending aortic aneurysm as the surgical indication; (B) three-dimensional reconstruction of postoperative CT findings, showing resection of the aneurysm using a total arch replacement technique (FET) with debranching of the supra-aortic vessels. CT: computed tomography, FET: frozen elephant trunk.

Figure 2

Postoperative course of kidney function.

Figure 3

Proposal for standardized assessment of thrombocytopenia, anemia, and AKI after cardiovascular surgery. The combination of (consumptive) thrombocytopenia, microangiopathic hemolytic anemia (often, DAT negative), and AKI suggests TMA and thus, testing for the enzymatic activity of ADAMTS13 and Shiga toxin-producing E. coli infection should be requested simultaneously. AKI: acute kidney injury, C-TMA: complement mediated thrombotic microangiopathy, DAT: direct antiglobulin test, LDH: lactate dehydrogenase, STEC-HUS: Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome, TTP: thrombotic thrombocytopenic purpura. ^† Anemia is defined as hemoglobin <5.0 mmol/L, thrombocytopenia defined as count below 150 × 10⁹/L, AKI defined as anuria, requirement for continuous veno-venous hemodialysis and/or triplication of pre-existing creatinine concentration. * Active bleeding is defined as >50 mL/h thoracic drain production after the first 48 h following surgery. ° Increased LDH defined as concentration >600 U/L, decreased haptoglobin defined as concentration <0.20 g/L. Please note that this is an expert opinion provided by the authors not necessarily reflected in literature.