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.

The Rationale of Complement Blockade of the MCPggaac Haplotype following Atypical Hemolytic Uremic Syndrome of Three Southeastern European Countries with a Literature Review

“…The MCPggaac haplotype has been associated with aHUS in sporadic and familial cases [9,17,32]. It seems that the clinical expression of the homozygous MCPggaac haplotype depends significantly on additional mutations in the aHUS spectrum, especially CFH and CFI, and if so, various infectious diseases or even drugs trigger aHUS in children who are genetically prone to aHUS onset [1,2,8,9,29,[33][34][35][36][37]. MCPggaac compound heterozygosity with additional risk polymorphisms can lead to re-peated aHUS relapses and renal deterioration [18].…”

“…The MCPggaac haplotype under additional complement-activating genetic conditions increases the probability and severity of atypical hemolytic uremic syndrome (aHUS) or at least activates secondary HUS [1][2][3][4][5][6]. This has been supported by the MCPggaac haplotype association with reduced gene transcription of membrane cofactor protein (MCP) in vitro [1,2,[7][8][9]. Recently, it was found that MCPggaac haplotype carriers were at a significantly higher risk of graft loss and acute allograft rejection [3,[10][11][12][13][14].…”

Off-pump versus on-pump coronary artery bypass grafting in patients with left main disease: a randomized controlled trial

“…7 This decrease is likely related not only to the procedure's technical complexity and steep learning curve, but also, and perhaps more importantly, to the procedure's decreased long-term patency, increased rate of incomplete revascularisation, and lower long-term survival rates. 8 The major justification for off-pump CABG is to avoid the negative consequences of on-pump CABG due to the systemic inflammatory mediators generated by blood components coming into touch with the bypass circuit's surface. Postoperative coagulopathy, neurological complications, thromboembolic complications, and organ dysfunction were all associated with on-pump CABG.…”