Infection in Patients with Suspected Thrombotic Microangiopathy Based on Clinical Presentation

Abstract

Background and objectivesIn contrast to shigatoxin-associated Escherichia coli (STEC) causing hemolytic uremic syndrome, STEC-unrelated infections associated with thrombotic microangiopathy are less characterized.Design, setting, participants, & measurementsOur retrospective study in a four-hospital institution of 530 consecutive patients with adjudicated thrombotic microangiopathies during the 2009–2016 period studied STEC-unrelated infections’ epidemiology and major outcomes (death, acute dialysis, and major cardiovascular events).ResultsSTEC-unrelated infection was present in 145 of 530 (27%) patients, thrombotic microangiopathies without infection were present in 350 of 530 (66%) patients, and STEC causing hemolytic and uremic syndrome was present in 35 of 530 (7%) patients. They (versus thrombotic microangiopathy without infection) were associated with age >60 years (36% versus 18%), men (53% versus 27%), altered consciousness (32% versus 11%), mean BP <65 mm Hg (21% versus 4%), lower hemoglobin and platelet count, and AKI (72% versus 49%). They were associated with more than one pathogen in 36 of 145 (25%) patients (either isolated [14%] or combined [86%] to other causes of thrombotic microangiopathy); however, no significant clinical or biologic differences were noted between the two groups. They were more frequently due to bacteria (enterobacteria [41%], Staphylococcus aureus [11%], and Streptococcus pneumonia [3%]) than viruses (Epstein–Barr [20%], cytomegalovirus [18%], influenza [3%], hepatitis C [1%], HIV [1%], and rotavirus [1%]). STEC-unrelated infections were independent risk factors for in-hospital death (odds ratio, 2.22; 95% confidence interval, 1.18 to 4.29), major cardiovascular event (odds ratio, 3.43; 95% confidence interval, 1.82 to 6.69), and acute dialysis (odds ratio, 3.48; 95% confidence interval, 1.78 to 7.03). Bacteria (versus other pathogens), and among bacteria, enterobacteria, presence of more than one bacteria, and E. coli without shigatoxin were risk factors for acute dialysis.ConclusionsInfections are frequent thrombotic microangiopathy triggers or causes, and they are mostly unrelated to STEC. Infections convey a higher risk of death and major complications. The most frequent pathogens were enterobacteria, S. aureus, Epstein–Barr virus, and cytomegalovirus.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_09_07_CJN17511120.mp3

How I Treat Complement-Mediated TMA

“…, gemcitabine, VEGF inhibitors, and calcineurin inhibitors), malignancy, metabolic ( e.g. , cobalamin deficiency), and transplant associated (1 –3).…”

“…Although some etiologies have distinct mechanisms, such as absent ADAMTS13 activity in TTP, many etiologies have complex and shared mechanisms. Initial evaluation should consider categories of TMA and TMA-mimics, including TTP, c-TMA, infection (e.g., Shiga toxin, Staphylococcus, Pneumococcus, EBV, and CMV), disseminated intravascular coagulation, connective tissue disease, pregnancy, malignant hypertension, monoclonal gammopathy, medications (e.g., gemcitabine, VEGF inhibitors, and calcineurin inhibitors), malignancy, metabolic (e.g., cobalamin deficiency), and transplant associated (1)(2)(3).…”

Complement‐driven hemolytic uremic syndrome

“…STEC‐unrelated, infection‐associated HUS may account for approximately 25% of the HUS cases 47 . This spectrum encompasses a wide range of pathogens from bacteria (enterobacteria, Staphylococcus aureus , and Streptococcus pneumoniae ) to viruses, including EBV, CMV, influenza, HIV, and more recently SARS‐CoV2 47–49 .…”

“…43,45,46 STEC-unrelated, infection-associated HUS may account for approximately 25% of the HUS cases. 47 This spectrum encompasses a wide range of pathogens from bacteria (enterobacteria, Staphylococcus aureus, and Streptococcus pneumoniae) to viruses, including EBV, CMV, influenza, HIV, and more recently SARS-CoV2. [47][48][49] The role of complement in infection-associated HUS is still ill-defined, with the exception of severe SARS-CoV2 infection, for which complement activation has been extensively characterized.…”

Thrombotic microangiopathy associated with anticancer and immune system targeting drugs: New insights from real‐world data using the WHO pharmacovigilance database

“…Thrombotic microangiopathy syndrome (TMA) constitutes a heterogeneous group of severe diseases [1] with often life-threatening consequences [2][3][4]. TMA pathophysiology is usually characterized by the formation of microthrombi with the presence of fibrin or platelet aggregates in the lumen leading to microvascular occlusion, with or without the involvement of complement alternate pathway dysregulation [5].…”