Etiology and Outcomes of Thrombotic Microangiopathies

Abstract

Background and objectivesThrombotic microangiopathies constitute a diagnostic and therapeutic challenge. Secondary thrombotic microangiopathies are less characterized than primary thrombotic microangiopathies (thrombotic thrombocytopenic purpura and atypical hemolytic and uremic syndrome). The relative frequencies and outcomes of secondary and primary thrombotic microangiopathies are unknown.Design, setting, participants, & measurementsWe conducted a retrospective study in a four-hospital institution in 564 consecutive patients with adjudicated thrombotic microangiopathies during the 2009–2016 period. We estimated the incidence of primary and secondary thrombotic microangiopathies, thrombotic microangiopathy causes, and major outcomes during hospitalization (death, dialysis, major cardiovascular events [acute coronary syndrome and/or acute heart failure], and neurologic complications [stroke, cognitive impairment, or epilepsy]).ResultsWe identified primary thrombotic microangiopathies in 33 of 564 patients (6%; thrombotic thrombocytopenic purpura: 18 of 564 [3%]; atypical hemolytic and uremic syndrome: 18 of 564 [3%]). Secondary thrombotic microangiopathies were found in 531 of 564 patients (94%). A cause was identified in 500 of 564 (94%): pregnancy (35%; 11 of 1000 pregnancies), malignancies (19%), infections (33%), drugs (26%), transplantations (17%), autoimmune diseases (9%), shiga toxin due to Escherichia coli (6%), and malignant hypertension (4%). In the 31 of 531 patients (6%) with other secondary thrombotic microangiopathies, 23% of patients had sickle cell disease, 10% had glucose-6-phosphate dehydrogenase deficiency, and 44% had folate deficiency. Multiple causes of thrombotic microangiopathies were more frequent in secondary than primary thrombotic microangiopathies (57% versus 19%; P<0.001), and they were mostly infections, drugs, transplantation, and malignancies. Significant differences in clinical and biologic differences were observed among thrombotic microangiopathy causes. During the hospitalization, 84 of 564 patients (15%) were treated with dialysis, 64 of 564 patients (11%) experienced major cardiovascular events, and 25 of 564 patients (4%) had neurologic complications; 58 of 564 patients (10%) died, but the rates of complications and death varied widely by the cause of thrombotic microangiopathies.ConclusionsSecondary thrombotic microangiopathies represent the majority of thrombotic microangiopathies. Multiple thrombotic microangiopathies causes are present in one half of secondary thrombotic microangiopathies. The risks of dialysis, neurologic and cardiac complications, and death vary by the cause of thrombotic microangiopathies.

<p>Epidemiology of Atypical Hemolytic Uremic Syndrome: A Systematic Literature Review</p>

“…However, overall reporting was sparse with only three studies extensively providing detailed baseline characteristics. Prevalence and incidence estimates were reported in four 23,25,27,29 and six 13,[24][25][26][27][28] studies, respectively ( Figures 2 and 3). Incidence was measured per million annually in all except one study, Jenssen 2014 measured incidence per 100,000.…”

“…Of the eight studies, five studies were retrospective, 13,[24][25][26][27] one study was prospective, 28 one study was cross-sectional, 29 and one study was initially crosssectional then data were collected prospectively after 2001. 23 Three studies were conducted in individuals of all ages, 13,24,27 four studies were conducted in pediatrics (<18 years old), 23,25,26,28 and one was conducted in adults (>18 years old). 29 Fremeaux-Bacchi et al (2013) included individuals of all ages; however, they reported baseline characteristics by age group (<16 years old, ≥16 years old).…”

“…23,25,26 Bayer et al (2019) and Fremeaux-Bacchi et al (2013) were more stringent in their case definitions whereby cases were excluded if they also had particular comorbidities such as an autoimmune disease or organ transplantation (Table 1). 13,24 Baseline characteristics are summarized in Table 2. Studies reporting pediatric baseline characteristics showed the mean age of diagnosis was under 2 years old and were approximately evenly split in gender.…”

“…13,23,26,28 The mean age of diagnosis in adults was between 31 and 37 years old and unlike the pediatric population, the majority of individuals affected were females. 13,24,29 The majority of patients required dialysis at the acute phase of aHUS and almost all were anemic. Five studies reported some form of baseline characteristics.…”

TMA: Tell Me About It!

“…It is questionable whether SLE-related TMA truly exists. Recent publications have listed multiple causes and differential diagnoses for TMA 13,14 , and in their listings, SLE is mentioned as a separate entity. A slightly different viewpoint is taken here -that all known causes for TMA should be considered in a patient with TMA accompanying SLE, and that perhaps "SLE-related TMA" does not exist.…”