Diagnostic Testing for Differential Diagnosis in Thrombotic Microangiopathies

Abstract

Thrombotic microangiopathies (TMAs) are multiple disease entitieswith different etiopathogeneses, characterized by thrombocytopenia,microangiopathic hemolytic anemia (MAHA) with schistocytosis,variable symptoms including fever, and multi-organ failure such asmild renal impairment and neurological deficits. The two paradigmsof TMAs are represented on one hand by acquired thromboticthrombocytopenic purpura (TTP) and on the other by hemolyticuremic syndrome (HUS). The differential diagnosis between thesetwo paradigmatic forms of TMA is based on the presence of eitherfrank renal failure in HUS or a severe deficiency (10% couldrule out the presence of a TTP form. However, it is often difficultto differentiate either a TTP or HUS clinical scenario presentingwith typical symptoms of TMA. There are in fact several additionaldiagnoses that should be considered in patients with ADAMTS13activity of >10%. Widespread inflammation with endothelial damageand adverse reactions to drugs play a central role in the pathogenesisof several forms of TMA, and in these cases, the differential diagnosisshould be directed at the underlying disease. Hence, a correct etiologicdiagnosis of TMA should involve a critical illness, cancer-associatedTMA, drug-induced TMA, and hematopoietic transplant-associatedTMA. A complete assessment of all the possible etiologies for TMAsymptoms, including acquired or congenital TTP, will allow for a moreaccurate diagnosis and application of a more appropriate treatment.

Özet

Trombotik mikroanjiyopatiler (TMA), farklı etiyopatogenezleri olan; trombositopeni, şistositlerin eşlik ettiği mikroanjiyopatik hemolitik anemi (MAHA), ateş, hafif böbrek yetmezliği ve nörolojik defisitler gibi çoklu organ tutulumlarıyla karakterize bir hastalıklar grubudur. TMA’ların iki paradigması bir yandan edinsel trombotik trombositopenik purpura (TTP) ve diğer yandan hemolitik üremik sendrom (HUS) ile temsil edilir. TMA’nın bu iki paradigmatik formu arasındaki ayırıcı tanı, HUS’de belirgin böbrek yetmezliği veya TTP’de çinko-proteaz ADAMTS13’ün (bir disintegrin ve metalloproteinaz trombospondin tip 1, üye 3) ciddi eksikliğinin (