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Review
. 2019 Nov 18;36(4):222-229.
doi: 10.4274/tjh.galenos.2019.2019.0165. Epub 2019 Jul 24.

Diagnostic Testing for Differential Diagnosis in Thrombotic Microangiopathies

Gina Zini  1   2 , Raimondo De Cristofaro  3
Affiliations
Review

Diagnostic Testing for Differential Diagnosis in Thrombotic Microangiopathies

Gina Zini et al. Turk J Haematol. .

Abstract
in English, Turkish

Thrombotic microangiopathies (TMAs) are multiple disease entities with different etiopathogeneses, characterized by thrombocytopenia, microangiopathic hemolytic anemia (MAHA) with schistocytosis, variable symptoms including fever, and multi-organ failure such as mild renal impairment and neurological deficits. The two paradigms of TMAs are represented on one hand by acquired thrombotic thrombocytopenic purpura (TTP) and on the other by hemolytic uremic syndrome (HUS). The differential diagnosis between these two paradigmatic forms of TMA is based on the presence of either frank renal failure in HUS or a severe deficiency (<10%) of the zinc-protease ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) in TTP. ADAMTS13 is an enzyme involved in the proteolytic processing of von Willebrand factor (vWF), and its deficiency results in formation of high-molecular-weight vWF-rich microthrombi in the environment of the microvasculature. The presence of these ultra-large vWF multimers in the microcirculation can recruit platelets, promoting multi-organ ischemic lesions. The presence of ADAMTS13 activity at >10% could rule out the presence of a TTP form. However, it is often difficult to differentiate either a TTP or HUS clinical scenario presenting with typical symptoms of TMA. There are in fact several additional diagnoses that should be considered in patients with ADAMTS13 activity of >10%. Widespread inflammation with endothelial damage and adverse reactions to drugs play a central role in the pathogenesis of several forms of TMA, and in these cases, the differential diagnosis should be directed at the underlying disease. Hence, a correct etiologic diagnosis of TMA should involve a critical illness, cancer-associated TMA, drug-induced TMA, and hematopoietic transplant-associated TMA. A complete assessment of all the possible etiologies for TMA symptoms, including acquired or congenital TTP, will allow for a more accurate diagnosis and application of a more appropriate treatment.

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 (<%10) varlığına dayanmaktadır. ADAMTS13, von Willebrand faktörünün (vWF) proteolitik işleminde yer alan bir enzimdir ve eksikliği, mikrovasküler ortamda yüksek molekül ağırlıklı vWF bakımından zengin mikrotrombüs oluşumuna yol açar. Bu ultra-büyük vWF multimerlerinin mikro dolaşımdaki varlığı, trombositleri toplayarak çok organlı iskemik lezyonları teşvik eder. ADAMTS13 aktivitesinin %10’dan büyük oluşu, bir TTP formunun varlığını dışlatabilir. Bununla birlikte, tipik TMA semptomları gösteren bir TTP veya HUS klinik senaryosunu ayırt etmek genellikle zordur. Aslında ADAMTS13 aktivitesi %10’dan büyük olan hastalarda göz önünde bulundurulması gereken birkaç ek tanı vardır. Endotel hasarı ve ilaçlara verilen yan etkilerle birlikte görülen yaygın yangı, birçok TMA formunun patogenezinde merkezi bir rol oynamaktadır ve bu durumlarda, ayırıcı tanı altta yatan hastalığa yönlendirilmelidir. Bu nedenle, TMA’nın doğru bir etiyolojik tanısı, kritik bir hastalık, kansere bağlı TMA, ilaca bağlı TMA ve hematopoetik transplant ile ilişkili TMA’yı içermelidir. Edinilmiş veya konjenital TTP dahil olmak üzere TMA semptomları için olası tüm etiyolojilerin tam bir değerlendirmesi, daha uygun bir tedavinin daha doğru bir şekilde teşhis edilmesine ve uygulanmasına olanak sağlayacaktır.

Keywords: Microangiopathic hemolytic anemia; Thrombotic microangiopathies; Anemia.

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Conflict of interest statement

Conflict of Interest: The authors of this paper have no conflicts of interest, including specific financial interests, relationships, and/or affiliations relevant to the subject matter or materials included.

Figures

Figure 1
Figure 1
Schistocytes should be evaluated on smears at medium microscope magnification.
Figure 2
Figure 2
Increased megakaryocytes in bone marrow associated with thrombocytopenia testify to the presence of peripheral platelet consumption.
Figure 3
Figure 3
Algorithm for differential laboratory diagnosis in patients with clinical suspicion of thrombotic microangiopathie.
See this image and copyright information in PMC

Comment in

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