Thrombotic microangiopathies: First report of 294 cases from a single institution experience in Argentina

MARÍA L ROMERO; SABRINA ROTONDO; ANALÍA SÁNCHEZ-LUCEROS; JUVENAL PAIVA; ANA C KEMPFER; MARÍA F ALBERTO; CÉLIA DOS SANTOS; MARA AGAZZONI; MARÍA M CASINELLI

eJHaem

JOHN WILEY & SONS INC

Año: 2020

Introduction: Thrombotic microangiopathies (TMAs) are rare disorders associated with fatal outcomes if left uncared for. However, healthcare problems in developing countries tend to limit medical assistance to patients.Methods: We prospectively studied an Argentine cohort of 294 consecutive patients from 2013 to 2016. Patients? subcategory classification relied on clinical symptoms and presence or absence of trigger events associated with TMA.Results: Main suspected disorders were the primary TMAs known as thrombotic thrombocytopenic purpura (TTP) (n = 72/294, 24%) and atypical haemolytic uraemic syndrome (aHUS) (n = 94/294, 32%). In acute phase, demographic parameters for acquired TTP (aTTP) (n = 28) and aHUS (n = 47) showed that both groups were characterised by a young median age (37 and 25 years, respectively) and female predominance (60% and 86%). Median of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 activity was significantly lower in aTTP than in aHUS group (1.4% vs 83%) and was associated with a more severe thrombocytopenia (15 × 109 vs 53 × 109/L). Creatinine (Cr) and urea (Ur) were significantly increased in aHUS compared to aTTP subjects (Cr: 3.7 vs 0.7 mg/dL, Ur: 118 vs 33 mg/dL). Gastrointestinal and neurological symptoms were more frequent in aHUS and aTTP, respectively.Conclusion: The first description of a TMA cohort in Argentina revealed similar clinical presentations to those of other countries.1 INTRODUCTIONThrombotic microangiopathies (TMAs) represent a group of rare diseases generally characterised by microangiopathic haemolytic anaemia (MAHA) with thrombocytopenia and organ injury of variable severity [1]. The microvascular lesion includes arterioles and capillary walls thickening, endothelial swelling and detachment, subendothelial accumulation of proteins and cell debris, fibrin and platelet‐rich thrombi obstructing vessel lumina with resultant tissue ischemia [2]. The list of entities belonging to TMA is extensive, and classification remains a challenge while some pathophysiological mechanisms associated with the syndromes are still unclear [3]. Haemolytic uraemic syndrome (HUS) is one of the two main TMA disorders investigated together with thrombotic thrombocytopenic purpura (TTP) in the past few decades. Although the two diseases have overlapping clinical features, HUS and TTP are pathophysiologically distinct entities [4]. TTP is characterised by severe acquired (aTTP) or congenital (cTTP) deficiency of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13). Both forms lead to persistent ultra large von Willebrand factor multimers, platelet activation and microvascular thrombosis [5]. The triad of acute MAHA, thrombocytopenia and acute kidney injury defines HUS. This syndrome is characterised by the typical form, secondary to an infection by Shiga toxin (Stx)‐producing Escherichia coli (STEC) and the extremely rare atypical form (aHUS), caused by the dysregulation of the alternative pathway of the complement, leading to its activation. Elucidated pathological mechanisms of aHUS involve genetic or acquired abnormalities identified in complement components or coagulation‐related factors [6]. TMA patient cohorts contributed to depict epidemiological and demographic background of the disease worldwide, except in Latin America where TMA reports are almost nonexistent. The aim of our study was to describe the demographic, laboratory and clinical features of an Argentine cohort of 294 consecutive patients with suspected TMA from 2013 to 2016.