Diagnosis in thrombotic microangiopathy

Abstract

Thrombotic microangiopathies (TMA) are relatively rare multisystem diseases characterised by microvascular endothelial damage with platelet-rich thrombus formation, consumption thrombocytopenia, mechanical haemolytic anaemia with schistocytes and multiorgan failure of variable severity. Thrombotic thrombocytopenic purpura (TTP) and haemolytic uraemic syndrome (HUS) are the two major disorders; other clinical entities that can be associated with TMA, are the HELLP syndrome, (haemolysis, elevated liver enzymes, low platelet count), the catastrophic antiphospholipid syndrome (CAPS) and bone marrow transplant (BMT). On the peripheral blood smears, the detection of schistocytes, that are fragments of red blood cells produced by extrinsic mechanical damage within the circulation, still remains an important morphological clue for the diagnosis of TMA. The International Council for Standardization in Hematology (ICSH) has prepared specific recommendations to standardise schistocyte identification, enumeration, and reporting. Measurement of activity of ADAMTS13 (a zinc-containing metalloprotease enzyme which cleaves and degrades large multimers of von Willebrand factor) remains the most reliable test to distinguish HUS from TTP, presenting with detectable and undetectable ADAMTS13 activity, respectively. Main clues in HELLP are weight gain, arterial hypertension, massive proteinuria, DIC, marked elevation of AST/ALT/LDH and detectable ADAMTS13 activity, while patients with CAPS present with weight loss, recent polyuria–polydipsia, vomiting, hypoglycaemia, jaundice (conjugated bilirubin), prolonged prothrombin time, reduced factor V and antithrombin levels, DIC and renal failure.