Thrombotic Microangiopathy (TTP and HUS): Advances in Differentiation and Diagnosis

Extract

Detection of the proteolytic enzyme ADAMTS-13 may be used to differentiate between the forms of thrombotic micro-angiopathy (TMA), thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS).

Thrombotic microangiopathy (TMA) is a form of systemic thrombosis with microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and microthrombi formation within arterioles and capillaries. One third of patients have hemoglobin values below 6 g/dL. MAHA is a form of anemia characterized by elevated reticulocyte count and serum lactate dehydrogenase (LD), decreased serum haptoglobin, and presence of schistocytes (fragmented erythrocytes) on the peripheral blood film. Most patients have normal prothrombin times (PT), activated partial thromboplastin times (PTT), and thrombin times (TT). When left untreated, patients die from systemic microvascular thrombosis causing cerebral and myocardial infarctions and renal failure. In the case reported by Moschcowitz in 1924, a 16-year-old female died of a form of TMA that included MAHA, petechiae, hemiparesis (partial paralysis) and fever.¹ Autopsy findings included hyaline thrombi in the terminal arterioles and capillaries of the heart and kidney.

When a patient presents with symptoms of gastroenteritis including abdominal pain and diarrhea, a significantly decreased platelet count, and schistocytes on the peripheral smear but normal coagulation studies, TMA should be strongly considered. Prompt recognition is important because this condition must be classified as either TTP or HUS. Both disorders present with thrombocytopenia and MAHA. Timely treatment with plasma-exchange is very effective for individuals with TTP while HUS does not respond to the same treatment. The majority of patients with HUS recover normal renal function with only…

ABBREVATIONS: ADAMTS = a disintegrin-like and metal-loprotease domain with thrombospondin type motifs; HUS = hemolytic-uremic syndrome; LD = lactate dehydrogenase; MAHA = microangiopathic hemolytic anemia; PT = prothrombin times; PTT = partial thromboplastin times; TMA = thrombotic microangiopathy; TT = thrombin times; TTP = thrombotic thrombocytopenic purpura; ULVWF = ultra-large VWF; VTEC = verotoxin-producing E coli; VWF = Von Willebrand factor; VWF-cp = VWF-cleaving protease.