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  • Thrombotic microangiopathy (TMA) describes a syndrome of microangiopathic hemolytic anemia (MAHA) and thrombocytopenia with various degrees of organ dysfunction, resulting from endothelial injury and disseminated microvascular thromboses.

  • Thrombotic thrombocytopenic purpura (TTP) may be caused by hereditary or acquired (or immune-mediated) deficiency of plasma ADAMTS13 activity, while hemolytic uremic syndrome (HUS) may be caused by Shiga toxin-producing Escherichia coli (STEC) and/or inherited or acquired abnormalities in complement activation and regulation or others.

  • TTP should be differentiated from HUS and other related TMA resulting from malignant hypertension, disseminated intravascular coagulation, collagen vascular diseases with vasculitis, catastrophic antiphospholipid syndrome, and Hemolytic anemia, Elevated Liver enzymes, and Low Platelets) (HELLP) syndrome, etc.

  • A triple therapy, including daily therapeutic plasma exchange, caplacizumab, and immunosuppressives (e.g., corticosteroids and rituximab), is considered the standard of care for immune-mediated TTP, while intermittent plasma infusion may be sufficient for hereditary TTP.

  • Therapy with anti-C5 monoclonal antibodies (e.g., eculizumab or ravulizumab) should be considered for atypical or complement-mediated HUS.


Moschowitz (1924) reported a previously unrecognized case of a 16-year-old girl presenting with pallor, petechiae, fever, and hemiparesis. Her disease progressed rapidly resulting in death. Postmortem examination revealed numerous hyaline thrombi in the terminal arterioles and capillaries.1 Amorosi and Ultmann (1966) established a diagnostic pentad for thrombotic thrombocytopenic purpura (TTP) including thrombocytopenia, microangiopathic hemolytic anemia (MAHA), neurologic symptoms, renal failure, and fever without origin.2 Later, Schulman et al (1960) reported a patient with a similar syndrome whose symptoms were dramatically improved with infusions of fresh human plasma.3 In 1978, Upshaw reported a case of 29-year-old female who had repeated thrombocytopenia and MAHA since her childhood. However, her conditions were improved sometime either spontaneously or after infusion of fresh frozen plasma (FFP).4 So, Upshaw and Schulman hypothesized that a plasma factor required for platelet production or platelet and red blood cell survival might have been missing in these cases.3,4 The mechanism of such a thrombotic microangiopathic syndrome remained a mystery until 2001, when a complete cDNA sequence of ADAMTS13, a plasma metalloprotease that cleaves von Willebrand factor (VWF), was first successfully determined.5,6 This paved a new avenue for the understandings of pathogenesis of TTP and the development of rapid and accurate diagnostic tools, and targeted therapies of such a potentially fatal syndrome.

Hemolytic uremic syndrome (HUS), a clinically similar thrombotic microangiopathic syndrome, was first described by Gasser et al (1955).7 Five children, aged 2 months to 7 years, presented with acquired hemolytic anemia, bizarre poikilocytes, and renal insufficiency. Three had thrombocytopenia and all patients died. Later, Kaplan et al (1975) reported 83 siblings from 41 families and suggested that both genetic and environmental factors might have contributed to the occurrence of familial cases of such a syndrome.8 Since then, numerous similar cases were reported.9–14 Thus, HUS is used to describe a syndrome with ...

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