Skip to Main Content

++

KEY POINTS

++

  • Thrombotic microangiopathy (TMA), a pathologic term, describes a syndrome of microangiopathic hemolytic anemia (MAHA) and thrombocytopenia with various degrees of organ dysfunction.

  • TMA includes thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndromes (HUS), as well as other related syndromes.

  • TTP is primarily caused by hereditary or acquired deficiency of plasma ADAMTS13, whereas HUS is mainly caused by Shiga toxin–producing E coli and/or abnormalities of complement activation and regulation.

  • TTP should be differentiated from HUS, disseminated intravascular coagulation (DIC), collagen vascular disease with vasculitis, and Hemolytic anemia, Elevated Liver enzymes, and Low Platelets) (HELLP) syndrome, etc.

  • Plasma therapy remains the mainstay of therapy for TTP and atypical HUS (aHUS). However, the treatment for aHUS has been less satisfactory. Adjunctive therapies such as corticosteroids, immunosuppressive agents, and anti-CD20 monoclonal antibodies such as rituximab or anti-C5 monoclonal antibodies such as eculizumab may be considered for refractory TTP or HUS cases.

++

INTRODUCTION

++

Thrombotic thrombocytopenic purpura (TTP) was first described by Eli Moschcowitz in 1924.1 He reported a previously unrecognized case of a 16-year-old girl presenting with a constellation of findings including palor, petechiae, fever, and hemiparesis which ultimately was fatal. Postmortem examination revealed numerous hyaline thrombi in the terminal arterioles and capillaries.1 After reviewing 271 cases, Amorosi and Ultmann in 19662 established a diagnostic pentad for TTP: thrombocytopenia, MAHA, neurologic symptoms, renal failure, and fever without origin. Later, Schulman et al (1960) reported a patient with this syndrome whose symptoms were dramatically improved with infusions of fresh human plasma (FFP).3 Again, Upshaw (1978)4 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. Upshaw and Schulman hypothesized that a plasma factor that is required for platelet production3 or platelet and red blood cell survival was missing.4 However, the mechanism of TTP remained a mystery until 2001 when a plasma metalloprotease that cleaves von Willebrand factor (VWF) was identified5,6 and cloned.7,8

++

Hemolytic uremic syndrome (HUS), a similar syndrome, was first described by Gasser et al in 1955.9 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)10 reported 83 siblings from 41 families with HUS and suggested that both genetic and environmental factors might have contributed to the occurrence of familial cases of HUS. Since then, numerous HUS cases were reported.11-14 HUS is used to describe a syndrome with MAHA, thrombocytopenia, and predominant renal failure in the presence or absence of diarrheal prodrome.

++

While the clinical signs and symptoms of HUS appear to be indistinguishable from TTP, the underlying etiologies and the molecular mechanisms of the disease may be quite different. In ...

Want remote access to your institution's subscription?

Sign in to your MyAccess profile while you are actively authenticated on this site via your institution (you will be able to verify this by looking at the top right corner of the screen - if you see your institution's name, you are authenticated). Once logged in to your MyAccess profile, you will be able to access your institution's subscription for 90 days from any location. You must be logged in while authenticated at least once every 90 days to maintain this remote access.

Ok

About MyAccess

If your institution subscribes to this resource, and you don't have a MyAccess profile, please contact your library's reference desk for information on how to gain access to this resource from off-campus.

Subscription Options

AccessAnesthesiology Full Site: One-Year Subscription

Connect to the full suite of AccessAnesthesiology content and resources including procedural videos, interactive self-assessment, real-life cases, 20+ textbooks, and more

$995 USD
Buy Now

Pay Per View: Timed Access to all of AccessAnesthesiology

24 Hour Subscription $34.95

Buy Now

48 Hour Subscription $54.95

Buy Now

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.