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INTRODUCTION

Thrombotic thrombocytopenic purpura (TTP) is defined clinically by the abnormalities caused by systemic thrombotic microangiopathy: thrombocytopenia and microangiopathic hemolytic anemia. Additional clinical features may include neurologic abnormalities, renal failure, and gastrointestinal symptoms

 

Hemolytic-uremic syndrome (HUS) is another clinical presentation of thrombotic microangiopathy. Like TTP, HUS is manifested by thrombocytopenia and microangiopathic hemolytic anemia with the additional abnormality of renal failure. Although it is commonly stated that HUS is manifested primarily by renal failure whereas TTP is manifested primarily by neurologic abnormalities, these 2 syndromes cannot be distinguished clinically, because many patients have both renal failure and severe neurologic abnormalities, or neither. The term HUS is often restricted to children. In adults, all syndromes are referred to as TTP, whether or not neurologic abnormalities or renal failure are present

 

Amorosi EL, Ultmann JE. Medicine (Baltimore) 1966;45:139–159

George JN. N Engl J Med 2006;354:1927–1935

Epidemiology

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Epidemiology
Incidence:
 Inherited: Very rare. Described in isolated case reports
 Acquired: 11.3 cases/106 population/year for all patients diagnosed with TTP; 1.7 cases/106 population/year for patients with ADAMTS13 deficiency
Male-to-female ratio: 1:3
Age: Rare in children, except for the typical diarrhea-associated HUS; TTP occurs in the complete age range of adults
Mortality: Untreated, TTP is fatal in 90% of patients. With effective treatment, mortality is decreased to approximately 15%

 

Amorosi EL, Ultmann JE. Medicine (Baltimore) 1966;45:139–159

Terrell DR et al. J Thromb Haemost 2005;3:1432–1436

Vesely SK et al. Blood 2003;102:60–68

Classification

Congenital:

Patients with congenital TTP, presumably caused by inherited abnormalities of the ADAMTS13 gene, may present in early childhood, as adults, or may remain asymptomatic. Also, congenital abnormalities of complement regulation can cause syndromes of HUS

 

Acquired:

  1. Idiopathic: Most patients with TTP present without an associated condition or apparent etiology

  2. Allogeneic hematopoietic stem cell transplantation: Although there are reports describing TTP as a specific complication of allogeneic hematopoietic stem cell transplantation, this may not exist as a specific entity. In most patients diagnosed with TTP following allogeneic hematopoietic stem cell transplantation, the clinical features suggesting thrombotic microangiopathy are caused by systemic infection (eg, aspergillus, cytomegalovirus), regimen-related toxicity, or acute graft-versus-host disease. These syndromes are now described as transplantation-associated thrombotic microangiopathy, not as TTP

  3. Pregnancy/postpartum: Pregnancy is a risk factor for developing TTP, particularly in patients with congenital TTP. Congenital and acquired TTP typically occur near term or postpartum. Other pregnancy-related complications, such as severe preeclampsia and the HELLP (Hemolysis, Elevated Liver function tests, and Low Platelets) syndrome may have clinical features identical to TTP

  4. Drug-associated, immune-mediated: Hypersensitivity reactions to drugs can cause the complete syndrome of TTP. Most frequent is quinine hypersensitivity; also reported are ticlopidine, clopidogrel

  5. Drug-associated, dose-dependent toxicity: The clinical and pathologic features of TTP can be caused by dose-dependent toxicity of chemotherapeutic agents, most commonly mitomycin, and immunosuppressive agents. Among the latter, most commonly cyclosporine

  6. Shiga toxin:...

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