Thrombotic thrombocytopenic purpura

Last updated: February 4, 2021

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Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy, a condition in which microthrombi, consisting primarily of platelets, form and occlude the microvasculature (i.e., the arterioles and capillaries). The other main thrombotic microangiopathy is hemolytic uremic syndrome (HUS). TTP occurs primarily in adults and is typically due to acquired autoantibodies against a proteolytic enzyme that cleaves von Willebrand factor (vWF). It is a clinical diagnosis based on the following pentad of findings: fever, neurological abnormalities, thrombocytopenia, microangiopathic hemolytic anemia, and impaired renal function. If TTP is strongly suspected and initial laboratory tests support the diagnosis, treatment should begin immediately, as the condition may be fatal if left untreated. First-line treatment is plasma exchange therapy.

  • Primarily adult individuals (median age at diagnosis: ∼ 40 years)
  • More common in women and in black populations

Epidemiological data refers to the US, unless otherwise specified.

TTP is a thrombotic microangiopathy, a condition in which microthrombi form and occlude the microvasculature. The other main thrombotic microangiopathy is hemolytic uremic syndrome (HUS). Although TTP and HUS share similarities in both pathophysiological findings and clinical features, these conditions differ in etiology; TTP, unlike HUS, is caused by a deficiency of ADAMTS13.

  1. Autoantibodies or gene mutationsdeficiency of ADAMTS13; (a metalloprotease that cleaves von Willebrand factor)
  2. ↓ Breakdown of vWF multimers → vWF multimers accumulate on endothelial cell surfaces
  3. Platelet adhesion and microthrombosis
  4. Microthrombi → fragmentation of RBCs with schistocyte formation → hemolytic anemia
  5. Arteriolar and capillary microthrombosis → end-organ ischemia and damage, especially in the brain and kidneys (potentially resulting in acute kidney injury or stroke)

ADAMTS13 deficiency → excess vWF microthrombus formation → blockage of small vessels RBC fragmentation (hemolysis) and end-organ damage

TTP patients are typically previously healthy adults. The pentad of clinical findings consists of: [2]

The typical patient is a previously healthy adult presenting with mental status changes, fever, petechiae, fatigue, and pallor. Laboratory tests will then indicate hemolytic anemia and possibly acute kidney injury (AKI). Impaired kidney function may not be present, and only a minority of patients will present with all five clinical findings.

Mnemonic for TTP symptoms: “Nasty Fever Ruined My Tubes” (N Neurological symptoms, F Fever, R Renal function impairment, M Microangiopathic hemolytic anemia, T Thrombocytopenia)

While PT and aPTT are normal or only mildly elevated in TTP and HUS (no consumption coagulopathy), they are markedly elevated in DIC (consumption of platelets and all coagulation factors).

See “Differential diagnosis of platelet disorders.”

The differential diagnoses listed here are not exhaustive.

Treatment should be started after a presumptive diagnosis is made based on clinical features and initial labs (e.g., blood count, peripheral smear, creatinine).

TTP requires urgent diagnosis and treatment! Waiting for test results to confirm ADAMTS13 deficiency should not delay treatment.

TTP can result in microthrombus formation and complications in many organs of the body. [3]

We list the most important complications. The selection is not exhaustive.

The prognosis depends primarily on prompt initiation of treatment. Timely treatment can prevent acute complications (AKI, coma, and death), as well as progression to chronic renal failure.

  1. Who Is at Risk for Thrombotic Thrombocytopenic Purpura?. Updated: February 1, 2016. Accessed: April 16, 2017.
  2. What Are the Signs and Symptoms of Thrombocytopenia?. Updated: September 25, 2012. Accessed: April 16, 2017.
  3. Brandenburg VM, Gaertner S, Lindemann-Docter K, et al. Underestimated complications in thrombotic thrombocytopenic purpura--haemolytic uraemic syndrome. Nephrol Dial Transplant. 2004; 19 (8): p.2142-2146. doi: 10.1093/ndt/gfh230 . | Open in Read by QxMD
  4. Thrombotic Thrombocytopenic Purpura (TTP) and Hemolytic-Uremic Syndrome (HUS). Updated: January 1, 2017. Accessed: April 16, 2017.

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