What are the diagnostic criteria for Thrombotic Thrombocytopenic Purpura (TTP)?

Diagnostic Criteria for Thrombotic Thrombocytopenic Purpura (TTP)

The diagnosis of TTP requires the presence of microangiopathic hemolytic anemia and thrombocytopenia without another apparent cause, with ADAMTS13 activity testing being essential for confirmation. 1

Core Diagnostic Features

Essential Criteria (Both Required)

• Microangiopathic hemolytic anemia with schistocytes on peripheral blood smear
• Thrombocytopenia (typically <150,000/mm³)

Supporting Laboratory Findings

• ADAMTS13 activity level <10% (severe deficiency) with or without inhibitor presence
• Peripheral blood smear showing:
  • Schistocytes (fragmented red blood cells)
  • Decreased platelets
  • Normal red blood cell morphology (except for fragmentation)
  • Normal white blood cell morphology 2

Additional Clinical Features (Not Required for Diagnosis)

• Neurological abnormalities
• Renal dysfunction
• Fever

Diagnostic Algorithm

1. Initial Presentation: Patient with unexplained thrombocytopenia and anemia

2. First-line Testing:

   • Complete blood count with differential
   • Peripheral blood smear examination (looking specifically for schistocytes)
   • Reticulocyte count
   • Lactate dehydrogenase (LDH) - typically elevated
   • Direct Coombs test (negative in TTP)
   • Coagulation studies (normal in TTP)

3. Confirmatory Testing:

   • ADAMTS13 activity and inhibitor levels
   • Note: Treatment should not be delayed while awaiting ADAMTS13 results if clinical suspicion is high 3, 1

4. Exclusionary Testing (to rule out other causes):

   • Renal and liver function tests
   • HIV testing
   • Pregnancy test in women of childbearing potential
   • Antinuclear antibodies
   • Antiphospholipid antibodies 2

Important Diagnostic Considerations

Evolution of Diagnostic Criteria

The historical "pentad" of TTP (thrombocytopenia, microangiopathic hemolytic anemia, neurological abnormalities, renal failure, and fever) is rarely seen in current practice. The presence of only microangiopathic hemolytic anemia and thrombocytopenia without another apparent cause is now sufficient to initiate therapy due to the high mortality of untreated TTP. 1, 4

Differential Diagnosis

• Hemolytic Uremic Syndrome (HUS)
• Disseminated Intravascular Coagulation (DIC)
• HELLP syndrome in pregnant women
• Malignancy-associated microangiopathy
• Drug-induced thrombotic microangiopathy 5

Clinical Pearls

• Severe ADAMTS13 deficiency (<10% activity) is characteristic of TTP but is neither 100% sensitive nor specific 1
• Patients may present with only microangiopathic hemolytic anemia and thrombocytopenia without neurologic or renal abnormalities 1
• TTP can present atypically, making diagnosis challenging - maintain high clinical suspicion 6
• Schistocytes may not be evident on initial peripheral blood smear but can appear later in the disease course 6

Common Pitfalls

• Delaying treatment while awaiting ADAMTS13 results in a clinically suspicious case
• Misdiagnosing as immune thrombocytopenic purpura (ITP) due to isolated thrombocytopenia
• Failing to repeat peripheral blood smear if initial examination doesn't show schistocytes
• Missing the diagnosis in patients who don't present with the complete pentad 6

Special Populations

Acquired vs. Congenital TTP

• Acquired TTP: Associated with autoantibodies against ADAMTS13
• Congenital TTP: Due to genetic mutations in ADAMTS13 gene

Demographics

• Predominantly affects young women
• Increased relative frequency in Black individuals 1

Early diagnosis and prompt initiation of plasma exchange therapy are critical for reducing mortality in TTP, which approaches 90% if left untreated but decreases to 10-20% with appropriate therapy. 1, 7