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

Diagnosis of Thrombotic Thrombocytopenic Purpura (TTP)

The diagnosis of TTP requires demonstration of severely deficient ADAMTS13 activity (<10%) along with clinical features of microangiopathic hemolytic anemia and thrombocytopenia. 1

Clinical Presentation and Initial Evaluation

TTP is characterized by:

• Microangiopathic hemolytic anemia
• Severe thrombocytopenia
• Organ ischemia due to microvascular platelet-rich thrombi
• Neurologic abnormalities
• Renal dysfunction
• Fever (in some cases)

Essential Diagnostic Tests

1. Complete blood count (CBC) - Shows thrombocytopenia and anemia
2. Peripheral blood smear - Critical for identifying schistocytes (fragmented RBCs)
3. ADAMTS13 activity level and inhibitor titer - The definitive test for TTP diagnosis 2
4. Hemolysis markers:
   • Elevated LDH
   • Decreased haptoglobin
   • Elevated indirect bilirubin
   • Elevated reticulocyte count
5. Coagulation studies:
   • Prothrombin time (PT)
   • Activated partial thromboplastin time (PTT)
   • Fibrinogen

Additional Relevant Tests

• Blood group and antibody screen
• Direct antiglobulin test (Coombs test)
• Serum creatinine
• Urinalysis
• Consider CT/MRI brain for patients with neurological symptoms
• Cardiac evaluation (ECG, troponin) if cardiac symptoms present 2

Diagnostic Algorithm

1. Initial suspicion based on:

   • Thrombocytopenia (often <30,000/μL)
   • Evidence of hemolytic anemia
   • Presence of schistocytes on peripheral smear
   • Absence of alternative explanation

2. Calculate PLASMIC score to estimate probability of severe ADAMTS13 deficiency:

   • Platelet count <30,000/μL
   • Hemolysis markers present
   • Absence of active cancer
   • Absence of solid organ/stem cell transplant
   • MCV <90 fL
   • INR <1.5
   • Creatinine <2.0 mg/dL
   • Higher score (5-7) indicates higher probability of TTP 1, 3

3. Definitive diagnosis:

   • ADAMTS13 activity <10% confirms TTP 1, 4
   • Presence of anti-ADAMTS13 autoantibodies indicates immune-mediated TTP
   • Genetic testing for ADAMTS13 mutations if congenital TTP is suspected

Important Diagnostic Considerations

• Do not delay treatment while awaiting ADAMTS13 results if clinical suspicion is high
• Differentiate from other thrombotic microangiopathies (HUS, DIC, HELLP syndrome)
• Drug history is essential - certain medications can trigger TTP (e.g., quinine, chemotherapy agents, tacrolimus, sirolimus) 2
• Rule out secondary causes - HIV, HCV, autoimmune disorders, pregnancy

Common Pitfalls in Diagnosis

1. Waiting for all classic pentad features - Less than 7% of TTP cases present with all five classic features (fever, neurologic abnormalities, thrombocytopenia, microangiopathic hemolytic anemia, and renal dysfunction) 5

2. Delaying treatment while awaiting ADAMTS13 results - Treatment should begin immediately in suspected cases as mortality is high without prompt intervention 1

3. Missing atypical presentations - TTP can present with isolated thrombocytopenia and minimal hemolysis initially

4. Failure to recognize drug-induced TTP - Thorough medication history is essential

5. Misdiagnosing as ITP - TTP often has schistocytes on smear and more severe clinical manifestations than ITP 2

Special Considerations

• Pediatric patients: TTP is less common in children; acceptable to defer plasma exchange for 24-48 hours until ADAMTS13 results confirm diagnosis 1

• Pregnancy-associated TTP: Must be differentiated from preeclampsia and HELLP syndrome

• Recurrent TTP: Regular monitoring of ADAMTS13 activity during remission is recommended to detect early relapse 1, 6

TTP is a medical emergency requiring rapid diagnosis and treatment. The combination of clinical features, laboratory findings, and ADAMTS13 activity testing provides the most accurate approach to diagnosis, with treatment often needing to be initiated before confirmatory test results are available.