What labs are used for the diagnosis and management of Thrombotic Thrombocytopenic Purpura (TTP)?

Laboratory Tests for Diagnosis and Management of Thrombotic Thrombocytopenic Purpura (TTP)

The essential laboratory tests for diagnosing TTP include complete blood count with peripheral blood smear examination, ADAMTS13 activity level and inhibitor titer, lactate dehydrogenase (LDH), haptoglobin, reticulocyte count, and bilirubin to identify microangiopathic hemolytic anemia and severe thrombocytopenia. 1

Initial Diagnostic Workup

First-line Laboratory Tests

• Complete blood count (CBC) with platelet count
  • TTP typically presents with severe thrombocytopenia (<30 × 10^9/L) 2
• Peripheral blood smear examination
  • Critical for identifying schistocytes (fragmented RBCs) 1, 3
  • Note: Absence of schistocytes initially does not rule out TTP 4
• ADAMTS13 activity level and inhibitor titer
  • Severe deficiency (<10 IU/dL) strongly supports TTP diagnosis 3
  • Presence of inhibitory autoantibodies confirms immune-mediated TTP 3
• Markers of hemolysis:
  • LDH (typically elevated)
  • Haptoglobin (decreased)
  • Reticulocyte count (elevated)
  • Bilirubin (elevated) 1, 5
• Coagulation studies:
  • Prothrombin time (PT)
  • Activated partial thromboplastin time (aPTT)
  • Fibrinogen 1, 6

Second-line Laboratory Tests

• Direct antiglobulin test (Coombs test) to rule out immune hemolytic anemia 6
• Blood group and antibody screen 1
• Renal function tests (BUN, creatinine) 1, 2
• Urinalysis to assess for renal involvement 6
• HIV and HCV testing (to rule out secondary causes) 1, 6

Diagnostic Criteria and Differentiation

TTP diagnosis is supported when:

1. Severe ADAMTS13 deficiency (<10 IU/dL) is present 3
2. Microangiopathic hemolytic anemia and thrombocytopenia are observed without other apparent causes 1, 5
3. Clinical prediction scores can help guide empirical treatment before ADAMTS13 results are available (platelet count <30 × 10^9/L and creatinine <2.0 mg/dL) 2

Normal to moderately reduced ADAMTS13 activity (>10 IU/dL) suggests alternative diagnoses like atypical hemolytic uremic syndrome (aHUS) or other thrombotic microangiopathies 3.

Additional Tests to Rule Out Other Conditions

• ANA testing (if systemic autoimmune disease is suspected) 6
• Helicobacter pylori testing (urea breath test or stool antigen test preferred) 1, 6
• Cytomegalovirus serology 1
• Brain imaging (CT or MRI) if neurological symptoms are present 1
• Cardiac assessment (ECG, troponin) to evaluate cardiac involvement 1, 4

Monitoring During Treatment

• Daily CBC to monitor platelet count response to treatment 1, 2
• LDH levels to assess hemolysis 2
• ADAMTS13 activity to guide therapy duration 2
• Renal function tests if renal involvement is present 7

Long-term Monitoring

• Regular monitoring of ADAMTS13 activity during remission
  • Levels <20% may indicate risk of relapse and need for preemptive treatment 2
• CBC monitoring weekly during dose adjustment phase and monthly after establishing stable treatment 6

Common Pitfalls and Caveats

1. Waiting for the full pentad of symptoms (fever, thrombocytopenia, microangiopathic hemolytic anemia, neurologic abnormalities, and renal failure) is dangerous - less than 7% of cases present with all five features 5

2. Schistocytes may not be present on initial blood smear examination - repeat testing may be necessary if clinical suspicion is high 4

3. ADAMTS13 results may take days to return - treatment decisions should be based on clinical presentation and initial laboratory findings 2, 5

4. Pseudo-thrombocytopenia due to EDTA-dependent platelet agglutination should be excluded by obtaining platelet count in a non-EDTA tube 1, 6

5. TTP can present atypically with predominant cardiac manifestations (as in myocardial infarction) without obvious hematologic abnormalities initially 4

Prompt diagnosis and treatment of TTP are crucial, as mortality approaches 90% without appropriate therapy but decreases to less than 10% with proper management 2, 5.