What are the diagnostic criteria for Thrombotic Thrombocytopenic Purpura (TTP) in a pediatric patient with a recent history of diarrhea?

Diagnostic Criteria for Thrombotic Thrombocytopenic Purpura (TTP)

In a pediatric patient with recent diarrhea, TTP diagnosis requires ADAMTS13 activity <10 IU/dL, but the clinical context strongly suggests STEC-HUS rather than TTP, making immediate ADAMTS13 testing critical to distinguish between these two life-threatening conditions. 1

The Critical Discriminator: ADAMTS13 Activity

• ADAMTS13 activity <10 IU/dL is diagnostic of TTP, while normal or mildly reduced levels indicate atypical HUS or STEC-HUS 1, 2
• Measure ADAMTS13 activity immediately when thrombotic microangiopathy (TMA) is suspected, as this single test definitively distinguishes TTP from HUS 1
• Do not delay treatment while awaiting ADAMTS13 results, as atypical HUS requires immediate complement inhibitor therapy while TTP requires plasma exchange 1

Essential Laboratory Workup

When any patient presents with anemia plus thrombocytopenia, immediately order the following tests 1:

• Complete blood count with peripheral blood smear - >1% schistocytes favors TMA, though absence does not exclude diagnosis 1
• Haptoglobin - reduced in both TTP and HUS 1
• LDH and indirect bilirubin - elevated in both conditions 1
• Direct Coombs test - negative in both, confirming non-immune hemolysis 1
• ADAMTS13 activity - the key discriminator 1
• Stool testing for verocytotoxin-producing E. coli (VTEC/STEC) - necessary to diagnose STEC-HUS 1
• Creatinine and urinalysis - essential to assess renal involvement 1

Clinical Features Distinguishing TTP from HUS in Pediatric Patients with Diarrhea

Features Favoring STEC-HUS (More Likely in This Case):

• Preceding diarrheal illness, especially bloody diarrhea 4-5 days before HUS symptoms - this is the hallmark of STEC-HUS 1
• Prominent acute renal injury with hematuria, proteinuria, and elevated creatinine 1
• Less severe thrombocytopenia and fewer schistocytes compared to TTP 1
• Less prominent neurological involvement than TTP 1
• STEC-HUS typically occurs 4-5 days after diarrhea onset 1

Features Favoring TTP (Less Likely with Diarrhea History):

• More prominent neurological involvement - confusion, seizures, focal deficits 1
• Fever is more common in TTP than HUS 1
• More gradual onset 1
• Less severe renal involvement 1
• More severe thrombocytopenia and more abundant schistocytes 1

Critical Timing Consideration

• If platelet count obtained within 7 days after gastrointestinal illness onset is not <150,000/mm³, consider alternative diagnoses 1
• Atypical HUS may have a shorter diarrhea period or simultaneous onset of diarrhea and HUS symptoms 1

Common Pitfalls to Avoid

• Do not assume TTP based on the classic pentad - only 40% of TTP patients present with all five features (microangiopathic hemolytic anemia, thrombocytopenia, neurological dysfunction, renal dysfunction, and fever) 3, 4
• Do not miss schistocytes on initial smear - repeat peripheral blood smear if clinical suspicion remains high, as schistocytes may not be present initially 4
• Do not delay plasma exchange in suspected TTP - mortality is extremely high without prompt treatment 2, 5
• In pediatric patients with bloody diarrhea, STEC-HUS is 10-fold more common than TTP - E. coli O157:H7 should be specifically sought 5

Physical Examination Red Flags

• Splenomegaly excludes primary TTP and suggests alternative diagnoses such as Gaucher's disease, thalassemia, myelodysplasia, or schistosomiasis 6
• The spleen is typically not palpable in TTP, though it may be palpable in approximately 12% of pediatric cases, particularly infants 6

Treatment Implications Based on Diagnosis

• TTP requires immediate plasma exchange with fresh frozen plasma replacement and immunosuppression with corticosteroids 1, 2
• Atypical HUS requires immediate complement inhibitor therapy 1
• STEC-HUS is typically managed supportively without plasma exchange 1