Thrombotic Thrombocytopenic Purpura (TTP): Clinical Features and Diagnosis
Clinical Presentation
TTP typically presents with severe thrombocytopenia and microangiopathic hemolytic anemia (MAHA), often accompanied by neuropsychiatric symptoms, renal dysfunction, and fever. 1, 2
The classic pentad (thrombocytopenia, MAHA, fever, neurological abnormalities, and renal dysfunction) is present in only 6% of patients, but thrombocytopenia and MAHA are mandatory for diagnosis. 3
Key Clinical Features to Identify:
- Thrombocytopenia: Platelet count typically <30,000/µL, often presenting with severe counts around 17-31 × 10⁹/L 1, 3, 4
- Neurological symptoms: Present in 83% of patients, ranging from mild confusion to severe manifestations including seizures, altered mental status, or coma 3, 4
- Renal dysfunction: Occurs in 36-79% of patients, though less severe than in hemolytic uremic syndrome 5, 3
- Fever: Present in 50-89% of cases 3, 4
- Bleeding manifestations: Mucous membrane bleeding or petechiae in approximately 50% 4
Diagnostic Approach
Immediate Laboratory Testing
Order ADAMTS13 activity and inhibitor testing immediately upon suspicion, but do not delay treatment while awaiting results. 6, 1
Essential First-Tier Tests:
- Peripheral blood smear: Must demonstrate schistocytes (fragmented red blood cells) to confirm MAHA 6, 1
- Complete blood count: Documents thrombocytopenia and anemia 1
- Hemolysis markers: Elevated LDH (median 635-885 U/L), elevated indirect bilirubin, decreased hemoglobin, elevated reticulocyte count 1, 7, 4
- Coagulation studies: PT, aPTT, and fibrinogen should be normal or only mildly abnormal, distinguishing TTP from DIC 1, 4
- ADAMTS13 activity level: <10% activity confirms TTP diagnosis 1, 2
- ADAMTS13 inhibitor titer: Detects autoantibodies in acquired TTP 1, 2
Risk Stratification Tool
In adults with suspected TTP, use the PLASMIC score to identify intermediate-to-high risk patients (score ≥5) who require immediate treatment. 8, 1
PLASMIC Score Components:
- Platelet count <30,000/µL
- Combined hemolysis variables (reticulocyte count >2.5%, undetectable haptoglobin, or indirect bilirubin >2 mg/dL)
- Absence of active cancer
- Absence of stem-cell or solid-organ transplant
- MCV <90 fL
- INR <1.5
- Creatinine <2.0 mg/dL 8, 1
Diagnostic Confirmation
TTP diagnosis is confirmed by ADAMTS13 activity <10% combined with thrombocytopenia and MAHA, though treatment must begin immediately on clinical suspicion before results return. 1, 2
Critical Diagnostic Pitfalls
Never delay therapeutic plasma exchange (TPE) while waiting for ADAMTS13 results, as untreated TTP has a mortality rate exceeding 90% and delay increases mortality dramatically. 6, 2
Important Distinctions:
- Coma/semicoma at presentation: This is a poor prognostic indicator with higher mortality risk 7
- Pediatric considerations: In children, TTP is less common and plasma exchange can be deferred 24-48 hours until ADAMTS13 results confirm diagnosis, as TPE carries considerable morbidity in this population 8, 1
- ADAMTS13 activity >10%: Suggests alternative diagnoses such as atypical hemolytic uremic syndrome (aHUS), complement-mediated TMA, or antiphospholipid syndrome, particularly in patients with systemic lupus erythematosus 8, 1
Differential Diagnosis Considerations:
When evaluating suspected TTP in lupus patients, consider lupus-associated TTP (ADAMTS13 <10%), antiphospholipid syndrome nephropathy (positive antiphospholipid antibodies), or complement-mediated TMA, as these require different management approaches. 8
Immediate Action Required
Initiate therapeutic plasma exchange immediately upon clinical suspicion without waiting for confirmatory testing, as this is life-threatening and requires hematology consultation. 6, 1, 2