Diagnosis of Thrombotic Thrombocytopenic Purpura (TTP)
TTP diagnosis requires severe ADAMTS13 deficiency (<10% activity) combined with thrombocytopenia and microangiopathic hemolytic anemia (MAHA), though treatment must begin immediately on clinical suspicion before ADAMTS13 results return. 1, 2, 3
Diagnostic Criteria
Essential Laboratory Findings
The diagnosis of TTP is confirmed by ADAMTS13 activity <10% with or without detectable inhibitory autoantibodies. 3, 4
- Severe thrombocytopenia (platelet count typically <30,000/µL) 2, 3
- Microangiopathic hemolytic anemia evidenced by:
Critical Diagnostic Testing
Order ADAMTS13 activity and inhibitor testing immediately, but do not delay treatment while awaiting results. 1, 2, 3
- Peripheral blood smear to confirm schistocytes and exclude other causes 2, 3
- Coagulation studies (PT, aPTT, fibrinogen) should be normal or only mildly abnormal, distinguishing TTP from DIC 2, 5
- Direct antiglobulin test (Coombs) should be negative 2
- Blood type and antibody screen before plasma exchange 2
Risk Stratification: PLASMIC Score
Use the PLASMIC score to identify intermediate-to-high risk patients (score ≥5) who require immediate treatment in adults. 1, 2
The PLASMIC score includes:
- Platelet count <30,000/µL
- Combined hemoLysis variables (reticulocyte count, bilirubin, undetectable haptoglobin)
- Absence of active cancer
- Absence of Stem-cell or solid-organ transplant
- MCV <90 fL
- INR <1.5
- Creatinine <2.0 mg/dL 1, 2
Physical Examination Findings
The spleen should NOT be palpable in adult TTP patients; splenomegaly suggests an alternative diagnosis. 6
- Neurologic deficits may be present but are not required for diagnosis 3, 7
- Fever may occur but is inconsistent 7
- Renal dysfunction is typically mild 3, 7
Atypical Presentations
Recognize that TTP can rarely present without overt hemolysis, though this is exceptional and should not delay ADAMTS13 testing if clinical suspicion exists. 5
Treatment Approach
Immediate Management (Before ADAMTS13 Results)
Initiate therapeutic plasma exchange (TPE) immediately when TTP is suspected, combined with high-dose corticosteroids. 2, 4
- Methylprednisolone 1 g IV daily for 3 days, with first dose given after the first TPE session 2
- Daily TPE using fresh frozen plasma until platelet count normalizes (≥150,000/µL) 2, 4
- Rituximab should be offered as part of initial therapy for acquired TTP 2, 4
Adjunctive Therapy
Caplacizumab should be considered for patients with severe ADAMTS13 deficiency, particularly with elevated inhibitor levels. 2, 8
- Initial dose: 11 mg IV bolus before first plasma exchange 8
- Maintenance: 11 mg subcutaneous daily after each plasma exchange, continuing for 30 days after stopping TPE 8
- Caplacizumab reduces time to platelet recovery and decreases TTP-related death, recurrence, and thromboembolic events during treatment 8
Critical Management Pitfalls
Avoid platelet transfusions unless life-threatening hemorrhage occurs, as they may worsen thrombosis. 2
- RBC transfusion should be minimized, targeting hemoglobin 7-8 g/dL in stable patients 2
- In children, TTP is less common and plasma exchange can be deferred 24-48 hours until ADAMTS13 results confirm the diagnosis 1
Refractory Disease
For patients not responding to standard therapy, consider additional immunosuppression with cyclosporine, cyclophosphamide, vincristine, mycophenolate mofetil, or anti-thymocyte globulin. 2, 7
Congenital TTP Management
Fresh frozen plasma transfusion alone is sufficient for congenital TTP (cTTP) to supplement ADAMTS13. 4, 9
Differential Diagnosis Considerations
ADAMTS13 activity >10% in a similar clinical context supports alternative diagnoses such as atypical hemolytic uremic syndrome (aHUS) or other thrombotic microangiopathies. 3