ADAMTS13 Testing and Immediate Management in Suspected Thrombotic Microangiopathy
When thrombotic microangiopathy is suspected, immediately send blood for ADAMTS13 activity and inhibitor testing, then start plasma exchange and glucocorticoids without waiting for results if the PLASMIC score is ≥5 (intermediate-to-high risk) in adults. 1
Diagnostic Testing Protocol
Immediate Laboratory Workup
Send these tests before any treatment:
- ADAMTS13 activity level (critical threshold: <10% confirms TTP) 1
- ADAMTS13 inhibitor titer or anti-ADAMTS13 IgG antibodies 1
- Antiphospholipid antibodies (to evaluate for APS nephropathy) 1
- Peripheral blood smear for schistocytes 1
- LDH, haptoglobin, reticulocyte count, indirect bilirubin 1
- Direct antiglobulin test (Coombs), urinalysis 1
- PT, aPTT, fibrinogen 1
- Serum creatinine 1
Risk Stratification Using PLASMIC Score
Calculate the PLASMIC score immediately (1 point each): 1, 2
- Platelet count <30 × 10⁹/L
- Hemolysis present
- No active cancer
- No stem cell or solid organ transplant history
- MCV <90 fL
- INR <1.5
- Creatinine <2 mg/dL
- 0-4 points (low risk): TTP unlikely; do not start plasma exchange
- 5 points (intermediate risk): 5.9% have severe ADAMTS13 deficiency
- 6-7 points (high risk): 60% have ADAMTS13 <10%; if score=7,100% have ADAMTS13 <5%
Immediate Treatment Algorithm
For Adults with Intermediate-to-High Risk (PLASMIC ≥5)
Start immediately without waiting for ADAMTS13 results: 1
- Plasma exchange (therapeutic plasma exchange within 4-8 hours of diagnosis) 1, 3
- High-dose glucocorticoids (methylprednisolone 1g IV daily × 3 days, with first dose after first plasma exchange) 1
- Hematology consultation (delay in identification increases mortality) 1
For Children with Suspected TTP
Defer plasma exchange for 24-48 hours until ADAMTS13 results available (plasma exchange has considerable morbidity in children; TTP is less common in this population) 1
Treatment Based on ADAMTS13 Results
If ADAMTS13 Activity <10% (Confirmed TTP)
Triple therapy is the current standard of care: 1, 4
- Continue plasma exchange (replenishes ADAMTS13) 1, 4
- Continue glucocorticoids (suppresses autoantibodies) 1
- Add rituximab (375 mg/m² weekly × 4 doses for immunosuppression) 1, 4
- Add caplacizumab (von Willebrand factor inhibitor; greatest benefit if started within 3 days of TMA recognition) 1, 5, 4
Discontinue plasma exchange when: 1
- Initial platelet count response achieved
- No exacerbation within 3-5 days after stopping
- Then taper steroids over 2-3 weeks
If ADAMTS13 Activity Normal and Antiphospholipid Antibodies Positive
Diagnose as antiphospholipid syndrome nephropathy: 1
- Anticoagulation with warfarin (long-term; superior to direct oral anticoagulants) 1
- Consider plasma exchange in catastrophic APS 1
If ADAMTS13 Activity Normal and Antiphospholipid Antibodies Negative
Evaluate for complement-mediated TMA or other etiologies: 1
- Send complement studies (C3, C4, CH50) 1
- Consider eculizumab (anti-C5 antibody: 900 mg weekly × 3-4 doses, then 1200 mg week 5, then 1200 mg every 2 weeks) for atypical HUS 1
- Evaluate for drug-induced TMA, infection-related causes, malignancy 1
Critical Pitfalls to Avoid
Do not delay treatment waiting for ADAMTS13 results if PLASMIC score ≥5 in adults—mortality increases with delayed plasma exchange 1, 3
Do not use direct oral anticoagulants for APS nephropathy—they are inferior to warfarin for preventing thromboembolic events 1
Do not transfuse platelets unless life-threatening bleeding—may worsen thrombosis in TTP 1
Recognize that rapid ADAMTS13 assays (HemosIL AcuStar CLIA) have turnaround <1 hour with 98% sensitivity and 99% specificity, potentially avoiding empiric treatment in non-TTP patients 6