Variations in common diagnostic criteria used for TA-TMA diagnosis
| . | BMT-CTN . | IWG . | Clinical TMA (C-TMA) (modified Cho) . | New consensus TA-TMAd (modified Jodele) . |
|---|---|---|---|---|
| Comment | Meeting all criteria | Meeting all criteria | Biopsy proven disease or meet all criteria concurrently for ≥2 times in 14 days | Biopsy proven disease or meet ≥4 of criteria (1) to (7) concurrently for ≥2 times in 14 days |
| (1) Schistocytesa | ≥2/HPF | ≥4% (8/HPF) | ≥2/HPF | Presence |
| (2) Thrombocytopenia | x | x | ≥50% Plt reduction from baseline after engraftment or transfusion dependence | |
| (3) Anemia | x | x | ≥1 g/dL Hb reduction from baseline after engraftment or transfusion dependence (rule out AIHA & PRCA) | |
| (4) Elevated LDH | x | x | xb | LDH > ULN |
| (5) Hypertension | 1. >99th percentile for age (<18 yr) 2. ≥140/90 (≥18 yr) | |||
| (6) Proteinuria | Spot rUPCR ≥1 mg/mg | |||
| (7) Elevated sC5b9 | sC5b9 > ULN | |||
| Low haptoglobin | x | |||
| Negative DAT (Coombs) | x | |||
| Renal or neurologic dysfunction | x | |||
| Rule out mimics or alternative causes of secondary TMAc | - Coagulopathy or DIC - AIHA or PRCA - Overt relapse of malignancy |
| . | BMT-CTN . | IWG . | Clinical TMA (C-TMA) (modified Cho) . | New consensus TA-TMAd (modified Jodele) . |
|---|---|---|---|---|
| Comment | Meeting all criteria | Meeting all criteria | Biopsy proven disease or meet all criteria concurrently for ≥2 times in 14 days | Biopsy proven disease or meet ≥4 of criteria (1) to (7) concurrently for ≥2 times in 14 days |
| (1) Schistocytesa | ≥2/HPF | ≥4% (8/HPF) | ≥2/HPF | Presence |
| (2) Thrombocytopenia | x | x | ≥50% Plt reduction from baseline after engraftment or transfusion dependence | |
| (3) Anemia | x | x | ≥1 g/dL Hb reduction from baseline after engraftment or transfusion dependence (rule out AIHA & PRCA) | |
| (4) Elevated LDH | x | x | xb | LDH > ULN |
| (5) Hypertension | 1. >99th percentile for age (<18 yr) 2. ≥140/90 (≥18 yr) | |||
| (6) Proteinuria | Spot rUPCR ≥1 mg/mg | |||
| (7) Elevated sC5b9 | sC5b9 > ULN | |||
| Low haptoglobin | x | |||
| Negative DAT (Coombs) | x | |||
| Renal or neurologic dysfunction | x | |||
| Rule out mimics or alternative causes of secondary TMAc | - Coagulopathy or DIC - AIHA or PRCA - Overt relapse of malignancy |
Schistocyte is required in all definitions except the new consensus criteria.
Various adult cohorts have used different LDH threshold including 1.5x or 2x due to its lack of specificity.
No singular laboratory testing is sufficient for diagnosing mimics or alternative triggers for secondary TMA; clinical diagnosis is required.
High-risk TA-TMA in the new consensus criteria is defined as those meeting standard risk criteria plus any one of the following: sC5b9 >ULN, rUPCR ≥1 mg/mg, organ dysfunction, LDH ≥2x ULN, concurrent grade 2 to 4 acute graft-versus-host disease, concurrent viral infection.
AIHA, autoimmune hemolytic anemia; DIC, disseminated intravascular coagulation; Hb, hemoglobin; HPF, high-power field; LDH, lactate dehydrogenase; Plt, platelet; PRCA, pure red cell aplasia; rUPCR, random urine protein creatine ratio; ULN, upper limit of normal; yr, year.