Comparison of syndromes with microangiopathic hemolytic anemia (MAHA) with thrombocytopenia
| Features . | DIC . | Thrombotic microangiopathies (TMAs) . | HLH . | ||
|---|---|---|---|---|---|
| TTP . | ST-HUS . | CM-TMA . | |||
| Etiology | Tissue factor–mediated thrombin activation | ADAMTS13 deficiency | Shiga toxin–induced endothelial injury | Complement activation; deficiency of complement inhibitors | CD8 T-cell activation |
| Pathology | Systemic microvascular thrombosis | Systemic microvascular thrombosis | Renal microvascular thrombosis | Renal microvascular thrombosis | INF-γ-mediated macrophage activation |
| Acquired causes | Infection, malignancy, trauma, vascular tumors, circuits | Autoantibodies to ADAMTS13; autoimmune disease | Shiga toxin from E. coli | Autoantibodies to complement proteins, HSCT, drug, pregnancy | Malignancy, autoimmune disease, rheumatologic disease |
| Genetic variants | Neonatal purpura fulminans: PROC | ADAMTS13 | None | Complement regulatory proteins: CFH, CD46, CFI, C3, CFB, THBD | Perforin trafficking and effector T-cell function: PRF1, UNC13D, STX11, STXBP2, Rab27A, SH2D1A, BIRC4, ITK |
| Renal involvement Other organ involvement | Variable Multiorgan dysfunction | Infrequent Brain | Frequent; AKI, proteinuria, HTN Brain | Frequent; AKI, proteinuria, HTN Lung, gastrointestinal system, brain, serositis | Variable Multiorgan dysfunction, hepatosplenomegaly, |
| Laboratory screening | ADAMTS13 nl, low; sC5b-9 nl; D dimer very high; ferritin high | ADAMTS13, very low; sC5b-9 nl D-dimer nl, high Ferritin nl, high | ADAMTS13 nl; sC5b-9 high; D-dimer nl, high; ferritin nl, high | ADAMTS13 nl; sC5b-9 high; D-dimer nl; Ferritin nl, high | ADAMTS13 nl; sC5b-9 nl; D dimer, high; ferritin, very high; sCD25, very high; CXCL9, very high |
| Diagnosis | ISTH DIC score ≥5 | ADAMTS13 < 10% | E. coli 0157:H7 in stool | TMA diagnostic criteria39 | HLH diagnostic criteria38 |
| Treatment | Treat primary cause | Plasma exchange; immunosuppression | Supportive; anti-complement considered with neurologic symptoms | Anti-complement therapy | Immunosuppression; Anti-T cell therapy; HSCT |
| Features . | DIC . | Thrombotic microangiopathies (TMAs) . | HLH . | ||
|---|---|---|---|---|---|
| TTP . | ST-HUS . | CM-TMA . | |||
| Etiology | Tissue factor–mediated thrombin activation | ADAMTS13 deficiency | Shiga toxin–induced endothelial injury | Complement activation; deficiency of complement inhibitors | CD8 T-cell activation |
| Pathology | Systemic microvascular thrombosis | Systemic microvascular thrombosis | Renal microvascular thrombosis | Renal microvascular thrombosis | INF-γ-mediated macrophage activation |
| Acquired causes | Infection, malignancy, trauma, vascular tumors, circuits | Autoantibodies to ADAMTS13; autoimmune disease | Shiga toxin from E. coli | Autoantibodies to complement proteins, HSCT, drug, pregnancy | Malignancy, autoimmune disease, rheumatologic disease |
| Genetic variants | Neonatal purpura fulminans: PROC | ADAMTS13 | None | Complement regulatory proteins: CFH, CD46, CFI, C3, CFB, THBD | Perforin trafficking and effector T-cell function: PRF1, UNC13D, STX11, STXBP2, Rab27A, SH2D1A, BIRC4, ITK |
| Renal involvement Other organ involvement | Variable Multiorgan dysfunction | Infrequent Brain | Frequent; AKI, proteinuria, HTN Brain | Frequent; AKI, proteinuria, HTN Lung, gastrointestinal system, brain, serositis | Variable Multiorgan dysfunction, hepatosplenomegaly, |
| Laboratory screening | ADAMTS13 nl, low; sC5b-9 nl; D dimer very high; ferritin high | ADAMTS13, very low; sC5b-9 nl D-dimer nl, high Ferritin nl, high | ADAMTS13 nl; sC5b-9 high; D-dimer nl, high; ferritin nl, high | ADAMTS13 nl; sC5b-9 high; D-dimer nl; Ferritin nl, high | ADAMTS13 nl; sC5b-9 nl; D dimer, high; ferritin, very high; sCD25, very high; CXCL9, very high |
| Diagnosis | ISTH DIC score ≥5 | ADAMTS13 < 10% | E. coli 0157:H7 in stool | TMA diagnostic criteria39 | HLH diagnostic criteria38 |
| Treatment | Treat primary cause | Plasma exchange; immunosuppression | Supportive; anti-complement considered with neurologic symptoms | Anti-complement therapy | Immunosuppression; Anti-T cell therapy; HSCT |
ADAMTS13, ADAM metallopeptidase with thrombospondin type 1 motif 13; CM-HUS, complement-mediated hemolytic uremic syndrome; DIC, disseminated intravascular coagulation; E. coli, Escherichia coli; HLH, hemophagocytic lymphohistiocytosis; HSCT, hematopoietic stem cell transplant; HTN, hypertension; ISTH, International Society on Thrombosis and Haemostasis; nl, normal; ST-HUS, Shiga toxin–mediated hemolytic uremic syndrome; TMA, thrombotic microangiopathy; TTP, thrombotic thrombocytopenic purpura.