Table 3.
Etiology-based subclassifications and clinical diagnoses of TMA
| Etiology-based subclassification | Etiology | Underlying cause | Clinical diagnosis | Important clinical findings |
|---|---|---|---|---|
| ADAMTS13-deficient TMA | Severe decrease in ADAMTS13 activity | ADAMTS13 gene abnormality | Congenital TTP (Upshaw-Schulman syndrome) | ADAMTS13 gene abnormality |
| Anti-ADAMTS13 autoantibodies | Immune-mediated TTP |
Severe decrease in ADAMTS13 activity and the presence of anti-ADAMTS13 autoantibodies |
||
| Infection-induced TMA | Infection | STEC (e.g., Escherichia coli O157) | STEC-HUS | STEC infection established by blood or stool culture |
| Neuraminidase-secreting Streptococcus pneumoniae | Pneumococcal-associated HUS | Proven pneumococcal infection | ||
| Complement-mediated TMA | Complement abnormality | Hereditary complement abnormalities (e.g., factors B, H, and I; C3; and membrane cofactor protein) | Atypical HUS |
Genetic complement factor abnormalities; Low C3 and normal C4 levels (not necessarily observed in all patients with atypical HUS) |
| Proven presence of anti-factor H antibodies | ||||
| Anti-factor H antibodies | ||||
| Coagulation-mediated TMA | Coagulation abnormality | Mutations in diacylglycerol kinase ε and thrombomodulin genes | Atypical HUS (possibly) | Proven genetic mutations |
| Secondary TMA | Unknown | Autoimmune diseases | Connective tissue disease–associated TMA, etc | SLE, scleroderma, or other connective tissue disorders |
| Hematopoietic stem cell transplant | Hematopoietic stem cell transplantation–associated TMA |
Unresponsive to platelet transfusion Hemolysis (accompanied with, e.g., low haptoglobin levels) |
||
| Organ transplant (e.g., kidney, liver) | Post–organ transplant TMA | Thrombocytopenia of unknown etiology and hemolysis (accompanied with, e.g., low haptoglobin levels) | ||
| Malignant tumors | Tumor-associated TMA | Frequently diagnosed in patients with malignant lymphomas, stomach cancer, and pancreatic cancer | ||
| Pregnancy | Pregnancy-associated TMA, HELLP syndrome | HELLP syndrome typically develops at ≥ 30 weeks of gestation in combination with hypertension | ||
| Drugs (e.g., mitomycin) | Drug-induced TMA | Medication prescription | ||
| Other TMAs | Unknown | Other | TTP-like disorders or similar | Classic TTP pentad |
TMA thrombotic microangiopathy; TTP thrombotic thrombocytopenic purpura; HUS hemolytic uremic syndrome; SLE systemic lupus erythematosus; THBD thrombomodulin; HELLP syndrome, hemolysis, elevated liver enzymes, and low platelet count syndrome