| Syndrome | Clinical features | Laboratory findings |
| Primary thrombotic microangiopathy (TMA) syndromes | ||
| Thrombotic thrombocytopenic purpura (TTP) | May have severe neurologic abnormalities. Inherited; may present in a newborn infant, a child with thrombocytopenia, or, less commonly, an adult. Among adults, a common presentation is during a first pregnancy. Acquired autoimmune: Uncommon in children. | Severe MAHA and thrombocytopenia; acute kidney injury is rare. Severe deficiency of ADAMTS13 (activity <10%). Acquired cases often have a detectable ADAMTS13 inhibitor (autoantibody). Inherited TTP has ADAMTS13 gene mutation. |
| Complement-mediated TMA | Inherited and acquired disorders may present in children or adults. | Renal failure is prominent. Inherited disorders usually have a heterozygous mutation in a gene encoding a regulatory protein in the alternate complement pathway (eg, CFH, CFI, CD46/MCP, C3, CFB, CFHRs). Acquired disorder has antibodies to complement factor H or I. |
| Shiga toxin-mediated hemolytic uremic syndrome (ST-HUS) | Abdominal pain; diarrhea (often bloody); possible history of outbreak or exposure to livestock or contaminated food, although most cases are sporadic. | Renal failure is prominent. Stool may be positive for the organism (Escherichia coli or Shigella dysenteriae) or Shiga toxin. |
| Drug-induced TMA | History of exposure to quinine or other implicated medication. Immune-mediated forms have an abrupt onset with fever, chills, abdominal pain, nausea, anuric acute kidney injury. Toxic, dose-related etiologies may arise gradually, or onset may be sudden with an intravenous toxic agent (eg, Opana-ER). | Immune mediated: Severe acute kidney injury; drug-dependent antibodies to platelets and/or neutrophils can be demonstrated. Toxic, dose related: May have gradual or sudden onset of renal failure and hypertension. |
| Coagulation-mediated TMA | Inherited, typically presents in children <1 year old. | DGKE, thrombomodulin, or plasminogen gene mutation. |
| Metabolism-mediated TMA | Inherited, typically presents in children <1 year old, but may also present in adults. | Elevated serum homocysteine and methylmalonic acid, and low methionine levels; increased urinary methyl-malonic acid. MMACHC gene mutation. |
| Systemic disorders that may present with MAHA and thrombocytopenia | ||
| Disseminated intravascular coagulation (DIC) | May be caused by infection, malignancy, postpartum hemorrhage with hypotension, or a vascular abnormality such as a giant hemangioma (eg, Kasabach-Merritt syndrome). | Thrombocytopenia, decreased fibrinogen, and elevated D-dimer are typical with acute or chronic DIC. MAHA may occur. Prolongation of the PT and aPTT are seen in acute DIC. |
| Systemic infection | May include bacterial, viral, rickettsial, or fungal organisms. High fever and shaking chills are common. | |
| Systemic malignancy | May occur with occult systemic malignancy. Breast, prostate, lung, pancreatic, or gastrointestinal tumors are often responsible. | Depends on specific tumor. |
| Pregnancy-related syndromes (eg, severe preeclampsia, HELLP) | Typically present in third trimester or postpartum. Severe hypertension and liver involvement are often present. Abnormalities resolve with delivery. | Elevated hepatic transaminases. Acute kidney injury is uncommon. |
| Severe hypertension | Typically, systolic BP >200 mm Hg and diastolic BP >100 mm Hg. Neurologic features including PRES may be present. Hypertension may also occur in primary TMAs with severe renal involvement, so the temporal relationship is important. Abnormalities resolve with control of the BP. | Often associated with severe renal failure. Renal biopsy demonstrates TMA identical to the primary TMA syndromes. |
| Systemic rheumatic diseases (eg, SLE, SSc, APS) | SLE may be associated with hypertension, renal insufficiency, and autoimmune cytopenias. APS typically presents with arterial and/or venous thromboembolism but can also produce a TMA. | Serologic testing may show autoantibodies characteristic of the underlying condition; APS may have prolonged aPTT. Renal biopsy may demonstrate TMA identical to the primary TMA syndromes. |
| Hematopoietic cell transplant | May occur with autologous or allogeneic transplant. May be associated with exposure to cytotoxic chemotherapy, radiation, systemic infection, or a calcineurin inhibitor. | No specific findings. |
| Solid organ transplant | May be associated with calcineurin inhibitor administration. May be associated with infection such as CMV in the setting of immunosuppression. In patients receiving a kidney transplant for a primary TMA syndrome, the syndrome may recur in the transplanted kidney. | Renal biopsy may have features of rejection. |
