Version May 2024
| Syndrome | Clinical features | Laboratory findings |
| Primary thrombotic microangiopathy (TMA) syndromes | ||
| Thrombotic thrombocytopenic purpura (TTP) | May have severe neurologic abnormalities. Immune TTP is uncommon in children. Hereditary TTP 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. | Severe MAHA and thrombocytopenia; acute kidney injury is rare. Severe deficiency of ADAMTS13 (activity <10%).
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| Complement-mediated TMA | Hereditary and acquired disorders may present in children or adults. | Kidney failure is prominent. Hereditary disorders usually are heterozygous for a pathogenic variant in a gene encoding a regulatory protein in the alternate complement pathway (eg, CFH, CFI, CD46/MCP, C3, CFB, CFHRs). Acquired disorders typically have antibodies to complement factor H. |
| 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. | Kidney 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 an implicated medication. Immune-mediated forms have an abrupt onset with fever, chills, abdominal pain, nausea, anuric acute kidney injury. Non-immune forms 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. Non-immune: May have gradual or sudden onset of kidney failure and hypertension. |
| Coagulation-mediated TMA | Heritable, typically presents in children <1 year old. | Pathogenic variants in the genes for diacylglycerol kinase epsilon (DGKE), thrombomodulin, or plasminogen. |
| Metabolism-mediated TMA | Heritable, typically presents in children <1 year old. Rarely, may be recognized for the first time in adults. | Elevated serum homocysteine and methylmalonic acid, and low methionine levels; increased urinary methyl-malonic acid. Pathogenic variants in the MMACHC gene. |
| 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 mmHg and diastolic BP >100 mmHg. Neurologic features including PRES may be present. Hypertension may also occur in primary TMAs with severe kidney involvement, so the temporal relationship is important. Abnormalities resolve with control of the BP. | Often associated with severe kidney failure. Kidney biopsy demonstrates TMA identical to the primary TMA syndromes. |
| Systemic rheumatic diseases (eg, SLE, SSc, APS) | SLE may be associated with hypertension, chronic kidney disease, 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. Kidney biopsy may demonstrate TMA identical to the primary TMA syndromes. |
| Hematopoietic stem cell transplantation | May occur with autologous or allogeneic hematopoietic stem cell transplantation. 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. | Kidney biopsy may have features of rejection. |
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