Thrombotic Microangiopathy Pathology Cases — Advanced

Acute renal TMA reflects endothelial injury and can show fibrin or platelet thrombi, endothelial swelling, mesangiolysis, and arteriolar damage. The pathology should trigger assessment for thrombocytopenia, hemolysis, hypertension, pregnancy, drugs, complement, and systemic disease.

The combination suggests a systemic TMA and raises concern for TTP, in which severe ADAMTS13 deficiency is typical. Testing should not delay urgent specialist-directed management when the clinical probability is high.

Chronic TMA can produce duplicated or double-contoured GBM, mesangiolysis, arteriolar intimal fibrosis, and onion-skin changes. These lesions indicate repeated or persistent endothelial injury and may be accompanied by chronic ischemic scarring.

Pregnancy-associated TMA has overlapping phenotypes and may reflect preeclampsia/HELLP, TTP, complement-mediated disease, or other secondary causes. Timing, ADAMTS13, complement evaluation, systemic findings, and response to delivery or treatment guide management.

Calcineurin inhibitors can cause endothelial injury and secondary TMA, as can several other drugs including certain antineoplastics and antiplatelet agents. Medication review is essential, but stopping or changing therapy must be coordinated with the treating specialty.

Mesangiolysis is a morphologic consequence of severe endothelial and mesangial injury, producing loss or dissolution of mesangial architecture. It supports TMA in the right context but should be interpreted alongside other lesions and clinical data.

Complement-mediated TMA can occur with genetic or acquired dysregulation of the alternative pathway, even when systemic hemolysis is modest. Complement studies, genetic testing, trigger assessment, and expert review may inform diagnosis and treatment.

Microangiopathic hemolysis is suggested by red-cell fragmentation, elevated LDH, reduced haptoglobin, and often indirect hyperbilirubinemia with reticulocytosis. The pattern should be interpreted with platelet count and organ injury.

Renal TMA is a pattern of injury rather than a single disease. Hypertension, pregnancy, drugs, infection, transplantation, autoimmune disease, TTP, and complement dysregulation can overlap histologically, so cause requires clinicopathologic integration.

Chronic ischemic lesions indicate cumulative vascular injury and reduced recovery potential. The activity-chronicity distinction helps determine whether removing a trigger or treating complement-mediated injury is likely to improve function.