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Art of Medicine: Thrombotic Microangiopathy

Thrombotic Microangiopathy
The above painting shows a glomerulus containing capillary loop fibrin thrombi, an arteriole with onion-skinning, and acute tubular injury, findings that can be seen in thrombotic microangiopathy.  Morphologic findings of thrombotic microangiopathy that can be seen on a renal biopsy include arteriolar or capillary loop fibrin or platelet thrombi, red blood cell fragmentation within glomerular capillary loops or within arteries, mesangiolysis, endothelial cell swelling,  glomerular basement membrane duplication, mucoid intimal edema of arteries, and a myointimal proliferation surrounding arterioles (onion-skinning like reaction). Thrombotic microangiopathy (TMA) has a wide clinical differential diagnosis, which can have substantial morphologic overlap on a kidney...

Antiphospholipid Antibody Syndrome

This biopsy shows glomerular arteriolar and capillary thrombi characteristic of thrombotic microangiopathy (TMA). Immunofluorescence studies (not shown) are negative for significant glomerular or tubulointerstitial immune complex deposits. The clinical history corresponding to such findings might involve an adult female patient with a history of rheumatoid arthritis and multiple miscarriages who presents with non-nephrotic range proteinuria, microscopic hematuria, hypertension, and no mental status changes. Laboratory workup could show thrombocytopenia, elevated LDH, low haptoglobin, and a positive lupus anticoagulant, and imaging studies might confirm findings of systemic thrombosis. A clinical diagnosis of antiphospholipid antibody syndrome related to underlying autoimmune disease (rheumatoid arthritis)...

Thrombotic Microangiopathy

The image (trichrome stain) shows the characteristic arteriolar lesion of acute thrombotic microangiopathy. Note the prominent mucoid intimal edema and extensive red blood cell fragmentation. The differential diagnosis based on this morphologic lesion is broad, and it includes infection, accelerated hypertension, antiphospholipid antibody syndrome, and malignancy, among others. The kidney biopsy was from a 75-year-old Caucasian woman seen in consultation for acute renal failure and hypertension which developed one week after the onset of severe diarrhea. Laboratory tests showed microangiopathic hemolytic anemia, and stool cultures were positive for Shiga toxin-producing E. coli. Hepatitis, ANA, anti-glomerular basement membrane, and ANCA tests...

Postpartum HUS

This 22-year-old Caucasian female presented with acute renal failure and proteinuria five days after delivering her first child. The pregnancy was uneventful. Serum creatinine at presentation was 6.2 mg/dL (baseline of 0.8 mg/dL), hemoglobin 2.5 g/dL, platelets 22,000 and LDH 2300 U/L. The biopsy shows glomeruli with endocapillary fibrin thrombi, associated with segmental mesangiolysis and red blood cell fragmentation.  These findings are diagnostic of a thrombotic microangiopathy (TMA).  Numerous etiologies may lead to a TMA, all of which show morphologic overlap with no morphologic finding specific for a single etiology.  Given the clinical history and the timing of disease presentation...