Kidney nontumor
Associated with systemic conditions
Hemolytic uremia syndrome / thrombotic thrombocytopenic purpura (HUS/TTP)

Author: Nikhil Sangle, M.D. (see Authors page)

Revised: 11 July 2018, last major update October 2016

Copyright: (c) 2003-2018, PathologyOutlines.com, Inc.

PubMed Search: Hemolytic uremia syndrome thrombotic thrombocytopenic purpura (HUS/TTP)

Cite this page: Sangle, N. Hemolytic uremia syndrome / thrombotic thrombocytopenic purpura (HUS/TTP). PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/kidneyhusttp.html. Accessed August 15th, 2018.
Definition / general
  • Thrombosis in capillaries and arterioles throughout the body, microangiopathic hemolytic anemia, thrombocytopenia, renal failure with platelet fibrin thrombi in interlobular renal arteries and glomeruli, necrosis and thickening of vessel walls
  • Morphologic changes resemble malignant hypertension, but usually no pre-existing hypertension
  • HUS and TTP are usually considered part of clinical spectrum, in which disease manifestations depend on distribution of microangiopathy (but see Arch Pathol Lab Med 2003;127:834)
  • HUS: fibrin / red cell rich thrombi, largely confined to kidney and often severe; usually no pancreas, adrenal gland, brain or heart involvement
  • Atypical HUS: due to excessive complement activation in microvasculature; inherited and acquired abnormalities affecting components of the alternative complement pathway are found in 60% (Hematology Am Soc Hematol Educ Program 2011;2011:15)
  • TTP: platelet rich thrombi in myocardial arteries; also pancreas, kidney, adrenal gland or brain; usually no permanent kidney damage
  • Pathophysiology: endothelial injury by toxins (certain strains of E. coli 0157:H7 producing Shiga-like toxin, Hum Pathol 1988;19:1102) or antibodies and activation cause intravascular thrombosis and platelet aggregation, which causes vascular obstruction and vasoconstriction, affects predominantly the renal vessels; TTP occurs due to enhanced platelet aggregation, e.g., metalloproteinase activity causing abnormal vWF-cleavage
Childhood HUS
  • 75% of cases occur after shiga-toxin producing E. coli O157:H7 infection (also called verocytotoxin because it damages Vero cells in culture)
  • Main cause of childhood acute renal failure
  • Usually infants and young children, may occur at any age
  • Symptoms: sudden onset of influenza, bleeding (hematemesis or melena), severe oliguria, hematuria, microangiopathic hemolytic anemia, neurologic changes in 1/3 and hypertension in 50%
  • Pathogenesis: related to Shiga-like toxin, which promotes adhesion of white blood cells to endothelium; also increases endothelin and decreases nitrous oxide production, causing vasoconstriction
Adult HUS/TTP
  • Poor prognosis with high mortality due to CNS disease or uncontrollable bleeding; survivors develop chronic renal failure
  • Causes: typhoid fever, E. coli (enterohemorrhagic strains), viral infections, shigellosis, antiphospholipid syndrome (primary or secondary to SLE), postpartum or after placental hemorrhage, vascular renal diseases such as scleroderma or malignant hypertension, drugs (mitomycin C, cyclosporine, bleomycin, cisplatin) and various malignancies
  • Lupus patients may have more severe disease (Am J Med Sci 2009;338:343, Nephron Clin Pract 2009;112:c177)
Idiopathic HUS/TTP
  • More common in women age 40 years or less; mortality 50%
  • Symptoms: CNS involvement dominant (fever, neurologic symptoms), hemolytic anemia, thrombotic thrombocytopenic purpura and renal involvement in only 50% (thrombi in glomerular capillaries and afferent arterioles)
Case reports
Treatment
Gross description
  • Patchy or diffuse renal cortical necrosis
Microscopic (histologic) description
    Early:
  • Fibrin deposits in capillary lumina
  • Fibrinoid necrosis of larger vessels, thrombosis and endothelial cell proliferation in small arteries and arterioles
  • Ischemic changes in glomeruli with endothelial swelling and capillary luminal narrowing
  • Expanded mesangial thrombi appear red on trichrome stain, thrombi are not essential for a pathologic diagnosis

    Later:
  • Intense basophilic thickening in small arteries and arterioles which restricts lumen, aneurysmal dilatation and proliferation of arterioles at hilus of glomerulus
  • May have double contour of glomerular basement membrane
Microscopic (histologic) images

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Case of the Week #403: numerous schistocytes and nucleated RBCs with extremely low platelets on peripheral smear



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HUS: kidney

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Atypical HUS: kidney

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TTP: kidney


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TTP: lesions of myocardium, adrenal gland, CNS, pancreas, other

Immunofluorescence
  • Demonstrates fibrin and fibrinogen, irregular staining for IgM, C3 and C1q, negative for IgA and IgG
Electron microscopy description
  • Widening of subendothelial space, filled with pale, finely particulate or fibrillar material (fibrinogen) and intraluminal platelet microthrombi causing narrowing of capillary lumen
  • Swollen mesangial cells with numerous phagolysosomes
  • Later: mucinous, onion skin-type obliterating endarteritis
Differential diagnosis
  • Antiphospholipid antibody syndrome: thrombosis in veins, arterioles, capillaries with glomerular subendothelial expansion
  • Malignant hypertension: similar vascular lesions but different clinical presentation
  • Systemic sclerosis: similar vascular lesions but different clinical presentation