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renal TMA

Friday 3 February 2006

Definition: Renal thrombotic microangiopathy is a lesion seen in many conditions, including hemolytic uremic syndrome (HUS), radiation nephritis, toxicity related to various drugs, and hereditary forms.

Synopsis

- fibrin thrombi within glomerular capillaries which may extend to arterioles

  • glomerular thrombotic microangiopathy
    • extensive fibrin thrombi
    • platelet plugs filling up the capillary loops
  • fibrin thrombi can extend from the glomerular capillary loop to the arteriolar vascular pole (worse prognosis)

- cortical necrosis (severe cases with extensive vascular lesions, lesions extended to larger vessels)

  • glomerular necrosis
  • tubular necrosis
  • fibrin filling glomeruli
  • fibrin filling interlobular arteries
    • arterial intimal fibrosis
    • fibrin occluding arterial lumen

- chronic stages of injury after thrombotic microangiopathy

  • organization of the injury
  • split appearance of the basement membrane (membranoproliferative-like lesion)

- no immune complexes

Ultrastructure

- acute stages

  • fibrin tactoids
  • endothelial cell swelling
  • expansion of the lamina rara interna
  • no deposits

- chronic stages

  • new basement membrane formed after the endothelial injury -* early interposition with expansion of the lamina rara interna

Differential diagnosis

- membranoproliferative lesions for chronic stage

Pathogenesis

The term thrombotic microangiopathy (TMA) encompasses a spectrum of clinical syndromes that includes TTP and HUS. The common feature in both of these conditions is the widespread formation of hyaline thrombi, comprised primarily of platelet aggregates, in the microcirculation.

Consumption of platelets leads to thrombocytopenia, and the intravascular thrombi provide a likely mechanism for the microangiopathic hemolytic anemia and widespread organ dysfunction.

The varied clinical manifestations of TTP and HUS are related to differing proclivities for thrombus formation in specific microvascular beds.

Clinical expression

- thrombotic thrombocytopenic purpura (TTP)

  • TTP is cmically associated with the pentad of fever, thrombocytopenia, microangiopathic hemolytic anemia, transient neurologic deficits, and renal failure.

- hemolytic and uremic syndrome (HUS)

  • HUS is also associated with microangiopathic hemolytic anemia and thrombocytopenia but is clinically distinguished from TTP by the absence of neurologic symptoms, the prominence of acute renal failure, and frequent affliction of children.

Etiology (Exemples)

- bone marrow allograft-associated thrombotic microangiopathy (#15153944#, #15077133#, #10455370#)

  • stem cell transplantation (SCT) (#15877808#)
  • combined bone marrow autograft-allograft (#15693795#)

- drug-induced thrombotic microangiopathy (TMA)

  • sirolimus-induced thrombotic microangiopathy (#16162193#)

- metabolic diseases

  • cblC type of combined methylmalonic aciduria and homocystinuria (MIM.277400)

Localization

- renal TMA
- intestinal TMA (#15077133#)

References

- Moake JL. Thrombotic microangiopathies. N Engl J Med. 2002 Aug 22;347(8):589-600. PMID: #12192020#