Pathology Associates Of Lexington, P.A.
Pathology Associates Of Lexington, P.A.
Pathology Associates Of Lexington, P.A.
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        anti-ADAMTS-13 antibody test, blood
      
HUS/TTP

Endothelial injury triggers these two disorders which sit on the ends of a clinical spectrum. Stellate Ito cells in the liver produce2 ADAMTS13, the deficit of which is involved in TTP. Microvascular thromboses cause microangiopathic RBC changes seen in blood smears. In TTP, the microthrombi occur throughout the microcirculation; and microvascular thromboses may be found in the brain, skin, intestines, skeletal muscle, pancreas, spleen, adrenals, and heart...CNS findings alert to the TTP end of the spectrum. On the other hand, in HUS, microthrombi are essentially confined to the kidneys.

In most cases of familial TTP and acquired idiopathic TTP, the endothelial cells become stimulated to secrete and release the ultra-large (UL) von Willebrand factor (ULVWF) multimers. There is a congenital variant. Acquired is commonly due to E. coli (O157:H7) (see CN-06-58). The sheering stress of fluid and platelet thrombi in the microcirculation should enhance proteolysis of ULVWF. The agitated endothelial cells are the main source of ULVWF multimers in the bloodstream where they bind to specific surface platelet receptors. In 1982, Moake, et. al., showed that the ULVWF multimers were unusually large in patients with chronic relapsing TTP. ULVWF multimers entangle with platelets adhering to the subendothelium. Two independent research groups reported a lack of ULVWF-cleaving protease activity in the blood of patients with TTP. The lack of ULVWF-cleaving protease activity was suggested to be (1) due to the presence of antibodies or (2) a severe deficiency of ULVWF-cleaving protease.

The ULVWF multimers are cleaved by the protease, ADAMTS-13, as they are secreted from endothelial cells. Failure to degrade the ULVWF multimers is believed to cause the familial and acquired idiopathic types of TTP. The ULVWF-cleaving protease, ADAMTS-13, is (1) presumed inhibited by the production of autoantibodies in acquired idiopathic TTP and (2) ADAMTS-13 gene mutations in familial TTP causing inactivity or decreased activity of ADAMTS-13.  In TTP, insufficiency of ADAMTS-13 may be the key component in the pathogenesis of ULVWF multimer–induced platelet thrombosis.

TTP differs from HUS by having a deficiency in ULVWF-cleaving protease ADAMTS-13 activity, a deficit not found in HUS, HUS having sufficient uninhibited protease. The intervention of plasma exchange is ineffective in HUS because the role of exchange in TTP is to (1) remove antibodies and (2) replace VWF-cleaving protease. Differentiating TTP from HUS benefits the patient because plasma exchange is not a benign intervention. This differentiation also saves costs and time. Research is ongoing; but, presently, TTP is suggested to be a different entity than HUS.

ULVWF multimers are abundant and fibrinogen/fibrin turnover is minimal in TTP, whereas fibrinogen/fibrin turnover is abundant in disseminated intravascular coagulation (DIC). The ULVWF multimer is a marker found in the plasma of patients most likely to have a recurrence of TTP. TTP can occur during pregnancy and is to be differentiated from the toxemia-related HELLP syndrome.

HUS is treated with supportive measures while TTP is treated by plasmapheresis.

CAUSES of HUS/TTP3:

  1. idiopathic.
  2. post-diarrhea due to entero. E. coli 0157:H7 (mainly childhood HUS)
  3. drug induced: quinine, Ticlopidine, Clipidogrel, chemotherapeutic agents, immunosuppressants, oral contraceptives, & valacyclovir.
  4. pregnancy & post-partum associated.
  5. AIDS & early symptomatic HIV.
  6. Autoimmune disease .
  7. Conditioning regimines for hematopoietic stem-cell transplantation.

References:

  1. check the eMedicine website:

  2. Zhou W, et. al., ADAMTS13 is Expressed in Hepatic Stellate Cells, Lab. Invest. 85:780-788, June 2005 (noted in June 2005 Modern Pathology).

  3. Sebastian A, et. al., "Thrombocytopenia and Elevated Bilirubin...," Labmedicine 38(10):610-612, October 2007
(posted 28 May 2005; addition 20 October 2007)
 
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