External quality assessment for thrombin generation tests: an exploration

Semin Thromb Hemost. 2010 Oct;36(7):791-6. doi: 10.1055/s-0030-1265296. Epub 2010 Oct 26.

Abstract

External Quality Control of Diagnostic Assays and Tests (ECAT) surveys on thrombin generation rests (TGTs) have identified that various tests show a more than 30-fold difference in time to peak (TTP). The survey included pooled normal plasmas, microparticle (MP)-depleted plasmas, and factor (F)XII-deficient patient plasma. Between 4 and 11 laboratories participated per test; analyzed were a time (TTP) and quantity variable (AUC). MP depletion of plasma showed a progressive increase in TTP up to 29% with a decreasing tissue factor. The same was found for the AUC with the largest decrease of 38%. It was observed that MP depletion showed large individual differences. The FXII-deficient plasma showed no effect on TTP for rapid tests, but for slow tests it increased from 248 to 331%. The AUC declined gradually the slower the test, reaching a decline of 85%. The effects of FXII deficiency were not mimicked by the addition of corn trypsin inhibitor but were confirmed by inhibiting activated FXI. Interlaboratory variability was between 11% and 57% for all methods, showing differences mainly related to the used normal pooled plasma. The different sensitivities of TGTs to MPs and contact activation predict that they will associate differently with clinical situations, according to which of these aspects are important. Future ECAT surveys should include samples with variation in MPs and contact activation to match with features of the TGT variants.

Publication types

  • Review

MeSH terms

  • Blood Coagulation Disorders / blood
  • Blood Coagulation Disorders / diagnosis
  • Blood Coagulation Tests / methods*
  • Blood Coagulation Tests / standards
  • Humans
  • Quality Control
  • Thrombin / metabolism*

Substances

  • Thrombin