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.
KEYWORDS
Thrombin generation test - external quality assessment - microparticles - factor XII
REFERENCES
-
1
Hemker H C, Giesen P, AlDieri R et al..
The calibrated automated thrombogram (CAT): a universal routine test for hyper- and hypocoagulability.
Pathophysiol Haemost Thromb.
2002;
32(5–6)
249-253
-
2
Hron G, Kollars M, Binder B R, Eichinger S, Kyrle P A.
Identification of patients at low risk for recurrent venous thromboembolism by measuring thrombin generation.
JAMA.
2006;
296(4)
397-402
-
3
Devreese K, Wijns W, Combes I, Van kerckhoven S, Hoylaerts M F.
Thrombin generation in plasma of healthy adults and children: chromogenic versus fluorogenic thrombogram analysis.
Thromb Haemost.
2007;
98(3)
600-613
-
4
Luddington R, Baglin T.
Clinical measurement of thrombin generation by calibrated automated thrombography requires contact factor inhibition.
J Thromb Haemost.
2004;
2(11)
1954-1959
-
5
Spronk H M, Dielis A W, Panova-Noeva M et al..
Monitoring thrombin generation: is addition of corn trypsin inhibitor needed?.
Thromb Haemost.
2009;
101(6)
1156-1162
-
6
Enjeti A K, Lincz L F, Scorgie F E, Seldon M.
Circulating microparticles are elevated in carriers of factor V Leiden.
Thromb Res.
2009;
, December 17 (Epub ahead of print)
-
7
Kluft C, Meijer P, Kret R et al..
Lipids, microparticles and coagulation factors as determinants of lag phase and rate of thrombin generation in plasma.
J Thromb Haemost.
2007;
5(Suppl 2)
PM114
-
8
van Beers E J, Schaap M C, Berckmans R J CURAMA study group et al.
Circulating erythrocyte-derived microparticles are associated with coagulation activation in sickle cell disease.
Haematologica.
2009;
94(11)
1513-1519
-
9
Gerotziafas G T, Depasse F, Busson J, Leflem L, Elalamy I, Samama M M.
Towards a standardization of thrombin generation assessment: the influence of tissue factor, platelets and phospholipids concentration on the normal values of Thrombogram-Thrombinoscope assay.
Thromb J.
2005;
3
16
-
10
Joop K, Berckmans R J, Nieuwland R et al..
Microparticles from patients with multiple organ dysfunction syndrome and sepsis support coagulation through multiple mechanisms.
Thromb Haemost.
2001;
85(5)
810-820
-
11
Scott C F, Schapira M, James H L, Cohen A B, Colman R W.
Inactivation of factor XIa by plasma protease inhibitors: predominant role of alpha 1-protease inhibitor and protective effect of high molecular weight kininogen.
J Clin Invest.
1982;
69(4)
844-852
Cornelis KluftPh.D.
ECAT Foundation
P.O. Box 30, 2300 AA Leiden, The Netherlands
Email: kluft@euronet.nl
