Thromb Haemost 1993; 70(05): 794-799
DOI: 10.1055/s-0038-1649672
Coagulation
Schattauer GmbH Stuttgart

Multi-Center Study of Replacement of the International Reference Preparation for Thromboplastin, Rabbit, Plain

A M. H. P van den Besselaar
The Haemostasis and Thrombosis Research Center, Department of Haematology, Leiden University Hospital, Leiden, The Netherlands
› Author Affiliations
Further Information

Publication History

Received 04 February 1993

Accepted after revision 15 June 1993

Publication Date:
05 July 2018 (online)

Summary

A multi-center study of the three W.H.O. international reference preparations (IRP) for thromboplastin has been performed. The main purpose of the study was the determination of the mean international sensitivity index (ISI) of a proposed replacement IRP for thromboplastin, rabbit, plain. Twenty laboratories in Europe, North America, and Australasia participated in the study. All clotting times were determined with the manual technique. The inter-laboratory variation of the ISI was considered as the relevant parameter for assessment of ISI precision. Low interlaboratory variation was observed in the calibration of rabbit thromboplastin against rabbit thromboplastin (2.9-3.0% coefficient of variation of calibration line slope). Relatively high interlaboratory variation was observed in the calibration of rabbit against human thromboplastin (3.7–7.2 CV). Intermediary interlaboratory variation was obtained in the comparison of rabbit or human plain thromboplastin with bovine combined thromboplastin (3.5-4.0% CV). These findings confirm the principle of like-to-like calibration in biological standardization.

The mean ISI values based on the IRP for rabbit thromboplastin (RBT/79) are in excellent agreement with those obtained with the IRP for bovine thromboplastin (OBT/79). In contrast, the mean ISI values determined with the IRP for human thromboplastin (BCT/253) were 6% lower than those with RBT/79. This bias may be caused by a difference in design of the two historical calibration studies. The mean ISI of the proposed replacement IRP for thromboplastin, rabbit, plain obtained by calibration against RBT/79 was 1.035 (standard error: 0.027). It is recommended to round the mean ISI off to 1.0.

Opportunity was also taken to compare a lyophilized normal pooled plasma with fresh individual normal plasmas. The mean PT-ratio of this lyophilized plasma obtained with RBT/79, and BCT/253 was 1.02, which was slightly but significantly higher than the mean PT-ratio obtained with OBT/79 (0.99).

INR equivalents were determined for a lyophilized pooled plasma derived from patients treated with oral anticoagulants. There were small but significant differences between the various thromboplastins, which may be caused by slight activation of the plasma or by the lyophilization process.

 
  • References

  • 1 WHO Expert Committee on Biological Standardization. Thirty-third Report. WHO Tech Rep Ser. 1983: 81-105
  • 2 Kirkwood TBL. Calibration of reference thromboplastins and standardisation of the prothrombin time ratio. Thromb Haemostas 1983; 49: 238-244
  • 3 Lewis SM. Thromboplastin and Oral Anticoagulant Control. Br J Haematol 1987; 66: 1-4
  • 4 Hermans J, Van den Besselaar AMHP, Loeliger EA, Van der Velde EA. A collaborative calibration study of reference materials for thromboplastins. Thromb Haemostas 1983; 50: 712-717
  • 5 Thomson JM, Tomenson JA, Poller L. The calibration of the second primary international reference preparation for thromboplastin (thromboplastin, human, plain, coded BCT/253). Thromb Haemostas 1984; 52: 336-342
  • 6 WHO Expert Committee on Biological Standardization. Thirty-fourth Report. WHO Tech Rep Ser. 1984: 19
  • 7 Van den Besselaar AMHP, Lewis SM, Mannucci PM, Poller L. Status of present and candidate international reference preparations (IRP) of thromboplastin for the prothrombin time. Thromb Haemostas 1993; 69: 85
  • 8 Van den Besselaar AMHP, Bertina RM. Multi-center calibration of the second reference material for thromboplastin, rabbit, plain, Coded CRM 149R. Thromb Haemostas 1991; 65: 263-267
  • 9 Van den Besselaar AMHP, Bertina RM. Multi-center study of thromboplastin calibration precision. Influence of Reagent Species, Composition, and International Sensitivity Index (ISI). Thromb Haemostas 1993; 69: 35-40
  • 10 Wissenschaftliche Tabellen, Teilband Statistik. 8. Auflage. Geigy Basel. 1980 par. 13B 206-207 and Table A, 51
  • 11 Reijnierse GLA, Van den Besselaar AMHP, Hermans J. Een nieuw verwerkingsprogramma van ingezonden uitslagen in het kader van externe kwaliteitsbewaking. Ervaringen in 1988. Tijdschr NVKC 1989; 14: 131-136
  • 12 Steigstra H, Jansen RTP, Baadenhuijsen H. Combi Scheme: New combined internal/external quality-assessment scheme in the Netherlands. Clin Chem 1991; 37: 1196-1204