Subscribe to RSS
DOI: 10.1055/s-0038-1653754
Effects of Two Different Doses of Hirudin on APTT, Determined with Eight Different Reagents
Publication History
Received 19 May 1994
Accepted after resubmission 20 October 1994
Publication Date:
09 July 2018 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/199502/lookinside/thumbnails/10-1055-s-0038-1653754-1.jpg)
Summary
The APTT has been considered the most suitable candidate to monitor the anticoagulant activity of hirudin. However, its use is hampered by problems of standardization, which make the results heavily dependent on the responsiveness of the reagent used. Our aim was to investigate if this different responsiveness of different reagents when added in vitro is to be confirmed in an ex vivo study.
Two different doses of r-hirudin (CGP 39393), 0.3 mg/kg and 1 mg/kg, were administered subcutaneously to 20 New Zealand male rabbits, and the differences in prolongation of APTT 2 and 12 h later were compared, using 8 widely used commercial reagents. All groups exhibited a significant prolongation of APTT 2 h after sc administration of hirudin, both at low and high doses. But this prolongation persisted 12 h later only when the PTTa reagent (Boehringer Mannheim) was used. In general, hirudin prolonged the APTT most with the silica- based reagents.
In a further study, we compared the same APTT reagents in an in vitro study in which normal pooled plasma was mixed with increasing amount of hirudin. We failed to confirm a higher sensitivity for silica- containing reagents. Thus, we conclude that subcutaneous administration of hirudin prolongs the APTT most with the silica-based reagents, but this effect is exclusive for the ex vivo model.
-
References
- 1 Walenga JM, Hoppensteadt D, Koza M, Wallock M, Pifarre R, Fareed J. Laboratory assays for the evaluation of recombinant hirudin. Haemostasis 1991; 21 Suppl (Suppl. 01) 49-63
- 2 Spannagl M, Bicher H, Lill H, Schramm W. A fast photometric assay for the determination of hirudin. Haemostasis 1991; 21 Suppl (Suppl. 01) 36-40
- 3 Marki WE, Wallis RB. The anticoagulant and antithrombotic properties of hirudins. Thromb Haemost 1990; 64: 334-348
- 4 Tripodi A, Chantarangkul V, Arbini AA, Moia M, Mannucci PM. Effects of hirudin on activated partial thromboplastin time determined with ten different reagents. Thromb Haemost 1993; 70 (02) 286-288
- 5 Monreal M, Galego G, Monreal L, Angles AM, Monasterio J, Oiler B. Comparative study on the antithrombotic efficacy of hirudin, heparin and a low-molecular weight heparin in preventing experimentally induced venous thrombosis. Haemostasis 1993; 23: 179-183
- 6 Monreal M, Angles AM, Monreal L, Roncales J, Monasterio J. Effects of r-hirudin on D-Dimer levels before and after venous thrombosis. Haemostasis 1994; 24: 338-343
- 7 Doutremepuich C, Lalanne MC, Doutremepuich F, Walenga J, Fareed J, Breddin HK. Comparative study of three recombinant hirudins with heparin in an experimental venous thrombosis model. Haemostasis 1991; 21 Suppl (Suppl. 01) 99-106
- 8 Agnelli G, Renga C, Weitz JI, Nenci GG, Hirsh J. Sustained antithrombotic activity of hirudin after its plasma clearance: Comparison with heparin. Blood 1992; 80: 960-965
- 9 Parent F, Bridey F, Dreyfus M, Musset D, Grimon G, Duroux P, Meyer D, Simonneau G. Treatment of severe venous thrombo-embolism with intravenous hirudin (HBW 023): An open pilot study. Thromb Haemost 1993; 70 (03) 386-388
- 10 Schiele F, Vuillemenot A, Kramarz Ph, Kieffer Y, Soria J, Soria C, Camez A, Mirshahi MC, Bassand JP. A pilot study of subcutaneous recombinant hirudin (HBW 023) in the treatment of deep vein thrombosis. Thromb Haemost 1994; 71 (05) 558-562
- 11 Gray E, Watton J, Cesmeli S, Barrowcliffe TW, Thomas DP. Experimental studies on a recombinant hirudin, CGP 39393. Thromb Haemost 1991; 65 (04) 355-359