aPTT in Heparinized Plasma: Influence of Reagent,Acute-Phase Reaction,and Interval Between Sampling and Testing

Abstract

Plasma samples from 10 healthy persons and 10 patients with acute-phase reaction were heparinized in vitro to obtain 0.00-0.70 U/ml. The activated partial thromboplastin time (aPTT) was then determined, using an optical method (Automated Coagulation Laboratory) and four reagents (actin, Cephotest, Platelin, and Throm bosil). The heparin sensitivity showed variation between individuals and was lower in acute-phase plasma than in normal plasma. There was also a marked difference in heparin sensitivity among the different reagents; actin was the least sensitive reagent, while Platelin was the most sensitive reagent in normal plasma and Thrombosil the most heparin-sensitive reagent in acute-phase plasma. Delay in testing prolonged the aPTT values in both acute- phase and normal heparinized plasma. With actin and Ce photest, a delay of 90 min at 22°C resulted in 30-50% prolongation of the aPTT. A delay of 150 min caused a prolongation of 75-110% with actin. Cephotest, Platelin, and Thrombosil were less prolonged. Ex vivo samples from heparinized plasma showed similar degrees of pro longation. Storage at 4°C resulted in less prolongation. Assuming a therapeutic range of 0.35-0.70 U/ml of hep arin, the therapeutic aPTT ratio ranges in heparinized, acute-phase plasma were 1.5-3.0 for actin and 2.5-4.5 for Cephotest, Platelin, and Thrombosil. These results un derscore certain limitations in monitoring heparin therapy with the aPTT system. Unless the assay is performed within 30 min after sampling, unduly prolonged aPTT val ues will be recorded. This may lead to underdosing of the patient.

Keywords

Key Words: Activated partial thromboplastin time Acute-phase reaction Deep venous thrombosis Drug monitoring Heparin.

Get full access to this article

View all access options for this article.

References

Brandt J. , Triplett D. Laboratory monitoring of heparin. Effect of reagents and instruments on activated partial thromboplastin time. Am Soc Clin Pathol 1981;76:530-7.

Hirsh J. , Dalen JE , Deykin D. Heparin: mechanism of action, pharmacokinetics, dosing considerations, monitoring, efficacy and safety. Chest 1992 ;4(Suppl):337-51.

Marci C. , Pager D. A review of the clinical indication for the plasma heparin assay. Am J Clin Pathol 1993;99:546-50.

Hull RD , Raskob GE , Rosenbloom D. Optimal level of heparin therapy in patients with deep venous thrombosis . Arch Intern Med 1992;152:1589-95.

Scialla S. Heparin monitoring by activated partial thromboplastin time. Am J Clin Pathol 1985;84:351-4.

Bjørnsson T. , Nash P. Variability in heparin sensitivity of aPTT reagents. Am J Clin Pathol 1986;86:199-204.

Bratt G. , Aberg W. , Johansson M. Two daily subcutaneous injections of Fragmin as compared with intravenous standard heparin in the treatment of deep venous thrombosis. Thromb Haemost 1990;64:506-10.

Koepke JA , Triplett DA , Banez G. The partial thromboplastin time for monitoring heparin therapy. In: Lundblad RL , Brown WV , Mann KG , Roberts HR , eds. Chemistry and biology of heparin. New York : Elsevier/North-Holland , 1981 :625-34.

Poller L. , Thomson JM Standardization of prothrombin time and partial thromboplastin time. Disorders of thrombin formation. In: Coleman RW , ed. New York: Churchill Livingstone , 1983:53-83.

10.

Thomsen JM The control of heparin therapy by the activated partial thromboplastin time: results of collaborative studies. Scand J Haematol 1980;25(Suppl):73-83.

11.

Bjørnsson TD Clinical pharmacology of heparin. In Turner P , Shand DG , eds. Recent advances in clinical pharmacology, Vol 3. Edinburgh: Churchill Livingstone , 1983:129-55.

12.

Holm HA , Abildgaard U. , Kalvenes S. , et al. The antithrombotic effect of heparin in deep venous thrombosis: relation to four heparin assays. Acta Med Scand 1984;216:287-93.

13.

Levine MN , Hirsh J. , Gent M. , et al. A randomized trial comparing activated thromboplastin time with heparin assay in patients with acute venous thromboembolism requiring large daily doses of heparin. Arch Intern Med 1994 ;154:49-56.

14.

Holm AH , Abildgaard U. , Kalvenes S. Heparin assays and bleeding complications in treatment of deep venous thrombosis with particular reference to retroperitoneal bleeding. Thromb Haemost 1985;55:278-81.

15.

Holm H. , Abildgaard U. Heparin treatment of deep venous thrombosis; correlation between clinical effects and heparin assays. In: Witt I , ed. Heparin. New biochemical and medical aspects. New York: Walter de Gruyter, 1982 :291-300.

16.

Hyers TM , Hull RD , Weg JG Antithrombotic therapy for venous thromboembolic disease. Chest 1992;102(Suppl): 408-25.

17.

Hirsh J. Heparin. N Engl J Med 1991;324:1565-74.

18.

Hirsh J. Antithrombotic therapy in deep vein thrombosis and pulmonary embolism . Am Heart J 1992;123:1115-22.

19.

Dahms RA , Wallace J. Heparin sensitivity study using three APTT reagents on the automated blood coagulation analyzer CA-1000™, Sysmex J. Int 1993;3:160-2.

20.

Van der Velde EA , Poller L. The APTT monitoring of heparin—the ISTH/ICSH collaborative study. Thromb Haemost 1995;73(1):73-81.

21.

Teien AN , Lie M. Heparin assay in plasma: a comparison of five clotting methods. Thromb Res 1975;7:777-88.

22.

Teien A. , Lie M. Evaluation of an amidolytic heparin assay method: increased sensitivity by adding purified antithrombin III. Thromb Res 1977;10:399-410.

23.

Van Putten JJ. Interindividual variation in relationship between heparin concentration and the results of five heparin assays. Clin Chem Acta 1982;122:261-70.

24.

Abildgaard U. , Norrheim L. , Larsen AE Monitoring therapy with LMW heparin: a comparison of three chromogenic substrate assays and the Heptest clotting assay. Haemostasis 1990;20:193-203.