Thromb Haemost 1979; 42(04): 1276-1285
DOI: 10.1055/s-0038-1657022
Original Article
Schattauer GmbH Stuttgart

Thrombin Time Dilution Test: A Simple Method for the Control of Heparin Therapy[*]

Javier Pizzuto
The Hospital General and from the Hospital de Enfermedades del Tórax, Centro Médico, Nacional, Instituto Mexicano del Seguro Social, Mexico City, México
,
Sergio Garcìa-Méndez
The Hospital General and from the Hospital de Enfermedades del Tórax, Centro Médico, Nacional, Instituto Mexicano del Seguro Social, Mexico City, México
,
Marìa de-la-Paz Reyna
The Hospital General and from the Hospital de Enfermedades del Tórax, Centro Médico, Nacional, Instituto Mexicano del Seguro Social, Mexico City, México
,
Manuel R Morales
The Hospital General and from the Hospital de Enfermedades del Tórax, Centro Médico, Nacional, Instituto Mexicano del Seguro Social, Mexico City, México
,
Agustìn Avilés
The Hospital General and from the Hospital de Enfermedades del Tórax, Centro Médico, Nacional, Instituto Mexicano del Seguro Social, Mexico City, México
,
Beatrìz Zavala
The Hospital General and from the Hospital de Enfermedades del Tórax, Centro Médico, Nacional, Instituto Mexicano del Seguro Social, Mexico City, México
,
Carlos Gaos
The Hospital General and from the Hospital de Enfermedades del Tórax, Centro Médico, Nacional, Instituto Mexicano del Seguro Social, Mexico City, México
› Author Affiliations
Further Information

Publication History

Received May 1978

Accepted 11 June 1978

Publication Date:
23 August 2018 (online)

Summary

A modification of the thrombin time test (TT), which permits quantitative measurement of plasma heparin activity during therapy is described. The prolonged TT of plasma containing heparin can be corrected by dilution with platelet-rich plasma (PRP). Clinical heparin activity is considered adequate when prolonged TT of the plasma can be corrected at dilutions of from 1:4 to 1:8 (±20%). In vitro studies of 30 PRP samples containing different amounts of heparin showed that 1:4 and 1:8 dilutions did not correct prolonged TT (P<0.05) in the presence of more than 0.2 and 0.3 U of heparin/ml respectively, indicating that the adequate dose of heparin should fall between those levels which show correction at these dilutions, using the diluted TT method.

Patients treated with 100 U of heparin/kg every 4 or 6 h were studied: 52 without previous coagulation defects and 22 with disseminated intravascular coagulation (DIC). The results in the first group showed adequate dosage in 29 cases, overdosage in 12 and underdosage in 11. Hemorrhage occurred in 5 of the overdosage group. In the DIC series, 4 with underdosage of heparin did not improve; in 13 of 18 with adequate dosage, both hemorrhage and coagulapathy disappeared, while the other 5, with more severe complications did not improve. Based on these findings, the diluted TT appears to be a useful test in the assessment of heparin therapy, even in patients with previous coagulation abnormalities.

*Presented in part at the Vlth International Congress of Hemostasis and Thrombosis, Philadelphia, Pa., June, 1977.


 
  • References

  • 1 Abildgaard ChF, Harrison J. 1972; Simultaneous use of multiple fibrometers for coagulation factor and heparin assays. American Journal of Clinical Pathology 58: 272
  • 2 Bacle G, De Broe M, De Weerdt CA, Ringoir S, Barbier F. 1972; Limitations of the activated partial thromboplastin time for determination of plasma heparin concentration and halflife in human subjects. Thrombosis 27: 107
  • 3 Basu D, Gallus A, Hirsh J, Cade J. 1972; A prospective study of the value of monitoring heparin treatment with the activated partial thromboplastin time. New England Journal of Medicine 287: 324
  • 4 Bauer G. 1969; Clinical experiences of a surgeon in the use of heparin. American Journal of Cardiology 14: 29
  • 5 Congdon JE, Kardinal CG, Wallin JD. 1973; Monitoring heparin therapy in hemodialysis. A report on the activated whole blood coagulation time tests. Journal of the American Medican Association 226: 1529
  • 6 Denson KW E, Bonnar J. 1973; The measurement of heparin. A method based on the potentiation of anti-factor Xa Thrombosis et Diathesis Haemorrhagica (Stuttgart) 30: 471
  • 7 Eika C, Godal HC, Kierulf P. 1972; Detection of small amounts of heparin by the thrombin clotting-time. Lancet 2: 376
  • 8 Gallus AS, Hirsh J. 1976; Treatment of venous thromboembolism. Seminars in Thrombosis and Hemostasis 2: 291
  • 9 Godal HC. 1960; A comparison of two heparin-neutralizing agents: protamine and polybrene. Scandinavian Journal of Clinical and Laboratory Investigation 12: 446
  • 10 Godal HC. 1974; Heparin assay methods for control of in vivo heparin effects. Thrombosis et Diathesis Haemorrhagica (Stuttgart) 33: 77
  • 11 Gurewich V, Thomas DF, Stuart RK. 1967; Some guide-lines for heparin therapy of venous thromboembolic disease. Journal of the American Medical Association 199: 116
  • 12 Handley AJ. 1974; Heparin therapy. A simpler test of control Journal of Clinical Pathology 27: 250
  • 13 Hirsh J, Gallus AS. 1973; The activated partial thromboplastin time. New England Journal of Medicine 288: 1410
  • 14 Howell WH, Holt E. 1918; Two new factors in blood coagulation heparin and proantithrombin. American Journal of Physiology 47: 328
  • 15 Jim RT S. 1957; A study of the plasma thrombin time. Journal of Laboratory and Clinical Medicine 50: 45
  • 16 Jiménez R, Atmentlla F. 1975; Comparaci�n de métodos para el control de laboratorio de la terapia con heparina. Bolet�n Médico del Hospital Infantil (México) 32: 977
  • 17 Kennedy CC, Rocks MJ. 1973; Bedside control of heparin therapy by a simple whole blood clotting method. Journal of Clinical Pathology 26: 893
  • 18 Lee RI, White PD. 1913; A clinical study of coagulation time of whole blood. American Journal of the Medical Sciences 145: 495
  • 19 Marder VJ. 1970; A simple technique for the measurement of plasma heparin concentration during anticoagulant therapy. Thrombosis et Diathesis Haemorrhagica (Stuttgart) 24: 230
  • 20 McLean J. 1916; The thromboplastic action of cephalin. American Journal of Physiology 41: 250
  • 21 O’sullivan EF, Hirsh J, McCarthy RA, De Gruchy GC. 1968; Heparin in the treatment of venous thromboembolic disease administration, control and results. Medical Journal of Australia 2: 153
  • 22 Owen Jr CA, Mann FD, Hurn MM, Stickney JM. 1955; Evaluation of disorders of blood coagulation in the clinical laboratory. American Journal of Clinical Pathology 25: 1417
  • 23 Pitney WR, Pettit JE, Armstrong L. 1970; Control of heparin therapy. British Medical Journal 4: 139
  • 24 Poller L. 1969. Progress in laboratory control of anticoagulant treatment. In Poller L. (Ed.) Recent Advances in Blood Coagulation. J. A. Churchill, L.T.D; London: p 137
  • 25 Proctor RR, Rapaport SI. 1961; The partial thromboplastin time with Kaolin. American Journal of Clinical Pathology 36: 212
  • 26 Rapaport SI, Ames SB. 1957; Clotting factor assays on plasma from patients receiving intramuscular or subcutaneous heparin. American Journal of the Medical Sciences 234: 678
  • 27 Ray PK, Harper TA. 1971; Comparison of activated recalcification and partial thromboplastin tests as controls of heparin therapy. Journal of Laboratory and Clinical Medicine 77: 901
  • 28 Reno J, Rotman K, Grumbine FC, Dennis LH, Mohler ER. 1974; Evaluation of the BART test (a modification of the whole-blood activated recalcification time test) as a means of monitoring heparin therapy. American Journal of Clinical Pathology 61: 78
  • 29 Rizza CR, Matthews JM. 1972; Management of the haemophilic child. Archives of Diseases of Childhood 47: 451
  • 30 Salzman EW, Deykin D, Shapiro RM, Rosenberg R. 1975; Management of heparin therapy. Controlled prospective trial New England Journal of Medicine 292: 1046
  • 31 Schatz IJ, Hathaway JC. 1963; Heparin therapy and thrombin times. Journal of the American Medical Association 186: 740
  • 32 Schriever HG, Epstein SE, Mintz MD. 1974; Statistical correlation and heparin sensitivity of activated partial thromboplastin time, whole blood coagulation time, and an automated coagulation time. American Journal of Clinical Pathology 60: 323
  • 33 Snedeco G, Cochran W. 1974; Métodos estad�sticos. Cía. Editorial Continental. México pág 336
  • 34 Soloway HB, Belliveau RR, Grayson Jr JW, Butler TJ. 1972; The in vitro effect of heparin on the activated partial thromboplastin time. American Journal of Clinical Pathology 58
  • 35 Soloway HB, Carnett BM, Grayson Jr JW. 1973; Comparison of various activated partial thromboplastin reagents in the laboratory control of heparin therapy. American Journal of Clinical Pathology 59: 587
  • 36 Spector I, Corn M. 1967; Control of heparin therapy with activated partial thromboplastin times. Journal of the American Medical Association 201: 157
  • 37 Sue TK, Jaques LB. 1973; An improved microprocedure for the determination of heparin. Canadian Journal of Physiology and Pharmacology 51: 994
  • 38 Teien AN, Abildgaard U. 1976; On the value of the activated partial thromboplastin time (APTT) in monitoring heparin therapy. Thrombosis and Haemostasis (Stuttgart) 35: 592
  • 39 Ts Ao ChH, Raymond J, Kolf T, Lo R. 1976; Effects of source and concentration of thrombin, and divalent cations, on thrombin time of heparinized plasma. American Journal of Clinical Pathology 65: 206
  • 40 Wessler S, Yin ET, Flute PT, Kakkar VV. 1972; Thrombin-time test. Lancet 11: 877
  • 41 Yin ET, Wessler S, Butler JV, Cole S. 1973; Plasma heparin: A unique, practical, submicrogram-sensitive assay. Journal of Laboratory and Clinical Medicine 81: 298
  • 42 Youssef A, Barkhan P. 1968; Relase of Platelet Factor 4 by Adenosine Diphosphate and other Platelet-agregatin agents. British Medical Journal 1: 746
  • 43 Zucker S, Cathey MH. 1969; Control of heparin therapy. Sensitivity of activated partial thromboplastin time for monitoring the antithrombotic effects of heparin Journal of Laboratory and Clinical Medicine 73: 320