Increased Hemostatic Molecular Markers in Patients Undergoing Anticoagulant Therapy

ABSTRACT

We evaluated several molecular markers of hemostasis in 92 patients with hypercoagulable states treated with anticoagulant therapy. In all patients, the average values of the international normalized ratio (INR) were 1.70 ± 0.50; this increase in INR was not, however, significant in patients under thrombotest (TT) monitoring. There were no thrombotic or severe bleeding complications in these patients during a period of 27 months. Plasma levels of thrombin-antithrombin complex (TAT), plasmin-plasmin inhibitor complex (PPIC), D-dimer, and soluble fibrin monomer (sFM) were slightly increased, suggesting that anticoagulant therapy was not completely effective in our Japanese patients based on the values of the TT. The INR was negatively correlated with TT, protein C, and protein S and particularly with TT between 10 and 80%. The range of TT was not correlated with the plasma level of TAT, PPIC, D-dimer, or sFM, but the range of INR was correlated with the plasma level of TAT, D-dimer, and sFM. The percentage of TAT, D-dimer, and sFM within normal range was significantly lower in patients with high INR. These findings show that INR is better than TT for the monitoring of warfarin therapy and that the therapeutic values of INR during the anticoagulant therapy should be > 1.7 in Japanese patients.

KEYWORD

D-dimer - anticoagulant therapy - INR - thrombotest

REFERENCES

• 1 Duvoisin G E, Brandenburg R O, McGoon D C. Factors affecting thromboembolism associated with prosthetic heart valves.  Circulation . 1967;  70-76 (70-76)
• 2 Akbarian M, Austen W G, Yurchak P M, Scannel J G. Thromboembolic complications of prosthetic cardiac valves.  Circulation . 1968;  37 826-831
• 3 Edmunds L H. Thrombotic and bleeding complications of prosthetic heart valves.  Ann Thorac Surg . 1987;  44 430-445
• 4 Hirsh J, Ginsberg J S, Marder V J. Anticoagulant therapy with coumarin agents. In: Colman RW, Hirsh J, Marder VJ, Salzman EW, eds. Hemostasis and Thrombosis. Basic Principles and Clinical Practice, 3rd ed Philadelphia: Lippincott, 1994: 1567-1583
• 5 Fuster V, Badimon L, Badimon J J, Chesebro J. Prevention of thromboembolism induced by prosthetic valves.  Semin Thromb Hemost . 1988;  14 50-58
• 6 Stein P D, Kantrowitz A. Antithrombotic therapy in mechanical and biological prosthetic heart valves and saphenous vein bypass grafts.  Chest . 1989;  107-117 (107-117)
• 7 Loeliger E A, Poller L, Samama M. Questions and answers on prothrombin time standardisation in oral anticoagulant control.  Thromb Haemost . 1985;  54 515-517
• 8 British Society for Haemotology. British Committee for Standards in Haematology, Haemostasis and Thrombosis Task Force. Guidelines on oral anticoagulation: Second edition.  J Clin Pathol . 1990;  43 177-183
• 9 Pengo V, Barbero F, Banzato A. A comparison of a moderate with moderate-high intensity oral anticoagulant treatment in patients with mechanical heart valve prosthese.  Thromb Haemost . 1997;  77 839-844
• 10 Petersen P, Godtfredsen J, Boysen G, Andersen E D, Andersen B. Placebo-controlled randomised trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation. The Copenhagen AFASAK study.  Lancet . 1989;  28 175-179
• 11 The Boston Area Anticoagulation Trial for Atrial Fibrillation Investigators. The effect of low-dose warfarin on the risk of stroke in patients with nonrheumatic atrial fibrillation.  N Engl J Med . 1990;  323 1505-1511
• 12 Stroke Prevention in Atrial Fibrillation Investigators. Stroke prevention in atrial fibrillation study. Final results.  Circulation . 1991;  84 527-539
• 13 Connolly S J, Laupacis A, Gent M, for the CAFA study coinvestigators. Canadian atrial fibrillation anticoagulation (CAFA) study.  J Am Coll Cardiol . 1991;  18 349-355
• 14 Ezekowitz M D, Bridgers S L, James K E. Warfarin in the prevention of stroke associated with nonrheumatic atrial fibrillation.  N Engl J Med . 1992;  327 1406-1412
• 15 Schluman S, Rhedin A-S, Lindmarker P. A comparison of six weeks with six months of oral anticoagulant therapy after a first episode of venous thromboembolism.  N Engl J Med . 1995;  332 1661-1665
• 16 Prandoni P, Lensing A WA, Cogo A. The long term clinical cause of acute deep venous thrombosis.  Ann Intern Med . 1996;  125 1-7
• 17 Schulman S. Optimal duration of oral anticoagulant therapy in venous thromboembolism.  Thromb Haemost . 1997;  78 693-698
• 18 Minamikawa K, Wada H, Wakita Y. Increased activated protein C- protein C inhibitor complex levels in patients with pulmonary embolism.  Thromb Haemost . 1994;  71 192-194
• 19 Tanigawa M, Wada H, Minamikawa K. Decreased protein C inhibitor after percutaneous transluminal coronary angioplasty in patients with acute myocardial infarction.  Am J Hematol . 1995;  49 1-5
• 20 Wada H, Minamikawa K, Wakita Y. Hemostatic study before onset of disseminated intravascular coagulation.  Am J Hematol . 1993;  43 190-194
• 21 Wada H, Wakita Y, Nakase T. Increased plasma or soluble fibrin monomer levels in patients with disseminated intravascular coagulation.  Am J Hematol . 1996;  51 255-260
• 22 Dahlbäck B, Carlson M, Svensson P J. Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C.  Proc Natl Acad Sci USA . 1993;  90 1004-1008
• 23 Rosendaal F R, Koster T, Vandenbrouke J P, Reitsma P H. High risk of thrombosis in patients with homozygous factor V Leiden (activated protein C resistance).  Blood . 1995;  85 1504-1508