Thromb Haemost 1997; 77(06): 1164-1167
DOI: 10.1055/s-0038-1656131
Fibrinolysis
Schattauer GmbH Stuttgart

Effects of Heparin Therapy on Fibrinolysis in Patients with Pulmonary Embolism

M C Minnema
1   The Center for Hemostasis, Thrombosis, Atherosclerosis and Inflammation Research, Academic Medical Center, Amsterdam, The Netherlands
3   Central Laboratory of the Netherlands Red Cross Blood Transfusion Service and Laboratory for Clinical and Experimental Immunology, University of Amsterdam, Amsterdam, The Netherlands
,
H ten Cate
1   The Center for Hemostasis, Thrombosis, Atherosclerosis and Inflammation Research, Academic Medical Center, Amsterdam, The Netherlands
2   Department of Internal Medicine, Slotervaart Hospital, Amsterdam, The Netherlands
,
E J R van Beek
1   The Center for Hemostasis, Thrombosis, Atherosclerosis and Inflammation Research, Academic Medical Center, Amsterdam, The Netherlands
,
A van den Ende
1   The Center for Hemostasis, Thrombosis, Atherosclerosis and Inflammation Research, Academic Medical Center, Amsterdam, The Netherlands
,
C E Hack
3   Central Laboratory of the Netherlands Red Cross Blood Transfusion Service and Laboratory for Clinical and Experimental Immunology, University of Amsterdam, Amsterdam, The Netherlands
,
D P M Brandjes
1   The Center for Hemostasis, Thrombosis, Atherosclerosis and Inflammation Research, Academic Medical Center, Amsterdam, The Netherlands
2   Department of Internal Medicine, Slotervaart Hospital, Amsterdam, The Netherlands
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received 24. September 1996

Accepted after resubmisssion 12. Februar 1997

Publikationsdatum:
12. Juli 2018 (online)

Summary

Previous investigations suggested that heparin administration to humans enhances the tissue type plasminogen activator (tPA) levels in blood, but it remains uncertain whether this effect induces fibrinolysis. We studied the effect of therapeutic levels of heparinization on plasma markers for fibrinolysis in patients suspected of pulmonary embolism (PE). Blood samples were taken from 49 consecutive patients; 28 had confirmed PE, 21 had PE excluded.

On admission, the plasma levels of plasmin-α2antiplasmin complexes and D-dimer were significantly higher in the patient group with PE compared to those in whom PE was excluded. After heparinization the tPA levels increased in both groups, showing that this effect was not dependent on the initial level of activity of fibrinolysis. In spite of this increment in tPA levels, the concentrations of plasmin-α2antiplasmin complexes and D-dimer decreased.

In conclusion, although heparinization in patients with or without pulmonary embolism does lead to elevated tPA: Ag levels, this is not accompanied by enhanced fibrinolysis.

 
  • References

  • 1 Becker RC, Ansell J. Antithrombotic therapy, an abbreviated reference for clinicians. Arch Intern Med 1995; 155: 149-161
  • 2 Hyers TM, Hull RD, Weg JG. Antithrombotic therapy for venous thromboembolic disease. Chest 1995; 108 (suppl) 335S-351S
  • 3 Francis CW, Marder VJ. Physiologic regulation and pathologic disorders of fibrinolysis. In: Colman RW, Hirsh J, Marder VJ, Salzman EW. editors Hemostasis and thrombosis: basic principles and clinical practice. JB LippincottCo; Philadelphia: 1994: 1076-1103
  • 4 Kluft C, Jie AFH, Rijken DC, Verheijen JH. Daytime fluctuations in blood of tissue-type plasminogen (t-PA) and its fast-acting inhibitor (PAI-1). Thromb Haemost 1988; 59: 329-332
  • 5 Eriksson E, Wollter IM, Christenson B, Stigedal L, Risberg B. Heparin and fibrinolysis – Comparison of subcutaneous administration of unfractioned and low molecular weight heparin. Thromb Haemost 1988; 59: 284-288
  • 6 Tripodi A, Moia M, Bottasso B, Tenconi PM, Gianese F, Mannucci PM. Effects of subcutaneously administered dermatan sulfate (MF 701) on the coagulation and fibrinolytic parameters of healthy volunteers. Thromb Res 1991; 62: 663-672
  • 7 De BoerA, Kluft C, Dooijewaard G, Kasper FJ, Kroon JM, Breimer DD, Stiekema JCJ, Cohen AF. Influence of heparin and a low molecular weight heparinoid on specific endogenous and exogenous fibrinolytic factors during rest and exercise. Thromb Haemost 1992; 68: 550-555
  • 8 Huber K, Resch I, Rose D, Probst D, Kaindl F, Binder BR. Heparin induced increase of t-PA antigen plasma levels in patients with unstable angina: no evidence for clinical benefit of heparinization during the initial phase of treatment. Thromb Res 1989; 55: 779-784
  • 9 Prisco D, Paniccia R, Gensini GF, Coppo M, Colella A, Filippini M, Brunelli T, Abbate R, Neri SernerGG. Effect of low-dose heparin treatment on fibrinolysis in patients with previous myocardial infarction. Haemostasis 1993; 23: 308-313
  • 10 Schulman S, Granqvist S, Wiman B, Lockner D. Thrombolysis and fibrinolytic parameters during heparin treatment of deep vein thrombosis. Thromb Res 1985; 39: 607-612
  • 11 Arnesen H, Engebretsen LF, Ugland OM, Seljflot I, Kierulf P. Increased fibrinolytic activity after surgery induced by low dose heparin. Thromb Res 1987; 45: 553-559
  • 12 Klein P. Plasma levels of t-PA:Ag under standard heparin therapy. Thromb Res 1989; 56: 649-653
  • 13 Faivre R, Neuhart E, Mirshahi M, Soria C, Soria J, Bassand JP, Caen JP, Mairat JP. Fibrinolytic and thrombolytic parameters in patients with deep vein thrombosis treated by low molecular weight and standard heparin. Sem Thromb Haemost 1989; 15: 435-439
  • 14 Vergnes C, Manciet G, Bourdenx V, Roudaut MF, Lacombe F, Boisseau MR. Standard heparin but not LMW heparin induces a concomitant increase of t-PA and PAI-1 without modification of global fibrinolysis: study after 60 days treatment. Thromb Res 1991; 63: 521-530
  • 15 Estivals M, Pelzer H, Sie P, Pichon J, Boccalon H, Boneu B. Prothrombin fragment 1+2, thrombin-antithrombin III complexes and D-dimers in acute deep venous thrombosis: effects of heparin treatment. Br J Haematol 1991; 78: 421-424
  • 16 Van BeekEJR, Tiel-van BuulMMC, Büller HR, van RoyenEA, ten CateJW. The value of lung scintigraphy in the diagnosis of pulmonary embolism. Eur J Nucl Med 1993; 20: 173-181
  • 17 Levi M, de BoerJP, Roem D, ten CateJW, Hack CE. Plasminogen activation in vivo upon intravenous infusion of DDAVP. Thromb Haemost 1992; 67: 111-116
  • 18 De BoerJP, Creasey AA, Chang A, Roem D, Brouwer MC, Eerenberg AJM, Hack CE, Taylor FB. Activation patterns of coagulation and fibrinolysis in baboons following infusion with lethal or sublethal dose of Escherichia coli. Circ Shock 1993; 39: 59-67
  • 19 Van BeekEJR, van den EndeA, Berckmans RJ, van der HeideYT, Brandjes DPM, Sturk A, ten CateJW. A comparative analysis of D-dimer assays in patients with clinically suspected pulmonary embolism. Thromb Haemost 1993; 70: 408-413
  • 20 Amelsberg A, Zurbom KH, Gärtner U, Kiehne KH, Preusse AK, Bruhn HD. Influence of heparin treatment on biochemical markers of an activation of the coagulation system. Thromb Res 1992; 66: 121-131
  • 21 DVTENOX Study group. Markers of hemostatic system activation in acute deep venous thrombosis-Evolution during the first days of heparin treatment. Thromb Haemost 1993; 70: 909-914
  • 22 Boneu B, Bes G, Pelzer H, Sié P, Boccalon H. D-Dimers, thrombin-anti- thrombin III complexes and prothrombin fragment 1+2: Diagnostic value in clinically suspected deep vein thrombosis. Thromb Haemost 1991; 65: 28-32
  • 23 Rapaport RS, Ronchetti-Blume M, Vogel RL, Hung PP. Heparin potentiates endothelial cell growth factor stimulation of plasminogen activator synthesis by diploid lung fibroblasts. Thromb Haemost 1988; 59: 514-522
  • 24 Chanquia CJ, Fontcubarta J, Fabra A, Rutllant M. Profibrinolytic activity associated heparins on human umbilical vein endothelial cell cultures (HUVEC) in vitro. Fibrinolysis 1988; 02: S59
  • 25 Hoylaerts M, Rijken DC, Lijnen HR, Collen D. Kinetics of the activation of plasminogen by human tissue plasminogen activator. Role of fibrin. J Biol Chem 1982; 257: 2912-2919
  • 26 Thorsen S, Philips M, Selmer J, Lecander I, Åstedt B. Kinetics of inhibition of tissue-type and urokinase type plasminogen activator by plasminogen-activator inhibitor type 1 and type 2. Eur J Biochem 1988; 175: 33-39
  • 27 Aoki N, Harpel PC. Inhibitors of the fibrinolytic enzyme system. Semin Thromb Haemost 1984; 10: 24
  • 28 Demers C, Ginsberg JS, Johnston M, Brill-Edwards P, Panju A. D-Dimer and thrombin-antithrombin III complexes in patients with clinically suspected pulmonary embolism. Thromb Haemost 1992; 67: 408-412