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Thromb Haemost 1997; 78(02): 876-879
DOI: 10.1055/s-0038-1657645
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Schattauer GmbH Stuttgart

Comparison of the Effects of Different Low Molecular Weight Heparins on the Hemostatic System Activation In Vivo in Man

Michael Wolzt
1   The Department of Clinical Pharmacology, Allgemeines Krankenhaus Wien, Austria
,
Michaela Eder
1   The Department of Clinical Pharmacology, Allgemeines Krankenhaus Wien, Austria
,
Ansgar Weltermann
2   The Department of Internal Medicine I/Division of Hematology and Hemostaseology Vienna University, Allgemeines Krankenhaus Wien, Austria
,
Jesusa Entlicher
1   The Department of Clinical Pharmacology, Allgemeines Krankenhaus Wien, Austria
,
Hans-Georg Eichler
1   The Department of Clinical Pharmacology, Allgemeines Krankenhaus Wien, Austria
,
Paul A Kyrle
2   The Department of Internal Medicine I/Division of Hematology and Hemostaseology Vienna University, Allgemeines Krankenhaus Wien, Austria
› Author Affiliations
Further Information

Publication History

Received 03 1997

Accepted after revision 11 March 1997

Publication Date:
12 July 2018 (online)

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Summary

In a double-blind, randomized, cross-over study the effects of single subcutaneous doses of 120 anti-Xa units/kg body wt. of three different low molecular weight heparin (LMWH) preparations were investigated in 15 healthy subjects by determination of thrombin-antithrombin El complex (TAT), prothrombin fragment 1.2 (fl.2), and β-thromboglobin (β-TG) in shed blood and in venous blood.

Certoparin, dalteparin, and enoxaparin significantly inhibited coagulation activation marker formation in shed blood. The substantial inhibition of TAT and fl.2 formation was slightly more pronounced in response to certoparin. β-TG was decreased following certoparin and enoxaparin, but not following dalteparin. However, no difference between groups was detectable. A small but consistent decrease of fl.2 formation in venous blood was noted for all LMWHs and dalteparin and enoxaparin, but not certoparin, inhibited TAT formation. Only a minor impact of the three LMWH preparations was noted on β-TG plasma concentrations.

Our data indicate that the studied LMWH preparations have a major impact on blood clotting in the activated state and inhibit in vivothe hemostatic system to a comparable extent.

 

  • References

  • 1 Hull RD, Raskob GE, Pineo GF, Green D, Trowbridge AA, Elliott CG, Lemer GR, Hall J, Sparling T, Brettell HR, Norton J, Carter CJ, George R, Merle G, Ward J, Mayo W, Rosenbloom D, Brant R. Subcutanous low-molecular-weight heparin compared with continuous intravenous heparin in the treatment of proximal vein thrombosis. N Engl J Med 1992; 326: 975-982
    CrossrefPubMedSearch in Google Scholar
  • 2 Imperiale TF, Speroff T. A meta-analysis of methods to prevent venous thromboembolism following total hip replacement. JAMA 1994; 271: 1780-1785
    CrossrefPubMedSearch in Google Scholar
  • 3 Kakkar VV. Effectiveness and safety of low molecular weight heparins (LMWH) in the prevention of venous thromboembolism (VTE). Thromb Haemost 1995; 74: 364-368
    Thieme ConnectPubMedSearch in Google Scholar
  • 4 Leizorovicz A, Simonneau G, Decousus H, Boissel JP. Comparison of efficacy and safety of low molecular weight heparins and unfractionated heparin in initial treatment of deep venous thrombosis: a meta-analysis. BMJ 1994; 309: 299-304
    CrossrefPubMedSearch in Google Scholar
  • 5 Lensing AW, Prins MH, Davidson BL, Hirsh J. Treatment of deep venous thrombosis with low-molecular-weight heparins. A meta-analysis. Arch Intern Med 1995; 155: 601-607
    CrossrefPubMedSearch in Google Scholar
  • 6 Prandoni P, Lensing AW, Biiller HR, Carta M, Cogo A, Vigo M, Casara D, Ruol A, ten CateJW. Comparison of subcutaneous low-molecular-weight heparin with intravenous standard heparin in proximal deep-vein thrombosis. Lancet 1992; 339: 441-445
    CrossrefPubMedSearch in Google Scholar
  • 7 Gurfmkel EP, Manos EJ, Mejail RI, Cerda MA, Duronto EA, Garcia CN, Daroca AM, Mautner B. Low molecular weight heparin versus regular heparin or aspirin in the treatment of unstable angina and silent ischemia. J Am Coll Cardiol 1995; 26: 313-318
    CrossrefPubMedSearch in Google Scholar
  • 8 Fragmin during instability in coronary artery disease (FRISC) study group. Low-molecular-weight heparin during instability in coronary artery disease. Lancet 1996; 347: 561-568
    CrossrefPubMedSearch in Google Scholar
  • 9 Cohen M, Demers C, Gurfmkel E, Fromell G, Langer A, Turpie AGG. ESSENCE Group. Primary end point analysis from the ESSENCE trial: Enoxaparin vs unfractionated heparin in unstable angina and non-Q wave infarction. Circulation 1996; 94: 1-554
    CrossrefPubMedSearch in Google Scholar
  • 10 Meyer G, Brenot F, Pacouret G, Simonneau G, Gillet JuvinK, Charbonnier B, Sors H. Subcutaneous low-molecular-weight heparin Fragmin versus intravenous unfractionated heparin in the treatment of acute non massive pulmonary embolism: an open randomized pilot study. Thromb Haemost 1995; 74: 1432-1435
    Thieme ConnectPubMedSearch in Google Scholar
  • 11 Collignon F, Frydman A, Caplain H, Ozoux ML, Le RouxY, Bouthier J, Thebault JJ. Comparison of the pharmacokinetic profiles of three low molecular mass heparins – dalteparin, enoxaparin and nadroparin – administered subcutaneously in healthy volunteers (doses for prevention of thromboembolism). Thromb Haemost 1995; 73: 630-640
    Thieme ConnectPubMedSearch in Google Scholar
  • 12 Azizi M, Veyssier-Belot C, Alhenc-Gelas M, Chatellier G, Billaud-Mesguish E, Fiessinger JN, Aiach M. Comparison of biological activities of two low molecular weight heparins in 10 healthy volunteers. Br J Clin Pharmacol 1995; 40: 577-584
    PubMedSearch in Google Scholar
  • 13 Eriksson BI, Soderberg K, Widlund L, Wandeli B, Tengbom L, Risberg B. A Comparative Study of three low-molecular weight heparins (LMWH) and unfractionated heparin (UFH) in healthy volunteers. Thromb Haemost 1995; 73: 398-401
    Thieme ConnectPubMedSearch in Google Scholar
  • 14 Stiekema JCJ, Van GriensvenJMT, Van DintherTG, Cohen AF. A crossover comparison of the anti-clotting effects of three low molecular weight heparins and glycosaminoglucuronan. Br J Clin Pharmacol 1993; 36: 51-56
    CrossrefPubMedSearch in Google Scholar
  • 15 Gerrard JM, Taback S, Singhroy S, Docherty JC, Kostolansky I, McNichol A, Kobrinsky NL, McKenzie JK, Rowe R. In vivo measurement of thromboxane B2and 6-keto-prostaglandin Flain humans in response to a standardized vascular injury and the influence of aspirin. Circulation 1989; 79: 29-38
    CrossrefPubMedSearch in Google Scholar
  • 16 Gresele P, Amout J, Deckmyn H, Huybrechts E, Pieters G, Vermylen J. Role of proaggregatory and antiaggregatory prostaglandins in hemostasis – studies with combined thromboxane synthase inhibition and thromboxane receptor antagonism. J Clin Invest 1987; 80: 1435-1445
    CrossrefPubMedSearch in Google Scholar
  • 17 Kyrle PA, Eichler HG, Jäger U, Lechner K. Inhibition of prostacyclin and thromboxane A2generation by low-dose aspirin at the site of plug formation in man in vivo. Circulation 1987; a 75: 1025-1029
    CrossrefPubMedSearch in Google Scholar
  • 18 Kyrle PA, Westwick J, Scully MF, Kakkar VV, Lewis GP. Investigation of the interaction of blood platelets with the coagulation system at the site of plug formation in vivo in man – effect of low-dose aspirin. Thromb Haemostas 1987; b 57: 62-66
    PubMedSearch in Google Scholar
  • 19 Nowak J, Fitzgerald GA. Redirection of prostaglandin endoperoxide metabolism at the platelet-vascular interface in man. J Clin Invest 1989; 83: 380-385
    CrossrefPubMedSearch in Google Scholar
  • 20 Weiss HJ, Lages B. Evidence for tissue factor-dependent activation of the classic intrinsic coagulation mechanism in blood obtained from bleeding time wounds. Blood 1988; 71: 629-635
    CrossrefPubMedSearch in Google Scholar
  • 21 Mielke CH, Kaneshiro MM, Mahler IA, Weiner J, Rapaport SI. The standardized Ivy bleeding time and its prolongation by aspirin. Blood 1969; 34: 204-215
    CrossrefPubMedSearch in Google Scholar
  • 22 Bauer KA. Laboratory markers of coagulation activation. Arch Pathol Lab Med 1993; 117: 71-77
    PubMedSearch in Google Scholar
  • 23 Bendetowicz AV, Kai H, Knebel R, Caplain H, Hemker HC, Lindhout T, Beguin S. The effect of subcutaneous injection of unfractionated and low molecular weight heparin on thrombin generation in platelet rich plasma: A study in human volunteers. Thromb Haemost 1994; 72: 705-712
    Thieme ConnectPubMedSearch in Google Scholar
  • 24 Wolzt M, Weltermann A, Nieszpaur-Los M, Schneider B, Fassolt A, Lechner K, Eichler HG, Kyrle PA. Studies on the neutralizing effects of protamine on unfractionated and low molecular weight heparin (Fragmin®) at the site of activation of the coagulation system in man. Thromb Haemost 1995; 73: 439-443
    Thieme ConnectPubMedSearch in Google Scholar
  • 25 Jensen AH, Beguin S, Josso F. Factor V and VIII activation “in vivo” during bleeding. Evidence of thrombin formation at the early stage of hemostasis. Pathol Biol Paris 1976; 24 (Suppl): 6-10
    PubMedSearch in Google Scholar
  • 26 Eichinger S, Wolzt M, Nieszpaur-Los M, Schneider B, Lechner K, Eichler HG, Kyrle PA. Effects of a low molecular weight heparin (Fragmin®) and of unfractionated heparin on coagulation and platelet activation at the site of plug formation in vivo. Thromb Haemost 1994; 72: 831-835
    Thieme ConnectPubMedSearch in Google Scholar
  • 27 Eichinger S, Wolzt M, Nieszpaur-Los M, Schneider B, Heinrichs H, Lechner K, Eichler HG, Kyrle PA. Effects of r-hirudin (HBW 023), low molecular weight heparin (LMWH, Fragmin®) and unfractionated heparin (UFH) on the coagulation system and on platelet activation at the site of plug formation in vivo. Arterioscler Thromb Vase Biol 1995; 15: 886-892
    CrossrefPubMedSearch in Google Scholar