Influence of Heparin and a Low Molecular Weight Heparinoid on Specific Endogenous and Exogenous Fibrinolytic Factors during Rest and Exercise

A de Boer; C Kluft; G Dooijewaard; F J Kasper; J M Kroon; D D Breimer; J C J Stiekema; A F Cohen

doi:10.1055/s-0038-1646316

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1992; 68(05): 550-555
DOI: 10.1055/s-0038-1646316

Original Article

Schattauer GmbH Stuttgart

Influence of Heparin and a Low Molecular Weight Heparinoid on Specific Endogenous and Exogenous Fibrinolytic Factors during Rest and Exercise

A de Boer

¹The Centre for Human Drug Research, University Hospital Leiden, The Netherlands

,

C Kluft

²The Gaubius Laboratory, IVVO-TNO, Leiden, The Netherlands

,

G Dooijewaard

²The Gaubius Laboratory, IVVO-TNO, Leiden, The Netherlands

,

F J Kasper

¹The Centre for Human Drug Research, University Hospital Leiden, The Netherlands

,

J M Kroon

¹The Centre for Human Drug Research, University Hospital Leiden, The Netherlands

,

D D Breimer

³The Center for Bio-Pharmaceutical Sciences, Division of Pharmacology, University of Leiden, The Netherlands

,

J C J Stiekema

⁴The Organon International B.V., Oss, The Netherlands

,

A F Cohen

¹The Centre for Human Drug Research, University Hospital Leiden, The Netherlands

› Author Affiliations

Abstract

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Summary

The effects of heparin (5,000 IU i.v.) and the low molecular weight heparinoid Org 10172 (Orgaran®) (3,250 anti-Xa units i. v.) on components of the fibrinolytic system were studied in two double-blind, randomised, placebo-controlled, cross-over trials using healthy subjects. In study A (n = 6) the effects were studied during rest and standardized exercise and in study B (n = 6) during a low dose infusion of recombinant tissue-type plasminogen activator (rt-PA; 80 µg over 16 min). At rest, heparin and Org 10172 did not influence the plasma concentrations of endogenous t-PA antigen, and activity, urokinase-type PA (u-PA) antigen, plasmin activatable pro-urokinase (scu-PA), active urokinase (tcu-PA) and plasminogen activator inhibitor-1 (PAI-1) antigen. Recombinant t-PA antigen and activity during rt-PA infusion were also not affected. During exercise, neither heparin nor Org 10172 influenced the area under the curve (AUC) of t-PA and u-PA antigen and t-PA activity when compared with placebo. Unexpectedly, after heparin the AUC of t-PA activity was 49% larger (range +19 to +245%) than after Org 10172 (p <0.05). The last difference was considered spurious. scu-PA, tcu-PA and PAI-1 antigen levels at 2 min after termination of exercise were unaffected by both compounds (p >0.05). Sulphated polysaccharides do not increase fibrinolytic activity of the plasma by changing the concentrations of the components of the fibrinolytic system.

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References

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