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Thromb Haemost 1989; 61(03): 357-362
DOI: 10.1055/s-0038-1646595
Original Article
Schattauer GmbH Stuttgart

Biological Activrty and Safety of the Subcutaneous Administration of High Doses of Low Molecular Weight Heparin for 8 Days in Human Volunteers

J Harenberg
1   The Department of Medicine, Klinikum Mannheim, University of Heidelberg, Mannheim, FRG
,
Ch Giese
1   The Department of Medicine, Klinikum Mannheim, University of Heidelberg, Mannheim, FRG
,
C E Dempfle
1   The Department of Medicine, Klinikum Mannheim, University of Heidelberg, Mannheim, FRG
,
G Stehle
1   The Department of Medicine, Klinikum Mannheim, University of Heidelberg, Mannheim, FRG
,
D L Heene
1   The Department of Medicine, Klinikum Mannheim, University of Heidelberg, Mannheim, FRG
› Author Affiliations
Further Information

Publication History

Received 11 November 1988

Accepted after revision 18 January 1989

Publication Date:
24 July 2018 (online)

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Summary

This study reports on the biological activity and safety of high dose low molecular weight (LMW) heparin therapy administered by two subcutaneous (s.C.) injections daily for 8 days in healthy human volunteers. Group 1 received 2 × 30 aPTT units LMW heparin/kg bodyweight, and group 2 received 2 × 50 aPTT units/kg per day.

In group 1, activated partial thromboplastin time (aPTT) and thrombin clotting time (TCT) were uniformly prolonged by 3-5 sec 4 hrs after s.c. administration of heparin. Heptest coagulation time values were prolonged consistently as well by 57 sec on day 1 to 68 sec on day 8. Factor Xa inhibition measured by the S 2222 chromogenic substrate method continuously increased from 0.16 units/ml on day 1 to 0.28 units/ml on day 8.

In group 2 prolongation of a aPTT and TCT values increased from 6 sec on day 1 to 15 sec on day 8 and of Heptest time from 70 sec on day 1 to 110 sec on day 8. S 2222 method showed factor Xa inhibitory activity which increased from 0.5 units/ml on day 1 to 0.75 units/ml on day 8. The clinical tolerance of the treatment was good. No changes in clinical chemistry parameters were detected, except for a reversible increase of serum transaminases.

The coagulation studies demonstrate accumulation of LMW heparin when high doses are given twice daily. The half life of LMW heparin of factor Xa inhibition increases with increasing doses.

Heptest coagulation values were prolonged to 4-6 times the normal values during administration of heparin. S 2222 chromogenic substrate values were in the same range as upon application of high doses of unfractionated heparin. aPTT and thrombin clotting time values ranged from 1.2 to 1.5 times the starting values.

Keywords

Heparin - Low molecular weight heparin - Factor Xa - Anticoagulation
 

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