Fibrinolytic and Anticoagulant Activity After a Single Subcutaneous Administration of a Low Dose of Heparin or a Low Molecular Weight Heparin-Dihydroergotamine Combination

V Grimaudo; A Omri; E K O Kruithof; J Hauert; F Bachmann

doi:10.1055/s-0038-1647501

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1988; 59(03): 388-391
DOI: 10.1055/s-0038-1647501

Original Article

Schattauer GmbH Stuttgart

Fibrinolytic and Anticoagulant Activity After a Single Subcutaneous Administration of a Low Dose of Heparin or a Low Molecular Weight Heparin-Dihydroergotamine Combination

V Grimaudo

The Haematology Division, Department of Medicine, University Hospital Center, CHUV, Lausanne, Switzerland

,

A Omri

The Haematology Division, Department of Medicine, University Hospital Center, CHUV, Lausanne, Switzerland

,

E K O Kruithof

The Haematology Division, Department of Medicine, University Hospital Center, CHUV, Lausanne, Switzerland

,

J Hauert

The Haematology Division, Department of Medicine, University Hospital Center, CHUV, Lausanne, Switzerland

,

F Bachmann

The Haematology Division, Department of Medicine, University Hospital Center, CHUV, Lausanne, Switzerland

› Author Affiliations

Abstract

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Summary

The anticoagulant and potential profibrinolytic effect of a combination of low molecular weight heparin with dihydroergotamine (LMWH-DHE) and of unfractionated heparin was studied in eight healthy volunteers. Each volunteer received a subcutaneous injection of either LMWH-DHE (1,500 U anti-Xa of LMWH + 0.5 mg DHE), unfractionated heparin (5,000 IU) or of placebo (saline) between 7 and 8 h in the morning on three different occasions. Anti-Xa activity, and fibrinolytic activity measured by the euglobulin clot lysis time (ECLT) and by the fibrin plate assay were determined before and at different times after administration of the three substances. Anti-Xa activity in plasma reached a maximum four hours after injection of both LMWH-DHE and unfractionated heparin. LMWH-DHE showed a better bioavailability when compared to unfractionated heparin; the anti-Xa activity peak was two and a half fold higher after LMWH-DHE despite injection of a three fold lower dose of anti-Xa units. The half-life of anti-Xa activity was approximately 4 hours for LMWH-DHE but only 90 min for unfractionated heparin. The fibrinolytic activity measured by ECLT as well as by fibrin plate assay, showed a significant increase during the day reaching a peak 8–12 h after injection regardless of the product administered (including the placebo). The profile of the diurnal fibrinolytic activity curve was identical for all three substances. The increase in fibrinolytic activity, observed after administration of LMWH-DHE or unfractionated heparin, was therefore not due to these drugs but reflected the circadian physiological fluctuation of fibrinolysis.

Keywords

Heparin - Fibrinolytic activity - Anti-Xa activity - Bioavailability

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References

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