Thromb Haemost 1992; 68(01): 030-032
DOI: 10.1055/s-0038-1656312
Original Article
Schattauer GmbH Stuttgart

Diurnal Rhythm in Anticoagulant Effect of Heparin during a Low Dose Constant Rate Infusion

A Study in Healthy Volunteers
J W M Krulder
1   The Department of General Internal Medicine, the University Hospital, Leiden, The Netherlands
,
A de Boer
2   The Centre for Human Drug Research, Leiden, the University Hospital, Leiden, The Netherlands
,
A M H P van den Besselaar
3   The Department of Hematology, the University Hospital, Leiden, The Netherlands
,
A F Cohen
2   The Centre for Human Drug Research, Leiden, the University Hospital, Leiden, The Netherlands
,
H C Schoemaker
2   The Centre for Human Drug Research, Leiden, the University Hospital, Leiden, The Netherlands
,
E Briët
3   The Department of Hematology, the University Hospital, Leiden, The Netherlands
,
A E Meinders
1   The Department of General Internal Medicine, the University Hospital, Leiden, The Netherlands
› Author Affiliations
Further Information

Publication History

Received 03 December 1991

Accepted after revision 04 February 1992

Publication Date:
03 July 2018 (online)

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Summary

The objective of the study was to investigate possible diurnal rhythms in coagulation tests during a continuous intravenous infusion of unfractionated heparin. Six volunteers participated in the study, which was divided in a treatment (500 U heparin/h for 30 h) and a control experiment. Under basal conditions, no rhythm was found in coagulation tests. During heparin treatment, APTT, thrombin clotting time and anti-Xa activity showed a greater anticoagulant effect at night, with a striking decrease in the morning.

In a search for the explanation of this phenomenon we looked for diurnal variations in the urinary excretion of heparin, in the plasma concentrations of antithrombin III and platelet factor 4, and in the effect of heparin added to the plasma samples in vitro. None of these studies provided the explanation.