Circadian changes in anticoagulant effect of heparin infused at a constant rate

Six patients with venous thromboembolism were treated with heparin, administered intravenously by a constant infusion pump. The initial daily dose of heparin was adjusted to keep the activated partial thromboplastin time, sampled at 0800, between 1.5 and 2.5 times the control level. Once that level...

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Bibliographic Details
Published in:	British Medical Journal (Clinical research ed.) Vol. 290; no. 6465; pp. 341 - 344
Main Authors:	Decousus, H A, Croze, M, Levi, F A, Jaubert, J G, Perpoint, B M, De Bonadona, J F, Reinberg, A, Queneau, P M
Format:	Journal Article
Language:	English
Published:	England British Medical Journal Publishing Group 02-02-1985 British Medical Association BMJ Publishing Group LTD
Subjects:	Aged Anticoagulants Blood Coagulation Tests Blood plasma Circadian Rhythm Clinical Research Coagulation Dosage Female Heparin Heparin - administration & dosage Heparin - therapeutic use Humans Infusions, Parenteral Intravenous injections Male Middle Aged Partial Thromboplastin Time Pulmonary Embolism - drug therapy Thrombin time Thrombophlebitis - drug therapy Venous thrombosis
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Summary:	Six patients with venous thromboembolism were treated with heparin, administered intravenously by a constant infusion pump. The initial daily dose of heparin was adjusted to keep the activated partial thromboplastin time, sampled at 0800, between 1.5 and 2.5 times the control level. Once that level was obtained, this dose was kept constant. Anticoagulation was thereafter measured, every four hours for 48 hours, by activated partial thromboplastin time, thrombin time, and coagulation factor Xa inhibition assay. The results of all three coagulation tests showed a circadian variation in the six patients. Maximum values were achieved at night and minimum values in the morning. These circadian variations were reproduced for two consecutive days. Differences between night and morning values reached almost 50% for activated partial thromboplastin time, 60% for thrombin time, and 40% for factor Xa inhibition assay. This circadian variation resulted from two rhythms, a circadian rhythm lasting 24 hours and an ultradian rhythm lasting 12 hours, which were detected by cosinor analysis for each coagulation test (p less than 0.01). A circadian rhythm was detected individually in most of the patients for each coagulation test (p less than 0.05). All patients had a nocturnal peak in activated partial thromboplastin time on both days. In four patients this peak exceeded the upper desired limit of activated partial thromboplastin time. These rhythms should be taken into account when evaluating the dosage of heparin to be administered.
Bibliography:	href:bmj-290-341.pdf PMID:3917812 local:bmj;290/6465/341 ark:/67375/NVC-3RBM2ZN3-K istex:FE9BA55FB6D3F82E5B9EAD72BC39DEF3153D7F96 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0267-0623 1468-5833
DOI:	10.1136/bmj.290.6465.341