Fibrinolytic and anticoagulant activity after a single subcutaneous administration of a low dose of heparin or a low molecular weight heparin-dihydroergotamine combination. 1988

V Grimaudo, and A Omri, and E K Kruithof, and J Hauert, and F Bachmann
Department of Medicine, University Hospital Center, CHUV, Lausanne, Switzerland.

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.

UI MeSH Term Description Entries
D007279 Injections, Subcutaneous Forceful administration under the skin of liquid medication, nutrient, or other fluid through a hollow needle piercing the skin. Subcutaneous Injections,Injection, Subcutaneous,Subcutaneous Injection
D008297 Male Males
D001777 Blood Coagulation The process of the interaction of BLOOD COAGULATION FACTORS that results in an insoluble FIBRIN clot. Blood Clotting,Coagulation, Blood,Blood Clottings,Clotting, Blood
D002940 Circadian Rhythm The regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs or environmental and physiological stimuli. Diurnal Rhythm,Nyctohemeral Rhythm,Twenty-Four Hour Rhythm,Nycthemeral Rhythm,Circadian Rhythms,Diurnal Rhythms,Nycthemeral Rhythms,Nyctohemeral Rhythms,Rhythm, Circadian,Rhythm, Diurnal,Rhythm, Nycthemeral,Rhythm, Nyctohemeral,Rhythm, Twenty-Four Hour,Rhythms, Circadian,Rhythms, Diurnal,Rhythms, Nycthemeral,Rhythms, Nyctohemeral,Rhythms, Twenty-Four Hour,Twenty Four Hour Rhythm,Twenty-Four Hour Rhythms
D004087 Dihydroergotamine A 9,10alpha-dihydro derivative of ERGOTAMINE. It is used as a vasoconstrictor, specifically for the therapy of MIGRAINE DISORDERS. Agit,Angionorm,Clavigrenin,D-Tamin Retard L.U.T.,D.H.E. 45,DET MS,DHE-45,DHE-Puren,DHE-Ratiopharm,Dihydergot,Dihydroergotamin AL,Dihydroergotamine Mesylate,Dihydroergotamine Methanesulfonate,Dihydroergotamine-Sandoz,Dihytamin,Erganton,Ergomimet,Ergont,Ergotam Von Ct,Ikaran,Migranal,Orstanorm,Seglor,Tamik,Verladyn,D Tamin Retard L.U.T.,DHE 45,DHE Puren,DHE Ratiopharm,DHE45,Dihydroergotamine Sandoz,Mesylate, Dihydroergotamine,Methanesulfonate, Dihydroergotamine,Von Ct, Ergotam
D004338 Drug Combinations Single preparations containing two or more active agents, for the purpose of their concurrent administration as a fixed dose mixture. Drug Combination,Combination, Drug,Combinations, Drug
D005342 Fibrinolysis The natural enzymatic dissolution of FIBRIN. Fibrinolyses
D006493 Heparin A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. Heparinic Acid,alpha-Heparin,Heparin Sodium,Liquaemin,Sodium Heparin,Unfractionated Heparin,Heparin, Sodium,Heparin, Unfractionated,alpha Heparin
D006495 Heparin, Low-Molecular-Weight Heparin fractions with a molecular weight usually between 4000 and 6000 kD. These low-molecular-weight fractions are effective antithrombotic agents. Their administration reduces the risk of hemorrhage, they have a longer half-life, and their platelet interactions are reduced in comparison to unfractionated heparin. They also provide an effective prophylaxis against postoperative major pulmonary embolism. LMWH,Low-Molecular-Weight Heparin,Low Molecular Weight Heparin,Heparin, Low Molecular Weight
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

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