Thromb Haemost 1986; 56(02): 225-228
DOI: 10.1055/s-0038-1661645
Original Article
Schattauer GmbH Stuttgart

Dose Response Relationships of Anticoagulant Activities After Subcutaneous Administration of Two Low Molecular Weight Heparins in Healthy Individuals

P Hellstern
The Abteilung für Klinische Haemostaseologie und Transfusionsmedizin, Universitat des Saarlandes, Homburg/Saar, FRG
,
R Kiehl
The Abteilung für Klinische Haemostaseologie und Transfusionsmedizin, Universitat des Saarlandes, Homburg/Saar, FRG
,
G von Blohn
The Abteilung für Klinische Haemostaseologie und Transfusionsmedizin, Universitat des Saarlandes, Homburg/Saar, FRG
,
M Köhler
The Abteilung für Klinische Haemostaseologie und Transfusionsmedizin, Universitat des Saarlandes, Homburg/Saar, FRG
,
U Meierhenrich
The Abteilung für Klinische Haemostaseologie und Transfusionsmedizin, Universitat des Saarlandes, Homburg/Saar, FRG
,
E Wenzel
The Abteilung für Klinische Haemostaseologie und Transfusionsmedizin, Universitat des Saarlandes, Homburg/Saar, FRG
› Author Affiliations
Further Information

Publication History

Received 12 May 1986

Accepted after revision 22 July 1986

Publication Date:
20 July 2018 (online)

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Summary

This study was performed to estimate appropriate dosages of two low molecular weight heparins (LMWH) for clinical trials on subcutaneous perioperative thrombosis prophylaxis. Anticoagulatory activities and platelet function were investigated after single doses of two LMWH and of unfractionated sodium heparin (UFH) in 24 healthy individuals. Twelve subjects received subcutaneous injections of 1000, 1500, and 2500 i.u. (aPTT) of LMHW 1, and the other 12 received LMWH 2 at same dosages. The following parameters were determined before 30 min, 1 h, 90 min, 2 h, 3 h, 4 h, 6 h, 8 h, and 10 h after either LMWH or 5000 i.u. (aPTT) UFH: aPTT, thrombin time, anti-Xa activity (S 2222, Coatest heparin), and anti-IIa activity (Chromozym TH). Bleeding time, platelet count, and adrenalin-, collagen-, and ADP-induced platelet aggregation were assessed before and 3 h after administration.

After application of 1500 i.u. LMWH 1 and LMWH 2, the anti-Xa and anti-IIa levels were already significantly higher than after 5000 i.u. UFH. 2500 i.u. LMWH 1 and LMWH 2 evoked significantly greater prolongations of aPTT and thrombin time values than did 5000 i.u. UFH. This was not the case after 1000 and 1500 i.u. LMWH. The half-lives of anticoagulatory effects after LMWH were markedly longer than after UFH. Platelet function was not altered by any of the heparins tested. Our results indicate that LMWH cause anticoagulatory effects in vivo that cannot be predicted by in vitro studies and that the appropriate single dosages of LMWH in subcutaneous perioperative thrombosis prophylaxis have to be estimated by dosage determinations in healthy subjects.