Lipolytic effect of low-molecular-weight-heparin (Fragmin®) and heparin/dihydroergotamine in thromboprophylactic doses during total hip replacement

Abstract

Eighteen patients admitted for implantation of a primary hip prosthesis were randomized to one of the following thromboprophylactic regimens: (1) dextran 500 ml 12 h⁻¹ on the day of surgery and 500 ml on days 1, 3, and 5 post-operatively, (2) heparin 5000 IU and dihydroergotamine 0.5 mg 8 h⁻¹, or (3) Fragmin® (Kabi-Pharmacia, Sweden) 2500 IU 12 h⁻¹ on the day of surgery and 5000 IU 24 h⁻¹ throughout the observation period. Fragmin® is a low molecular-weight heparin which has proven both efficient and safe as a thromboprophylactic drug. The purpose of the study was to elucidate whether Fragmin® had a lower lipolytic (fatty acid-mobilizing) effect than standard heparin. The plasma level of lipoprotein lipase (LPL) was increased on the first post-operative day both in the heparin/dihydroergotamine (preoperative 217±79 μU ml⁻¹ vs. 1289±318, n=6, p < 0.05) and the Fragmin®-groups (136±16 vs. 668±123, n=6, p < 0.05). This increase in plasma LPL was significantly higher in the heparin/dihydroergotamine-group compared to the Fragmin®-group (p < 0.05). In both groups, the enzyme activity gradually decreased during the next 2 days. The circulating level of non-esterified fatty acids increased post-operatively only in the heparin/dihydroergotamine-group. Thus, the lower lipolytic effect of Fragmin® compared to standard heparin is detectable using thromboprophylactic doses during surgery in patients on a standard hospital diet. From a theoretical viewpoint, the use of Fragmin® is advantageous in patients with myocardial ischaemia and patients risking respiratory distress problems due to a low circulating level of non-esterified fatty acids.

Key Words:

• low-molecular-weight-heparin
• thromboprophylaxis
• lipolysis