Low Molecular Weight Heparin (KABI2165) as Thromboprophylaxis in Elective Visceral Surgery

Summary

In two randomized double-blind studies perioperative bleeding complications and thromboembolic events were assessed in 189 patients (pts) undergoing elective visceral surgery after subcutaneous administration of a low molecular weight (LMW) heparin fragment (KABI fragment 2165) or unfractionated (UF) heparin. The first study comparing 1 x 7′500 anti-factor Xa IU LMW heparin daily with 2 x 5′000 IU UF heparin was interrupted because of excessive bleeding complications (LMW heparin: 11/23 pts, UF heparin: 2/20 pts, p <0.01). In the second study (146 pts) the dose of LMW heparin was reduced to 1 x 2′500 anti-factor Xa IU. Bleeding complications (LMW heparin: 14.9%, UF heparin: 15.3%) and thromboembolic events (LMW heparin: 2.86%, UF heparin: 2.94%) were equal among the two groups.

2′500 anti-factor Xa IU/day of this LMW heparin fragment, corresponding to 15 mg/day, is the lowest dose of a LMW heparin used in a randomized clinical trial and was found to be a safe and efficient regimen in perioperative thrombosis prophylaxis. An advantage of LMW heparin over UF heparin is its once daily administration.

Key words

Low molecular weight heparin - Bleeding complications - Administration once daily - F Xa-inhibition

• References

• 1 International Multicenter Trial. Prevention of fatal postoperative pulmonary embolism by low doses of heparin. Lancet 1975; ii: 45-51
• 2 Gruber UF, Saldeen T, Brokop T, Eklof B, Eriksson I, Goldie I, Gran L, Hohl M, Jonsson T, Kristersson S, Ljungstrom KG, Lund T, Maartman Moe H, Svensjo E, Thomson D, Torhorst J, Trippestad A, Ulstein M. Incidences of fatal postoperative pulmonary embolism after prophylaxis with dextran 70 and low-dose heparin: an international multicenter study. Br Med J 1980; 280: 69-72
• 3 Thomas DP, Morton RE, Lewis WE, Barrowcliffe TW. Studies in man and experimental animals of a low molecular weight heparin fraction. Thromb Haemostas 1981; 45: 214-218
• 4 Bergqvist D, Hedner U, Sjorin E, Holmer E. Anticoagulant effects of two types of low molecular weight heparin administered subcutaneously. Thromb Res 1983; 32: 381-391
• 5 Carter CJ, Kelton JG, Hirsch J, Cerskus A, Santos AV, Gent M. The relationship between the hemorrhagic and antithrombotic properties of low molecular weight heparin in rabbits. Blood 1982; 59: 1239-1245
• 6 Thomas DP, Morton RE. A low molecular weight heparin compared with unfractionated heparin. Thromb Res 1982; 28: 343-350
• 7 Kakkar VV, Djazaeri B, Fok J, Fletcher M, Scully MF, Westwick J. Low-molecular weight heparin and prevention of postoperative deep vein thrombosis. Brit Med J 1982; 284: 375-379
• 8 Cifonelli JA. Reaction of heparitin sulfate with nitrous acid. Carbohyd Res 1968; 8: 233-242
• 9 Schmitz-Huebner U, Bünte H, Freise G, Reers B, Rüschemeyer C, Scherer R, Schulte H, van de Loo J. Clinical efficacy of low molecular weight heparin in postoperative thrombosis prophylaxis. Klin Wochenschr 1984; 62: 349-353
• 10 Kakkar VV, Murray WI G. Efficacy and safety of low-molecular weight heparin (CY 216) in preventing postoperative venous thrombo-embolism: a co-operative study. Br J Surg 1985; 72: 786-791
• 11 Bergqvist D, Burmark US, Frisell J, Hallbook T, Lindblad B, Risberg B, Tomgren S, Wallin G. Low molecular weight heparin once a day compared with conventional low dose heparin. A prospective doubleblind multicenter trial on prevention of postoperative thrombosis. Br J Surg 1986; 73: 204-208
• 12 Barrowcliffe TW, Curtis AT, Tomlinson TP, Hubbard AR, Johnson EA, Thomas DP. Standardization of low molecular weight heparins: a collaborative study. Thromb Haemostas 1985; 54: 675-679
• 13 Holmer E, Mattsson C, Nilsson S. Anticoagulant and antithrombotic effects of heparin and low molecular weight heparin fragments in rabbits. Thromb Res 1982; 25: 475-485
• 14 Thomas DP. Annotation. Heparin, low molecular weight heparin, and heparin analogues. Br J Haematol 1984; 58: 385-390