Is More Heparin Necessary for Low-Dose Heparin Prophylaxis in Uremic Patients?

Summary

Heparin dose requirements for s. c. heparin prophylaxis were investigated in control individuals and in uremic patients. Heparin levels (neutralisation of factor Xa activity, neutralisation of Xa amidolytic activity; PTT and thrombin time) at timed intervals after single and repetitive s. c. doses of 5,000 or 7,500 IU were measured in 11 uremic patients and 9 individuals with normal renal function. At a dose of 2 × 5,000 IU/d heparin s. c. no difference between controls and uremic individuals was found. In contrast, in uremic patients, peak concentrations and area under the curve (AUC) were significantly lower and plasma half life shorter after 3 × 5,000 IU heparin s. c.

After repeated administration of heparin, heparin concentrations (24hrs) had fallen to nil in uremic patients whereas in controls measurable activity was still demonstrable. After i.v. bolus injection of heparin, peak concentrations were identical in controls and in uremic patients, but elimination half life was prolonged in uremic patients. It is therefore suggested that lower plasma heparin concentration after heparin s. c. is the result of diminished net absorption from the subcutaneous depot

It is concluded that in order to achieve a given plasma activity, higher s. c. doses of heparin must be administered to uremic patients than to non-uremic individuals. But further studies are required to demonstrate safety and efficacy of heparin prophylaxis in uremic individuals.

Keywords

Heparin metabolism - Low dose heparin - Renal insufficiency

• References

• 1 Kakkar V, Field E, Nicolaides A, Fossard D, Flute P, Flute P, Wessler S, Yin E. Low doses of heparin in the prevention of deep vein thrombosis. Lancet 1971; 2: 669-671
• 2 An international multicentre trial. Prevention of fatal postoperative pulmonary embolism by low doses of heparin. Lancet 1975; 2: 45-51
• 3 Hellem A. The adhesiveness of human blood platelets in vitro. Scand J Clin Lab Invest 1960; 12 Suppl (Suppl. 53) 1-117
• 4 Denson K, Bonnar J. The measurement of heparin. A method based on the potentiation of antifactor Xa Thrombos Diathes Haemorrh 1973; 30: 471-479
• 5 Teien A, Lie M, Abildgaard U. Assay of heparin in plasma using a chromogenic substrate for activated factor X. Thromb Res 1976; 8: 413-416
• 6 Langdell R, Wagner R, Brinkhous K, Hill C. Effect of antihemophilic factor on one stage clotting tests. J Lab Clin Med 1953; 41: 637-647
• 7 Quick A. The normal antithrombin of the blood and its relation to heparin. Am J Physiol 1938; 123: 712-719
• 8 Ødegaard O, Lie M, Abildgaard U. Heparin cofactor activity measured with an amidolytic method. Thromb Res 1975; 6: 287-294
• 9 Teien A, Bjørnson J. Heparin elimination in uremic patients on haemodialysis. Scand J Haematol 1976; 17: 29-35
• 10 Perry P, Herron G, King J. Heparin half life in normal and impaired renal function. Clin Pharm Ther 1974; 16: 514-519
• 11 Koivisto V, Felig P. Effects of leg exercise on insulin absorption in diabetic patients. N Engl J Med 1978; 298: 77-83