Is more heparin necessary for low-dose heparin prophylaxis in uremic patients?
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 x 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 x 5,000 IU heparin s.c. After repeated administration of heparin, heparin concentrations (24 hrs) 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.
D000328:Adult; D000991:Antithrombins / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D005260:Female; D006493:Heparin / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D013927:Thrombosis / Q000517:prevention & control; D014511:Uremia / Q000378:metabolism*
D000991:Antithrombins; D006493:Heparin