Low dose calcium heparin in horses: plasma heparin concentrations, effects on red blood cell mass and on coagulation variables



Low dose calcium heparin was administered subcutaneously at 12 hourly intervals to six healthy horses at an initial dose of 150 iu of heparin/kg bodyweight (bwt) and at a maintenance dose of 120 iu/kg bwt. All injections were given at 0900 and 2100 h. Blood samples for monitoring plasma heparin concentrations were obtained prior to, at 2 hourly intervals for 84 h (treatment period), and at Hours 24, 32, 48 and 96 of the control period. Blood samples for monitoring red blood cell (RBC) mass, plasma antithrombin III activity (AT III), activated partial thromboplastin time (APTT), and thrombin time (TT) were taken at 8 hourly intervals during the treatment period and at all of the Control Period Hours. Mean plasma heparin concentrations increased significantly (P<0.01) from 2 h after the first to 32 h after the last (seventh) injection. Mean values corresponding to the desired range of heparin in plasma (0.05 to 0.20 iu/ml) were achieved at 21 h after initiation of heparin treatment and were maintained during the following 81 h. Great individual variations in the sensitivity to heparin among horses, cumulation of heparin in plasma with prolonged administration and a marked circadian periodicity in the disposition of heparin affected actually measured plasma heparin values. A chronodiagram revealed peak values around 1300 h, trough values around 0500 h. The peak-trough difference amounted to about 50 per cent. Increasing plasma heparin concentrations were associated with erratic prolongations of mean APTT and TT values. The AT III curve was not affected significantly. Low dose heparin treatment induced significant RBC mass depletion by about 30 to 35 per cent and agglutination of erythrocytes in vitro in healthy horses. In a splenectomised, otherwise healthy pony, given large doses of heparin, only a minor decrease in the RBC mass was evident. The RBC indices of the horses and the pony were not significantly altered. Four days after cessation of heparin administrations all values were within the baseline range. The agglutination could be reversed by adding trypsin to the sample, but not by neutralising heparin in the sample or by incubation of washed, agglutinated cells with plasma from an untreated horse. Incubation of washed erythrocytes from an untreated horse with plasma from a heparinised horse did not produce RBC agglutination. Other than some degree of pale mucous membranes no clinically detectable signs were attributable to the heparin-induced agglutination-anaemia phenomenon. The outlined heparin regimen may be useful for efficacious low-dose heparin treatment in horses.