EFFECTS OF UNFRACTIONATED AND LOW-MOLECULAR-WEIGHT HEPARINS ON PLATELET THROMBOXANE BIOSYNTHESIS IN-VIVO

Several ''in vitro'' and ''in vivo'' studies indicate that heparin adm inistration may affect platelet function. In this study we investigate d the effects of prophylactic heparin on thromboxane (Tx)A(2) biosynth esis ''in vivo'', as assessed by the urinary excretion of major enzyma tic metabolites 11-dehydro-TxB(2) and 2,3-dinor-TxB(2). Twenty-four pa tients who were candidates for cholecystectomy because of uncomplicate d lithiasis were randomly assigned to receive placebo, unfractionated heparin, low molecular weight heparin or unfractionaed heparin plus 10 0 mg aspirin. Measurements of daily excretion of Tx metabolites were p erformed before and during the treatment. In the groups assigned to pl acebo and to low molecular weight heparin there was no statistically s ignificant modification of Tx metabolite excretion while patients rece iving unfractionated heparin had a significant increase of both metabo lites (11-dehydro-TxB(2): 3844 +/- 1388 vs 2092 +/- 777, p <0.05; 2,3- dinor-TxB(2): 2737 +/- 808 vs 1535 +/- 771 pg/mg creatinine, p <0.05). In patients randomized to receive low-dose aspirin plus unfractionate d heparin the excretion of the two metabolites was largely suppressed thus suggesting that platelets are the primary source of enhanced thro mboxane biosynthesis associated with heparin administration. These dat a indicate that unfractionated heparin causes platelet activation ''in vivo'' and suggest that the use of low molecular weight heparin may a void this complication.