BIOCHEMICAL AND CELLULAR EFFECTS OF HEPARIN-PROTAMINE INJECTION IN RABBITS ARE PARTIALLY INHIBITED BY A PAF-ACETHER RECEPTOR ANTAGONIST

The origin of the thrombocytopenia and leucopenia induced by protamine -heparin complexes is unknown. We studied the biochemical and cellular effects of protamine (6 mg X kg(-1), i.v.) injected after heparin (5 mg X kg(-1), i.v.) in New Zealand rabbits. After protamine injection ( 0.5 min) increases in blood platelet-activating factor (PAF-acether, P AF) (27.6 +/- 27.6 to 148.2 +/- 48.9 pg X ml(-1) P < 0.05), thrombocyt openia (403 +/- 64 to 166 +/- 13 cells X 10(-3) X mm(-3), P < 0.05) an d leucopenia (7650 +/- 930 to 4300 +/- 668 cells X mm(-3) P < 0.05) we re noted. Plasma thromboxane B-2 increased at 1 min (125.6 +/- 24.4 to 879.7 +/- 141.0 pg X ml(-1), P < 0.01). Protamine alone induced no ch ange. Indomethacin (3 mg X kg(-1), i.v.) did not counteract the effect s of heparin-protamine. Pretreatment with the PAF receptor antagonist BN 52021 an-5,9,12-(4H)trione,3-tert-butylhexahydro-4,7b,11 hydroxy-8 methyl] alone (3 mg X kg(-1) i.v.) delayed thrombocytopenia and reduce d plasma thromboxane B-2 concentration but did not modify leucopenia. Thus thrombocytopenia and thromboxane B-2 release triggered by heparin -protamine may be potentiated by the release of PAF.