Biochemical and cellular effects of heparin-protamine injection in rabbits are partially inhibited by a PAF-acether...

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, PAF) (27.6 +/- 27.6 to 148.2 +/- 48.9 pg x ml-1, P < 0.05), thrombocytopenia (403 +/- 64 to 166 +/- 13 cells x 10(-3) x mm-3, P < 0.05) and leucopenia (7650 +/- 930 to 4300 +/- 668 cells x mm-3, P < 0.05) were noted. Plasma thromboxane B2 increased at 1 min (125.6 +/- 24.4 to 879.7 +/- 141.0 pg x ml-1, P < 0.01). Protamine alone induced no change. Indomethacin (3 mg x kg-1, i.v.) did not counteract the effects of heparin-protamine. Pretreatment with the PAF receptor antagonist BN 52021 [9H1, 7a-(epoxymethano)-1 H,6aH-cyclopenta[c]furo[2,3-b]furo-[3',2',3,4]cyclopenta[1,2-d]fur 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 reduced plasma thromboxane B2 concentration but did not modify leucopenia. Thus thrombocytopenia and thromboxane B2 release triggered by heparin-protamine may be potentiated by the release of PAF.