Role of platelet activating factor in development of thrombocytopenia and neutropenia in dogs with endotoxemia

Objective-To determine the role of platelet activating factor (PAF) in lipo polysaccharide (LPS)-induced thrombocytopenia and neutropenia in dogs. Animals-42 clogs. Procedures-Blood samples were obtained from dogs given LPS (40 mu g/kg of b ody weight; n = 16), PAF (1 mu g/kg; 6), PAF (5 mu g/kg/h for 90 minutes; 4 ), or physiologic saline (0.9% NaCl) solution (0.1 ml/kg/h for 90 minutes; 3) IV to monitor changes in blood cell counts, using automated counters and blood smears stained with Giemsa. Blood samples were also obtained from do gs given LPS (40 mu g/kg) that had (n = 5) or had not (6) been treated befo rehand with TCV-309, a potent PAF antagonist. Concentration of PAF in blood was determined by use of I-125-radioimmunoassay in dogs given LPS at 1 mg/ kg (n = 3) and 40 mu g/kg (9). Results-Thrombocytopenia and neutropenia were found in all dogs except thos e given saline solution. The LPS-induced thrombocytopenia was significantly suppressed by prior treatment with TCV-309. The PAF concentrations increas ed markedly 1 hour after injection of 1 mg/kg of LPS and increased slightly but significantly 10 minutes after injection of 40 mu g/kg of LPS. Conclusion and Clinical Relevance-PAF plays an important role in the develo pment of LPS-induced thrombocytopenia and neutropenia in dogs. Control of P AF production, PAF-induced effects, or both may be important in the treatme nt of dogs with gram-negative bacterial infections and associated thrombocy topenia and neutropenia.