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

Abstract

Objective - To determine the role of platelet, activating factor (PAF) in lipopolysaccharide (LPS)-induced thrombocytopenia and neutropenia in dogs. Animals - 42 dogs. Procedures - Blood samples were obtained from dogs given LPS (40 μg/kg of body weight; n = 16), PAF (1 μg/kg; 6), PAF (5 μg/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 dogs given LPS (40 μg/kg) that had (n = 5) or had not (6) been treated beforehand with TCV-309, a potent PAF antagonist. Concentration of PAF in blood was determined by use of 125I-radioimmunoassay in dogs given LPS at 1 mg/kg (n = 3) and 40 μg/kg (9). Results - Thrombocytopenia and neutropenia were found in all dogs except those given saline solution. The LPS-induced thrombocytopenia was significantly suppressed by prior treatment with TCV-309. The PAF concentrations increased markedly 1 hour after injection of 1 mg/kg of LPS and increased slightly but significantly 10 minutes after injection of 40 μg/kg of LPS. Conclusion and Clinical Relevance - PAF plays an important role in the development of LPS-induced thrombocytopenia and neutropenia in dogs. Control of PAF production, PAF- induced effects, or both may be important in the treatment of dogs with gram- negative bacterial infections and associated thrombocytopenia and neutropenia.