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

Ryo Tsuchiya From the Laboratory of Internal Medicine II, School of Veterinary Medicine, Azabu University, 1-17-71 Fuchinobe, Sagamihara City, Kanagawa 229-8501, Japan (Tsuchiya, Kyotani, Nishizono, Ashida, Mochizuki, Kitao, Yamada, Kobayashi), and the Veterinary Medical Diagnostic Laboratory, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211 (Scott).

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Kazumi Kyotani From the Laboratory of Internal Medicine II, School of Veterinary Medicine, Azabu University, 1-17-71 Fuchinobe, Sagamihara City, Kanagawa 229-8501, Japan (Tsuchiya, Kyotani, Nishizono, Ashida, Mochizuki, Kitao, Yamada, Kobayashi), and the Veterinary Medical Diagnostic Laboratory, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211 (Scott).

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Michael A. Scott From the Laboratory of Internal Medicine II, School of Veterinary Medicine, Azabu University, 1-17-71 Fuchinobe, Sagamihara City, Kanagawa 229-8501, Japan (Tsuchiya, Kyotani, Nishizono, Ashida, Mochizuki, Kitao, Yamada, Kobayashi), and the Veterinary Medical Diagnostic Laboratory, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211 (Scott).

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Kazuya Nishizono From the Laboratory of Internal Medicine II, School of Veterinary Medicine, Azabu University, 1-17-71 Fuchinobe, Sagamihara City, Kanagawa 229-8501, Japan (Tsuchiya, Kyotani, Nishizono, Ashida, Mochizuki, Kitao, Yamada, Kobayashi), and the Veterinary Medical Diagnostic Laboratory, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211 (Scott).

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Yoshinori Ashida From the Laboratory of Internal Medicine II, School of Veterinary Medicine, Azabu University, 1-17-71 Fuchinobe, Sagamihara City, Kanagawa 229-8501, Japan (Tsuchiya, Kyotani, Nishizono, Ashida, Mochizuki, Kitao, Yamada, Kobayashi), and the Veterinary Medical Diagnostic Laboratory, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211 (Scott).

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Toshihiko Mochizuki From the Laboratory of Internal Medicine II, School of Veterinary Medicine, Azabu University, 1-17-71 Fuchinobe, Sagamihara City, Kanagawa 229-8501, Japan (Tsuchiya, Kyotani, Nishizono, Ashida, Mochizuki, Kitao, Yamada, Kobayashi), and the Veterinary Medical Diagnostic Laboratory, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211 (Scott).

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Satoshi Kitao From the Laboratory of Internal Medicine II, School of Veterinary Medicine, Azabu University, 1-17-71 Fuchinobe, Sagamihara City, Kanagawa 229-8501, Japan (Tsuchiya, Kyotani, Nishizono, Ashida, Mochizuki, Kitao, Yamada, Kobayashi), and the Veterinary Medical Diagnostic Laboratory, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211 (Scott).

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Takatsugu Yamada From the Laboratory of Internal Medicine II, School of Veterinary Medicine, Azabu University, 1-17-71 Fuchinobe, Sagamihara City, Kanagawa 229-8501, Japan (Tsuchiya, Kyotani, Nishizono, Ashida, Mochizuki, Kitao, Yamada, Kobayashi), and the Veterinary Medical Diagnostic Laboratory, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211 (Scott).

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Kousaku Kobayashi From the Laboratory of Internal Medicine II, School of Veterinary Medicine, Azabu University, 1-17-71 Fuchinobe, Sagamihara City, Kanagawa 229-8501, Japan (Tsuchiya, Kyotani, Nishizono, Ashida, Mochizuki, Kitao, Yamada, Kobayashi), and the Veterinary Medical Diagnostic Laboratory, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211 (Scott).

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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. (Am J Vet Res 1999;60; 216-221)

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. (Am J Vet Res 1999;60; 216-221)

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