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

Am J Vet Res. 1999 Feb;60(2):216-21.

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 microg/kg of body weight; n = 16), PAF (1 microg/kg; 6), PAF (5 microg/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 microg/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 microg/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 microg/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.

MeSH terms

  • Animals
  • Blood Coagulation Tests / veterinary
  • Dog Diseases / etiology*
  • Dogs
  • Endotoxemia / complications
  • Endotoxemia / veterinary*
  • Female
  • Isoquinolines / pharmacology
  • Leukocyte Count / veterinary
  • Lipopolysaccharides / pharmacology
  • Male
  • Neutropenia / etiology
  • Neutropenia / veterinary*
  • Pilot Projects
  • Platelet Activating Factor / metabolism*
  • Platelet Activating Factor / pharmacology
  • Platelet Aggregation Inhibitors / pharmacology
  • Platelet Count / veterinary
  • Pyridinium Compounds / pharmacology
  • Radioimmunoassay / veterinary
  • Tetrahydroisoquinolines*
  • Thrombocytopenia / etiology
  • Thrombocytopenia / veterinary*

Substances

  • Isoquinolines
  • Lipopolysaccharides
  • Platelet Activating Factor
  • Platelet Aggregation Inhibitors
  • Pyridinium Compounds
  • Tetrahydroisoquinolines
  • TCV 309