Comprehensive characterization of platelet function in dogs with hyperadrenocorticism

Area of Science:

• Veterinary Medicine
• Hematology
• Endocrinology

Background:

• Hyperadrenocorticism (HAC) is linked to hypercoagulability and thromboembolic disease risk in humans and dogs.
• Platelets are crucial for thrombosis and hemostasis, but their function in HAC dogs remains uncharacterized.

Purpose of the Study:

• To investigate platelet function and its molecular mechanisms in dogs with HAC.
• To compare platelet responses between dogs with HAC and healthy controls.

Main Methods:

• Prospective cross-sectional study involving 7 dogs with HAC and 15 healthy dogs.
• Evaluation of platelet aggregation, dense-granule secretion, and thromboxane A2 generation.
• Analysis of ERK and AKT phosphorylation in response to thrombin.

Main Results:

• Platelet aggregation and secretion induced by 2-MeSADP and thrombin were significantly reduced in HAC dogs.
• Prednisolone inhibited platelet function in normal dogs but not in HAC dogs, indicating cortisol's role.
• A negative correlation was observed between platelet aggregation and post-ACTH cortisol levels.
• Thromboxane A2 generation and ERK/AKT phosphorylation were suppressed in HAC dogs.

Conclusions:

• Excessive cortisol in canine HAC negatively impacts platelet function.
• Cortisol suppresses thromboxane A2 generation by regulating ERK and AKT phosphorylation.
• These findings elucidate a molecular mechanism for altered hemostasis in canine HAC.