Thromboxane Responsiveness of Platelets

Platelets, also called thrombocytes, are cell-like particles that are smaller than red or white blood cells. They are fewer in number than red blood cells, with a ratio of about 1 platelet to every 20 red blood cells. They help in the clotting process by gathering at a bleeding site and clumping together to form a plug that helps seal the blood vessel. At the same time, platelets release substances that help promote further clotting. Platelet receptors can engage with tumor cells contributing to cancer metastasis.4 Human platelets increase the survival of colonic and ovarian adenocarcinoma cells treated with two standard anticancer drugs.5 When the number of platelets is too low (thrombocytopenia), bruising and abnormal bleeding develop. When the number of platelets is too high (thrombocythemia), blood may clot excessively, producing a stroke or a heart attack. Platelet function is influenced by breed and higher platelet aggregation response is found in some dog breeds.



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There is now acceptance that platelets act as sentinel cells performing surveillance, responding to microbial invasion, orchestrating leukocyte recruitment and migrating through tissue, causing damage, and influencing repair processes in chronic diseases. The actions of platelets therefore influence the development of diverse inflammatory diseases in various body organs, including parasitic and bacterial infection, allergic inflammation (especially asthma and rhinitis), allergies, chronic obstructive pulmonary disease, rheumatoid arthritis, inflammatory bowel disease, and atherosclerosis.

Thromboxanes are substances synthesised predominantly by platelets and act to promote decreasing the diameter of the blood vessels, platelet aggregation, and narrowing of the bronchi in the lungs. The key thromboxane is TxA2, a powerful unstable inducer of platelet activation and aggregation. It has been suggested that TxA2 promotes constricting coronary arteries of the heart and formation of blood clots (thrombi). Platelets from most dogs are TxA2 insensitive (TXA2-), meaning they do not aggregate irreversibly, although they bind TxA2. In contrast, a minority of dogs have TxA2-sensitive (TXA2+) platelets that are responsive to TxA2 and become activated. Activated platelets stimulate thrombus formation in response to rupture of an atherosclerotic plaque or endothelial cell erosion, promoting atherothrombotic disease, such as pulmonary arterial thromboembolism (PTE). PTE is common in dogs and is marked by difficulty breathing, exercise intolerance, depression, and coughing blood.

References

  1. Novel uses for anti-platelet agents as anti-inflammatory drugs. S. C. Pitchford
  2. Thromboxane-insensitive dog platelets have impaired activation of phospholipase C due to receptor-linked G protein dysfunction. G J Johnson, L A Leis and P C Dunlop. In: Volume 92, Issue 5 (November,1993) doi:10.1172/JCI116855.
  3. Jose A Guerrero, Leyre Navarro-Nuñez, María L Lozano, Constantino Martinez, Vicente Vicente, Jonathan M Gibbins, and Jose Rivera. Flavonoids inhibit the platelet TxA2 signalling pathway and antagonize TxA2 receptors (TP) in platelets and smooth muscle cells.
  4. Platelets and their interactions with other immune cells
  5. Platelets increase survival of adenocarcinoma cells challenged with anticancer drugs: mechanisms and implications for chemoresistance



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