Thromboxane Responsiveness of Platelets

Platelets, also called thrombocytes, are cell-like particles that are smaller than red or white blood cells. Platelets 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. 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 heart attack.

Thromboxanes are substances synthesised predominantly by platelets and act to promote decreasing the diameter of the blood vessels, platelet aggregation, narrowing of the bronchi in lung. The key thromboxane is TxA2. They act as local hormones due to their short lives, and they are excreted in the kidney. It has been suggested that Txa2 promotes constricting coronary arteries of the heart and formation of blood clots (thrombi). Recent evidence reveals platelet activation is sometimes critical in the development of inflammation.

Role of Platelets in Inflammation

There is now acceptance that platelets act as sentinel cells undergoing surveillance, responding to microbial invasion, orchestrating leukocyte recruitment, and migrating through tissue, causing damage and influencing repair processes in chronic disease. 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 (COPD), rheumatoid arthritis (RA), inflammatory bowel disease (IBD) and atherosclerosis.

Thromboxane A2 (TxA2) is a powerful unstable inducer of platelet activation and aggregation.

Platelets from most dogs are TxA2 (thromboxane) insensitive (TXA2-), meaning they do not aggregate irreversibly or secrete although they bind TxA2, but they respond normally to thrombin (an enzyme that promotes blood clotting). In contrast, a minority of dogs have TxA2-sensitive (TXA2+) platelets that are responsive to TxA2. Platelet function is influenced by breed. Higher platelet aggregation response is found in some dog breeds.

Aspirin and and some other drugs (Clopidogrel, Heparin) along with thrombolytic therapy with enzymes such as streptokinase and tissue plasminogen activator prevent formation of thromboxane thus preventing platelet aggregation and clot formation. However, aspirin is neither efficient in all patients nor free of an increased risk of bleeding or other undesirable complications. Recent research of flavonoids, natural antioxidants found in many fruits and vegetables, revealed that these compounds have beneficial effects on cardiovascular disease.³

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.

Add Comments