Nadim,

Within the body the platelets can be activated by thrombin, arachidonic acid, adenosine diphosphate, epinephrine, collagen or ristocetin. If there is a foreign body in the body even if it is a needle or catheter, the platelets may be activated. Now when you say "External" what do you exactly mean by that? When the blood is in contact with any thing other than the inner lining of the blood vessel, the platelets can get activated. Activated platelets can promote clot formation thrombin generation and TAT complex generation. Even in patients with infection, the bacteria from the environment get into the blood stream and can activate the platelets, leading to thrombin generation and TAT complex formation.

The blood having been drawn from the body and left in the syringe or put into the tube can also cause activation of platelets and coagulation activation leading to TAT generation. I hope this answers your question. Should you have any doubt or any specific question please let me know.

Omer

Thank you Dr. Iqbal for your insight into the matter. However what I meant by 'external' was a molecule that has no connection to the tissue factor pathway and the associated cascade. Senario would be as follows:

General frame is tumor-driven platelet activation. A tumor sheds material (whatever it is) into the blood stream, if this material can activate platelets specifically, would that lead to considerable elevation in the level of TATs?Normally the activation of platelets occurs in the frame of the coagulation cascade initiation. In that setting the two processes are kind of reinforcing and the surface of activated platelets sort of catalyzes certain processes and ofcourse additional thrombin is generated by activated platelets... my question comes in the setting of separate platelet activation, would it be sufficient enough to generate a substantial elevation in TATs?...

Nadim,

Thank you very much. Thanks for clarifying your question. Ofcourse the tumors can express cytokines such as TNF-alpha and other tumor-derived procoagulants or cancer procoagulants and these can not only activate the platelets but can also activate the coagulation process both resulting in the generation of thrombin which can eventually trigger the conversion of fibrinogen to fibrin. And when the thrombin is generated the body tries to combat thrombin by expressing more antithrombin and then the thrombin can combine with antithrombin generating TAT complex. The degree of generation of TAT due to cancer procoagulants may be higher than otherwise. Likewise it might differ from one cytokine to the other. We should also realize that TAT could be generated either by platelet activation or coagulation activation. So any thing which is activating the coagulation cascade can increase the levels of TAT and that platelets may be directly or indirectly activated. The coagulation process and platelet activation are complex processes. I hope this answers your question. Otherwise please let me know and then I can further elaborate. Thanks.

Omer

Thank you Dr. Iqbal. It is indeed a complicated matter :)

Any change in blood matrix might fold F12 into F12a or prekallikrein into kallikrein. Kallikrein directly activates prothrombin to thrombin, a potent platelet activator. TAT might be formed but TAT is a poor marker for in vivo thrombin generation, here amidolytic thrombin activity (thrombin entrapped in alpha2-macroglobulin) is much better because TAT levels "jump", i.e. there might be sudden unexplainable increases or decreases, amidolytic thrombin activity does not "jump".