Platelet Activation

Platelets bud from megakaryocytes in the bone marrow, and then normally circulate about 10 days in the blood. Since they are fragments of cells, they have no nucleus. But platelets do have most other cellular organelles, including microtubules, which help hold the unactivated platelet in a nice, crisp discoid shape. But most important for us are two types of secretion vesicles:

• dense granules, which contain ADP.
• alpha granules, which contain various proteins, including VWF, thrombin and certain growth factors.

(In lab, we are looking at figure 3.2, which shows an unactivated platelet and figure 3.10b in Wheater, which shows activated platelets.)

Platelet Activation

When platelets are circulating through vessels with an intact, healthy endothelium, the platelets remain in their original, unactivated state. The absence of activating factors and the release of prostacyclin (prostaglandin I2) by the healthy endothelium supports this state.

However, when a platelet encounters a break in the endothelium, it encounters molecules that trigger its activation. One such molecule is collagen, which is characteristically found almost everywhere except inside a blood vessel. In addition, thromboxane A2, ADP and thrombin are other factors that trigger the same activation.

The following are some of the main things that happen as a platelet is activated:

• exocytosis of the dense granules and alpha granules
• activation of the membrane enzyme phospholipase A2, leading to the formation of thromboxane A2 (TXA2)
• change in shape to a more amorphous form with projecting fingers
• platelets adhere to one another and to collagen under the endothelium, forming a platelet plug. On the surface of the activated platelet are receptors both for VWF, which promotes the binding to collagen, and for fibrinogen, which causes the activated platelets to adhere to one another. The fibrinogen is found in the blood and also a little is released from the alpha granules.
• coagulation reactions are promoted at the surface (see below)

Coagulation Reactions and Platelets

The coagulation reactions tend to occur along with platelet activation. Together, the two systems form a clot.

As with platelet activation, the blood coagulation reactions are set in motion by damage to a blood vessel. One especially important factor for starting this sequence of reactions is contact of the blood with tissue factor, which is found especially in the tissue surrounding blood vessels.

Figure 12-74 in Vander shows the resulting sequence schematically. In each step an inactive protein in the blood plasma is converted to an active proteolytic enzyme. The active enzyme in turn promotes the next step. Finally, prothrombin is converted to the active enzyme thrombin. But this sequence is dependent on platelets, since the surface of activated platelets is important for some of the reactions.

Thrombin converts the blood protein fibrinogen to fibrin (similar to conversion procollagen to tropocollagen). The fibrin then assembles into long fibrils.

The blood coagulation reactions occur somewhat more slowly than platelet activation and may not be necessary to seal small breaks in the endothelium. Platelet plugs created by rapid platelet activation may be suffficient. But for larger breaks in blood vessels, the fibrin must form too. As the developing fibrils of fibrin form, they trap interspersed, activated platelets, forming a clot.

Note that the blood coagulation reactions also tend to accentuate platelet activation, for example, by releasing thrombin. Thus, both systems tend to be mutually reinforcing.

(The following assumes you have read the pertinent part of the disorders section of the handout.)