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:

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

QUESTION: Name three factors that not only are produced or released as a result of platelet activation but also cause platelet activation.

QUESTION: Is this an example of negative or positive feedback?

QUESTION: Some people take one "baby" aspirin a day to reduce the risk of a myocardial infarction. What molecules are affected by the aspirin?

QUESTION: Why is such a small amount of the drug effective?

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 on cells in the tissue surrounding blood vessels.

In each step, an inactive protein (called a "factor") 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.

The sequence from damage to the blood vessel to the active thrombin is complex (The classical representation, for example, is shown in Figure 12-74 in Vander.) But don't worry about the details and just focus on the above bold-faced terms.

Thrombin converts the blood protein fibrinogen to fibrin. Fibrinogen is a large soluble protein (with three polypeptide chains) that remains dispersed in the plasma. But after thrombin cleaves off peptides, the resulting fibrin molecules begin adhering to one another and assemble into long fibrils. Thus, fibrinogen plays two quite different roles: as "platelet glue" and as the protein that is the starting point for the formation of the long protein fibrils of a blood clot.

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 lecture handout.)

Quick Quiz

Fill in Answer Correct False Correct Answer
What do dense granules in platelets contain?
What specific term refers to a clot of coagulated blood and platelets?
What is the term for a low level of platelets in the blood?
Name an eicosanoid that prevents platelet activation.
Name an eicosanoid that causes platelet activation.
Name a term for purple or red areas that appear in the skin as a result of low levels of platelets.

(Spelling must be correct)
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