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You may occasionally see thrombocytes, commonly known as platelets, referred to as a type of cell, but that is not accurate. A thrombocyte is not a cell but rather a fragment of the cytoplasm of a cell called a megakaryocyte that is surrounded by a plasma membrane.
Megakaryocytes are descended from myeloid stem cells and are large, typically 50–100 µm in diameter, and contain an enlarged, lobed nucleus. As noted in a previous lesson, thrombopoietin, a glycoprotein secreted by the kidneys and liver, stimulates the proliferation of megakaryoblasts, which mature into megakaryocytes.
These remain within bone marrow tissue and ultimately form platelet-precursor extensions that extend through the walls of bone marrow capillaries to release into the circulation thousands of cytoplasmic fragments, each enclosed by a bit of plasma membrane. These enclosed fragments are platelets. This production process is known as thrombopoiesis. Each megakaryocyte releases 2,000–3,000 platelets during its lifespan. Following platelet release, megakaryocyte remnants, which are little more than a cell nucleus, are consumed by macrophages.
Platelets are critical to hemostasis, which is the stoppage of blood loss following damage to a vessel. They also secrete a variety of growth factors essential for the growth and repair of tissue, particularly connective tissue. Infusions of concentrated platelets are now being used in some therapies to stimulate healing.
Platelets are key players in hemostasis, the process by which the body seals a ruptured blood vessel and prevents further loss of blood. Although rupture of larger vessels usually requires medical intervention, hemostasis is quite effective in dealing with small, simple wounds. There are three steps to the process: vascular spasm, the formation of a platelet plug, and coagulation (blood clotting). Failure of any of these steps will result in hemorrhage—excessive bleeding.
When a vessel is severed or punctured, or when the wall of a vessel is damaged, vascular spasm occurs. In vascular spasm, the smooth muscle in the walls of the vessel contracts dramatically. This smooth muscle always has circular layers, while larger vessels also have longitudinal layers. The circular layers tend to constrict the flow of blood, whereas the longitudinal layers, when present, draw the vessel back into the surrounding tissue.
The vascular spasm response is believed to be triggered by several chemicals called endothelins that are released by vessel-lining cells and by pain receptors in response to vessel injury. This phenomenon typically lasts for up to 30 minutes, although it can last for hours.
In the second step, platelets, which normally float free in the plasma, encounter the area of vessel rupture with the exposed underlying connective tissue and collagenous fibers. The platelets begin to clump together, become spiked and sticky, and bind to the exposed collagen and endothelial lining. This process is assisted by a glycoprotein in the blood plasma called von Willebrand factor, which helps stabilize the growing platelet plug.
As platelets collect, they simultaneously release chemicals from their granules into the plasma that further contribute to hemostasis. Among the substances released by the platelets are:
Those more sophisticated and more durable repairs are collectively called coagulation, the formation of a blood clot. The process is sometimes characterized as a cascade because one event prompts the next as in a multi-level waterfall. The result is the production of a gelatinous but robust clot made up of a mesh of fibrin—an insoluble filamentous protein derived from fibrinogen, the soluble plasma protein introduced earlier—in which platelets and blood cells are trapped.
The figure below summarizes the three steps of hemostasis.
When your body needs to stop bleeding, it uses a series of steps called the coagulation cascade. This process involves special chemicals called clotting factors (or coagulation factors) that help form a blood clot. There are two main pathways that start the coagulation cascade process:
All three pathways are dependent upon the 12 known clotting factors, including Ca²⁺ and vitamin K, listed in the table below. Clotting factors are secreted primarily by the liver and the platelets. The liver requires the fat-soluble vitamin K to produce many of them. Vitamin K (along with biotin and folate) is somewhat unusual among vitamins in that it is not only consumed in the diet but is also synthesized by bacteria residing in the large intestine. The calcium ion, considered factor IV, is derived from the diet and from the breakdown of bone. Some recent evidence indicates that activation of various clotting factors occurs on specific receptor sites on the surfaces of platelets.
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Clotting Factors Table *Vitamin K required | ||||
|---|---|---|---|---|
| Factor number | Name | Type of molecule | Source | Pathway(s) |
| I | Fibrinogen | Plasma protein | Liver | Common; converted into fibrin |
| II | Prothrombin | Plasma protein | Liver* | Common; converted into thrombin |
| III | Tissue thromboplastin or tissue factor | Lipoprotein mixture | Damaged cells and platelets | Extrinsic |
| IV | Calcium ions | Inorganic ions in plasma | Diet, platelets, bone matrix | Entire process |
| V | Proaccelerin | Plasma protein | Liver, platelets | Extrinsic and intrinsic |
| VI | Not used | Not used | Not used | Not used |
| VII | Proconvertin | Plasma protein | Liver* | Extrinsic |
| VIII | Antihemolytic factor A | Plasma protein factor | Platelets and endothelial cells | Intrinsic; deficiency results in hemophilia A |
| IX | Antihemolytic factor B (plasma thromboplastin component) | Plasma protein | Liver* | Intrinsic; deficiency results in hemophilia B |
| X | Stuart–Prower factor (thrombokinase) | Protein | Liver* | Extrinsic and intrinsic |
| XI | Antihemolytic factor C (plasma thromboplastin antecedent) | Plasma protein | Liver | Intrinsic; deficiency results in hemophilia C |
| XII | Hageman factor | Plasma protein | Liver | Intrinsic; initiates clotting in vitro, and activates plasmin |
| XIII | Fibrin-stabilizing factor | Plasma protein | Liver, platelets | Stabilizes fibrin; slows fibrinolysis |
The quicker responding and more direct extrinsic pathway (also known as the tissue factor pathway) begins when damage occurs to the surrounding tissues, such as in a traumatic injury. Upon contact with blood plasma, the damaged extravascular cells, which are extrinsic to (external to) the bloodstream, release factor III. To this, factors IV and VII sequentially bind, forming an enzyme complex. This enzyme complex leads to the activation of factor X, which activates the common pathway discussed below. The events in the extrinsic pathway are completed in a matter of seconds.
The intrinsic pathway (also known as the contact activation pathway) is longer and more complex. In this case, the factors involved are intrinsic to (present within) the bloodstream. This pathway is most often initiated when factor XII comes into contact with foreign materials such as a glass test tube outside the body or molecules produced by previous chemical reactions inside the body. Upon contact, factor XII activates and in turn, activates factor XI, which then activates factor IX. Activated factor IX then combines with factor VIII to activate factor X, leading to the common pathway. Alternatively, the pathway can be prompted by damage to the tissues, resulting from internal factors such as arterial disease. The events in the intrinsic pathway are completed in a few minutes.
Both the intrinsic and extrinsic pathways lead to the common pathway, in which fibrin is produced to seal off the vessel. Once factor X has been activated by either pathway, the enzyme prothrombinase converts factor II, the inactive enzyme prothrombin, into the active enzyme thrombin. (Note that if the enzyme thrombin were not normally in an inactive form, clots would form spontaneously, a condition not consistent with life.) Then, thrombin converts the soluble blood protein fibrinogen (factor I) into the insoluble fibrin protein strands. Factor XIII then stabilizes the fibrin clot. This sequence of steps ensures that a stable blood clot forms to seal off the vessel and stop bleeding.
Once the clot is formed, contractile proteins within the platelets contract, pulling on the fibrin threads and bringing the edges of the clot more tightly together. This is somewhat similar to what you do when tightening loose shoelaces. This process also wrings out of the clot a small amount of fluid called serum, which is blood plasma without its clotting factors.
To restore normal blood flow as the vessel heals, the clot must eventually be removed. Fibrinolysis is the gradual degradation of the clot. Again, there is a fairly complicated series of reactions that involve factor XII and protein-catabolizing enzymes. During this process, the inactive protein plasminogen is converted into the active plasmin, which gradually breaks down the fibrin of the clot. Additionally, bradykinin, a vasodilator (promoting the dilation of blood vessels), is released, reversing the effects of the serotonin and prostaglandins from the platelets. This allows the smooth muscle in the walls of the vessels to relax and helps to restore the circulation.
An anticoagulant is any substance that opposes coagulation. Several circulating plasma anticoagulants play a role in limiting the coagulation process to the region of injury and restoring a normal, clot-free condition of blood. For instance, a cluster of proteins collectively referred to as the protein C system inactivates clotting factors involved in the intrinsic pathway. TFPI (tissue factor pathway inhibitor) inhibits the conversion of the inactive factor VII to the active form in the extrinsic pathway. Antithrombin inactivates factor X and opposes the conversion of prothrombin (factor II) to thrombin in the common pathway.
Additionally, as noted earlier, basophils release heparin, a short-acting anticoagulant that also inhibits thrombin and factor X. Heparin is also found on the surfaces of cells lining the blood vessels.
EXAMPLE
Multiple pharmaceutical forms of heparin are often administered therapeutically in surgical patients at risk for blood clots.SOURCE: THIS TUTORIAL HAS BEEN ADAPTED FROM OPENSTAX “ANATOMY AND PHYSIOLOGY 2E”. ACCESS FOR FREE AT OPENSTAX.ORG/BOOKS/ANATOMY-AND-PHYSIOLOGY-2E/PAGES/1-INTRODUCTION. LICENSE: CREATIVE COMMONS ATTRIBUTION 4.0 INTERNATIONAL.
