is required for clotting of blood
Answers
Answer:
● Platelets are required for clotting of blood.
Explanation:
Index to this page
Initiating the Clotting Process
Amplifying the Clotting Process
Platelets
Bleeding Disorders
Treating Hemophilia A and B
Controlling Clotting
Dissolving Clots
Angiogenesis
Blood Clotting
When blood vessels are cut or damaged, the loss of blood from the system must be stopped before shock and possible death occur. This is accomplished by solidification of the blood, a process called coagulation or clotting.
A blood clot consists of
a plug of platelets enmeshed in a
network of insoluble fibrin molecules.
Platelet aggregation and fibrin formation both require the proteolytic enzyme thrombin. Clotting also requires:
calcium ions (Ca2+)(which is why blood banks use a chelating agent to bind the calcium in donated blood so the blood will not clot in the bag).
about a dozen other protein clotting factors. Most of these circulate in the blood as inactive precursors. They are activated by proteolytic cleavage becoming, in turn, active proteases for other factors in the system.
By tradition, these factors are designated by Roman numerals. I find this somewhat cumbersome and will use Arabic numerals as well.
Initiating the Clotting Process
There are two processes that can initiate clotting:
A very rapid process the so-called extrinsic pathway (upper right) and
a slower but larger intrinsic pathway (upper left).
The Extrinsic Pathway
Damaged cells display a surface protein called tissue factor (TF)
Tissue factor binds to activated Factor 7 (VII).
The TF-7 heterodimer is a protease with two substrates:
Factor 9 (IX) and
Factor 10 (X).
The Intrinsic Pathway
Factor 12 (XII) (also called the Hageman factor) circulates in the blood.
If blood escapes into tissue spaces (e.g., as a result of an injury), contact with collagens in the tissue space activates Factor 12.
Activated Factor 12 is a serine protease that activates Factor 11 (XI) which, in turn, activates
Factor 9 which, in turn, activates
Factor 10.
The Two Pathways Converge
Factor 10 — produced by either or, more likely, both pathways — binds and activates Factor 5 (V). This heterodimer is called prothrombinase because it is a protease that converts prothrombin (also known as Factor II) to thrombin.
Thrombin has several different activities. Two of them are:
proteolytic cleavage of fibrinogen (aka "Factor I") to form:
soluble molecules of fibrin and a collection of small
fibrinopeptides
activation of Factor 13 (XIII) which forms covalent bonds between the soluble fibrin molecules converting them into an insoluble meshwork — the clot.
(Thrombin and activated Factors 10 ("Xa") and 11 ("XIa") are also serine proteases. Link to discussion.)
Amplifying the Clotting Process
The clotting process also has several positive feedback loops which quickly magnify a tiny initial event into what may well be a lifesaving plug to stop bleeding.
The TF-7 complex (which started the process) also activates Factor 9.
Factor 9 binds to Factor 8 (VIII), a protein that circulates in the blood stabilized by another protein, von Willebrand Factor (vWF).
This complex activates more Factor 10.
As thrombin is generated, it activates more
Factor 5
Factor 8 (VIII), and
Factor 11 (all shown above with green arrows).
Factor 11 amplifies the production of activated Factor 9.
Thus what may have begun as a tiny, localized event rapidly expands into a cascade of activity.
Platelets
Platelets are cell fragments produced from megakaryocytes.
Blood normally contains 150,000 to 400,000 per microliter (µl). If this value should drop much below 20,000/µl, there is a danger of uncontrolled bleeding. This is because of the essential role of platelets
in maintaining the integrity of the adherens junctions that provide a tight seal between the endothelial cells that line the blood vessels;
in forming a clot where blood vessels have been broken.
When blood vessels are damaged, fibrils of collagen in the extracellular matrix (ECM) are exposed. Platelets then begin to adhere to the collagen through the action of
specific receptors for collagen present on their plasma membrane
von Willebrand factor which links the platelets to the collagen.
These actions cause a plug of platelets to form at the site.
The bound platelets release
ADP and thromboxane A2, which recruit and activate still more platelets circulating in the blood. (This role of thromboxane accounts for the beneficial effect of low doses of aspirin — a cyclooxygenase inhibitor — in avoiding heart attacks.)
tissue factor
serotonin, which enhances their clumping and promotes constriction of the blood vessel.
ReoPro® is a monoclonal antibody directed against platelet receptors. It inhibits platelet aggregation and appears to reduce the risk that "reamed out" coronary arteries (after coronary angioplasty) will plug up again.
B.