Blood Clotting: Mechanisms and Stages | Blood | Hematology | Biology

In this article we will discuss about the mechanisms and stages of blood clotting.

Mechanism of Blood Clotting:

Blood Clotting is one of three mechanisms that reduce the loss of blood from broken blood vessels.

The three Mechanisms are:

i. Vascular Spasm:

The smooth muscle in blood vessel walls contracts immediately the blood vessel is broken. This response reduces blood loss for some time, while the other haemostatic mechanisms become active.

ii. Platelet Plug Formation:

When blood platelets encounter a damaged blood vessel they form a “platelet plug” to help to close the gap in the broken blood vessel. (The key stages of this process are called platelet adhesion, platelet release reaction, and platelet aggregation)

iii. Coagulation:

Following damage to a blood vessel, vascular spasm occurs to reduce blood loss while other mechanisms also take effect. Blood platelets congregate at the site of damage and amass to form a platelet plug. This is the beginning of the process of the blood “breaking down” from its usual liquid form in such a way that its constituents play their own parts in processes to minimize blood loss.

Blood normally remains in its liquid state while it is within the blood vessels but when it leaves them the blood may thicken and form a gel (coagulation). Blood clotting (technically “blood coagulation”) is the process by which (liquid) blood is transformed into a solid state.

This blood clotting is a complex process involving many clotting factors (incl. calcium ions, enzymes, platelets, damaged tissues) activating each other.

Stages of Blood Clotting:

1. Formation of Prothrombinase:

Prothrombinase can be formed in two ways, depending of which of two “systems” or “pathways” apply.

These are:

i. Intrinsic System:

This is initiated by liquid blood making contact with a foreign surface, i. e. something that is not part of the body; or

ii. Extrinsic System:

This is initiated by liquid blood making contact with damage tissue.

Both the intrinsic and the extrinsic systems involve interactions between coagulation factors. These coagulation factors have individual names but are often referred to by a standardised set of Roman Numerals, e.g. Factor VIII (anti-haemophilic factor), Factor IX (Christmas factor).

2. Prothrombin Converted Into the Enzyme Thrombin:

Prothrombinase (formed in stage 1.) converts prothrombin, which is a plasma protein that is formed in the liver, into the enzyme thrombin.

3. Fibrinogen (Soluble) Converted to Fibrin (Insoluble):

In turn, thrombin converts fibrinogen (which is also a plasma protein synthesized in the liver) into fibrin.

Fibrin is insoluble and forms the threads that bind the clot

There are two pathways that lead to the conversion of prothrombin to thrombin:

(1) The intrinsic pathway and

(2) The extrinsic pathway.

(1) Intrinsic Pathway:

The intrinsic pathway, which is triggered by elements that lie within the blood inself (intrinsic to the blood), occurs in the flowing way. Damage to the vessel wall stimulates the activation of a cascade of clotting factors (for the sake of simplicity we will not consider the individual factors). This cascade results in the activation of factor X.

Activated factor X is an enzyme that converts prothrombin to thrombin. Thrombin converts fibrinogen to fibrin monomers, which then polymerize in fibrin fibers. Fibirin fibers form a losse meshwork that is stabilized by crosslinks created by factor XIII. The stabilized meshwork of fibrin fibers ins now a clot that traps red blood cells and platelets and thus stops the flow of blood.

(2) Extrinsic Pathway:

The extrinsic pathway is triggered by tissue damage outside of the blood vessel. This pathway acts to clot blood that has escaped from the vessel into the tissues. Damage to tissue stimulates the activation of tissue thromboplastin, an enzyme that catalyzed the activation of factor X. At this point the intrinsic and extrinsic pathways converge and the subsequent steps are the same as those described above.

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Thrombocytopenia:

Small tears of the capillaries and arterioles are happening all the time Platelets are responsible for quickly sealing these tears before the slower process of clotting completes the job.

In the absence of adequate numbers of platelets these micro blotches (thrombocytopenia purpura) visible on the skin. Thrombocytopenia can be acute or chronic and has many causes. Severe, untreated cases result in death.

3. Clotting of Blood:

The blood contains about a dozen clotting factors. These factors are proteins that exist in the blood in an inactive state, but can be called into action when tissues or blood vessels are damaged.

The activation of clotting factors occurs in a sequen­tial manner. The first factor in the sequence activates the second factor, which activates the third factors and so on. This series of reactions is called the clotting cascade.

Blood clotting is the transformation of liquid blood into a semisolid gel. Clots are made from fibers (polymers) of a protein called fibrin. Fibrin monomers come from an inactive precursor called fibrinogen.

The body of the fibrinogen molecule has caps on its ends that mast fibrin-to-fibrin binding sites. If the caps are removed then fibrin monomers polymerize to form fibrin polymers. This process required thrombin the enzyme that converts fibrinogen to fibrin.

This process also requires calcium, which acts as a kind of glue to hold the fibrin monomers to each other to form the polymeric fiber. The fibrin fibers form a loose mesh work that is stabilized by clotting factor XIII. The stabilized meshwork of fibrin fibers traps erythrocytes, thus forming a clot that stops the flow of blood.

Clot Busting Drugs:

Blood clots can be life-threatening if they form inappropriately in critically locations. Clots that block coronary arteries cause the heart attacks, while clots that block arteries in the brain cause stroke. Drugs that can mediate the removal of clots, “clot busters”, are used in cases of heart attract and stroke to decrease the damage caused by the clot.

Drugs used clinically to remove cots include:

1. Tissue plasminogen activator (TPA) was recently cloned and is now produced in mass quantities by the biotech fig, Amgen. It is used clinically to dissolved clots in coronary arteries following a heart attack. It is also used to dissolved clots in the brain following stroke.

2. Streptokinase is an enzyme that directly dissolved blood clots. It is produced by streptococcus bacteria. The bacteria use streptokinase to dissolve clots that nega­tively affect their growth in the human host. This clot dissolving enzyme is appar­ently as effective as recombinant TPA.

Streptokinase cost $2 dollars per does while TPA costs $2000 dollars per dose. Based on economic concerns, streptokinase is the drug of choice. However, streptokinase is not a human enzyme, therefore the immune system sees it as a foreign molecule that should be distorted.

The immune response increases with repeated use of this limits the effectiveness of the drug over time. TPA, on-the-other-hand is a huna molecule whole which the im­mune system does not destroy.