One of the most fascinating systems in our bodies is the circulatory system. The system whose center is the heart from which vessels branch functions to supply the body with its need for oxygen and nutrients. The perfect carrier for such substances is the blood. Our blood is formed of a fluid medium called the plasma in which cells flow. Our blood cells are red blood cells, white blood cells, and the cellular fragments, the platelets.
Why do we need coagulation?
Our blood must be fluid to pass with ease through the small capillaries to supply every inch of our bodies. This comes with the problem of bleeding. The fluidity of blood will allow it to flow easily through even small wounds which can be life-threatening. That is why we need coagulation. Coagulation is the ability of the blood to form solid plugs whenever a tissue defect is present in our blood vessels. This must be done promptly within minutes or an excessive amount of blood will be lost.
How does our coagulation system work?
Our blood is prevented from flowing endlessly by three main mechanisms:
- Our blood vessels: Blood vessels aren’t rigid pipes and their walls are formed of elastic fibers with muscles. If a blood vessel is injured, it will reflexively contract, causing a decrease in blood flow, minimizing blood loss.
- Platelets: Platelets are fragments of larger cells in the bone marrow called megakaryocytes. Platelets have different functions and lay the groundwork for forming the blood clot. They are considered the first responders when a blood vessel injury occurs.
- Coagulation factors: Coagulation factors are proteins present in an inactive form. They are activated in a cascade-like manner by two pathways, the extrinsic and intrinsic ones. Coagulation factors are mostly produced by the liver and are the main site of action of blood thinners like Warfarin and Heparin.
When the blood vessel is injured, its inner lining becomes rough, stimulating platelets to adhere to it. Platelets then signal each other to aggregate on the defect occluding it. Platelets also start the coagulation cascade through the activation of factor XII (12) by the release of specific polymers. The cascade proceeds in a domino-like fashion and ends by the formation of fibrin threads. These threads eventually trap red blood cells, white blood cells, and platelets forming the blood clot.
For coagulation to occur, a disturbance must happen either in the intactness of blood vessels lining, the activation of coagulation factors, or the regular, seamless flow of blood. This is called Virchow’s triad.
A double-edged weapon
Blood clotting should never occur except when an injury happens. Otherwise, the blood clot will unnecessarily occlude a blood vessel, depriving tissues of oxygen and nutrients causing their death. This is called ischemia if the occlusion is incomplete or infarction if it is complete. A prime example can be seen in the heart’s blood vessels when a heart attack happens due to a blood clot. Therefore, coagulation is kept in a delicate balance by the action of natural anticoagulants and fibrinolytics.
Anticoagulants are natural proteins found in the blood in an inactive form. They are activated once coagulation occurs to maintain the balance. They act directly on coagulation factors, limiting their activation. Anticoagulants include antithrombin III, protein C, protein S and thrombomodulin.
The fibrinolytic system is concerned with dissolving the blood clot once it serves its purpose as well as getting rid of abnormally formed blood clots -as in healthy blood vessels-. The main fibrinolytic is called plasmin in its active form and plasminogen in its inactive form. One of the most effective therapies in strokes is an activator for this enzyme. Plasmin breaks fibrin down to smaller molecules called fibrin degradation products. The major fibrin degradation product is called D-dimer and is frequently assessed when a deep venous thrombosis is suspected.
Preventing blood clotting
Blood clotting is essential for the body to function properly, and an impaired coagulation system can be fatal in some cases. Nevertheless, it can also be excessive and needs to be toned down. This is seen in some congenital disorders, autoimmune conditions like antiphospholipid syndrome, or can even be a result of some cancers. Blood vessels may also be diseased by atherosclerosis and their walls become so rough that anticoagulation is needed to prevent clotting within them. In some cases, artificial heart valves or blood vessel grafts may need anticoagulation since their surface is rougher than their natural counterparts.
Anticoagulation can be achieved by 2 main mechanisms; the first is antiplatelet drugs which don’t act directly on the coagulation system, but rather impair platelet function. The main drugs used for that purpose are Aspirin and Clopidogrel. They prevent platelets from adhering to the vessel wall and aggregating. The second, more effective method involves direct action on the coagulation factors. Common drugs used for that purpose include Warfarin which acts on vitamin K, which is needed to produce 4 essential coagulation factors: II, VII, IX, and X. Warfarin is the most widely used anticoagulant because it doesn’t need injections. Other anticoagulants include heparin, which acts by increasing the activity of the natural anticoagulant, antithrombin III, while low molecular weight heparin acts on factor X. There are some drugs like Warfarin that need regular monitoring through some tests to make sure that anticoagulation is controlled; otherwise, bleeding may be severe.
Treating blood clots
Blood clots occluding arteries or veins can cause severe complications including the death of the tissue they supply with oxygen. A small gap of a few minutes usually exists between the complete occlusion and the start of tissue death, and in this small gap, doctors try to restore the circulation. This can be achieved by:
- Anticoagulation: Blood clot keeps growing once it settles in the blood vessel, and its control by anticoagulation is essential.
- Mechanical removal: Removal of the blood clot is done by a catheter inserted into the blood vessels of the thigh and moved up to the site of occlusion. This is the most definitive method of treatment.
- Fibrinolytic drugs; Fibrinolytic drugs like streptokinase or alteplase act by dissolving the blood clot either directly or through the activation of the body’s innate fibrinolytic system (plasmin). They may not be as effective as mechanical removal but can be the only choice in patients not fit to do any invasive procedure or those choosing not to. It also carries a higher risk of bleeding from the same or other sites.