Blood Coagulation: Overview, Definition, Factors, Facts, Signs and Treatment

What is Blood Coagulation?

Blood coagulation or clotting is a complicated process in which blood is changed from liquid to gel, forming a blood clot to prevent maximum blood loss due to damage to the vessel. This vital function comprises a sequence of events through which the activation of platelets and plasma proteins takes place to form a stable fibrin clot.

Blood Coagulation Process

The blood coagulation process represents a well-orchestrated sequence involving rapid and effective clotting. All these stages include vascular spasm, platelet plug formation, the coagulation cascade, clot retraction and repair, and finally fibrinolysis.

Vascular Spasm

When blood vessels are damaged, the circularly arranged smooth muscle contracts immediately, a reaction called vascular spasm. This reduces blood loss for several minutes to several hours. The spasm is caused by damage to the smooth muscle, by substances released from activated platelets, and by reflexes initiated by pain receptors.

Platelet Plug Formation

The adherence of platelets to the site of injury and their subsequent aggregation by each other onto fibrinogen, thereby forming a temporary "plug". The formation of platelet plug has following stages:

• Adhesion: The platelets are associated with exposed collagen fibres of the injured vessel.

• Activation: Chemicals released by the platelets attract more platelets.

• Aggregation: Platelets clump together, forming the plug.

Coagulation Cascade (Intrinsic, Extrinsic, Common Pathways)

Clotting is a complex cascade of enzymatic reactions in which each clotting factor activates many molecules of the next one in a fixed sequence. The involved factors range from I to XIII and include thrombin-like enzymes. Finally, a large quantity of product (the insoluble protein fibrin) is formed. Clotting can be divided into three stages:

• Intrinsic Pathway: This pathway is triggered by an injury in the vascular wall.

• Extrinsic Pathway: It gets activated on trauma, and blood is lost from the lumen of the vessel.

• Common Pathway: The intrinsic and extrinsic pathways merge to yield the production of fibrin.

Clot Retraction and Repair

Once a clot is formed, it plugs the ruptured area of the blood vessel and thus stops blood loss. Clot retraction is the tightening of the fibrin clot. As the clot retracts, it pulls the edges of the damaged vessel closer together, decreasing the risk of further damage.

Normal retraction depends on platelets in the clot, which release factor XIII and other factors, thereby strengthening and stabilizing the clot. Permanent repair of the blood vessel can then take place. In time, fibroblasts form connective tissue in the ruptured area, and new endothelial cells repair the vessel lining.

Fibrinolysis

Dissolution of a clot is called fibrinolysis. When a clot is formed, an inactive plasma enzyme called plasminogen is incorporated into the clot. Both body tissues and blood contain substances that can activate plasminogen to plasmin or fibrinolysin, an active plasma enzyme. Once plasmin is formed, it can dissolve the clot by digesting fibrin threads.

Coagulation Factors and Their Roles

Clotting involves several substances known as clotting (coagulation) factors. These factors include calcium ions (Ca2+), several inactive enzymes that are synthesized by liver cells and released into the bloodstream. Most clotting factors are identified by Roman numerals that indicate the order of their discovery.

Clotting Time and Methods

Clotting timings gauge how long it takes for a clot to develop. In the majority of tests, an activator is used to start coagulation and assess how well one or more parts of the coagulation cascade model respond. A reduced number or function of the coagulation components involved might cause abnormalities in clotting times.

There are three methods that can be used to estimate clotting time:

Capillary Method

• Use the lancet to prick the finger.

• The capillary will instantly fill if you place it above the blood.

• Now, rupture the capillary at regular intervals.

• The endpoint and clotting time is when a clot begins to form.

Test Tube Method

• Conduct this experiment at 37 ° C.

• Start the timer after collecting 4 ml of blood with the tube method. Take note of the moment the clot development initially appears.

• To improve accuracy, this test can be performed in many tubes.

Lee and White Method

• Take two 10-centimetre externally borated siliconised tubes.

• These tubes are prewarmed in a water bath at 37 °C.

• Take a sample of blood, primarily from the antecubital vein.

• 1 mL of the blood is placed in each test tube after 2 to 2.5 mL of the blood is drawn.

• As soon as you notice the blood in the syringe, start two stopwatches.

• Keep the blood in the water bath and tilt each tube every 30 to 60 seconds to check for clotting.

• Tilt the tube beyond a 90-degree angle.

• As soon as you notice the clot in the tube, stop the stopwatch.

Disorders of Blood Coagulation

The disorders lead to either an increase or a decrease in clotting, both conditions presenting significant health risks.

Hypercoagulability

• Excess clotting tendency due to genetic factors, drugs, or conditions such as cancer.

• Associated Conditions: Deep vein thrombosis, pulmonary embolism

• Treatment and Management: Anticoagulants, lifestyle modifications

Hypercoagulability

• The low ability of blood to form clots is usually due to genetics or as an effect of drugs.

• Conditions Associated: Haemophilia, von Willebrand disease.

• Treatment and Management: Replacement of clotting factors and supportive therapies.

Thrombosis and Deep Vein Thrombosis

A blood clot in the circulatory system is known as a thrombus. It adheres to the area where it originated and stays there, obstructing blood flow.

• Causes: Sedentary lifestyle, genetic propensity to blood clotting, develop after an artery, vein, or surrounding tissue is damaged.

• Symptoms: pain, swelling, and warmth in a limb, or chest pain and sudden shortness of breath

• Complications: Blood vessel clots can restrict blood flow. They can also separate and move about throughout your body, and if a clot lodges itself in a vital organ like your brain or lungs, it may result in serious conditions or even death.

Deep vein thrombosis or DVT refers to a circulatory disorder characterised by the formation of a blood clot or thrombus in the deep vein, usually of the lower limbs.

• Causes: Prolonged immobility, surgery, certain medications.

• Symptoms: Swelling, pain, redness, and warmth in the affected leg.

• Complications: The clot breaks loose and travels in the bloodstream to the lungs where it causes a pulmonary embolism.

Blood Coagulation Diagnostic Tests

Several tests are used to diagnose coagulation disorders and monitor the treatment of these disorders.

Prothrombin Time (PT)

• Purpose and Procedure: This test will determine how long it takes for blood to clot. It measures the extrinsic pathway.

• Interpretation of Results: Prolonged PT indicates clotting disorders or vitamin K deficiency.

Activated Partial Thromboplastin Time (aPTT)

• Purpose and Procedure: This is a measure of the time blood takes to clot, and tests intrinsic pathways.

• Interpretation of Results: Long aPTT is indicative of haemophilia or heparin therapy.

D-Dimer Test

• Purpose and Procedure: Assay fragments produced in the process of clot breakdown; are used to diagnose thrombotic disorders.

• Interpretation of Results: Elevated values indicate active clot formation and lysis.

Platelet Count

• Purpose and Procedure: Determine the number of platelets present in blood.

• Interpretation of Results: Too few, thrombocytopenia, excessive bleeding; too many, thrombocytosis, tendency to form clots.

Blood Coagulation NEET MCQs (With Answers & Explanations)

Types of questions that can be asked from this topic in NEET exam are:

• Process of blood coagulation

• Understanding the roles of clotting factors

• Intrinsic and extrinsic pathways in coagulation cascade

Q1. The blood cells involved in blood clotting are

1. Erythrocytes

2. Macrophages

3. Leucocytes

4. Thrombocytes

Correct answer: 4) Thrombocytes

Explanation:

Formed elements or blood cells constitute 45% of the blood. Blood corpuscles are of three types i.e. leukocytes (white blood cells), erythrocytes (red blood cells) and thrombocytes (blood platelets). The functions of RBC include the transport of O2 and CO2, maintenance of pH etc. The function of leukocytes in the defence against microbes and foreign particles. The function of thrombocytes is in blood clotting. The function of thrombocytes is in blood clotting.

Hence, the correct answer is option 4) Thrombocytes.

Q2. Haemolytic disease of the newborn occurs due to the passage of ____ in the foetus through the mother’s blood. Choose the correct option to fill in the blank

1. Anti-Rh antibodies

2. Rh antigens

3. ABO antibodies

4. None of the above

Correct answer: 4) Anti-Rh antibodies

Explanation:

Haemolytic disease of the newborn, or HDN, is a condition arising from the transmission of Rh antibodies from a mother to her foetus. This disorder typically occurs due to Rh incompatibility, where the mother is Rh-negative and the foetus is Rh-positive. During gestation, if there is a breach in the maternal-foetal barrier, such as during delivery or placental damage, the mother's body may identify the foetal Rh-positive red blood cells as foreign and mount an immune response by producing anti-Rh antibodies. In subsequent pregnancies with an Rh-positive foetus, these antibodies are capable of crossing the placenta and targeting the foetal erythrocytes, resulting in their destruction, a process known as haemolysis. This can lead to severe health issues for the newborn, emphasizing the importance of understanding and managing such conditions in medical practice.

Hence, the correct answer is option 1) Anti-Rh antibodies.

Q3. Factor -II a glycoprotein synthesised in the liver by vitamin - K is

1. Fibrin

2. Accelarine

3. Thrombin

4. Prothrombin

Correct answer: 4) Prothrombin

Explanation:

Factor II, commonly referred to as prothrombin, is a vital glycoprotein that is synthesized within the hepatic cells under the influence of vitamin K. This substance plays an indispensable role in the intricate process of hemostasis, specifically within the coagulation cascade. Upon activation by prothrombinase, prothrombin is converted into thrombin, which is a key enzyme facilitating the formation of blood clots. The significance of vitamin K lies in its role in the post-translational modification of prothrombin, namely the γ-carboxylation process, which equips the protein with the capability to bind calcium ions, thus enhancing its participation in coagulation. The synthesis of prothrombin occurs in the liver, where it is produced as an inactive precursor known as a zymogen, which is later activated during the critical steps of blood clot formation.

Hence, the correct answer is option 4) Prothrombin.

Also Read:

• MCQs on Blood Coagulation

• Body Fluids and Circulation

• Breathing and Exchange of Gases

Recommended Video on Blood Coagulation