Hemostasis - Causes, Stages, Pathways, And Related Disorders.

What Is Hemostasis?

Hemostasis is a biological or physiological process that arrests the blood flow at the site of the injury, preventing blood loss, and maintaining the fluid state of the blood in the bloodstream. The mechanism of hemostasis comprises four steps, including the primary and secondary stages.

How Does Blood Regulate Normally in the Body?

Before describing more about hemostasis, it is essential to understand how the blood keeps itself naturally thin and prevents itself from becoming a clot.

Blood vessels have a thin layer of cells - called the endothelium (largest endocrine organ) made up of endothelial cells which are in direct contact with blood and then they are called vascular endothelial cells, connective tissues like collagen, smooth muscle cells, which have specific types of receptors, and some pain receptors.

The endothelial cells secrete some chemical such as nitric oxide and prostacyclin (PGI2), which binds with the flowing platelet in the blood and prevents the platelet from attaching to the surface. In addition, some other proteins are present over the surface of the endothelial cells, like heparin sulfate and thrombomodulin, which will inactivate the clotting factors.

What Are the Stages of Hemostasis?

Hemostasis has four steps that occur in a continuous rapid sequence.

• Constriction of blood vessels.

• Formation of the platelet plug.

• Coagulation.

1) Constriction of Blood Vessels-

Constriction of blood vessels is also known as vasoconstriction or vascular spasms. Vasoconstriction means narrowing blood vessels, which increases blood pressure and decreases blood flow directed by underlying smooth muscle.

Vasoconstriction Mechanism - The vasoconstriction mechanism has three events.

1. Endothelin - When the endothelial cells get injured, they secret an endothelin chemical. This endothelin binds with the receptors on smooth muscles and activates intracellular mechanisms, causing vasoconstriction.

2. Myogenic - If the injury directly enters the endothelium wall or comes in direct contact with the smooth muscles causes vasoconstriction.

3. Nociceptors - These are the pain receptors present in the structure of endothelium. Whenever these receptors get stimulated, they cause pain, leading to vasoconstriction at the time of injury.

2) Formation of Platelet Plug-

• Platelets are small enucleate cells about one to four micrometers in size; these are the tiny pieces of a giant cell called megakaryocytes in the bone marrow.

• These cells help form clots and slow the blood flow; the normal platelet count is 150,000 to 450,000 per microliter of blood.

• The formation of the platelet plug comes under the primary stage. It starts when there is an injury resulting in damage to endothelium cells, collagen, or the smooth muscle, the endothelium cells release a protein called Von Willebrand factor.

• A specific protein, glycoprotein 1b (Gp1b), binds to the surface of the factor to which the platelets get attached and activated.

• As platelets are activated, their granules start releasing three types of chemicals, i.e., adenosine diphosphate (ADP), thromboxane (TxA2), and serotonin; when an adenosine diphosphate (ADP) and thromboxane (TxA2) chemicals combine and activate the platelets to bind to the site of injury.

• This process is known as an aggregation of platelets. And thromboxane (TxA2) and serotonin bind with the smooth muscle at the site of the injury resulting in vasocontraction to enhance vascular spasms and form the platelet plug.

3) Coagulation -

Coagulation is when blood loses fluidity and forms a clot. Clotting factors are proteins in the form of enzymes needed for coagulation. Coagulation of the blood goes through a sequel of clotting factors involved in converting proenzymes to active enzymes. Blood contains different factors produced by the liver.

Blood clotting or coagulation occurs in three stages -

1. Formation of prothrombin activator.

2. Conversion of prothrombin into thrombin.

3. Conversion of fibrinogen into fibrin.

All these stages occur through three pathways.

1) Intrinsic Pathway- The intrinsic pathway follows the following steps

1. The endothelium, smooth muscle, and collagen get damaged and exposed at the site of injury.

2. The exposed collagen activates factor XII (Hageman factor) in the presence of a high molecular weight kininogen.

3. The activated factor XII (Hageman factor) converts the factor XI (plasma thromboplastin antecedent factor) into active factor XI (plasma thromboplastin antecedent factor)

4. The activated factor XI (plasma thromboplastin antecedent factor) activates factor IX (Christmas factor) in the presence of factor V (calcium).

5. The activated factor IX (Christmas factor) activates factor X (Stuart-Prower factor) in the presence of factor VIII (antihemophilic factor) and calcium.

6. The exposed collagen comes in contact with platelets and releases phospholipids.

7. The activated factor X (Stuart-Prower factor), phospholipids, and factor V (Calcium) react to form a prothrombin activator.

2) Extrinsic Pathway - The extrinsic pathway follows the following steps.

1. At the site of injury, the damaged tissues release factor III (thromboplastin).

2. Factor III (thromboplastin) contains proteins, phospholipids, and glycoproteins.

3. Glycoprotein and phospholipids components of thromboplastin convert factor X (Stuart-Prower factor) into active factor X (Stuart-Prower factor) in the presence of factor VII (stable factor).

4. The activated factor X (Stuart-Prower factor) with factor V (calcium) and phospholipids react to form a prothrombin activator.

3) Common Pathway -

1. The prothrombin activator formed in intrinsic and extrinsic pathways converts prothrombin into thrombin in the presence of factor V (calcium).

2. The effect of thrombin is called positive feedback.

3. The thrombin converts inactive fibrinogen into activated fibrinogen; the activated fibrinogen is called – a fibrin monomer.

4. The fibrin monomer polymerizes with other monomers and forms loosely arranged fibrin strands.

5. These loose strands of fibrin are modified into dense and tight fibrin threads by factor XIII (fibrin-stabilizing factor) in the presence of calcium ions.

6. All the tight fibrin threads are aggregated to form a meshwork of stable clots.

What Is Fibrinolysis?

• Fibrinolysis is a process of breaking the blood clot inside the blood vessel.

• The process needs a primary substance called plasmin or fibrinolysin.

• Plasmin is formed from inactivated plasminogen synthesized in the liver.

• Plasminogen is converted into plasmin by the plasminogen activator (tPA), lysosomal enzymes, and thrombin.

• Plasminogen activator (tPA) is activated by the thrombin binding protein, thrombomodulin, secreted by the endothelium cells.

What Are Anticoagulants?

Anticoagulants are substances that prevent blood coagulation, also known as blood thinners.

• Heparin -

  • Heparin is a naturally produced anticoagulant in the body.

  • It prevents blood clotting by its antithrombin activity, and it also inactivates the active form of other clotting factors like factor IX (Christmas factor), factor X (Stuart-Prower factor), factor XI (plasma thromboplastin antecedent ), factor XII (Hegeman factor).

• Warfarin and Discoumoral -

  • Warfarin and discoursal prevent blood clotting by inhibiting the action of vitamin K.

  • Vitamin factor is essential for the formation of the various clotting factors, like factor II (prothrombin), factor VII (stable factor), factor IX (Christmas factor), and factor X (Stuart-Prower factor).

What Are the Disorders Related to Hemostasis?

Bleeding Disorder is a condition characterized by prolonged bleeding or clotting time.

1) Hemophilia -

Hemophilia is a genetically transmitted disorder causing prolonged clotting time.

It is caused mainly by the deficiency of factor VIII (antihemophilic factor).

2) Purpura -

Purpura is characterized by prolonged bleeding time.

There is a clinical feature of hemorrhagic spots over the skin due to the ruptured capillaries beneath the skin.

3) Von Willebrand Disease -

Von Willebrand Disease is characterized by excessive bleeding.

It is caused due to the deficiency of the Von Willebrand factor, which is secreted by the endothelium.

4) Thrombosis -

Thrombosis is known as the coagulation of the blood inside the blood vessels. The causes of thrombosis are-

1. Injury to blood vessels.

2. Decreased rate of blood flow.

3. Toxic thrombosis.

4. Absence of protein C.

5. Absence of protien S.

6. Absence of antithrombin 3.

7. Presence of mutated factor V Leiden.

8. Essential Thrombocytosis.

9. Polycythemia.

What Are Investigation Tests for Hemostasis?

1. Bleeding time.

2. Clotting time.

3. Prothrombin time.

4. Partial prothrombin time.

5. D- dimer.

6. Thrombin time.

What Are the Signs and Symptoms of Hemostasis for Self-Assessment?

Some basic day-to-day activities can help an individual understand if their bleeding and clotting time is prolonged or regular.

Following are some signs of bleeding disorders -

• Mild injury bleeds too much.

• Dark-colored bruises are present.

• Gum bleeding.

• Nose bleeding or epistaxis.

Conclusion -

Hemostasis is a natural way for the body to maintain balance and fight against infection. It has three stages that work in harmony in normal conditions. Clotting factors play an essential role in the coagulation process. One can take recommended medical attention to mitigate threats when hemostasis is diagnosed.