Hemostasis and the Clotting Cascade

Introduction to Hemostasis

• Hemostasis is the process by which the body stops bleeding.
• Involves the clotting cascade, where factors 1 to 13 play a role.

Importance of Blood Clotting

• Damage to a blood vessel exposes its internal contents, allowing blood plasma, red blood cells, white blood cells, ions, solutes, etc., to escape.
• Loss of blood contents can lead to decreased blood volume, oxygen carrying capacity, and potential death.
• Clots are formed to prevent this loss and facilitate healing.

Steps of Hemostasis

1. Vascular Spasm

• Reflexive vasoconstriction of a damaged blood vessel to mitigate blood loss.
• Involves release of vasoconstrictors:
  • Thromboxane A2: promotes vasoconstriction and platelet aggregation.
  • Serotonin and noradrenaline: also involved in vasoconstriction.

2. Platelet Plug Formation

• Damage exposes collagen in the basement membrane, which is negatively charged and sticky.
• Platelets (thrombocytes) adhere to exposed collagen.
• Von Willebrand factor (vWF) is released from endothelia and platelets:
  • Facilitates adhesion between platelets and collagen.
• Clinical note: Von Willebrand disease affects vWF secretion, impacting clotting ability.

3. Clotting (Coagulation) Cascade

• Converts fibrinogen to fibrin to form a stable clot.
• Clotting factors involved: 1, 2, 5, 7, 8, 9, 10, 11, 12, 13 (no factors 3, 4, or 6 used).

Clotting Cascade Pathways

Intrinsic Pathway

• Triggered by damage to the blood vessel itself.
• Factors involved: 12, 11, 9, 8, 10.

Extrinsic Pathway

• Triggered by tissue damage without blood vessel injury.
• Involves tissue factor (thromboplastin) and factor 7.

Common Pathway

• Both pathways converge at factor 10.
• Prothrombin (factor 2) is converted to thrombin.
• Thrombin converts fibrinogen (factor 1) to fibrin.
• Factor 13 cross-links fibrin to stabilize the clot.

Role of Vitamin K and Calcium

• Vitamin K carboxylates factors, allowing them to bind calcium.
• Calcium acts as a bridge, allowing factors to adhere to the site of injury.
• Deficiency can impair clotting, necessitating vitamin K injections in newborns.
• Blood samples are treated with anticoagulants like citrate to prevent clotting in vitro.

Conclusion

• Hemostasis is critical in preventing blood loss and ensuring survival.
• Understanding the clotting cascade and the roles of various factors is crucial for medical studies and practice.