Hemostasis and Blood Clotting

Hemostasis

• Hemostasis is the process of stopping bleeding.
• It involves three key steps:
  • Vascular spasm: Narrowing of the blood vessel to reduce blood flow.
  • Platelet plug formation: Platelets adhere to the damaged vessel wall, forming a temporary plug.
  • Coagulation cascade: A complex series of reactions leading to the formation of a stable blood clot.

Platelet Plug Formation

• ADP and Thromboxane A2 are important in platelet activation.
• Platelets adhere to exposed collagen and other proteins (like von Willebrand factor).
• Platelets release granules containing substances that activate more platelets.
• Activated platelets cross-link, forming a plug.

Blood Clot Formation

• Prothrombin activator converts prothrombin to thrombin.
• Thrombin converts soluble fibrinogen to insoluble fibrin.
• Fibrin threads form a mesh, trapping blood cells and platelets.
• Factor XIII stabilizes fibrin.

Intrinsic and Extrinsic Pathways

• The intrinsic pathway is activated by damage to the inside of the blood vessel.
• The extrinsic pathway is activated by damage outside the blood vessel.
• Both pathways converge to activate Factor X, which is a key step in the common pathway.

Fate and Course of the Clot

• Fibroblasts invade the clot, converting it into a fibrous tissue.
• The clot is usually completely organized within 1 to 2 weeks.
• Clots form in response to damage to the small holes in the blood vessels.
• The clot ultimately dissolves through a process of fibrinolysis (breakdown).

Natural Anti-clotting Mechanism

• Blood fluidity is maintained by endothelial surface factors.
  • Smoothness of endothelial surface prevents activation of the intrinsic pathway.
  • Glycocalyx (mucopolysaccharide layer) repels clotting factors and platelets.
  • Thrombodulin on endothelial membranes activates protein C, which inactivates factors V and VIII.
• Blood factors:
  • Adsorption: 85-90% of thrombin is adsorbed to fibrin threads, preventing clot spread.
  • Fibrinolytic system: Continuously removes small clots.
  • Antithrombin III: Combines with unbound thrombin and inactivates it.

Heparin

• Produced by mast cells and basophils in tissues surrounding the lungs and liver.
• Co-factor for antithrombin III.
• When combined, Heparin and antithrombin III greatly increase the activity of antithrombin III (100-1000 times).
• Heparin-antithrombin complex removes several activated factors (XII, XI, IX, X).

Fibrinolytic System (Plasmin System)

• Plasminogen (profibrinolysin): Inactive plasma protein.
• Plasmin: Active enzyme that digests fibrin and other clotting factors (V, VIII, prothrombin, XII).
• Plasminogen activation converts plasminogen to plasmin.

Mechanism of Plasminogen Activation

• Tissue plasminogen activator (t-PA) and Urokinase.

  • t-PA is released by injured tissues and converts plasminogen to plasmin.
  • Urokinase is produced by certain types of bacteria (like hemolytic streptococci).
  • Thrombin and active factor XII activate plasminogen along with t-PA.
  • t-PA and urokinase are used in the treatment of early acute myocardial infarction to dissolve the clot.

• Plasmin inhibitor: Regulates the activity of plasmin.

Protein C Role in Fibrinolysis

• Protein C inactivates the inhibitor for tissue plasminogen activator (t-PA).
• This release in turn stimulates fibrinolysis.

Significance of Fibrinolysis

• Reopens blood vessels after flow blockage by clots.
• Prevents blood clotting in the urinary tract.
• Prevents blood clots in menstrual blood.
• Stimulates early stages of myocardial infarction fibrinolysis by intravenous injection of t-PA or local injection of streptokinase or urokinase via cardiac catheter.

Anti-coagulants

• In vitro: prevent clotting in collected blood samples using citrate, EDTA, silicone-coated tubes, or heparin addition.
  • Citrate: used to precipitate calcium.

Anti-coagulants (In vivo)

• Heparin: Acts by activating antithrombin III
• Coumarin derivatives (e.g., dicumarol, warfarin): Inhibit vitamin K dependent clotting factors.

Thromboembolic Conditions

• Thrombus: Abnormal blood clot inside a blood vessel.
• Embolus: Detached thrombus that travels through blood vessels.
• Deep Vein Thrombosis (DVT): Blood clot in a deep vein.
  • Causes include slow blood flow, rough endothelium, and long bed rest.

Thromboembolic Conditions: Prevention and Treatment

• Prevention: Anticoagulant drugs (heparin, warfarin), tissue plasminogen activators (t-PA).
• Treatment: t-PA, streptokinase, urokinase for clot dissolution.

This quiz covers the essential processes of hemostasis, including vascular spasm, platelet plug formation, and the coagulation cascade. Test your knowledge on the key components and pathways involved in stopping bleeding and forming blood clots.