Hemostasis: Vascular Spasm & Clotting Cascade

• Hemostasis minimizes blood loss for 20-30 minutes.

Vascular Spasm

• Vasoconstriction is due to vessel walls being pressed together, becoming adherent.
• Most vasoconstriction results from direct injury to vascular smooth muscle cells.
• Endothelin released from endothelial cells contributes to vasoconstriction.
• Neural reflexes from local pain receptors also contribute to vasoconstriction.

Clotting Cascade

• Coagulation cascade refers to a series of steps that forms a blood clot after injury by activating clotting factors.
• There are 12 clotting factors.
• The three pathways are intrinsic, extrinsic, and common pathways.

Intrinsic Pathway

• Stops bleeding within a cut vessel.
• Factor XII (Hageman Factor) is the starting point.
• Clotting factors involved are XII, XI, IX, VIII, and X.

Extrinsic Pathway

• Clots blood that has escaped into tissues.
• Factor III (Tissue Thromboplastin) is the starting point.
• Clotting factors involved are III, VII, and X.

Common Pathway

• Convergence point of the intrinsic and extrinsic pathways toward clot formation.
• Factor X is activated, leading to the activation of prothrombin into thrombin, which then converts fibrinogen into fibrin.
• Fibrin is stabilized by Factor XIII to form a stable fibrin clot.

Disorders of Blood Coagulation

• Hereditary deficiency of clotting factors leads to conditions like hemophilia A (factor VIII deficient) and hemophilia B (factor IX deficient).
• Vitamin K deficiency can cause decreased synthesis of prothrombin and factors VII, IX, and X in the liver.
• Liver diseases can cause defective production of coagulation factors, as the liver produces most clotting factors.
• Common symptoms of hemophilia include bruising, nosebleeds, bleeding into joints, prolonged bleeding from cuts or injuries, bleeding of the mouth and gums, and blood in the urine or stool.

Role of Thrombin in Hemostasis

• Prothrombin, a plasma protein, is formed in the liver with vitamin K and is converted to thrombin.
• Thrombin acts on fibrinogen (in the liver) to be turned into fibrin.
• Thrombin stimulates tissue factor formation.
• Thrombin stimulates the release of platelet factor-3.
• Thrombin forms a positive feedback loop, involving both the intrinsic and extrinsic pathways, and accelerates clotting.

Bleeding Time

• Bleeding time is a laboratory test assessing platelet function and the body's ability to form a clot.
• The test involves making a puncture wound in a superficial skin area and monitoring the bleeding time.
• Normal bleeding time is 4-9 minutes.

Characteristics of Platelets

• Platelet membranes contain receptors for collagen, Von Willebrand factor (for platelet adhesion), and fibrinogen.
• The platelet membrane contains phospholipids that play roles in blood clotting.
• Platelet cytoplasm contains actin, myosin, glycogen, and lysosomes.
• Platelets have two types of granules: dense granules (ADP, ATP, serotonin) and granules containing clotting factors and platelet-derived growth factor.

Clot Dissolution

• Clots are slowly dissolved by plasmin, a "fibrin splitting" enzyme.
• Plasminogen, an inactive precursor, is activated by Factor XII (Hageman Factor) during clot formation to become plasmin.
• Plasmin, trapped in the clot, dissolves it by breaking down the fibrin meshwork.

Platelet Adhesion Prevention

• Platelets do not adhere to the endothelium (inner lining) of undamaged blood vessels due to intact endothelial cells being very smooth.
• Intact endothelial cells release nitric oxide and prostaglandin (prostacyclin) to prevent platelet aggregation.
• These chemicals restrict platelet aggregation to the site of injury.