Hemostasis and Blood Coagulation

Hemostasis

• Hemostasis is the localized stoppage of blood flow.
• Hemostasis is initiated following damage to blood vessels.
• Five steps are involved in the hemostasis process: vascular spasm, platelet plug formation, coagulation, clot retraction and repair, and fibrinolysis.

Blood's Natural Anti-Coagulant Mechanisms

• Endothelial cells secrete nitric oxide and prostacyclin, inhibiting platelet activation and preventing platelet adhesion to the endothelial lining.
• Heparin sulfate, a glycosaminoglycan on the plasma membrane, activates antithrombin III.
• Activated antithrombin III inactivates clotting factors II, IX, and X.
• Thrombomodulin binds to thrombin (factor II).
• Thrombin activates protein C, which degrades factors V and VIII, preventing their activation.

Vascular Spasm

• Vascular spasm is the immediate constriction of blood vessels following injury.
• Endothelin, released by injured endothelial cells, binds to smooth muscle receptors, causing contraction.
• Myogenic mechanism: Direct injury or contact with the smooth muscle wall triggers contraction.
• Nociceptors activated by inflammatory chemicals (e.g., histamines, leukotrienes, prostaglandins) trigger a reflex leading to vasoconstriction.

Platelet Plug Formation

• Injured endothelial cells release von Willebrand factor.
• Platelets bind to von Willebrand factor through glycoprotein 1B receptors.
• Activated platelets release ADP, thromboxane A2, and serotonin.
• ADP and thromboxane A2 stimulate platelet aggregation, forming a platelet plug.
• Thromboxane A2 and serotonin bind to smooth muscle receptors, causing vasoconstriction and enhancing vascular spasm.

Coagulation Cascade

• Platelet membranes have negatively charged phospholipid groups, attracting clotting proteins.
• The intrinsic pathway begins with factor XII activation by contact with the negatively charged surface of platelets.
• Activated factor XII activates factor XI.
• Activated factor XI activates factor IX.
• Factor IX, along with factor VIII, platelet factor 3, and calcium, activate factor X.
• The extrinsic pathway is initiated by tissue factor (factor III) release from damaged tissues.
• Tissue factor activates factor VII.
• Activated factor VII can activate factor IX or directly contribute to the common pathway.
• The common pathway involves the activation of factor X.

Coagulation Cascade Summary

• Intrinsic Pathway: The cascade starts with factor XII (12) and the sequence involves factors 11, 9, 8, and 10.
• Extrinsic Pathway: The process begins with factor III (3) and factor VII (7) interaction leading to activation of factor X.
• Common Pathway: A series of reactions involving factors V (5), thrombin (2), and fibrinogen (soluble precursor to fibrin), culminates in fibrin (insoluble) formation.

Thrombin and Fibrin

• Thrombin (activated factor II) converts fibrinogen (soluble) into fibrin (insoluble).
• Fibrin polymerizes into a meshwork, trapping the platelet plug and forming a clot.
• Factor XIII (fibrin stabilizing factor) cross-links fibrin, strengthening the meshwork.

Clot Retraction and Repair

• Platelets contain contractile proteins (actin and myosin), pulling the ruptured edges of the blood vessel closer.
• Platelets release platelet-derived growth factor (PDGF), stimulating smooth muscle cell proliferation and connective tissue patch formation.
• Platelets release vascular endothelial growth factor (VEGF), regenerating the endothelial lining.

Fibrinolysis

• Tissue plasminogen activator (tPA) converts plasminogen into plasmin.
• Plasmin digests fibrin, breaking down the clot.
• Fibrin digestion releases D-dimers, used in diagnostic procedures.

Drugs Affecting Hemostasis

• Heparin: Enhances antithrombin III activity, inhibiting clotting factors.
• Aspirin: Inhibits thromboxane A2 production, reducing platelet aggregation.
• Clopidogrel: Inhibits ADP action, reducing platelet aggregation.
• Abciximab: Inhibits glycoprotein IIb/IIIa interaction, preventing platelet aggregation.
• Warfarin: Inhibits vitamin K reductase, reducing clotting factor production.

Other Points

• The intrinsic pathway can occur in vitro; the extrinsic pathway needs factors from surrounding tissues.
• The extrinsic pathway is generally faster than the intrinsic pathway.
• tPA can be administered to dissolve clots in patients with stroke or other thromboembolic conditions.

Explore hemostasis, the body's process for stopping blood flow after injury. Learn five crucial steps: vascular spasm, platelet plug formation, coagulation, clot retraction, and fibrinolysis. Understand natural anticoagulant mechanisms and the role of endothelial cells.