Drugs Affecting Blood Coagulation

Overview of Blood Coagulation

• The cardiovascular (CV) system is a closed system that maintains homeostasis via pressure regulation.
• Blood moves from high-pressure areas to low-pressure areas, with any damage altering flow and potentially harming tissues.

Body's Response to Damage

• The CV system responds to injury by forming a clot (coagulation), which helps keep blood pressure normal.
• Procoagulation mode may lead to large clots during major trauma, while plasma enzymes simultaneously work to dissolve these clots to prevent tissue perfusion loss.

Hemostasis Mechanisms

• Internal mechanisms prevent excessive blood loss, including:
  • Vascular constriction: narrowing of blood vessels at the injury site.
  • Platelet plug formation: platelets adhere to the injury site and aggregate to form a plug.
  • Coagulation cascade activation: a series of biochemical events lead to blood clot formation.
  • Blood clot formation: solid mass forms at the injury to prevent further bleeding.

Coagulation Cascade

• Initial Injury Response:
  • Vasoconstriction occurs as the first response to injury.
  • Collagen exposure prompts platelet stimulation leading to shape change, substance release, and aggregation.
  • Fibrinogen is converted into fibrin through the intrinsic and extrinsic pathways.

Clotting Factors

• Definition: Proteins synthesized in the liver that regulate coagulation.
• Activation Order: Requires activation in a specific order with Vitamin K essential for synthesis.
• Calcium ions play a crucial role in activating many clotting factors.

Clot Dissolution Importance

• Uncontrolled clotting can lead to:
  • Loss of flow = tissue hypoxia
  • Tissue hypoxia = cell death.

Pathways of Coagulation

• Intrinsic Pathway: Triggered within the vascular system, converting prothrombin into thrombin, essential for clot formation internally.
• Extrinsic Pathway: Triggered by external injury, activating clotting factors upon exposure to thromboplastin, leading to clot formation externally.

Dysfunctional States of Coagulation

• Thrombosis: Characterized by inappropriate clotting, potentially causing hypoxia or necrosis.
• Bleeding disorders: Conditions like Hemophilia and thrombocytopenia that result in excessive bleeding.

Drug Classes Affecting Coagulation

• Antiplatelet Agents:

  • Decrease platelet aggregation and responsiveness.
  • Example: Aspirin, Clopidogrel.
  • Uses include post-MI and peripheral arterial disease.

• Anticoagulants:

  • Interfere with the coagulation process by acting on the clotting cascades.
  • Examples: Heparin, Warfarin, Dabigatran.
  • Commonly used in DVT, PE treatment, and stroke prevention.

• Thrombolytic Agents:

  • Dissolve formed clots (thrombi).
  • Examples: Alteplase, Reteplase (for acute myocardial infarction, stroke).

Antiplatelet and Anticoagulant Pharmacokinetics

• Antiplatelet agents: Can be oral or IV, well absorbed, metabolized in the liver.
• Anticoagulants: Vary in action time; Heparin has immediate onset, while Warfarin takes longer.

Monitoring Coagulation

• Clotting Studies: Helper tests for adjusting anticoagulant dosages include:
  • aPTT: Measures intrinsic pathway activity.
  • PT: Measures extrinsic pathway activity.

Antidotes for Overdose

• Heparin: Treated by Protamine sulfate.
• Warfarin: Prothrombin complex concentrate for bleeding; Vitamin K for high INR levels.

Conclusion

• Understanding blood coagulation mechanisms and pharmacological interventions is crucial for managing conditions related to clotting disorders and ensuring patient safety during treatment.