Hemostasis Overview and Steps

Hemostasis

• A complex process involving multiple steps and clotting factors
• Maintains a balance between clot formation and clot breakdown

Steps in Hemostasis

• Vascular Phase:
  • Damage to blood vessels initiates vascular spasm (vasoconstriction)
  • Slows or stops blood flow
• Platelet Phase:
  • Platelets adhere to endothelial cells in larger vessels
  • Platelet aggregation forms a platelet plug
• Coagulation Phase:
  • Fibrinogen (plasma protein) converts to fibrin (insoluble protein) via thrombin
  • Fibrin forms a network that traps blood cells and platelets, creating a thrombus (clot)
• Extrinsic Pathway:
  • Initiated by material outside the blood
  • Rapid process
  • Smaller clots
• Intrinsic Pathway:
  • Initiated by blood's contact with exposed collagen in vessel walls
  • Slower
  • Larger clots
• Clot Retraction:
  • Begins 2 to 3 days after clot formation
  • Contractile proteins within platelets contract, tightening the clot

Anticoagulants

• Warfarin:
  • Coumarin derivative
  • Mechanism of Action (MOA): Inhibits vitamin K synthesis
  • Route: Oral or IV
  • Monitoring: Prothrombin Time - International Normalized Ratio (PT-INR)
  • Target: INR 2-3
• Heparin:
  • Sulfated glycosaminoglycan
  • MOA: Activates antithrombin III
  • Route: IV or subcutaneous (SC), IM is contraindicated (risk of hematoma)
  • Monitoring: Activated Partial Thromboplastin Time (aPTT)
  • Target: 1.5-2.5x control

Vitamin K

• Procoagulant used as an antidote for Warfarin toxicity
• Signs of Warfarin toxicity: bruising, bleeding gums, nosebleeds, blood in urine or stool
• Uses: Management of thrombosis associated with Heparin-induced thrombocytopenia
• Idarucizumab: Humanized monoclonal antibody fragment that binds to dabigatran (direct thrombin inhibitor) and reverses its anticoagulant effect

Antithrombotic - Antiplatelet Drugs

• Regulate platelet function
• Substances developed outside the platelet:
  • Catecholamines
  • Collagen
  • Thrombin
  • Prostacyclin
• Agents generated internally within the platelet interacting with membrane receptors:
  • ADP
  • Prostaglandin D2
  • Prostaglandin E2
  • Serotonin
• Agents generated internally within the platelet interacting within the platelet:
  • Prostaglandin endoperoxidases
  • Thromboxane A2
  • cAMP
  • cGMP
  • Ca2+

Antiplatelet Drugs

• Prolong bleeding time by interfering with platelet aggregation
• Subclasses:
  • TXA2 synthesis blocker: Aspirin
  • ADP receptor blockers: Clopidogrel, Ticlopidine, Prasugrel,
  • Glycoprotein IIb/IIIa receptor blockers: Abciximab, Eptifibatide, Tirofiban
  • PDE inhibitors: Dipyridamole

Aspirin (Acetylsalicylic Acid)

• MOA: Irreversible inhibition of COX
• Uses: Prophylactic for transient cerebral ischemia and to reduce the incidence of recurrent MI
• Adverse effects: Increased hemorrhagic stroke, gastrointestinal bleeding, Salicylism (tinnitus)
• Contraindication: Anticoagulants (increased bleeding), Ibuprofen (antagonizes platelet inhibition)
• Dose: 100 to 325 mg

ADP Receptor Blockers (Thienopyridines)

• MOA: Irreversibly inhibit the binding of ADP to its receptors on platelets
• Examples: Clopidogrel, Ticlopidine, Prasugrel, Ticagrelor
• Preferred agent in ischemic heart disease events: Clopidogrel
• Ticlopidine causes: Neutropenia/agranulocytosis, Thrombotic Thrombocytopenic Purpura (TTP), Aplastic anemia

Glycoprotein IIa/IIb Receptor Blockers

• Drugs: Abciximab, Eptifibatide, Tirofiban
• Abciximab: Chimeric monoclonal antibody given IV with heparin or ASA for patients undergoing angioplasty
• Side effects: Bleeding

Phosphodiesterase Inhibitor

• Example: Dipyridamole
• Coronary vasodilator typically given in combination with aspirin or warfarin
• Ineffective alone
• Side Effect: Coronary steal phenomenon

Thrombolytics

• Used to dissolve existing clots

Hemophilia

• Hemophilia A: Factor VIII (FVIII) deficiency or classic hemophilia
• Hemophilia B: Factor IX (FIX) deficiency or Christmas disease
• Von Willebrand Disease: Genetic disorder caused by missing or defective von Willebrand factor (VWF)
  • Type 1: 60% to 80% of patients
  • Type 2: 15% to 30% of patients
• Hemophilia occurs in approximately 1 in 5,000 live births
• Hemophilia A is four times as common as Hemophilia B
• More than half of patients with Hemophilia A have the severe form.

Explore the intricate process of hemostasis, including its phases and pathways. This quiz covers vascular, platelet, and coagulation phases, highlighting how clots form and retract. Test your knowledge on the mechanisms that maintain blood balance.