LMWHs Pharmacology
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Questions and Answers

What are the three major elements leading to VTE, as described in Virchow's Triad?

  • Stasis in blood flow, Vascular endothelial injury, and Hypercoagulable state (correct)
  • Stasis in blood flow, Vascular endothelial injury, and Hypertension
  • Vascular endothelial injury, Hypercoagulable state, and Vasospasm
  • Stasis in blood flow, Hypercoagulable state, and Atherosclerosis
  • What is the result of reduced blood flow rate on the clearance of activated clotting factors?

  • Unclear relation between blood flow rate and clearance of activated clotting factors
  • Increased clearance of activated clotting factors
  • No effect on clearance of activated clotting factors
  • Reduced clearance of activated clotting factors (correct)
  • What is the function of endothelial cells inside blood vessels?

  • To promote platelet adherence and activation of coagulation cascade
  • To create substances that inhibit platelet adherence and prevent activation of coagulation cascade (correct)
  • To stimulate the immune system to respond to injury
  • To facilitate vasospasm and vasoconstriction
  • What is the role of von Willebrand's factor (vWF) in platelet adherence?

    <p>It facilitates platelet adherence to subendothelium</p> Signup and view all the answers

    What is the result of platelet activation?

    <p>Release of a number of procoagulants</p> Signup and view all the answers

    What is the function of glycoprotein (GP) 1b receptors in platelet adherence?

    <p>They facilitate platelet adherence to subendothelium</p> Signup and view all the answers

    What is the consequence of injury to the vessel wall?

    <p>The vessel wall becomes more prone to thrombogenesis</p> Signup and view all the answers

    What is the role of activated Protein C resistance in VTE?

    <p>It increases the risk of VTE</p> Signup and view all the answers

    What is the consequence of the additive effect of Virchow's Triad?

    <p>An increased risk of VTE</p> Signup and view all the answers

    What is the primary function of the hemostatic plug?

    <p>To seal the vessel wall</p> Signup and view all the answers

    Study Notes

    LMWHs

    • Each LMWH has a slightly different molecular weight distribution and pharmacologic properties
    • They exhibit less protein binding, resulting in a more predictable response
    • They have a lower incidence of HIT and osteopenia
    • Dosing is once or twice daily due to longer half-lives (usually 3-6 hours, but agent-specific)
    • Half-lives are prolonged in patients with renal impairment, increasing the risk of drug accumulation and bleeding
    • SQ bioavailability is >90%
    • Peak effect is 3-5 hours after SQ dose
    • Baseline prothrombin time (PT), INR, aPTT, CBC, and serum creatinine (SCr) should be obtained
    • Platelet count should be checked every 2-3 days during the first 2 weeks and every 2-4 weeks with extended use

    Mechanism of Action

    • Halt propagation and growth of thrombi
    • Anticoagulant effect is from AT binding
    • Cannot bind AT and thrombin simultaneously
    • Have greater activity against factor Xa
    • Inhibit thrombin (IIa) to a lesser degree
    • Xa:IIa ratio is anywhere from 2:1 to 4:1, depending on the agent

    Dosing

    • Dosing is based on patient's weight
    • Dalteparin: 200 units/kg SQ daily or 100 units/kg twice daily
    • Enoxaparin: 1.5 mg/kg SQ daily or 1 mg/kg twice daily

    Clinical Presentation and Diagnosis

    • Majority of VTEs begin in the lower extremity
    • VTE symptoms are very nonspecific, including:
      • Unilateral leg pain, warmth, and swelling
      • Shortness of breath and/or cough
      • Tachypnea and/or tachycardia
      • Hemoptysis
    • Objective tests used to confirm VTE include radiographic studies and D-dimer test
    • D-dimer test can distinguish between acute VTE and PTS

    Monitoring

    • aPTT is the most widely used test for monitoring
    • aPTT should be obtained at baseline, 6 hours after initiation, and 6 hours after each dose change
    • aPTT should be 1.5-2.5x control value (reference value)
    • CBC and BP should also be monitored

    Virchow's Triad

    • Three major elements leading to VTE:
      • Stasis in blood flow (venous stasis)
      • Vascular endothelial injury
      • Hypercoagulable state
    • These risk factors are additive

    Pathophysiology

    • Vessel injury leads to the formation of a hemostatic plug
    • Inappropriate response can lead to clot formation
    • Endothelial cells create substances that:
      • Inhibit platelet adherence
      • Prevent activation of coagulation cascade
      • Facilitate fibrinolysis
    • Injury exposes subendothelium, leading to platelet adherence and activation
    • Platelet activation leads to the release of procoagulants and platelet aggregation

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