LMWHs Pharmacology

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