LMWHs Pharmacology

Study Notes

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

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

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

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

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