Pharmacotherapy

Non-pharmacologic Prophylaxis

• Intermittent pneumatic compression devices (IPCD) – External sleeves applied to lower extremities that compress at regular intervals to promote venous blood flow. Often used when anticoagulation is contraindicated. Reduces DVT risk by 60-70% compared to no prophylaxis.
• Graduated compression stockings (GCS) – Elastic stockings applying graduated pressure to the lower legs and thighs to boost venous return. Should exert 30-40 mm Hg of pressure at the ankle. Effective for VTE prevention post-op.

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Anticoagulant Options

Unfractionated Heparin

• Inhibits thrombin and activated factor X. Prevents clot propagation but not initiation.
• Dosing: 5000 units SC every 8-12 hours
• Rapid onset allows for titration based on aPTT monitoring to therapeutic range.
• Bleeding risk of about 1-3%. Can be rapidly reversed with protamine sulfate.
• Contraindicated in HIT. Greater risk of osteoporosis and HIT than LMWH.
• Monitoring: aPTT, platelets, signs of bleeding
• Clinical Pearl
  • Controversial whether twice daily vs three times daily lead to a significant difference in efficacy and safety
    

Low Molecular Weight Heparins (LMWH)

• Includes enoxaparin, dalteparin, tinzaparin. Improved bioavailability and half-life over UFH.
• Inhibit factor Xa to prevent clot propagation. Do not require aPTT monitoring.
• Dosing:
  •  Enoxaparin 40 mg SC daily or 30 mg SC every 12 hours
    • if CrCl <30 mL/min or weight <50 kg 30 mg daily
  • Dalteparin 5000 units SC daily.
• Less bleeding risk than UFH. No reversal agent available except for protamine sulfate partially reversing enoxaparin.
• Contraindicated in severe renal impairment and HIT. Lower risk of HIT and osteoporosis than UFH.
• Monitoring: signs of bleeding, platelets, anti-Xa levels in certain scenarios

Fondaparinux

• Synthetic selective inhibitor of factor Xa. 100% bioavailable with once daily SC dosing.
• Dosing: 2.5 mg SC daily for thromboprophylaxis if CrCl >30 mL/min
• No laboratory monitoring required. No reversal agent. Lower bleeding risk than LMWH or UFH.
• Contraindicated in severe renal impairment. Avoid if CrCl <30 mL/min due to bleeding risk.
• Monitoring: renal function, signs of bleeding

Direct Oral Anticoagulants (DOACs)

• Includes factor Xa inhibitors (rivaroxaban, apixaban, betrixaban) and factor IIa inhibitor dabigatran. Fixed dosing without routine monitoring.

Rivaroxaban

• Direct factor Xa inhibition. Oral bioavailability of 80-100%. Peak in 2-4 hours. Half-life 5-9 hours in young, 11-13 hours in elderly.
• Dosing: 10 mg PO daily starting post-op for hip or knee arthroplasty. Treatment dose is 15 mg PO twice daily then 20 mg PO daily.
• No required monitoring. Lower bleeding risk than enoxaparin. Contraindicated with CrCl <30 mL/min.
• Reversal agent is andexanet alfa but data in prophylaxis limited.

Apixaban

• Direct factor Xa inhibitor with oral bioavailability of 50%. Peak in 3-4 hours. Half-life 8-15 hours.
• Dosing: 2.5 mg PO twice daily for extended VTE prophylaxis in high risk groups. Treatment dose is 10 mg twice daily for 7 days then 5 mg twice daily.
• No routine monitoring required. Lower bleeding risk than LMWH or warfarin for extended prophylaxis. Contraindicated with CrCl <25 mL/min.
• No specific reversal agent. Activated charcoal if recently ingested.

Betrixaban

• Direct factor Xa inhibitor. Oral bioavailability 34%. Peak 3-4 hours. Long half-life of 19-27 hours.
• Dosing: Initial dose 160 mg then 80 mg once daily. Reduce dose if age >65, weight <60 kg, or CrCl 15-30 mL/min.
• No routine monitoring required. Dose adjust if CrCl <15 mL/min. Less major bleeding than enoxaparin in trials.
• No reversal agent. Hemodialysis can remove some drug.

Dabigatran

• Direct thrombin inhibitor. Oral bioavailability 3-7%. Peak at 2 hours. Half-life 12-17 hours.
• Dosing: 110 mg PO 1-4 hours post-op then 220 mg PO daily. Reduce to 150 mg if age >75 or high bleeding risk.
• No routine monitoring required. Dose adjust if CrCl <30 mL/min.
• No specific reversal agent. Hemodialysis removes 62% of drug.

Warfarin

• Vitamin K antagonist that inhibits synthesis of clotting factors II, VII, IX, X. Delayed onset over 5-7 days.
• Dosing: Initiate dosing along with heparin or LMWH. Typical starting dose is 5 mg PO daily, adjusted per INR.
• Target INR 2-3 for prophylaxis. Monitor INR daily initially until in range.
• Antidote is vitamin K and prothrombin complex concentrate. Numerous drug and dietary interactions.
• Contraindicated in pregnancy. Increased intracranial hemorrhage risk versus LMWH.

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VTE Prophylaxis by Patient Population

Major Orthopedic Surgery

• LMWH, fondaparinux, apixaban, dabigatran, rivaroxaban, or warfarin x 35 days
• LMWH preferred in hips over UFH
• IPCDs, aspirin, or GCS may have additive benefit
• Extended prophylaxis x 35 days after hospital discharge

Non-Orthopedic Surgery

• LMWH, low-dose UFH, or fondaparinux
• IPCDs for high bleeding risk
• Extended prophylaxis x 7-10 days for abdominal or pelvic surgery with high VTE risk

Medical/Surgical ICU

• LMWH or low-dose UFH
• Mechanical prophylaxis only until bleeding risk abates

Medically Ill

• LMWH, low-dose UFH, or fondaparinux x duration of acute illness
• Avoid pharmacologic prophylaxis in low risk patients

Trauma

• LMWH or UFH when bleeding risk decreases, typically after 24-48 hours
• Mechanical prophylaxis until pharmacologic prophylaxis can start

Pregnancy/Postpartum

• LMWH during and after pregnancy instead of warfarin

Malignancy

• LMWH for at least 3-6 months over warfarin