anticoagulation

Indications

• treatment of deep vein thrombosis, pulmonary embolus, atrial fibrillation or valvular heart disease: INR 2.0-3.0; atrial fibrillation with rheumatic valve disease: INR 2.5-3.5
• antiphospholipid antibody syndrome: INR 3.0-4.0
• mechanical prosthetic heart valves:* INR 2.5-3.5
• arterial thrombosis or prevention of recurrent myocardial infarction: INR 2.5-3.5
• treatment of arterial thromboembolism, 1st generation mechanical heart valves (Star-Edwards or Bjork-Shiley): INR 2.5-3.5 + aspirin 80-100 mg QD
• recurrent systemic embolism: INR 3.0-4.5
• long-term low-intensity anticoagulation for patients with idiopathic deep vein thrombosis: INR 1.5-2.0 (after 3 months of standard therapy) not recommended

* except 1st generation mechanical heart valves (Star-Edwards or Bjork-Shiley); may be combined with aspirin for high- risk patients at the cost of increased risk of bleeding

Contraindications

• high risk of falls may not be an absolute contraindication
• warfarin may cause more harm than benefit in patients with atrial fibrillation & end-stage renal disease (ESRD)*

* apixaban may be used in ESRD with close monitoring

Benefit/risk

• treatment of deep vein thrombosis & pulmonary embolism
  • no benefit in mortality or prevention of pulmonary embolism
  • number needed to harm: 50-111 to cause 1 major hemorrhage
  • widely accepted in clinical practice, thus preventing initiating of randomized clinical trials due to ethical concerns

Monitor

• after stabilization of dose, INR is monitored monthly for most patients (every other month for low-intensity anticoagulation)
• self management may be appropriate for subgroup

Complications

(also see warfarin)

• intracranial hemorrhage
  • risk associated with INR > 3.5, age > 85
  • reversal of INR to < 1.3 within 4 hours & systolic BP to < 160 mm Hg at 4 hours is associated with lower rate of intracranial hematoma enlargement
• bleeding, especially GI bleeding
  • 6 fold increased risk of intracerebral hemorrhage
  • risk of major hemorrhage 13.1 events/100 patient years in elderly >= 80 vs 4.75 in patients < 80
  • scoring systems no better than physician clinical judgment in predicting major hemorrhage
  • risk of bleeding increased in patients with advanced renal failure
    • risks of bleeding & thrombosis lower with apixaban than warfarin in patients with ESRD
  • when to restart anticoagulation after GI blood is controversial
    • after resolution of GI bleed
    • especially in patients with malignancy
    • within 7 days to reduce risk of thromboembolic event
  • predicted rates of major bleeding from clinical trials underestimate rates actually observed with warfarin or dabigatran
  • heavy menstrual bleeding (menorrhagia)
    • 22-65% with warfarin
    • 32% with rivaroxaban
    • 28% with apixaban
    • 25% with edoxaban
  • concurrent use of antiplatelet agents (including SSRI) further increases risk of bleeding
• resumption of oral anticoagulant therapy is associated with a lower risk of ischemic events

Management

• anticoagulation for non-cardiac surgery
  • see perioperative anticoagulation
• contraception for women on warfarin anticoagulation
  • do not use estrogen-containing contraceptives
    • increased risk of thromboembolism
  • progestin-only contraceptives appear safe
  • intrauterine device (IUD)
    • levonorgestrel-releasing intrauterine device (LNG-IUD) is effective for heavy menstrual bleeding associated with anticoagulation or bleeding disorders
• pregnancy
  • switch to unfractionated heparin or LMW heparin after week 6; switch to unfractionated heparin at week 37 to term
  • exception: mechanical heart valve
    • follow procedure under mechanical heart valve
  • in some cases, continued use of warfarin may be justified
  • week 37 to term, switch to unfractionated heparin to allow abrupt discontinuation of anticoagulation during labor & delivery
  • continuation of LMW heparin to term discontinuing 24 hours prior to delivery
• lactation
  • warfarin considered safe; does not appear in breast milk
  • LMW heparin considered safe; does not appear in breast milk
  • unknown whether direct oral anticoagulants appear in breast milk
  • fondaparinux excreted in breast milk of lactating rats
• anticoagulation in patients with active malignancy
  • LMW heparin anticoagulant of choice
  • thromboprophylaxis with direct oral anticoagulants in ambulatory patients with cancer is safe & effective
  • direct oral anticoagulants are non-inferior to LMW heparin in preventing venous thromboembolism in patients with cancer over 6 months
  • compared with LMW heparin & warfarin, direct oral anticoagulants are associated with better medication compliance, lower incidence of venous thromboembolism, lower risk of bleeding & lower mortality
• end-stage renal disease, renal dialysis
  • warfarin
    • treatment of choice in patients with chronic renal failure stage 5 (NEJM)
  • apixaban may be used with close monitoring
  • also see atrial fibrillation (Management:) anticoagulation in renal failure
• inferior vena cava filter for prevention of pulmonary embolism in patients with contraindication(s) to anticoagulation
• newer anticoagulants (direct oral anticoagulants)
  • see direct oral anticoagulant (DOAC) for safety vs warfarin
  • excluding mechanical heart valves, hypertrophic cardiomyopathy
    • DOAC ok for atrial fibrillation in patients with bioprosthetic values
  • dabigatran, rivaroxaban, & apixaban are safe & effective in the elderly
  • direct oral anticoagulants are safer than wafarin in the very old
• dosage-adusted warfarin
  • mechanical heart valves, hypertrophic cardiomyopathy
• adding aspirin to warfarin associated with increased risk of bleeding without a benefit for thrombosis prevention
• tranexamic acid in oral doses every 6-8 hours or a single 10-mg/kg intravenous dose to control acute hemorrhaging
• in patients for whom heparin is initiated for anticoagulation, & titration to therapeutic effect is difficult, consider antithrombin deficiency

* risk factors for perioperative thrombosis

• DVT within 1 year or history of recurrent DVT
• atrial fibrillation with CHADS score > 2
  • if CHADS score >= 4, especially in the setting of prior thromboembolic event or intracardiac thrombus, perioperative bridging with enoxaparin is appropriate
• prior stroke
• active malignancy (treated within 6 months or palliatively)
• hypercoagulable state
• mechanical heart valve

* high-risk patients undergoing cardiac device surgery have fewer complications continuing warfarin than switching to heparin

More general terms

• pharmacologic therapy

More specific terms

• perioperative anticoagulation
• perioperative antiplatelet therapy

Additional terms

• coagulation cascade
• coagulation factor
• direct oral anticoagulant; novel oral anticoagulant (DOAC, NOAC)
• heparin
• International normalized ratio (INR)
• prophylaxis for venous thromboembolism (VTE)
• warfarin (Coumadin, Panwarfin, Jantoven)