MD Notes

creation date: 2026-06-18 04:04
tags: Pharmacology

Anticoagulants

Background

Anticoagulants are used for stroke prevention, and treatment and prevention of emboli.

Absolute Contraindications

Generally, anticoagulation is absolutely contraindicated for:

  • Active major bleeding
  • Acute intracranial or spinal hemorrhage
  • Major trauma
  • Recent, planned, or emergency high-bleeding-risk surgery/procedure
  • Severe bleeding diathesis (eg. disseminated intravascular coagulation or decompensated cirrhosis)
  • Severe thrombocytopenia (eg, platelet counts <25,000/microL)

Types

Warfarin

Mechanism of Action
  1. Inhibits proteins C and S (physiologic anticoagulants) initially; creates early hypercoagulable state
  2. Inhibits vitamin K epoxide reductase, preventing vitamin K activation and thus function of clotting factors II, VII, IX, X

INR affecting factors
Increase INR (increases effectiveness of warfarin)

  • Cytochrome inhibitors (particularly CYP3A4)
    • Clarithromycin
    • Metronidazole
    • Azole antifungals
    • Grapefruit juice
  • Liver disease
  • Malnutrition (reduced vitamin K intake)
  • Hyperthyroidism (catabolism of clotting factors)

Decrease INR

  • Cytochrome inducers
    • Rifampin
    • Phenytoin
    • Carbamazepine
    • Phenobarbital
    • St. John’s Wort
  • Cholestyramine
  • High vitamin K intake (leafy greens)
  • Hypothyroidism
Indications
  • Atrial fibrillation (may be preferred over newer options if severe renal disease)
  • Venous thromboembolism
  • Prophylaxis with mechanical heart valve
Contraindications

Absolute:

  • Active bleeding
  • Pregnancy (teratogenic) - causes fetal warfarin syndrome
  • Recent CNS or ophthalmologic surgery, or wide incision surgery
  • Severe liver disease

Relative:

  • Uncontrolled hypertension
  • Alcohol use disorder
  • Risk of nonadherence (due to strict INR range)
Complications / Side Effects
  • Initial hypercoagulability - use heparin bridge until INR in therapeutic range
    • Thrombosis can result in skin necrosis
  • Bleeding
  • Skin rash
Monitoring

Therapeutic INR ranges are:

  • 2.0-3.0: most patients
  • 2.5-3.5: mechanical heart valve, antiphospholipid syndrome with arterial thrombosis
Reversal

Indications for reversal are:

  • Serious bleeding or intracranial bleeding
  • INR >10 despite no bleeding
  • Urgent surgery

Reversal is by:

  • Vitamin K (no active bleeding; onset: 24h PO, 6-12h IV)
  • Prothrombin Complex Concentrate (if severe bleeding)
  • Fresh Frozen Plasma (30-60 minutes onset)

For INR >4.5 but <10 without clinically relevant bleeding, temporary cessation without use of vitamin K is generally adequate. The exact dose to withhold is described here.

Heparin

Unfractionated Heparin

Mechanism of Action
  • Inhibits factors IIa and Xa by binding to antithrombin-3
  • Due to varied side chains, effect can vary by individual
  • Metabolized in the kidney and liver
Indications
  • During surgeries as it can be rapidly reversed
Contraindications
  • Active bleeding
Complications / Side Effects
  • Heparin-induced thrombocytopenia (HIT) - if varied chains cases binding to plasma proteins other than clotting factors
    • Type 1: drops platelet 10-20%, benign
    • Type 2: drops platelet by 50% via type 2 hypersensitivity reaction, life-threatening
Reversal
  • Protamine (binds and neutralizes heparin)

Low Molecular Weight Heparin (LMWH)

Mechanism of Action
  • Like UFH except:
    • Shorter chains
    • Longer half-life
    • Metabolized primarily in kidney
Indications
  • VTE prophylaxis
  • Severe liver disease
Contraindications
  • Active bleeding
Complications / Side Effects
Reversal
  • Protamine (binds and neutralizes heparin) - is less effective than with UFH
Examples
  • Enoxaparin
  • Dalteparin

Direct Oral Anticoagulants (DOACs)

Factor Xa Inhibitors

Mechanism of Action
  • Inhibits factor Xa
Indications
  • Stroke prevention for atrial fibrillation
  • Treatment for DVT
Contraindications
Complications / Side Effects
Reversal
  • Andexanet alfa (sequesters factor Xa inhibitors)
Examples
  • Apixaban BID
  • Rivaroxaban daily

Direct Thrombin (IIa) Inhibitors

Mechanism of Action
  • Inhibition of thrombin (factor IIa)
Indications
Contraindications
Complications / Side Effects
Reversal
  • Idarucizumab (for dabigatran)
Examples
  • Dabigatran
  • Argatroban
  • Bivalrudin

Others

Fondaparinux

Mechanism of Action
  • Similar mechanism to low molecular weight heparins
Indications
  • Alternative to heparin if diagnosed with HIT
Contraindications
  • Avoid if GFR <30
Complications / Side Effects
Reversal

References

Tools / Guidelines

Thrombosis Canada

Additional Reading

Backlinks