Anticoagulant medicines

Definition and Purpose

Anticoagulant medicines are a class of drugs used to reduce the formation of blood clots by inhibiting components of the coagulation cascade or thrombin activity

They are prescribed for the prevention and treatment of thromboembolic disorders including deep vein thrombosis (DVT), pulmonary embolism (PE), atrial fibrillation (AF)-related stroke, mechanical heart valve thrombosis, and myocardial infarction-related complications

Unlike antiplatelet agents, which act on platelet aggregation, anticoagulants primarily interfere with the coagulation pathways that lead to fibrin clot formation

Main Categories of Anticoagulants

1. Vitamin K Antagonists (VKAs)

Warfarin

Acenocoumarol

Phenprocoumon

Act by inhibiting the enzyme vitamin K epoxide reductase, reducing synthesis of active clotting factors II, VII, IX, and X

2. Direct Oral Anticoagulants (DOACs)

Divided into two subclasses

a. Direct Thrombin Inhibitor

Dabigatran etexilate

Inhibits thrombin (factor IIa) directly and reversibly

b. Direct Factor Xa Inhibitors

Rivaroxaban

Apixaban

Edoxaban

Betrixaban

Inhibit activated factor X (Xa), blocking the conversion of prothrombin to thrombin

3. Parenteral Anticoagulants

a. Unfractionated Heparin (UFH)

Binds to antithrombin III, accelerating its inhibition of thrombin and factor Xa

Requires intravenous or subcutaneous administration

Dose adjusted according to activated partial thromboplastin time (aPTT)

b. Low Molecular Weight Heparins (LMWHs)

Enoxaparin

Dalteparin

Tinzaparin

Preferentially inhibit factor Xa through antithrombin, longer half-life than UFH, administered subcutaneously once or twice daily

c. Synthetic Pentasaccharide

Fondaparinux

Selective indirect inhibitor of factor Xa via antithrombin III

4. Parenteral Direct Thrombin Inhibitors

Argatroban

Bivalirudin

Desirudin

Used in patients with heparin-induced thrombocytopenia (HIT)

Mechanism of Action Summary

Vitamin K antagonists: inhibit hepatic synthesis of clotting factors

Heparins: accelerate antithrombin activity

LMWH: selectively inhibit factor Xa

DOACs: directly inhibit thrombin or factor Xa

DTIs: bind and inactivate thrombin directly

Clinical Indications

Venous Thromboembolism (VTE)

Treatment and prevention of DVT and PE

Surgical prophylaxis in orthopedic and abdominal surgeries

Cardiac and Vascular Disorders

Atrial fibrillation: prevention of stroke and systemic embolism

Mechanical heart valves (warfarin only)

Post-myocardial infarction anticoagulation

Left ventricular thrombus

Thrombophilia and Hypercoagulable States

Antiphospholipid syndrome

Protein C/S or antithrombin III deficiency

Other Conditions

Cancer-associated thrombosis

Heparin-induced thrombocytopenia (DTIs, fondaparinux)

Extracorporeal circulation (e.g. during dialysis or cardiopulmonary bypass with heparin)

Common Anticoagulant Agents and Brand Examples

Warfarin

Brand: Coumadin, Marevan

Tablet form, long half-life

Requires INR monitoring

Reversed by vitamin K, prothrombin complex concentrate (PCC), or fresh frozen plasma

Dabigatran

Brand: Pradaxa

Oral prodrug

Reversal agent: idarucizumab

Primarily renally excreted

Apixaban

Brand: Eliquis

Twice-daily oral dosing

Used in stroke prevention in AF, VTE treatment, and prophylaxis

Reversal agent: andexanet alfa

Rivaroxaban

Brand: Xarelto

Once-daily dosing

Approved for VTE prevention, treatment, and stroke prevention

Partial reversal by andexanet alfa or PCC

Edoxaban

Brand: Lixiana

Once-daily oral dosing

Approved for stroke prevention in AF and treatment of DVT/PE

Enoxaparin

Brand: Clexane

Subcutaneous administration

Weight-based dosing

Partial reversal with protamine sulfate

Fondaparinux

Brand: Arixtra

No direct antidote

Long half-life

Safe in HIT

Argatroban

IV infusion

Used in HIT

Short half-life

Hepatic metabolism

Bivalirudin

Used in PCI (percutaneous coronary intervention)

Short half-life

Cleared via blood proteases and partially renally

Monitoring Parameters

Warfarin

International Normalized Ratio (INR): target 2.0–3.0 for most indications

Frequent INR checks during initiation and dose adjustments

Unfractionated Heparin

aPTT (activated partial thromboplastin time): therapeutic range 1.5–2.5 times control

LMWH

Usually does not require monitoring

Anti-Xa level monitoring in obesity, renal failure, pregnancy, or children

DOACs

No routine monitoring needed

Specific assays available (e.g., dilute thrombin time for dabigatran, anti-Xa assay for apixaban and rivaroxaban)

Adverse Effects

All Anticoagulants

Bleeding: most common and potentially serious

Bruising

Hematuria

Hemoptysis

Gastrointestinal bleeding

Intracranial hemorrhage

Menorrhagia

Warfarin

Skin necrosis (rare, early in therapy)

Purple toe syndrome

Teratogenicity: contraindicated in pregnancy

Drug and food interactions

Heparin

Heparin-induced thrombocytopenia (HIT)

Osteoporosis with long-term use

Alopecia

LMWH

Lower risk of HIT

Injection site pain or hematoma

Dabigatran

Dyspepsia

High renal clearance: avoid in severe renal impairment

Apixaban and Rivaroxaban

Minor bleeding: nosebleeds, gum bleeding

Increased risk in patients with liver disease

Contraindications

Absolute

Active major bleeding

Severe bleeding diathesis

Severe uncontrolled hypertension

Recent hemorrhagic stroke

Hypersensitivity to the agent

Warfarin in pregnancy

Relative

Thrombocytopenia

Recent surgery

Peptic ulcer disease

Liver disease with coagulopathy

Severe renal impairment (DOACs and LMWH caution)

Drug Interactions

Warfarin

Extensive CYP450 interactions

Enzyme inducers (e.g. rifampin, carbamazepine) reduce effect

Enzyme inhibitors (e.g. amiodarone, fluconazole) increase effect

Vitamin K–rich foods reduce effect (e.g. green leafy vegetables)

Antibiotics may enhance warfarin effect via microbiome disruption

DOACs

P-glycoprotein inhibitors (e.g. verapamil, amiodarone) increase levels

Strong CYP3A4 inducers (e.g. phenytoin, rifampin) reduce levels

Strong CYP3A4 inhibitors (e.g. ketoconazole) increase bleeding risk

Heparin/LMWH

Additive bleeding with antiplatelets or NSAIDs

Protamine reverses UFH fully but only partially reverses LMWH

Antidotes and Reversal Strategies

Warfarin

Vitamin K (phytonadione): oral or IV

Prothrombin complex concentrate (PCC)

Fresh frozen plasma

UFH and LMWH

Protamine sulfate

1 mg neutralizes 100 units of UFH

Partially reverses LMWH

Dabigatran

Idarucizumab: monoclonal antibody fragment

Factor Xa inhibitors

Andexanet alfa: decoy receptor

Off-label use of PCC

Perioperative Considerations

Warfarin

Stop 5 days prior to surgery

Bridge with LMWH if high risk

Restart when hemostasis achieved

DOACs

Stop 24–48 hours prior to surgery, depending on bleeding risk and renal function

LMWH

Last dose 24 hours before elective surgery

Special Populations

Pregnancy

Warfarin is teratogenic: avoid

LMWH preferred

DOACs not recommended due to lack of safety data

Elderly

Increased bleeding risk

Dose adjustments needed for renal function

Renal Impairment

DOACs have renal clearance; avoid or adjust

Dabigatran is most affected

Liver Disease

Avoid rivaroxaban and apixaban in significant hepatic impairment

Warfarin used with careful INR monitoring

Examples of Brand Names

Warfarin – Coumadin, Marevan

Dabigatran – Pradaxa

Rivaroxaban – Xarelto

Apixaban – Eliquis

Edoxaban – Lixiana

Enoxaparin – Clexane

Fondaparinux – Arixtra

Argatroban – Argatra

Bivalirudin – Angiomax

Comparison Summary of Common Anticoagulant Medicines

Warfarin requires regular monitoring through INR blood tests to ensure it stays within the therapeutic range. It is taken orally, has a slow onset of action that typically takes 48 to 72 hours to reach full effect, and can be reversed effectively using vitamin K, prothrombin complex concentrate (PCC), or fresh frozen plasma in cases of bleeding.

Unfractionated heparin (UFH) is administered intravenously, has an immediate onset of action, and requires frequent monitoring using activated partial thromboplastin time (aPTT). It can be fully reversed using protamine sulfate and is typically used in hospital settings where rapid anticoagulation and reversibility are necessary.

Low molecular weight heparins (LMWH), such as enoxaparin, are given subcutaneously and have a moderate onset of action, usually within 3 to 5 hours. They do not generally require routine monitoring but anti-Xa levels may be checked in special populations such as pregnant women or those with renal impairment. Protamine sulfate only partially reverses their anticoagulant effect.

Direct oral anticoagulants (DOACs), including dabigatran, apixaban, rivaroxaban, and edoxaban, are taken orally and typically begin to act within 2 to 4 hours. These agents do not usually require routine laboratory monitoring, which makes them convenient for outpatient use. Dabigatran can be reversed using idarucizumab, while factor Xa inhibitors like apixaban and rivaroxaban may be reversed with andexanet alfa or, off-label, with prothrombin complex concentrate in emergencies.

Each of these agents has distinct advantages and limitations, and selection depends on clinical context, patient comorbidities, renal and hepatic function, bleeding risk, and the need for reversibility or monitoring.

Key Clinical Tips

DOACs preferred over warfarin for nonvalvular AF and VTE due to fixed dosing and no routine monitoring

Warfarin remains necessary in valvular AF and mechanical heart valves

LMWH is standard in cancer-associated thrombosis and during pregnancy

Patients with HIT require non-heparin anticoagulants such as argatroban or fondaparinux

Always assess renal and hepatic function before initiating anticoagulants

Careful patient education required on adherence, bleeding signs, and interaction avoidance

Bridging therapy and timing with surgical procedures must be personalized

Use bleeding risk scores (e.g. HAS-BLED) and thromboembolism risk scores (e.g. CHA₂DS₂-VASc) to guide therapy decisions