Anticoagulant Pharmacology

Anticoagulant Pharmacology Overview

• John Togami, PharmD, PhC is a Pharmacist Clinician & Clinic Director at the Antithrombosis Clinic, the University of New Mexico Hospital and the University of New Mexico College of Pharmacy
• Anticoagulant Pharmacology presentation date: February 28, 2025

Objectives of Anticoagulation Therapy

• Describe the key characteristics of common oral and parenteral anticoagulants. Characteristics include the mechanism of action, pharmacokinetics, advantages, disadvantages, side effects, monitoring, and contraindications
• Review the clinical indications for anticoagulation therapy
• Describe therapy recommendations and treatment/prevention strategies for venous thromboembolism and stroke prevention in atrial fibrillation
• Given a patient case, choose an appropriate anticoagulation plan

Topics of Discussion For This Presentation

• Pharmacology Review: oral and parenteral anticoagulants
• Brief Review of Anticoagulation Treatment Principles: venous thromboembolism and atrial fibrillation
• Cases

Anticoagulants

• Anticoagulants decrease clotting time and slow the coagulation cascade
• Anticoagulants are not an actual "blood thinner"
• Drug Classes
  • Vitamin K Antagonist: Warfarin
  • Factor Xa Inhibitor: Apixaban, Rivaroxaban, Edoxaban, Fondaparinux
  • Direct Thrombin Inhibitor: Dabigatran, Bivalirudin (IV), Argatroban (IV)
  • Heparin: Unfractionated Heparin and Low Molecular Weight Heparin

Oral Anticoagulants

• Vitamin K Antagonist (VKA)
• Direct-acting Oral Anticoagulants (DOACs)

Vitamin K Antagonist: Warfarin (Coumadin, Jantoven)

• Warfarin inhibits vitamin K epoxide reductase complex enzyme (VKORC)
• Warfarin depletes functional vitamin K reserves
• Warfarin reduces hepatic synthesis of vitamin K dependent coagulation factors II, VII, IX, and X
• Warfarin reduces the synthesis of Protein C and Protein S (endogenous anticoagulants)
• Administered orally
• Exhibits nonlinear and unpredictable pharmacokinetics
• Onset of action occurs in 24-72 hours
  • Peak therapeutic effect: 5-7 days
  • Steady state: 7-10 days
• Has no effect on circulating activated coagulation factors
• Half-life of 40 hours
• There is no renal excretion
• Metabolism: hepatic (CYP2C9 > CYP2C8, 2C18, 2C19, 1A2, 3A4)

Warfarin Dosing

• Dosed in the evening (once-a-day)
• The standard initial dose is 5mg daily, and loading doses ≥10mg should be avoided
• Consider a lower initial dose when increased warfarin sensitivity is perceived: age >75, cirrhosis, low albumin, decompensated CHF, drug interactions, high bleed risk, thyroid storm
• Avoid prescribing >1 strength of warfarin tablet
• Variable colors and shapes
• Maintenance dose: based on INR response and patient-specific characteristics
• Example maintenance dose: warfarin 5mg Mon/Wed/Fri and 7.5mg all other days, using 5mg tablets
• Warfarin maintenance dose on the bottle may not match what the patient is taking from the pharmacy
• If a dose is missed, take it if w/i ~8 hours of usual administration time
• Adherence is very important -- use pillbox, dosing handout/calendar, phone alarm, etc.

Warfarin Dosage Adjustment Based on INR

• Goal INR 2-3

  • If INR is < 1.5: Consider a one-time dose increase of 1½ - 2 times daily maintenance dose. If adjustment to maintenance dose needed, increase dose by 10-20%. Repeat INR in 1 week
  • If INR is 1.5-1.7: Consider a one-time dose increase of 1½ times daily maintenance dose. If adjustment to maintenance dose needed, increase dose by 5-15%. Repeat INR in 2 weeks
  • If INR is 1.8-1.9: No dosage adjustment may be necessary if the last two INRs were in range. Repeat INR within 8 weeks. Consider a one-time dose increase of 1½ times daily maintenance dose. If adjustment to maintenance dose needed, increase dose by 5-10%. Repeat INR in 2 weeks
  • If INR is 2-3: Desired range. Repeat INR within 8 weeks
  • If INR is 3.1-3.2: No dosage adjustment may be necessary if the last two INRs were in range. Repeat INR within 8 weeks. Consider a one-time dose decrease of ½ of daily maintenance dose. If adjustment to maintenance dose needed, decrease dose by 5-10%. Repeat INR in 2 weeks
  • If INR is 3.3-4.0: Consider holding ½ to 1 dose. If adjustment to maintenance dose needed, decrease dose by 5-10%. Repeat INR in 2 weeks

• Goal INR 2.5-3.5

  • If INR is < 2.0: Consider a one-time dose increase of 1½ - 2 times daily maintenance dose. If adjustment to maintenance dose needed, increase dose by 10-20%. Repeat INR in 1 week
  • If INR is 2.0-2.2: Consider a one-time dose increase of 1½ times daily maintenance dose. If adjustment to maintenance dose needed, increase dose by 5-15%. Repeat INR in 2 weeks
  • If INR is 2.3-2.4: No dosage adjustment may be necessary if the last two INRs were in range. Repeat INR within 8 weeks. Consider a one-time dose increase of 1½ times daily maintenance dose. If adjustment to maintenance dose needed, increase dose by 5-10%. Repeat INR in 2 weeks

• If INR is 2.5-3.5: Desired range. Repeat INR within 8 weeks

  • If INR is 3.6-3.7: No dosage adjustment may be necessary if the last two INRs were in range. Repeat INR within 8 weeks. Consider a one-time dose decrease of ½ of daily maintenance dose. If adjustment to maintenance dose needed, decrease dose by 5-10%. Repeat INR in 2 weeks
  • If INR is 3.8-4.4: Consider holding ½ to 1 dose. If adjustment to maintenance dose needed, decrease dose by 5-10%. Repeat INR in 2 weeks

• For the following INRs, hold 1-2 doses:

  • If INR is 4.0-6.0 (decrease dose by 5-15%, repeat INR w/n 1 week)
  • If INR is 6.1-8.9 (decrease dose by 10-20%, repeat INR w/n 5 days, and consult clinic supervisor if an outpatient)

• If INR >9.0, hold until INR < upper limit of therapeutic range then:

  • Consider use of vitamin K PO 2.5mg - 5mg, repeating INR in 1-2 days and consult the clinic medical director if an outpatient
  • When safe, resume warfarin at lowered dose (10-20%)

Warfarin Monitoring

• Often managed by an Antithrombosis Clinic or Antithrombosis Provider
• Prothrombin Time (PT) is expressed as International Normalized Ratio (INR)
• Baseline INR (normal: 0.8 – 1.2)
• First INR within 3-5 days of warfarin initiation
• INR reflects dosing from the previous 7-10 days. Dosing from the previous 2-3 days will have the most prominent effect
• INR every 1-12 weeks (mean: 4 weeks)
• Standard goal INR range: 2.0 – 3.0 (sometimes 2.5 – 3.5) – varies by indication
• Point-of-care (POC) INR monitoring or venous INR monitoring
• Monitor baseline albumin and LFTs then periodically (annually) and a baseline CBC then periodically (every 3-12 months)

Warfarin Interactions

• Drug-Diet interactions: Vitamin-K rich foods replenish vitamin K stores and decrease warfarin efficacy. Monitor PO intake
• Drug-Drug interactions: Antibiotics, antifungals, corticosteroids, antiepileptics, alcohol, antiplatelets (e.g., aspirin, clopidogrel), and NSAIDs (e.g., ibuprofen, naproxen) all interact with warfarin
• Drug-Disease State Interactions: Constipation, diarrhea, fever, major changes in tobacco use, acute infection/illness, decompensated heart failure, and malignancy all interact with warfarin

Warfarin Drug-Drug Interactions

• Lists not all-inclusive
• Inhibitors of warfarin metabolism (may require less warfarin): Amiodarone, Azole antifungals, Bactrim, Cephalosporins, Chemotherapy, Diltiazem, Doxycycline, Fibrates, H2RAs, Isoniazid, Macrolides, Metronidazole, Protease inhibitors, Quinolones
• Inducers of warfarin metabolism (may require more warfarin): Azathioprine, Barbiturates, Carbamazepine, Nafcillin, Phenytoin, Primidone, Rifamycins
• Increased bleeding risk: Aspirin, Clopidogrel, Fondaparinux, NSAIDs, Prasugrel, Ticagrelor, UFH/LMWHs

Warfarin Contraindications, Adverse Effects and Reversal

• Contraindications: Active bleeding, pregnancy (safe w/ breastfeeding)
• Adverse Effects: bleeding/bruising, warfarin necrosis (often due to high loading doses), purple toe syndrome (w/i first few weeks of initiation), hair loss/thinning (following extended use)
• Reversal: Vitamin K (PO, IV), 4-Factor Prothrombin Complex Concentrate (PCC)

Warfarin Advantages/Disadvantages

• Advantages : Decades of experience and evidence - a gold standard for decades, effective, inexpensive to the patient, reliable, and readily available assay to monitor anticoagulant activity and adherence
• Disadvantages: Requires frequent monitoring and dose adjustment, numerous interactions, difficult pharmacokinetics with a prolonged onset and long half-life, a narrow therapeutic index, efficacy concern (poor/low time within therapeutic range or TTR), and safety concerns for bleeding risk

Factors to Consider When Choosing Initial Warfarin Dose

• Baseline albumin level
• Concomitant disease state(s)
• Age
• Concomitant medications

Factors Which May Potentiate the Effects of Warfarin and Increase INR

• Antibiotic therapy
• Alcohol

Direct-Acting Oral Anticoagulants (DOACs)

Mechanism of Action

• Inhibits Factor Xa: apixaban (Eliquis), rivaroxaban (Xarelto), edoxaban (Savaysa)
• Inhibits Factor IIa (thrombin): dabigatran (Pradaxa)
• Non-vitamin K pathway = no diet interactions

DOAC: Routes of Administration and Pharmacokinetics

• Administered orally
• Exhibits linear and predictable pharmacokinetics
• Apixaban (Eliquis)
  • Peak Effect: 1-3 hours
  • Half-life: 9-14 hours
  • Renal Excretion: 25%
• Rivroxaban (Xarelto)
  • Peak Effect: 2-4 hours
  • Half-life: 5-9 hours
  • Renal Excretion: 33%
• Edoxaban (Savaysa)
  • Peak Effect: 1-2 hours
  • Half-life: 9-11 hours
  • Renal Excretion: 35-50%
• Dabigatran (Pradaxa)
  • Peak Effect: 1.5-3 hours
  • Half-life: 12-17 hours
  • Renal Excretion: 80%

DOAC Dosing: Strategies and Considerations

• Fixed-dosing (once-a-day or twice-a-day)
• Rivaroxaban must be taken with food (15 mg and 20 mg doses)
• Dabigatran cannot be split/crushed and must be kept in its original packaging
• Dose may be adjusted based on indication, age, weight, drug-drug interactions, and renal function
• Adherence is vital
• Calculate creatinine clearance using actual body weight for the Cockcroft-Gault equation
• If a DOAC dose is missed, take it as soon as you realize it was missed, within ~4-6 hours

DOAC Drug-Drug Interactions

• Apixaban, Rivaroxaban, Edoxaban and Dabigatran are all P-glycoprotein substrates
• Apixaban and Rivaroxaban are CYP3A4 substrates
• Apixaban and rivaroxaban: avoid use with combined strong inhibitors/inducers of P-gp and CYP3A4
• Edoxaban and dabigatran: avoid use with strong inhibitors/inducers of P-gp

DOAC Drug-Drug Interactions in Detail

• Dabigatran & Edoxaban
  • P-gp INHIBITORS: Amiodarone, Carvedilol, Clarithromycin, Conivaptan, Cyclosporine, Diltiazem, Dronaderone, Erythromycin, Grapefruit, Itraconazole, Ketoconazole, Lapatinib, Mefloquine, Saquinivir, Tamoxifen, Verapamil
  • P-gp INDUCERS: Barbiturates, Carbamazepine, Dexamethasone, Nelfinavir, Nicardipine, Phenytoin, Rifampin, and St. John's Wort
• Apixaban & Rivaroxaban
  • Dual P-gp and CYP 3A4 INHIBITORS: Clarithromycin, Conivaptan, Cyclosporine, Diltiazem, Dronaderone, Grapefruit, Indinavir, Itraconazole, Ketoconazole, Nelfinavir, Posaconazole, Ritonavir, Saquinivir, Tamoxifen
    • Dual P-gp and CYP 3A4 INDUCERS: Barbiturates, Carbamazepine, Phenytoin, Rifampin, St. John's Wort

DOAC Lab Monitoring & Contraindications

• Monitoring
  • Baseline CBC then periodically (every 3-12 months)
  • Baseline renal function then periodically (every 3-12 months)
  • Baseline LFT's then periodically (annually)
  • DO NOT CHECK INR
• Contraindications
  • Active bleeding
  • Pregnancy and breastfeeding
  • Inappropriate indication/population
  • Severe renal impairment (in general: CrCl <25-30 ml/min)
  • Severe hepatic impairment (CHILD-PUGH C (apixaban), CHILD-PUGH B (all other DOACs)
  • Known Gl absorption issues

DOAC Adverse Effects and Reversal

• Adverse Effects
  • Bleeding/bruising
  • Increased risk of GI bleed compared to warfarin (rivaroxaban, dabigatran, edoxaban)
  • Dyspepsia (dabigatran)
• Reversal
  • Factor Xa inhibitors (apixaban, rivaroxaban): andexanet alpha (Andexxa)
  • Thrombin inhibitor (dabigatran): idarucizumab (Praxbind)

DOAC Advantages vs. Warfarin

• Advantages:

  • Rapid onset of action
  • short half-life (rapid offset of action)
  • predictable/linear pharmacokinetics
  • fewer drug interactions
  • few diet/disease state interactions
  • routine drug level monitoring unnecessary
  • better safety profile
  • more convenient for patients and poses a possibly less burden on the healthcare system

• Disadvantages:

  • Difficult to monitor adherence
  • short half-life
  • potential drug accumulation with renal dysfunction
  • no reliable assays to monitor drug levels
  • more expensive for patient
  • less experience/evidence in special populations

DOAC Review Questions

• Dabigatran is not a Factor Xa inhibitor.

• Rivaroxaban must be taken with food

• Age, Weight, Indication and Renal Function should all be evaluated to determine the need for a DOAC dose adjustment

Oral Anticoagulant Longitudinal Monitoring

• Follow-up interval:
  • 4 weeks for Warfarin (mean) - typically in clinic
  • 3-12 months for DOACs - in-clinic or virtual
• Labs
  • INR for Warfarin
  • CBC and LFTs for Warfarin
  • SCr for DOACs
• Key Follow Up Questions include: unusual bleeding/bruising or other side effects ; new or changed medications and/or adherence; potential major diet changes (for warfarin); upcoming procedures or surgeries; presence of new kidney or liver issues; insurance coverage or other affordability issues; inquiry about appropriate dose; recent urgent care or emergency department visits; discussion of duration and/or discontinuation of anticoagulation

Parenteral Anticoagulants

• Heparins
• Factor Xa Inhibitors
• Direct Thrombin Inhibitors

Parenteral Anticoagulants Include Heparin

• Options: Unfractionated heparin
  • Origin: Porcine intestinal tissue
  • Mechanism of Action: Binds to antithrombin III and inhibits the activity of activated coagulation factors (IIa, Xa, IXa, XIa, XIIa)
  • Routes of Administration: Intravenous (IV) preferred or subcutaneous (SC)
  • Pharmacokinetics: Non-linear and unpredictable Onset of Action: Immediate Half-life: very short (~1-1.5 hours) Renal excretion: No
  • Dosing Strategies: For IV administration (drip), base dosing on weight adjusted with a thrombolitic nomogram. For SC administration, dosing is weight-based without adjustment
  • Monitoring: Chromogenic anti-Xa level (IV), aPTT (IV), CBC (especially platelets)
  • Contraindications: Active bleeding, heparin-induced thrombocytopenia (HIT)
  • Adverse Effects: Bleeding/bruising, Heparin-induced thrombocytopenia (HIT), Osteoporosis
  • Reversal: Protamine (100%)

Parenteral Anticoagulants Include Low Molecular Weight Heparin

• Options: Enoxaparin (Lovenox) and dalteparin (Fragmin)
  • Origin: Porcine intestinal tissue
  • Mechanism of Action: Binds to antithrombin III and inhibits the activity of activated coagulation factors (Xa > IIa)
  • Routes of Administration: Subcutaneous (SC)
  • Pharmacokinetics: Linear and predictable
    • Onset of Action: 3-4 hours
    • Half-life: Short (4-7 hours)
    • Renal excretion: Yes
  • Dosing Strategies: For SC administration for treatment, base dosing on weight. Dosing may also be fixed for prophylaxis
  • Round dose to nearest commercially available strength. Multiple injections required for morbid obesity
  • Monitoring: Chromogenic anti-Xa level , renal function, and CBC (especially platelets)
  • Contraindications: Active bleeding, heparin-induced thrombocytopenia, and severe renal impairment (generally CrCl < 30)
  • Adverse Effects: Bleeding/bruising, HIT, and burning during injection
  • Reversal: Protamine (partial ~50%)

Parenteral Anticoagulants Include Fondaparinux

• Options: Fondaparinux (Arixtra)
  • Origin: The origin is synthetic.
  • Mechanism of Action: Its mechanism Inhibits factor Xa.
  • Routes of Administration: Subcutaneous (SC)
  • Pharmacokinetics: Linear and predictable; onset of action occurs in 2-3 hours, a half-life of 17-21 hours, and is renally excreted
  • Dosing Strategies: Subcutaneous weight-based (treatment) or fixed dosing (prophylaxis) once-a-day without dose adjustment for morbid obesity
  • Monitoring: Chromogenic anti-Xa, creatinine level, complete cell count,
  • Contraindications: Active bleeding or severe renal impairment (CrCl < 30)
  • Adverse Effects: Bleeding / bruising
  • Reversal: None FDA approved

Parenteral Anticoagulants Clinical Pearls

• Unfractionated Heparin (UFH)
  • Advantages: Preferred in severely impaired renal function or dialysis, short half-life allows for rapid discontinuation of anticoagulation in cases when needed intravenously and has available reversal agent
  • Disadvantages: Less predictable kinetics = requires frequent drug level monitoring and dose adjustment, Reduced efficacy and safety compared to LMWH/fondaparinux, Risk of heparin-induced thrombocytopenia and SC difficult to find at pharmacies and more difficult for patient use = not ideal for outpatient use.
• Low Molecular Weight Heparin (enoxaparin) – gold standard
  • Advantages: Preferred over IV UFH due to improved efficacy and safety with most evidence, predictable pharmacokinetics with no drug level monitoring, longer half-life allows for once-a-day or twice-a-day dosing, it has a lower risk of HIT and osteoporosis compared to UFH and comes in pre-filled syringes for patient ease-of-use.
  • Disadvantages: Renal impairment may preclude use and has only partial reversibility.
• Fondaparinux
  • Advantages: Predictable pharmacokinetics where there is no drug level monitoring, a longer half-life allows for once-a-day dosing, no risk of heparin induced thrombocytopenia, and is easier to use in morbid obesity compared to LMWH with prefilled syringes.
  • Disadvantages: There exists less evidence and experience for use and cannot be used in patients with renal impairment

Review Questions For Parenteral Anticoagulants

• Enoxaparin, Fondaparinux and Unfractionated Heparin can cause thrombocytopenia
• Unfractionated heparin can be used in dialysis
• Enoxaparin and Fondaparinux come in commercially available pre-filled syringes

Conditions Typically Managed with Anticoagulant Medications

• Venous thromboembolism (VTE): deep Vein Thrombosis (DVT) and pulmonary Embolism (PE)
• Ischemic cerebrovascular accident (CVA) due to cardioembolic sources or atrial fibrillation/flutter and mechanical heart valve replacement
• Left ventricular thrombus
• Chronic thromboembolic pulmonary hypertension (CTEPH)
• Thrombophilia (inherited or acquired clotting disorders)

Venous Thromboembolism (VTE) Treatment Overview

• Goals of Treatment: therapeutic anticoagulation for at least 3 months, prevent additional clot formation, prevent clot propagation, prevent progression to PE (if DVT), reduce morbidity and mortality, and prevent post-thrombotic syndrome and PAH
• General Measures: elevation of the affected limb, early ambulation, analgesics, possible oxygen therapy
• Majority of VTE events can be managed in the outpatient setting

Management of Venous Thromboembolism (VTE)

• Direct oral anticoagulants alone as a single drug approach, unless patient has qualifying criteria for hospitalization and thrombolytic therapy
• In instances when VTE can be managed in the clinic rather than in the hospital, use either Rivaroxaban, apixaban, edoxaban or dabigatron as a single drug approach
• If VTE is in the lower extremities, consideration should be given for an IVC filter
• Oral Warfarin is still reasonable, however VTE requires a 5-day overlap with IV UFH or LMWH before INR is within therapeutic range

Venous Thromboembolism Treatment (VTE) Guidelines

• 2024 CHEST VTE Guidelines recommend direct-acting oral anticoagulant (DOAC) over vitamin K antagonist (VKA) therapy
• 2020 ASH Guideline suggest use of direct-acting oral anticoagulant (DOAC) over vitamin K antagonist (VKA) therapy.
• VKA therapy = conventional therapy = VKA (goal INR 2.0 – 3.0) + overlap with parenteral anticoagulant

DOAC Superiority for Venous Thromboembolism (VTE) Treatment

• Meta-analysis of ~27,000 patients – DOACs vs. warfarin
  • Equal efficacy compared to warfarin (non-inferior)
  • A 63% reduction in intracranial hemorrhage
  • A 39% reduction in major bleeding
  • A 64% less fatal bleeding profile
• DOACS = Significantly Safer

Stroke Prevention in Atrial Fibrillation Treatment Overview

• Goals of Treatment: therapeutic anticoagulation and potential mechanical intervention such as LAA closure or excision
• Rate and Rhythm Control: pharmacologic therapy, electrical cardioversion, and ablation or MAZE procedure

CHAD2DS2-VASc Score for Stroke Prevention in Atrial Fibrillation

Anticoagulation Recommendations Based on CHAD2DS2-VASc Scores

Offer Anticoagulation

Anticoagulation for Atrial Fibrillation By Indication

No Overlap with a Parenteral Anticoagulant Needed

Atrial Fibrillation Treatment Guidelines

• 2023 ACC/AHA/ACCP/HRS Atrial Fibrillation Guideline (published 2024) state direct-acting oral anticoagulant (DOAC) are recommended over vitamin K antagonist (VKA) therapy*
• 2018 CHEST Atrial Fibrillation Guideline state direct-acting oral anticoagulant (DOAC) are recommended over vitamin K antagonist (VKA) therapy*.
  *VKA therapy with goal INR 2.0 – 3.0

DOACs Outperform Warfarin for the Treatment of Atrial Fibrillation

• Meta-analysis of ~72,000 patients – DOACs vs. warfarin shows:
  • Equal efficacy (possibly better efficacy) compared to warfarin
  • ~50% reduction in the risk of intracranial bleed
  • ~10% reduction in the risk of mortality
  • ~25% increase in risk of GI bleed (dabigatran, rivaroxaban, high-dose edoxaban)

DOACS = Significantly Safer

Patient Counselling and Education

• Indication(s) for anticoagulation therapy and goals of therapy (e.g., what is the goal INR range?) should be explained
• Inform patient as to the brand and generic names of the agent being used
• Required monitoring and potential diet/alcohol interactions must be discussed
• A thorough explanation of potential drug-drug and disease-drug interactions
• Procedures or surgeries must be explained in detail to the patient
• Ensure the adherence of the patient and their understanding of how to address a missed dose as well as ensure their Pillbox use
• Ensure the drug-specific administration requirements and that they have acquired emergency alert jewelry or identification with important information, namely their anticoagulant. Encourage patients to avoid injury, including falls or motor vehicle accidents
• Explain the potential increased risk of recurrent thrombosis, DVT, PE, and or stroke while on an anticoagulant therapy
• Explain the potential side effects, focusing on the topic of bleeding or bruising. Ensure the patient also knows to explain the difference between expected bruises versus those that are unusual.

Patient Counseling & Education on Bleeding/Bruising

• Self-resolve can occur with time and/or pressure (emergent evaluation unlikely needed) - Expected on-therapy bleeding includes cuts, abrasions, and epistaxis - Expected on-therapy bruising
• In the event of the following, seek emergent evaluation - Excessive bleeding: Cuts, abrasions, epistaxis - Internal bleeding: CVA symptoms, hematemesis, coffee-ground emesis, hemoptysis, hematochezia, melena - Excessive bruising – full-body bruising, rapidly growing hematoma(s) - Trauma (mechanical fall resulting in head injury, motor vehicle accident, etc.)

Mitigating Bleed Risk

• Stop antiplatelet agents (e.g. aspirin, clopidogrel, ticagrelor) whenever possible
• Low dose aspirin (81-100mg) + anticoagulant confers a 2-fold increased risk of major bleed
• P2Y12 inhibitor + anticoagulant confers a >2-fold increased risk of major bleed
• Low dose aspirin + P2Y12 inhibitor + anticoagulant confers a >3 fold increased risk of major bleed
• Avoid NSAIDs whenever possible
• NSAIDs (even PRN use) confers a near 2-fold increased risk of major bleed
• Optimize blood pressure control and minimize fall risk
• Correct anemia
• Optimize time in therapeutic range (warfarin), otherwise consider DOAC

Consider the Following Special Population Considerations:

• Pediatrics, pregnancy, bariatric surgery, and older adults
• With other cardiac-related indications such as intracardiac thrombosis and cardiac valve replacement
• With other thrombosis-related indications such as cancer-related thrombosis and thrombophilia (clotting disorders)

Key Takeaways

• DOACs are preferred over vitamin K antagonist therapy for the most common indications for anticoagulation for equal/better efficacy and a better safety profile (also improved patient convenience and satisfaction)
• Ask the question: Why shouldn't this patient be on a DOAC?
• Be mindful of any nuances with each specific DOAC
• Patient counseling and education is imperative
• Mitigate bleed risks whenever possible
• When choosing which therapy is most appropriate, be mindful of special population considerations and if needed, consult an antithrombosis expert.