Rx Anticoagulants

    Notes

    • Do not need to stop warfarin therapy for minor dental procedures (includes extractions)
    • Source: NEJM+

    Antiplatelet Agents

    • Dipyridamole - Usually used if aspirin not tolerated
    • Aspirin
      • Irreversible platelet inhibitor (takes 6 days or so to back to normal)
      • Not appropriate for VTE prophylaxis / treatment. (shown no benefit)
      • Aspirin is effective for ARTERIAL thrombi (stroke, MI)
    • Ticlopidine - Not used for stroke prevention - Bad S/E profile.

    Anticoagulant Agents

    TABLE UNDER CONSTRUCTION

     

    Agent Class/Mech Indications Cautions Reversal Notes

    Warfarin

    (Coumadin)

    Vitamin K

    Antagonist

    (Factors II,

    VII, IX, and X)

    - AFib

    - VTE

    - VTE proph

    - PE

    - Congenital

     Prothromboic

    - Requires INR

      monitoring

    Vitamin K

    FFP

    PCC (Octoplex)

      - works fast

      - less volume

      - more expensive

    - Affects factors 10, 9, 7, 2, Protein C,

      Protein S (1972 Canada vs. Soviets)

    - Target INR 2-3 (or 2.5-3.5 for mech

      valves)

    Unfractionated

    Heparin

    - 5000u SC q8-12h
    for VTE proph (TID 

    for high risk)
    5000 U IV bolus,

    then 1000 U/h

    (target PTT 1.5-2.5

    *normal PTT)

    Binds antithrombin-3

    (AT3), Heparin-AT3 

    complex inactivates 

    F II (thrombin), IXa,

    Xa, XIa, XIIa

    Thrombin inhibited 

    at very low doses 

    (before other factors

    so VTE proph very

    effective at low dose)

    - Safer in Renal

      Failure

    - AFib/VTE

    VTE proph/

    congenital/

    cancer VTE

    - Heparin-AT3

    complex can

    bind Platelet

    Factor 4 - Ab

    formed against it

    causes Heparin-

    Induced

    Thrombocytopenia

    (HIT)

    - Requires PTT

      monitoring

    - PTT   poorly 

         predictable.

    - Protamine (must

      be in monitored 

      setting)

    - Must monitor PTT and titrate

    - High Risk of Heparin Induced

       Thrombocytopenia (HIT)

    - Usually give as infusion or frequent

       bolus

    - Duration of action ~4hr

    - Fast on-off if needs to go for surgery.

    Reversible with protamine [LMWH is not as reversible with protamine]

     (1mg IV protamine for 100 units of UFH in last 4 hrs.  

      Give protamine over 1-3min, do not exceed

      50mg/10min.)

    or 1mL (10mg) of protamine for each 1000IU of heparin

     

    LMWH

    - Enoxaparin

     (1.5mg/kg q24h)

     

    - Dalteparin

      (200UI/kg q24h)

      (aka Fragmin)

     

    - Tinzaparin

     (175 U/kg q24h)

     

    LMWH

    Inhibits:

    - Factor Xa

    - Antithrombin
    Heparin has different

    molecular sizes, 

    smaller ones = more

    anticoagulation.

    Same as UH  

    - Protamine

    Reverses anti-

     thrombin, but 

    partially reverses

    Factor Xa activity

    - Monitoring not needed

    - Can monitor anti-factor Xa activity

        if need (i.e. obese or renal failure)

    - Very predictable anticoagulation

    - Low risk of heparin-induced

      thrombocytopenia (HIT)

    Argatroban

    (NO trade name)

    Synthetic

    Direct Thrombin

    Inhibitor

    - HIT requiring

     anticoagulation

    - Hepatically cleared

     

    - Cleared by liver (no renal dosing)

    (adjust for hepatic insufficiency)

    Lepirudin

    (not used,

    replaced by 

    Argatroban)

    Direct Thrombin
    Inhibitor

    Derived from

    medicinal 

    leech

    - like Argatroban

    - Renally Cleared

    (not used in renal

    pts)

    - IV bolus = risk 

     of anaphylaxis

     

    - Rarely used

    Fondaparinux

    (chemically related

    to LMWH)

    Daily Dosing

    5mg SC od (for <50kg)

    or

    7.5 mg SC od (for

              50-100kg),

    or

    10mg if >100kg

    Anti-Thrombin III

    potentiator

    (indirectly inhibits

    Factor Xa)

    Synthetic penta-

    saccharide

    - NSTEMI

    - ...

    - Renally cleared
    (contraindicated

    if GFR < 30 and 

    < 50kg pts)

     

    - Can be used to manage HIT, but 

      does not carry the FDA indication.

      (easy - single daily dose)

    - Insufficient data to recommend it 

      over argatroban

    - Same efficacy as enox for hip+knee

    surgeries.

    Bivalirudin

    Direct Thrombin

    Inhibitor

    - Derived from

    hirudin in leech 

    saliva

    - STEMI/NSTEMI

    undergoing PCI

    Some renal

    clearance

    Mostly plasma

    protein cleavage

    Halflife: 

    Normal renal function: 25 minutes

    Severe (CrCl 10-29): 57 minutes

    IHD-dependent (off dialysis): 3.5 hours

    - NO need

    - activity

    ends 1hr 

    after d/c

    - inhibits both circulating + clot-bound thrombin

    - quick onset, short halflife

    - Unlike heparin doesnt bind plasma proteins, so

     has a predictable response

     

    Dabigatran

    Direct thrombin

    inhibitor

       

    Idarucizumab

    Dialyzable!!!

     
    Rivaroxaban

    Direct factor Xa

    inhibitor

        Andexanet alfa  
    Apixaban

    Diret factor Xa

    inhibitor

        Andexanet alfa  

     

    Heparin Induced Thrombocytopenia (HIT)

    • More common with Heparin than LMWH
    • Antibodies bind complexes formed between heparin and platelet factor 4 (PF4).
    • See decreasing platelet counts
    • Surprisingly, HIT is a pro-coagulant phenomena - perhaps antibody-PF4 complexes release procoagulants from circulation. So need to monitor patients for arterial clots.
    • Treat with argatroban (FDA approved) but some use fondaparinux (not FDA approved)

    Pro-Coagulant Agents

    • Tranexamic Acid
      • Lysine derivative
      • Competitively inhibits plasminogen --> Acts as anti-fibrinolytic.

    Pneumatic Compression Devices

    • Only shown to decrease VTE risk in surgical patients.
    • Not been demonstrated to significantly reduce incidence of PE.
    • Compliance is an issue.

     

    INR & Warfarin

    • Do not use Vitamin K in a non-bleeding patient unless INR > 9.0.
      • IF INR > 9.0, can give Oral Vitamin K 2.5-5mg and withhold warfarin + follow INR.
    • Most common drugs that raise INR: (based on population based study)
      • Septra
      • Amoxicillin
      • Clarithromycin
      • Norfloxacin 
    • Starting/Titrating Warfarin:
    • Doc - Jul 30 2017 - 1-03 PM - p1.jpg

     

    Holbrook A, Schulman S, Witt DM, et al. Evidence-based management of anticoagulant therapy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012 Feb;141(2 Suppl):e152S-84S

    Resources

     

    • Kahn SR, Lim W, Dunn AS, et al. Prevention of VTE in nonsurgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e195S-226S. PMID: 22315261
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