The Anticoagulant and Antiplatelet Refresher

anticoagulation

Anticoagulants and antiplatelets are the most common group of medications setting questioning in motion at my job.  Whether it is surgeons asking about washout periods or other colleagues admitting to not knowing the latest medications in the this category, I find myself constantly learning and relearning this topic.  I decided to put together a brief overview of what we have, how it is used and some of the nuances to remember.

1.        FACTOR Xa INHIBITORS (Anticoagulants):

  • Rivaroxaban (Xarelto)Deep vein thrombosis (DVT), pulmonary embolism (PE) treatment, Reduction in the risk of recurrent DVT/PE (in select patients), nonvalvular atrial fibrillation (to prevent stroke and systemic embolism), and postoperative DVT thromboprophylaxis.
    • Caution in pts w/moderate renal impairment (CrCl 30-50 mL/min)  and avoid in patients with severe renal impairment (CrCl <30 mL/min).
    • CYP3A4 substrate and P-gly transporters
    • No reversal agent
    • Discontinue at least 24 hours before any procedure in normal renal function.  If CrCl <50 and elderly, need 48 hours washout.
  • Fondaparinux (Arixtra): Prophylaxis of DVT in patients undergoing surgery for hip replacement, knee replacement, hip fracture, or abdominal surgery, treatment of acute PE, treatment of acute DVT without PE.  Unlabeled: DVT prophylaxis with HIT
    • CrCl 30-50 mL/min: use caution.  Contraindicated in <30 mL/min.
  • Apixaban (Eliquis): hip or knee replacement DVT, nonvalvular AFib, unlabeled initial tx of VTE
    • Nonvalvular atrial fibrillation 5 mg BID, adjust in serum creatinine >1.5 and either age >/=80 or body weight </=60 kg: 2.5 mg BID.

2.  DIRECT THROMBIN INHIBITORS (Anticoagulants):

  • Bivalirudin (Angiomax):
    • Current recommendations are to adjust the dose for renal impairment in patients with a CrCl of 10–29 ml/min undergoing PCI and in patients with a CrCl<60 ml/min being treated for heparin-induced thrombocytopenia. Current manufacturer recommendations state that dosing modifications are not necessary in patients with hepatic impairment.
    •  No Reversal Agent.  Modified ultrafiltration and hemodialysis may facilitate removal (45-69% removal w/ultrafilt and 25% with HD).  Recombinant factor VII can be administered at a dose of 90 mcg/kg IV.  FFB, etc…
  • Dabigatran (Pradaxa):
    • Dosed as a twice daily oral tablet, dabigatran reaches a peak plasma concentration after 1–2 h with a half-life of 12–17 h. Renal clearance accounts for 80–85% elimination of dabigatran. Doses should be reduced in patients with moderate renal impairment (defined as CrCl 30–50 ml/min) and should be avoided in patients with severe renal impairment (defined as CrCl 15–30 ml/min) and concomitant use of medications requiring use of P-glycoprotein). Current manufacturer recommendations state that dosing modifications are not necessary in patients with hepatic impairment.
    • No Antidote.  FFP can be tried.  HD can be effective in removing as much as 60% of circulating drug, as the majority of drug is unbound to protein; but unsuff data to support this.
    •   Withhold for 2 days in patients with normal renal function and high risk of bleeding or major surgery.  For otherwise avg risks, 24 hours.
  • Desirudin (Iprivask):

3.  P2Y-12 RECEPTOR INHIBITORS (Antiplatelets):

  • Clopidogrel (Plavix):
    • Peak platelet inhibition:  300 mg load 6 hours, 600 mg load 2 hours.
    • Approved for ACS medically or PCI
    • Discontinue 5 days before surgery.  CABG hold time 5 days.
    • 2C19 and 3A4 metabolism (PPIs can reduce the effect of antiplatelet by inhibiting 2C19)
    • Loading dose:  300-600 mg; Maintenance dose:  75 mg/day
  • Ticagrelor (Brilinta): 
    • Peak platelet inhibition:  180 mg less than hour
    • LD: 180 mg, maintenance dose: 90 mg twice daily
    • Contraindications: ICH, severe hepatic disease
    • Not prodrug, reversible, noncompetitive binding, 3A4 (primary), 3A5, P-gp
    • Careful with asthma, bradycardia, enhanced bleeding with NSAIDs, VKA, strong 3A4 inhibitors increases Ticagrelor conc, strong 3A4 inducers decrease Ticagrelor conc, do not exceed 40 mg of simvastatin or lovastatin.  Limit ASA < 100 mg.
    • CABG hold time 5 days
    • Box warning: age-related bleeding CVA
  • Prasugrel (Effient): 
    • Peak platelet inh 60 mg load 1-1.5 hrs.
    • LD: 60 mg MD: 10 mg daily (5 mg if <60 kg; bw >/=75 yrs)
    • CIs: TIA/stroke
    • Bleeding risk higher than clopidogrel
    • D/C 7 days before surgery (CABG included), avoid in patient with active bleeding or a history of TIA or stroke and over 75 old unless pt has DM or history of MI
    • Box warning: aspirin dosing > 100 mg

4.  HEPARIN AND LOVENOX (Anticoagulants):  

  • Heparin:
    • No renal adjustment required
    • Different dosing depending on indication
    • Watch for HIT:  1-2% of patients.  Typically the platelet count will fall 5-14 days after heparin is first given; if someone has received heparin in the previous three months, the fall in platelets may occur sooner, sometimes within a day.

Enoxaparin (Lovenox):

  • Renal adjust < 30 mL/hr (treatment and prophylaxis)

  • HIT still an issue (it is a low molecular weight heparin)

Hopefully this review will help you identify which are anticoags, which are antiplatelets, and which could overlap or not based on profile.

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