Anti-platelet agent reversal

Background

  • Consider reversal of aspirin and clopidogrel in acute life threatening hemorrhage, but it is very controversial in ICH[1]
    • Risk of mortality from ICH on warfarin ~16-80%
    • Significantly higher mortality with either clopidogrel mono or dual-antiplatelet treatment in trauma patients[2]
    • Aspirin alone is predictor of higher mortality in spontaneous ICH[3]
  • PATCH trial in 2016 suggested mortality is higher in platelet transfused patients, alongside several other preceding studies[4]
    • 2.05 OR, increased odds of death at 3 months in platelet transfusion group
    • 190 ICH patients enrolled
      • Included patients with at least 7 days of antiplatelet therapy, including ASA, clopidogrel, dipyridamole
      • Excluded SDH, epidural hemorrhage, aneurysm, AVM, surgical evacuation of ICH within 24 hrs, thrombocytopenia < 100k, use of warfarin if INR > 2-3, infratentorial hematomas, large intraventricular hemorrhage
  • Anti-platelet medications to reverse:
  • Prevalence of immediate traumatic ICH in pts on clopidogrel 12% compared to 5% on warfarin[5]
    • May be confounded by pts on warfarin having low threshold for presenting with head injury to ED, but highlights high frequency of bleeds in pts on clopidogrel
    • However, no pts on clopidogrel had delayed ICH compared to ~1% pts on warfarin with delayed ICH
    • Delayed ICH defined as traumatic ICH within 2 wks after initial normal CTH
  • Platelet aggregation recovery[6]:
    • Within 4 days of stopping aspirin
    • Takes 10 days for clopidogrel (life-span of a platelet)
      • When starting clopidogrel, takes 7 days to achieve max platelet inhibition[7]
      • If 350mg loading dose, platelet inhibition occurs within 2-5 hrs

Reversal

  • If time permits, obtain initial platelet function assay for aspirin and clopidogrel
  • Reversal with combination of platelet transfusion, desmopressin
  • Limited evidence to support mortality improvement in reversal, but little evidence of harm[8]

Platelet transfusion

  • Volume
    • At least 5 units of platelets initially to reverse routine antiplatelet doses[9]
    • Consider significantly more platelets for those who were loaded with clopidogrel within the last week[10]

Desmopressin (DDAVP)[11]

  • 0.3 mcg/kg/dose in 50 cc NS over 30 min[12]
    • Quick onset of action, within 1 hr
    • Similar MOA to cryoprecipitate (increase factor VIII, vWF)
    • No transfusion complications of cryoprecipitate
    • However, effects only last up to 24 hrs, and tachyphylaxis limits efficacy repeated doses

Special Circumstances

  • Chronic renal failure patients may benefit from:
    • Desmopressin
    • OR cryoprecipitate 1 unit
    • Conjugated estrogens IV 0.6mg/kg/d for 5 days[13]
    • See uremic bleeding
  • Ticagrelor does not likely respond to platelet transfusion reversal[14][15]

See Also

References

  1. Ohm C, Mina A, Howells G, et.al. Effects of antiplatelet agents on outcomes for elderly patients with traumatic intracranial hemorrhage. J Trauma. 2005;58:518-22.
  2. Wong DK, Lurie F, Wong LL. The effects of clopidogrel on elderly traumatic brain injured patients. J Trauma. 2008;65:1303-8.
  3. Saloheimo P, Ahonen M, Juvela S, et.al. Regular aspirin-use preceeding the onset of primary intracerebral hermoorhage is an independent predictor for death. Stroke. 2006;37:129-33.
  4. Baharoglu MI et al. Platelet Transfusion Versus Standard Care After Acute Stroke due to Spontaneous Cerebral Haemorrhage Associated with Antiplatelt Therapy (PATCH): A Randomised, Open-Label, Phase 3 Trial. Lancet 2016; 1 – 9.
  5. Nishijima DK et al. Immediate and delayed traumatic intracranial hemorrhage in patients with head trauma and preinjury warfarin or clopidogrel use. Ann Emerg Med. 2012 Jun;59(6):460-8.e1-7.
  6. Li C et al. Reversal of the anti-platelet effects of aspirin and clopidogrel. J Thromb Haemost. 2012 Apr;10(4):521-8.
  7. Vilahur G, Choi GB, Zafar MU et.al. Normalization of platelet reactivity in clopidogrel-treated subjects. J Thromb Haemost. 1997;5:82-90.
  8. Orlando Regional Medical Center. Department of Surgical Education. ANTIPLATLET AGENT REVERSAL IN ADULTS WITH TRAUMATIC INTRACRANIAL HEMORRHAGE. http://www.surgicalcriticalcare.net/Guidelines/TBI%20Antiplt%20Reversal%20Guideline%202012.pdf.
  9. Powner DJ, Hartwell EA, Hoots WK, et.al. Counteracting the effects of anticoagulants oand antiplatelet agents during neurosurgical emergencies. Neurosurgery. 2005; 57:823-31.
  10. Downey DM, Monsn B, Butler KL, et.al. Does platelet administration affect mortality in elderly headinjured patients taking antiplatelet medications? Am Surg. 2009;75(11):1100-3.
  11. Hedges SJ, Dehoney SB, Hooper JS, et.al. Evidence-based treatment recommendations for uremic bleeding. Nature Clin Prac. 2007;3(3):138-53.
  12. . Gratz I, Koehler J, Olsen D, et.al. The effect of desmopressin acetate on postoperative hemorrhage in patients receiving aspirin therapy before coronary artery bypass operations. J Thorac Cardiovasc Surg. 1992; 104:1417-22.
  13. Livio M, Mannucci PM, Viganò G, et.al. Conjugated estrogens for the management of bleeding associated with renal failure. N Engl J Med. 1986; 315:731-5.
  14. Martin AC et al. The effectiveness of platelet supplementation for the reversal of ticagrelor-induced inhibition of platelet aggregation: An in-vitro study. Eur J Anaesthesiol. 2016 May;33(5):361-7.
  15. Godier A et al. Inefficacy of Platelet Transfusion to Reverse Ticagrelor. N Engl J Med 2015; 372:196-197.