Anti-platelet agent reversal

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  • 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 patients on warfarin having low threshold for presenting with head injury to ED, but highlights high frequency of bleeds in patients on clopidogrel
    • However, no patients on clopidogrel had delayed ICH compared to ~1% pts on warfarin with delayed ICH
    • Delayed ICH defined as traumatic ICH within 2 weeks 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


  • 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

See Also


  1. Ohm C, Mina A, Howells G, 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, 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 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.
  9. Powner DJ, Hartwell EA, Hoots WK, Counteracting the effects of anticoagulants oand antiplatelet agents during neurosurgical emergencies. Neurosurgery. 2005; 57:823-31.
  10. Downey DM, Monsn B, Butler KL, 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, Evidence-based treatment recommendations for uremic bleeding. Nature Clin Prac. 2007;3(3):138-53.
  12. . Gratz I, Koehler J, Olsen D, 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, 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.