Anti-platelet agent reversal: Difference between revisions
 
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==Background==
==Background==
*Consider reversal of [[aspirin]] and [[clopidogrel]] in acute life threatening hemorrhage, primarily [[ICH]]<ref>Ohm C, Mina A, Howells G, et.al. Effects of antiplatelet agents on outcomes for elderly patients with
*Consider reversal of [[aspirin]] and [[clopidogrel]] in acute life threatening hemorrhage, but it is very controversial in [[ICH]]<ref>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.</ref>
traumatic intracranial hemorrhage. J Trauma. 2005;58:518-22.</ref>
**Risk of mortality from ICH on [[warfarin]] ~16-80%
**Risk of mortality from ICH on [[warfarin]] ~16-80%
**Significantly higher mortality with either clopidogrel mono or dual-antiplatelet tx in trauma patients<ref>Wong DK, Lurie F, Wong LL. The effects of clopidogrel on elderly traumatic brain injured patients. J
**Significantly higher mortality with either clopidogrel mono or dual-antiplatelet treatment in trauma patients<ref>Wong DK, Lurie F, Wong LL. The effects of clopidogrel on elderly traumatic brain injured patients. J
Trauma. 2008;65:1303-8.</ref>
Trauma. 2008;65:1303-8.</ref>
**Aspirin alone is predictor of higher mortality in spontaneous ICH<ref>Saloheimo P, Ahonen M, Juvela S, et.al. Regular aspirin-use preceeding the onset of primary
**Aspirin alone is predictor of higher mortality in spontaneous ICH<ref>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.</ref>
intracerebral hermoorhage is an independent predictor for death. Stroke. 2006;37:129-33.</ref>
*[[PATCH trial]] in 2016 '''suggested mortality is higher in platelet transfused patients''', alongside several other preceding studies<ref>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.</ref>
**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:
*Anti-platelet medications to reverse:
**[[Aspirin]]
**[[Aspirin]]
**[[Clopidogrel]]
**[[Clopidogrel]]
**[[Ticagrelor]]
**[[Ticagrelor]]
**Ticlopidine (rarely used anymore)
**[[Ticlopidine]] (rarely used anymore)
*Prevalence of immediate traumatic ICH in pts on clopidogrel 12% compared to 5% on [[warfarin]]<ref>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.</ref>
**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<ref>Li C et al. Reversal of the anti-platelet effects of aspirin and clopidogrel. J Thromb Haemost. 2012 Apr;10(4):521-8.</ref>:
*Platelet aggregation recovery<ref>Li C et al. Reversal of the anti-platelet effects of aspirin and clopidogrel. J Thromb Haemost. 2012 Apr;10(4):521-8.</ref>:
**Within 4 days of stopping aspirin
**Within 4 days of stopping aspirin
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***When starting clopidogrel, takes 7 days to achieve max platelet inhibition<ref>Vilahur G, Choi GB, Zafar MU et.al. Normalization of platelet reactivity in clopidogrel-treated subjects.
***When starting clopidogrel, takes 7 days to achieve max platelet inhibition<ref>Vilahur G, Choi GB, Zafar MU et.al. Normalization of platelet reactivity in clopidogrel-treated subjects.
J Thromb Haemost. 1997;5:82-90.</ref>
J Thromb Haemost. 1997;5:82-90.</ref>
***If 350 mg loading dose, plt inhibition occurs within 2-5 hrs
***If 350mg loading dose, platelet inhibition occurs within 2-5 hrs


==Reversal==
==Reversal==
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*Reversal with combination of platelet transfusion, [[desmopressin]]
*Reversal with combination of platelet transfusion, [[desmopressin]]
*Limited evidence to support mortality improvement in reversal, but little evidence of harm<ref>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.</ref>
*Limited evidence to support mortality improvement in reversal, but little evidence of harm<ref>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.</ref>
*Platelet transfusion volume:
 
===[[Platelet transfusion]]===
*Volume
**At least 5 units of platelets initially to reverse routine antiplatelet doses<ref>Powner DJ, Hartwell EA, Hoots WK, et.al. Counteracting the effects of anticoagulants oand
**At least 5 units of platelets initially to reverse routine antiplatelet doses<ref>Powner DJ, Hartwell EA, Hoots WK, et.al. Counteracting the effects of anticoagulants oand
antiplatelet agents during neurosurgical emergencies. Neurosurgery. 2005; 57:823-31.</ref>
antiplatelet agents during neurosurgical emergencies. Neurosurgery. 2005; 57:823-31.</ref>
**Consider significantly more platelets for those who were loaded with clopidogrel within the last week<ref>Downey DM, Monsn B, Butler KL, et.al. Does platelet administration affect mortality in elderly headinjured
**Consider significantly more platelets for those who were loaded with clopidogrel within the last week<ref>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.</ref>
patients taking antiplatelet medications? Am Surg. 2009;75(11):1100-3.</ref>
*Desmopressin ([[DDAVP]])<ref>Hedges SJ, Dehoney SB, Hooper JS, et.al. Evidence-based treatment recommendations for uremic
 
bleeding. Nature Clin Prac. 2007;3(3):138-53.</ref>
===Desmopressin ([[DDAVP]])<ref>Hedges SJ, Dehoney SB, Hooper JS, et.al. Evidence-based treatment recommendations for uremic
**0.3 mcg/kg/dose in 50 cc NS over 30 min<ref>. Gratz I, Koehler J, Olsen D, et.al. The effect of desmopressin acetate on postoperative hemorrhage in
bleeding. Nature Clin Prac. 2007;3(3):138-53.</ref>===
*0.3 mcg/kg/dose in 50 cc NS over 30 min<ref>. 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
patients receiving aspirin therapy before coronary artery bypass operations. J Thorac Cardiovasc
Surg. 1992; 104:1417-22.</ref>
Surg. 1992; 104:1417-22.</ref>
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==Special Circumstances==
==Special Circumstances==
*Chronic renal failure pts may benefit from:
*Chronic renal failure patients may benefit from:
**Desmopressin
**[[DDAVP|Desmopressin]]
**OR cryoprecipitate 1 unit  
**OR [[cryoprecipitate]] 1 unit  
**Conjugated estrogens IV 0.6 mg/kg/d for 5 days<ref>Livio M, Mannucci PM, Viganò G, et.al. Conjugated estrogens for the management of bleeding
**Conjugated estrogens IV 0.6mg/kg/d for 5 days<ref>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.</ref>
associated with renal failure. N Engl J Med. 1986; 315:731-5.</ref>
**See [[uremic bleeding]]
**See [[uremic bleeding]]
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*[[Coagulopathy (main)]]
*[[Coagulopathy (main)]]
*[[Anticoagulant reversal for life-threatening bleeds]]
*[[Anticoagulant reversal for life-threatening bleeds]]
*[[Antiplatelet medications]]


==References==
==References==

Latest revision as of 03:01, 6 March 2021

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 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

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

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.
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