Antiplatelet Therapy and Intra-cranial Hemorrhage (ICH)

Treatment:

Spontaneous ICH (intra-parenchymal)
  • Studies suggest platelets may increase poor outcomes. (PATCH trial, etc)
  • Note: trials excluded ruptured aneurysm, SDH and EDH
Traumatic ICH (SDH, EPH)
  • If neurosurgical intervention is NOT planned, recommendation is NOT to give platelets.
  • If neurosurgical intervention IS planned within 24 hours:
    • Obtain platelet function testing if possible
      • If testing is normal, patient is anti-platelet resistant or non-compliant with med and no transfusion is recommended.
      • If testing is abnormal, proceed with transfusion.
      • If testing is not available, empiric transfusion is acceptable.
    • Platelet transfusion of 1 unit apheresis platelets then retest platelet function
    • DDAVP may provide be considered. Dose: 0.4 mcg/kg IV

Background:

Antiplatelet therapy consists of medication in several categories:
  • Irreversible cyclooxygenase inhibitors: Aspirin and Triflusal (outside the US only)
  • Adenosine diphosphate (ADP) receptor inhibitors:
    • Clopidogrel (Plavix)
    • Prasugrel (Effient)
    • Tricagrelor (Brilinta)
    • Ticlopidine (Ticlid)
  • Phosphodiesterase inhibitors : Cilostazol (Pletal)
  • Protease-activated receptor-1 (PAR-1) antagonists: Vorapaxar (Zontivity)
  • Glycoprotein IIB/IIIA inhibitors – IV only
    • Abciximab (ReoPro)
    • Eptifibatide (Integrilin)
    • Tirofiban (Aggrastat)
  • Adenosine Reuptake Inhibitors
    • Dipyrimadole (Persantine) 
    • Aspirin/Dipyrimadole (Aggrenox)

These medications are prescribed for vascular disease conditions including: myocardial infarction, coronary artery disease, carotid artery disease, thrombotic stroke, and peripheral vascular disease. They are commonly prescribed to aging patients who are also at risk for falls and traumatic injuries.

Studies have shown that patients on these platelet inhibitors with spontaneous intracranial hemorrhage do not benefit from platelet transfusion6. In addition, platelet transfusions are associated with increased mortality and morbidity. However, the evidence is not as strong for traumatic intracranial hemorrhage, specifically subdural and epidural hematomas. These injuries were excluded in early trials of spontaneous hemorrhage and they are more likely to undergo surgical intervention. As such, it is a common occurrence to see patients with these injuries, taking antiplatelet medications, and ask: what do we do now?

The most comprehensive guidelines published to date come from a combined publication by the Neurocritical Care Society  and the Society of Critical Care Medicine1,2. They appeared the journal of Neurocritical Care and Critical Care Medicine in 2016. Since their publication, the American College of Cardiology has adopted similar recommendations but stops short of recommendations before surgical intervention3.

It is important to note that despite the agreement across specialties, the level of evidence for most of these recommendations is “low” to “moderate” due to the small size of the trials available. There are newer publications suggesting that DDAVP may be of some value in these instances, but insufficient evidence exists to make a definitive recommendation. Institutional guidelines vary widely based on the interpretations of these small studies. DDAVP is suggested due to its mechanism of action. It increases factor VIII and von Willebrand factor levels. However, the effect may only be transient, up to 3 hours.

References:

  1. Frontera JA, Lewin JJ, Rabinstein AA, et al. Guideline for Reversal of Antithrombotics in Intracranial Hemorrhage: A Statement for Healthcare Professionals from the Neurocritical Care Society and Society of Critical Care Medicine. Neurocrit Care. 2016;24(1):6-46. PubMed
  2. Frontera JA, Lewin JJ, Rabinstein AA, et al. Guideline for Reversal of Antithrombotics in Intracranial Hemorrhage: Executive Summary. A Statement for Healthcare Professionals From the Neurocritical Care Society and the Society of Critical Care Medicine. Crit Care Med. 2016;44(12):2251-2257.  PubMed
  3. Tomaselli GF, Mahaffey KW, Cuker A, et al. 2017 ACC Expert Consensus Decision Pathway on Management of Bleeding in Patients on Oral Anticoagulants: A Report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways. J Am Coll Cardiol. 2017;70(24):3042-3067.  PubMed
  4. Batchelor JS, Grayson A. A meta-analysis to determine the effect on survival of platelet transfusions in patients with either spontaneous or traumatic antiplatelet medication-associated intracranial haemorrhage. BMJ Open 2012;2:e000588. doi: 10.1136/bmjopen-2011-000588 PubMed
  5. Nishijima DK, Zehtabchi S, Berrong J, Legome E. Utility of Platelet Transfusion in Adult Patients with Traumatic Intracranial Hemorrhage and Pre-Injury Anti-Platelet Use: A Systematic Review. The journal of trauma and acute care surgery. 2012;72(6):1658-1663. doi:10.1097/TA.0b013e318256dfc5. PubMed
  6. Baharoglu MI, Cordonnier C, Al-shahi salman R, et al. Platelet transfusion versus standard care after acute stroke due to spontaneous cerebral haemorrhage associated with antiplatelet therapy (PATCH): a randomised, open-label, phase 3 trial. Lancet. 2016;387(10038):2605-13. PubMed
  7. Antiplatelet Agent Reversal In Adults With Traumatic Intracranial Hemorrhage, Institutional Guideline, Orlando Regional Medical Center, rev 2017. Download PDF
  8. Kim DY, O’leary M, Nguyen A, et al. The Effect of Platelet and Desmopressin Administration on Early Radiographic Progression of Traumatic Intracranial Hemorrhage. J Neurotrauma. 2015;32(22):1815-21. PubMed
  9. Patal R, Jonas-kimchi T, Margalit N, et al. [The effect of platelet transfusion on traumatic intracranial hemorrhage among patients treated with aspirin]. Harefuah. 2012;151(1):29-33, 62, 61. PubMed
  10. Nishijima DK, Zehtabchi S, Berrong J, Legome E. Utility of platelet transfusion in adult patients with traumatic intracranial hemorrhage and preinjury antiplatelet use: a systematic review. J Trauma Acute Care Surg. 2012;72(6):1658-63. PubMed
  11. Joseph B, Pandit V, Sadoun M, et al. A prospective evaluation of platelet function in patients on antiplatelet therapy with traumatic intracranial hemorrhage. J Trauma Acute Care Surg. 2013;75(6):990-4. PubMed
  12. Naidech AM, Maas MB, Levasseur-franklin KE, et al. Desmopressin improves platelet activity in acute intracerebral hemorrhage. Stroke. 2014;45(8):2451-3. PubMed
  13. Schnüriger B, Inaba K, Abdelsayed GA, et al. The impact of platelets on the progression of traumatic intracranial hemorrhage. J Trauma. 2010;68(4):881-5. PubMed
  14. Briggs A, Gates JD, Kaufman RM, Calahan C, Gormley WB, Havens JM. Platelet dysfunction and platelet transfusion in traumatic brain injury. J Surg Res. 2015;193(2):802-6. PubMed
  15. Interview with Dr. Debbie Yi Madhok, Co-Author of “Update on the ED Management of Intracranial Hemorrhage” ALiEM, Podcast Follow-up, April 2018 Podcast Link

Leave a Reply

This site uses Akismet to reduce spam. Learn how your comment data is processed.