1. The Effect of Platelet Administration in Antiplatelet Associated Intracerebral Hemorrhage
Caitlin Jenkins, PharmD
PGY-1 Pharmacy Resident
St. Joseph’s/Candler Health System
Co-Investigator: Sabrina Croft, PharmD, BCPS
Hannah Matson, PharmD Candidate
Joseph Crosby, PhD, RPh
Thank you for that introduction.
Our purpose was to see what we were doing before the new guidelines and if it was safe and efficacious.

2. Disclosure Statement
Disclosure statement: these individuals have the following to disclose concerning possible personal or financial relationships with commercial entities (or their competitors) that may be referenced in this presentation
Caitlin Jenkins, PharmD: nothing to disclose
Sabrina Croft, PharmD, BCPS: nothing to disclose
Hannah Matson, PharmD Candidate: nothing to disclose
Joseph Crosby, PhD, RPh: nothing to disclose

3. Background Intracerebral Hemorhage
10% of all CVAs are intracerebral hemorrhages (ICH)
Overall CVA mortality has decreased by 35%
No change in ICH mortality
Of all strokes, 87% are ischemic and 10% are intracerebral hemorrhage (ICH) strokes, whereas 3% are subarachnoid hemorrhage (SAH) strokes.
Thirty day mortality estimates have been reported to be approximately 40–50% in ICH and while the death rate of stroke overall (ischemic, ICH, and SAH) has decreased by 35% since 2001, there has been no change in ICH case fatality or long term mortality.
Mozaffarian et.al. A Report From the American Heart Association. Circulation. 2015;131:e29-e322.
Zahuranec et.al. Neurology. 2014;82:2180–2186.

4. Background Antiplatelet agents Used to prevent CVA and CAD
Increases the risk for developing a hemorrhagic stroke
Complicates outcomes after hemorrhagic stroke
With the population trending towards longer life expectancy, we see more and more patients on medications for cardiovascular disease such as anticoagulants and antiplatelet agents. These agents, while used to prevent stroke as well as other cardiovascular complications, can increase the risk for developing a hemorrhagic stroke and can complicate outcomes when a patient presents with a hemorrhagic stroke, especially ICH since these medications can potentially cause hematoma volume expansion A study by Hankey et.al. demonstrated that antiplatelet medication use increased a patient’s chance of having an ICH by 0.3 – 0.4%
Franke et.al. Stroke J Cereb. 1990;21:726–30.
Rosand et.al. Arch Intern Med. 2004;164:880–4.
Flibotte et.al. Neurology. 2004;63:1059–64.

5. Background AHA/ASA Guidelines NCCS/SCCM Guidelines
Neither recommend for or against the use of platelets in ICH for patient’s on antiplatelet medications
NCCS/SCCM Guidelines
Platelet transfusion is NOT recommended
If neurosurgical procedure will not be performed
If platelet function is within normal limits
Prior to a neurosurgical procedure in patients exposed to NSAIDs or GP IIb/IIIa inhibitors
Platelet transfusion is recommended
Prior to a neurosurgical procedure in patients exposed to ASA or P2Y12 inhibitors
American Heart Association/American Stroke Association
Neurocritical Care Society/Society of Critical Care Medicine
Currently, platelet administration to patients taking antiplatelet medications in the setting of ICH is controversial due to conflicting literature.15-17
Neither recommend for, nor recommend against…….
NCCS/SCCM Guidelines:
NOT recommended: Prior to a neurosurgical procedure in patients exposed to NSAIDs, or GP IIb/IIIa inhibitors (abciximab, eptifibatide, or tirofiban)
Platelet transfusion is recommended: Prior to a neurosurgical procedure in patients exposed to ASA, clopidogrel, prasugrel, or ticagrelor
Hemphill et.al. Stroke. 2015;46:
Frontera et.al. Neurocrit Care 2016;24:6–46.

6. Background NCCS/SCCM Guidelines
Initial dose of one single-donor apheresis unit of platelets
Platelet testing suggested prior to repeat transfusion
Repeat transfusion only for those with persistently abnormal platelet function tests and/or ongoing bleeding
Desmopressin 0.4 mcg/kg IV x 1 dose
Regardless of platelet transfusion
Repeat transfusion only for those with persistently abnormal platelet function tests and/or ongoing bleeding
Should receive a 0.4 mcg/kg IV dose of DDAVP in those patients undergoing a neurosurgical procedure and exposed to ASA, clopidogrel, prasugrel, or ticlopidine
Frontera et.al. Neurocrit Care. 2016;24:6–46.

7. Background
The PATCH trial was a multicenter, randomized, open-label parallel trial designed to determine the efficacy and safety of platelet transfusion in nonsurgical patients in the setting of antiplatelet associated ICH
The primary measure was difference in functional outcome at 3 months after randomization scored with the modified Rankin Scale (mRS) score
Higher in the platelet transfusion group than in standard care group (OR 2.22; 95% CI 1.20–4.09; p=0.0108)
PATCH is the first randomized trial to investigate the effects of platelet transfusion on acute intracerebral hemorrhage after the use of antiplatelet therapy
19% in patch trial were excluded
40 out of 97 (42%) participants who received platelet transfusion had a serious adverse event, as did 28 out of 93 (29%) who received standard care
24 (25%) participants assigned to platelet transfusion and 15 (16%) assigned to standard care died while in hospital
Safety outcomes in the intention-to-treat population did not differ between groups
ODDs shifted towards death or disability with platelet administration – platelet group higher odds/worse outcomes
Baharoglu et.al. Lancet 2016; 387: 2605–13.

8. Background mRS Score No symptoms at all 1
No symptoms at all 1
No significant disability despite symptoms 2
Slight disability 3
Moderate disability 4
Moderately severe disability 5
Severe disability 6
Dead
0 = no symptoms
1 = able to carry out all usual duties and activities
2 = unable to carry out all previous activities, but able to look after own affairs without assistance
3 = requiring some help, but able to walk without assistance
4 = unable to walk without assistance and unable to attend to own bodily needs without assistance
5 = bedridden, incontinent and requiring constant nursing care and attention
6 = dead

9. Purpose
To evaluate the effect of platelet transfusion on patient outcomes in nonsurgical patients taking antiplatelet medications prior to ICH 9

10. Study Objectives Primary Objective Secondary Objectives
mRS score at discharge
Secondary Objectives
Hospital mortality
Critical care unit mortality
Critical care unit length of stay (LOS)
Hospital LOS
Hematoma expansion 24 hours after admission
Safety of platelet transfusion
To evaluate the effect of platelet transfusion ….. in patients taking antiplatelet medications prior to ICH

11. Study Center St. Joseph’s/Candler Health System
Community health system with 714 inpatient beds divided between two anchor hospitals
Candler: 20-bed adult medical/surgical ICU, certified stroke center
St. Joseph’s: 10-bed adult medical/surgical ICU, 16-bed cardiovascular unit, 12-bed neuro ICU, and certified stroke center

12. Methods Study design Population
Retrospective, observational investigation
Population
Adult patients admitted to a critical care unit at St. Joseph’s/Candler Health System from January 1, 2010 to December 31, 2015 that were on antiplatelet medication prior to admission and were admitted for ICH

13. Methods Inclusion criteria:
Males and non-pregnant females of at least 18 years of age with non-traumatic ICH
On antiplatelet medication for at least 7 days prior to admission
Glasgow Coma Scale (GCS) score of 8 – 15 at the time of admission
mRS score of 0 – 1 at the time of admission

14. Methods Exclusion criteria:
Transferred into a critical care unit from an outside hospital when no information was available within 24 hours of transfer
Evidence of epi/subdural hematoma on CT
An underlying aneurysm or arteriovenous malformation
Planned surgical evacuation of ICH within 24 hours of admission
Previous adverse reaction to platelet transfusion
Known use of vitamin K antagonist (unless international normalized ratio ≤1.3) or history of coagulopathy
Known use of direct oral anticoagulants
Known use of heparin, low molecular weight heparin, or fondaparinux
Known thrombocytopenia (<100 cells × 10⁹/L)
Apparent imminent death

15. Methods Outcome variables Primary Secondary mRS score at discharge
Hospital mortality
Critical care unit mortality
Critical care unit LOS (days)
Hospital LOS (days)
Hematoma expansion within 24 hours
Safety of platelet transfusion

16. Methods Data analysis Mann Whitney U tests for ordinal data
modified Rankin Scale score
Fisher’s exact tests for categorical data
Hospital mortality and critical care unit mortality
Student t-tests for continuous variables
Hospital LOS, critical care unit LOS, and hematoma expansion
p<0.05 was statistically significant

17. Patient Selection 17 526 Patients Evaluated 29 Patients Included
5 Platelet Group
24 Control Group
497 Patients Excluded
N=351, not on antiplatelet;
N=9, apparent imminent death within 24 hours;
N=2, AVM or aneurysm;
N=12, mRS > 1 at admission;
N=26, no follow-up CT;
N=95, on anticoagulant with INR ≥ 1.3;
N=2, ICH related to trauma; 17

18. Demographics and Clinical Characteristics
Results
Demographics and Clinical Characteristics
Control (n=24)
Platelets (n=5)
P-value
Age, years ± SD
69 ± 5.42
70 ± 15.91
0.429
Male, n (%)
12 (50)
3 (60)
0.535
HTN, n (%)
21 (87.5)
5 (100)
0.554
Ischemic Stroke, n (%)
9 (37.5)
0.131
ICH, n (%)
2 (8.33)
1 (20)
0.446
Statin Use, n (%)
38% african american 18

19. Primary Outcome
Results are not statistically significant. Mann-Whitney U test results: p-value =0.271
Control (n=24) 0=0, 1=3, 2=0, 3=1, 4=12, 5=5, 6=3
Platelets (n=5) 0=0, 1=1, 2=0, 3=0, 4=1, 5=2, 6=1 19

20. Results Secondary Outcomes Control (n=24) Platelets (n=5) P-value
Hospital Mortality, n (%)
3 (12.5)
1 (20)
0.553
ICU Mortality, n (%)
ICU LOS, days ± SD
6.5 ± 2.56
7 ± 9.79
0.437
Hospital LOS, days ± SD
11.7 ± 4.50
8.2 ± 9.96
0.248
Hematoma Expansion, cm ± SD
0.35 ± 0.270
0.41 ± 0.747
0.425
Infusion Related Reactions, n – 20

21. Discussion Platelets were administered to 17% of patients in the study
Of the five patients that received platelets, none had any serious adverse reactions to the transfusion
54% of patients that were on antiplatelets were excluded due to concurrent use with anticoagulants with INR ≥ 1.3
40 (42%) participants who received platelet transfusion had a serious adverse event, as did 28 (29%) who received standard care
Only 19% of patch excluded 21

22. Limitations
Small, retrospective cohort nature limits external validity
Inconsistent documentation led to potential bias for the available data reviewed
67% of patients screened were excluded due to lack of home antiplatelet use
See trend? 22

23. Conclusions
Platelet transfusion appears to make no difference in the outcome of discharge mRS scores or any other secondary outcome
PATCH showed worse outcomes in all outcomes except for infusion related reactions 23

24. Acknowledgements Sabrina Croft, PharmD, BCPS
Hannah Matson, PharmD Candidate
Joseph Crosby, PhD, RPh
I would like to thank my colleagues for their contributions to this study.

25. Self Assessment Purpose: Self Assessment Question:
To evaluate the effect of platelet transfusion on patient outcomes in nonsurgical patients taking antiplatelet medications prior to ICH
Self Assessment Question:
For which antiplatelet medications is it recommended that patients receive platelet transfusion prior to surgery for ICH management?

26. Self Assessment
For which antiplatelet medications is it recommended that patients receive platelet transfusion prior to surgery for ICH management?
Aspirin or P2Y12 inhibitors

27. References
Mozaffarian D, Benjamin EJ, Go AS, et.al. on behalf of the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics—2015 Update: A Report From the American Heart Association. Circulation. 2015;131:e29-e322.
Zahuranec DB, Lisabeth LD, Sánchez BN, et.al. Intracerebral hemorrhage mortality is not changing despite declining incidence. Neurology. 2014;82:2180–2186.
Franke CL, de Jonge J, van Swieten JC, Op de Coul AA, van Gijn J. Intracerebral hematomas during anticoagulant treatment. Stroke J Cereb. 1990;21:726–30.
Rosand J, Eckman MH, Knudsen KA, Singer DE, Greenberg SM. The effect of warfarin and intensity of anticoagulation on outcome of intracerebral hemorrhage. Arch Intern Med. 2004;164:880–4.
Flibotte JJ, Hagan N, O’Donnell J, Greenberg SM, Rosand J. Warfarin, hematoma expansion, and outcome of intracerebral hemorrhage. Neurology. 2004;63:1059–64.
Hemphill III JC, Greenberg SM, Anderson CS, et.al. Guidelines for the Management of Spontaneous Intracerebral Hemorrhage: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2015;46:
Frontera JA, Lewin III 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;24:6–46.
Baharoglu MI, Cordonnier C, Salman RAS, 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: 2605–13.

28. The Effect of Platelet Administration in Antiplatelet Associated Intracerebral Hemorrhage
Caitlin Jenkins, PharmD
PGY-1 Pharmacy Resident
St. Joseph’s/Candler Health System
Co-Investigator: Sabrina Croft, PharmD, BCPS
Hannah Matson, PharmD Candidate
Joseph Crosby, PhD, RPh
FFP = all coagulation factors and labile factors (5 and 8)
Feiba = non-activated factors 2, 9, and 10, and activated 7
Cryoprecipitate = fibrinogen, factor 8 concentrate, factor 8 vWF, platelets, and fibronectin 28