Franciscan Health Indianapolis

Medication Use Evaluation

Pharmacy and Therapeutics Committee

DATE PRESENTED TO P&T COMMITTEE:

PRESENTED BY: Kenedie Krout, PharmD

TOPIC: Treatment of intracranial hemorrhage for patients on antiplatelet therapies

SAMPLE: Subjects were selected using an EPIC report for patients admitted to Franciscan Health
Indianapolis Hospital from January 1, 2022 to December 31, 2023, and treated for an intracranial
hemorrhage (ICH) while on antiplatelet therapy. A total of 20 patients were included in the data
analysis.

CRITERIA: Patients who were admitted to Franciscan Health Indianapolis and received treatment for an
ICH with desmopressin and/or platelet transfusion.

REFERENCES:
1. Cleveland Clinic Medical. Brain Bleed: When to Call for Help (2023). Cleveland Clinic. Accessed 21
Mar, 2024.
2. Al-Shahi Salman R, Dennis MS, Sandercock PAG, et al. JAMA Neurol. 2021;78(10):1179–1186.
doi:10.1001/jamaneurol.2021.2956
3. Neurocritical Care Society (2016). Guideline for Reversal of Antithrombotic in Intracranial
Hemorrhage. 24: 6-46. DOI 10.1007/s12028-015-0222-x
4. Feldman, E., et al. Critical Care Medicine 47 (12):p 1759-1765, December 2019. DOI
10.1097/CCM.0000000000004021.
5. Westfall, K.M., et al. A multicenter study of DDAVP versus platelet transfusions for antiplatelet
agent reversal in patients with traumatic brain injury. Neurol Sci (2024).

RATIONALE: □ high risk □ high volume □ high cost X problem prone

An intracranial hemorrhage (ICH) is a life-threatening emergency that occurs when a blood vessel
supplying blood and oxygen to the brain bursts or leaks. This causes a pooling of blood within the skull
and can lead to increased intracranial pressure, preventing oxygen perfusion to the brain. An ICH can
happen as a result of head trauma, atherosclerosis of the brain, blood clot rupture, a weakening of the
blood vessels of the brain, or a leak from an abnormally formed connection between arteries and veins
within the brain. Risk factors for an ICH include hypertension, substance use disorder, pregnancy and
childbirth-related conditions such as eclampsia and postpartum vasculopathy, as well as
hypercoagulable states that require treatment with blood-thinning agents such as anticoagulants and
antiplatelets.1 According to the study done by Salman and colleagues as an extension of the RESTART
Randomized Clinical Trial, at least one-third of adults with stroke caused by an ICH are already taking an
oral antithrombotic (antiplatelet or anticoagulant) prior to their incident. 2 The Neurocritical Care Society
and Society of Critical Care Medicine created guidelines for the reversal of antithrombotic agents in
patients with ICH. In reference to antiplatelet therapy reversal, the recommendation is to discontinue
the antiplatelet agent when ICH is present or suspected and administer one unit of platelet transfusion
only in those patients who will undergo a neurologic procedure. Those patients who are not undergoing
a neurologic procedure may consider a single dose of desmopressin (DDAVP) at 0.4 mcg/kg IV. The
guidelines recommend against platelet transfusion for patients who will not undergo a procedure,
regardless of the type of platelet inhibitor, platelet function testing, hemorrhage volume, or
neurological exam. Platelet transfusion is associated with risks including, but not limited to, transfusion-
related acute lung injury, thrombotic coagulopathies, and transfusion-related sepsis.3
In accordance with the guideline recommendation of using DDAVP in ICH patients, a 2019 retrospective
study by Feldman and colleagues assessed adult patients taking at least one antiplatelet agent based on
presenting history and documented evidence of intracranial hemorrhage on CT scan. The primary
effectiveness outcome was ICH expansion on the repeat CT scan with expansion defined as ≥ 3 mL
increase in ICH volume. The secondary effectiveness outcome was discharge functional status assessed
using the Modified Rankin Score. Most of the study’s patients (N=124) were on a single antiplatelet
agent with aspirin 81-325 mg being the most common (72.5%) followed by clopidogrel 75 mg (8.9%). As
a result of this study, patients receiving DDAVP had smaller median changes in ICH volume (-0.2 to 0.3
mL in the treatment group versus 0.7 mL in the non-treatment group) and the median Modified Rankin
Score was similar between groups (4 [3-6] in the DDAVP group versus 4 [3.5-5] in the non-treatment
group). Many patients were on two antiplatelet agents (18.5%), and those patients were more likely to
receive DDAVP (11.6%, p = 0.046). Overall, the authors concluded that DDAVP was associated with a
decreased likelihood of ICH expansion.4
Additionally, a multicenter, retrospective cohort study published in February 2024 by Westfall and
colleagues explored DDAVP versus platelet transfusions for antiplatelet agent reversal in patients with
traumatic brain injury. The primary outcome was mortality/discharge to hospice, and the secondary
outcomes were time to operating room (OR), hospital length of stay, ICU length of stay, and occurrence
of hospital complications such as pulmonary embolism, stroke, deep vein thrombosis, or return to the
OR or ICU. There were 5,525 patients included with 173 (3.1%) receiving DDAVP, 461 (8.4%) receiving
platelet transfusion, 172 (3.1%) receiving both therapies, and 4,696 (85.4%) receiving no reversal. The
primary outcome of death or hospice discharge occurred in 429 (9.1%) of patients with no reversal
versus 21 (12.1%, p = 0.23) of patients that received DDAVP, 77 (16.7%, p = 0.35) of patients who
received platelet transfusions, and in 46 (26.7%, p = 0.11) of patients who received both reversal agents.
For the secondary outcomes, 18 (10.5%) patients that received both reversals had hospital
complications compared to 189 (4.0%) of the no reversal group. Patients in the cohort that received
both reversal agents and the platelet transfusion cohort had longer hospital and ICU length of stay, 3
days [2-7] and 2 days [2-5], respectively (p = <0.001). There was no difference in time to operation
between any groups. Overall, this study showed no statistically significant difference in mortality
between reversing with DDAVP, platelets, both agents, or neither agent; however, patients who
received either platelets or both agents had a statistically significant longer length of hospital stay and
length of ICU stay. 5
In conclusion, studies have shown worse outcomes in patients who receive platelet transfusion or
platelet transfusion plus DDAVP for the reversal of antiplatelet therapy in ICH. According to the
Neurocritical Care Society guidelines, patients are to receive platelet transfusions only if undergoing a
neurologic procedure. This may be overlooked or disregarded, leading to overtreatment of patients in
which transfusion is not indicated and causing worse outcomes. This study's purpose was to evaluate
the use of DDAVP and/or platelet transfusion for appropriateness for antiplatelet reversal in the setting
of ICH at Franciscan Health Indianapolis.
FINDINGS AND CONCLUSION:

Twenty patients were included in this analysis. Baseline characteristics can be found in Table 1. Of the
20 patients that were reviewed, there were 13 (65%) patients that received platelet infusions, one (5%)
patient received DDAVP, and six (30%) patients received both a platelet infusion as well as DDAVP to
reverse the effects of antiplatelet therapy in the setting of ICH. Of the four (20%) patients that
experienced a negative mortality outcome, all received platelet transfusions; however, these patients
had a poorer prognosis at initial presentation documented by the provider as “no meaningful survival”
and cannot be directly correlated to therapy received for antiplatelet reversal. Of the 19 patients that
received platelet transfusions, three (15.8%) patients underwent neurologic procedure, and therefore
were indicated for a platelet transfusion. Of the patients that received platelets, three (15.8%) patients
received greater than a 1-unit transfusion dose. Of the seven (35%) patients that received DDAVP, none
of the patients received the correct recommended dose of 0.4 mcg/kg. Of these seven patients, none
experienced hyponatremia after receiving DDAVP therapy. One (5.3%) patient of the 19 that received
platelets experienced an infusion-related reaction including rash, itching, and hives.
From the results of this study, it is probable that reversal of antiplatelet therapy in the setting of ICH is
not always being treated with guideline recommendations at Franciscan Health Indianapolis. Though not
all patients presented to our facility with an ICH that would result in meaningful survival, it is important
to maintain consistency with guideline-directed efforts in these patients’ treatment. Based on platelet
transfusion in patients not undergoing neurologic procedure and the rarity in using DDA VP for this
patient population, there is no clear protocol being followed for this indication. As shown in this study,
Franciscan Health Indianapolis needs a streamlined process for treating these patients.

Table 1:

Patient Baseline Characteristics (N=20)

Average Age 76.2 years

Gender Male: 10 (50%)

Female: 10 (50%)

Indication for Antiplatelet Therapy CVA History: 7 (35%)

MI History: 2 (10%)

CAD: 8 (40%)

TIA History: 3 (15%)

Unknown Indication: 2 (10%)

Antiplatelet Agents* ASA: 10 (50%)

 Clopidogrel: 1 (5%)

ASA + Clopidogrel: 9 (45%)

CVA=cerebrovascular accident, MI=myocardial infarction, CAD=coronary artery disease,

TIA=transient ischemic attack, ASA=aspirin
*No patients in this study were taking ticagrelor or prasugrel prior to ICH.

Figure 1:

Figure 2:
 Table 2:

Received Platelets
1-unit transfusion 16 (84%) patients
>1 unit transfusion 3 (15.8%) patients
Received DDAVP
0.3 mcg/kg dose 6 (85.7%) patients
>0.3 mcg/kg dose 1 (14%) patient
(2 x 0.3 mcg/kg dose)
Guideline recommended 0 (0%) patients
dose: 0.4 mcg/kg

SUMMARY:
• Of the 20 patients who had ICH, 13 (65%) received a platelet transfusion, one (5%) received
DDAVP, and six (30%) received both platelet transfusion and DDAVP.
• There were three patients (15%) who underwent neurological procedures. One of the three
patients received platelet transfusion, and the other two patients received both platelet
transfusion and DDAVP therapy.
• Of the 20 patients assessed in this study, 18 (90%) patients received therapy that was not
guideline-recommended for antiplatelet reversal in ICH.
• Based on the above data, it is recommended that additional strategies be implemented to
prevent inappropriate treatment with platelet transfusion and streamline appropriate
treatment with desmopressin for antiplatelet reversal in patients with ICH.

ACTION:

Action Power of Timeline/ Person(s) Complete

Strategy Due date Responsible Date
(see table below)
1. Provide education to ordering 1 Kenedie 10/2023
providers facility-wide regarding (on EM
the appropriate indication(s) for rotation)
platelet transfusions and
associated side effects and
monitoring
2. Implement ICH/antiplatelet order 3/9 Kenedie
set with recommendations for
DDAVP vs platelets or require
indication for platelet orders
3. Request an add for desmopressin 8/6 Kenedie
0.4 mcg/kg as a dosing
option/button in EPIC when
ordering desmopressin
 Error-Reduction Strategy Power
(leverage)
Fail-safes and constraints 10
Forcing Functions 9
Automation and computerization 8
Standardization 6
Redundancies 5
Reminders and checklists 3
Rules and policies 2
Suggestions to be more careful or vigilant, 1
Education

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