Prior Antiplatelet Therapy, Platelet Infusion Therapy, and Outcome after Intracerebral Hemorrhage

doi:10.1016/j.jstrokecerebrovasdis.2008.10.007

Journal of Stroke and Cerebrovascular Diseases

Volume 18, Issue 3, May–June 2009, Pages 221-228

https://doi.org/10.1016/j.jstrokecerebrovasdis.2008.10.007 Get rights and content

Background

Recent studies examining the effect of prior antiplatelet therapy (APT) on outcome in patients with spontaneous intracerebral hemorrhage (ICH) have shown conflicting results. The effect of platelet infusion therapy (PIT) on outcome in patients with ICH taking APT is unknown.

Methods

We reviewed records of patients with ICH admitted to a single hospital, excluding those with international normalized ratio greater than or equal to 1.5. Baseline characteristics were compared by APT status in all patients and by PIT status in the subgroup of patients on APT. We used multivariate analyses to generate propensity and prognostic scores for exposures (APT and PIT) and outcomes (favorable outcome and hospital death), respectively. We examined the associations between exposures and outcomes and adjusted these for propensity and/or prognostic scores. We then validated our findings with a sensitivity analysis.

Results

Of 368 patients identified, 121 (31.3%) were taking APT, mostly aspirin. Patients on APT were older and more likely to have vascular comorbidities than those not. The APT group also had a higher initial Glasgow Coma Scale score at presentation. In analyses adjusted for both propensity and prognostic scores, APT was associated with a higher likelihood of hospital death (odds ratio [OR] 2.4; 95% confidence interval [CI] 1.1-5.6); PIT did not prevent hospital death (OR 1.2; 95% CI 0.3-5.5) or increase favorable outcome (OR 1.4; 95% CI 0.4-5.4).

Conclusions

In patients with ICH, APT is associated with an increased risk of hospital death. In the subgroup of patients on APT, PIT did not prevent death or improve outcome.

Section snippets

Methods

We conducted a single-center retrospective study based on review of medical records. We included 368 consecutive patients with nontraumatic spontaneous ICH and an international normalized ratio less than 1.5 between May 2001 and September 2003, who were admitted to a Joint Commission primary stroke center that serves as a tertiary referral center for patients with severe neurologic diseases. Patients with a secondary cause for their hemorrhage, such as ruptured aneurysm, primary ischemic

Results

We identified 368 eligible patients with ICH of whom 121 (31.3%) were on APT. All but 3, who were taking clopidogrel alone, were on aspirin (118 of 121), either alone (105 of 121) or in combination with clopidogrel (11 of 121) or extended-release dipyridamole (2 of 121). Of the 121 patients on APT, 53 received PIT.

The results of the bivariate analyses for APT and PIT are summarized in Table 2. Compared with patients not on APT, those on APT were significantly older and had more comorbid

Discussion

Having excluded patients with an international normalized ratio of 1.5 or more, whether on anticoagulants or not, we found that almost a third of patients (31.3%) in this study were on APT with all but 3 on aspirin, either alone or in combination with other antiplatelet agents. The results suggest that patients with ICH are more likely to die in hospital if they are taking APT before the event. The increased risk of death was evident only after adjusting for factors related to: (1) use of APT;

Conclusions

This study adds to the evidence that patients with ICH on APT are more likely to die than those not on APT. Whether PIT could improve outcomes in patients with ICH on APT is not answered by this study, but to our knowledge, this is the only study that has addressed the effect of PIT on outcome in patients with ICH. A randomized trial in which platelets are given by a standard protocol and within a specific time interval from ICH symptom onset will ultimately be required to determine whether PIT

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There are no established guidelines for transfusing platelets in the setting of traumatic brain injury (TBI)-related intracranial hemorrhage for patients on pre-injury antiplatelet medications (APT). Existing literature has produced mixed results regarding the effectiveness of platelet transfusion in containing bleed size or avoiding craniotomy. We compared outcomes of patients on APT with an intracranial bleed due to trauma, between those who did and who did not receive routine platelet transfusion.
This retrospective cohort study included patients on APT with TBI-associated intracranial hemorrhage treated at a level II trauma center between 1/1/2014 and 7/31/2018: before March 2017, patients received routine platelet transfusion during initial management (“old protocol”). From March 2017 patients received platelets only if needing craniotomy (“new protocol”). Primary outcome was need for operative management. APT type, intracranial bleed type, bleed size and shift on CT scans, demographic and clinical variables were obtained.
Patients were in their mid-70′s and most had sustained a fall. Old protocol patients were more likely to be on clopidogrel (32.5% vs. 18.2% for new protocol, p = 0.016) and had larger bleeds on initial CT (10.1 vs. 6.9 for new protocol, p = 0.038). When stratifying by aspirin only and clopidogrel±aspirin, old protocol and new protocol patients did not differ on need for operative management (aspirin only p = 1.0; clopidogrel p = 0.55), change in bleed size (aspirin only p = 0.37, clopidogrel p = 0.068), or other outcomes.
We found no evidence that restricting platelet transfusion to patients needing operative management increased the risk of poor outcomes among patients on APT with TBI-associated intracranial hemorrhage.
Clinical effects of restarting antiplatelet therapy in patients with intracerebral hemorrhage
2022, Clinical Neurology and Neurosurgery
Antiplatelet (APT) medications have been used to treat ischemic stroke and cardiovascular diseases. However, they involve a risk of re-bleeding, especially in patients with intracerebral hemorrhage (ICH), which limits their clinical application. This study aimed to compare the incidence of recurrent ICH and ischemic events in ICH survivors on APT, as well as to assess the clinical effect and safety of APT resumption.
We retrospectively reviewed the medical records of patients with spontaneous ICH at two tertiary medical centers between January 2011 and December 2020. We included adult patients with ICH who regularly took APT medications for various medical conditions. The patients were divided into two groups based on their APT resumption. Subsequently, we performed between-group comparisons of clinical or radiological characteristics; moreover, analyzed the incidence of re-bleeding and ischemic events, as well as the various risk factors for each event.
We included 202 patients; among them, 118 patients restarted APT after initial ICH (APT resumption group) while 84 patients did not (no-APT resumption group). Compared with patients in the no-APT resumption group, those in the APT resumption group were more likely to have hyperlipidemia (p < 0.001) and a previous ischemic stroke event (p = 0.026). Recurrent ICH and ischemic vascular events occurred in 14 and 15 patients, respectively. Univariate analysis demonstrated that the risk factors for recurrent ICH were older age, renal dysfunction, and no APT resumption; however, only renal dysfunction significantly increased the risk of re-bleeding in multivariate analysis (HR, 4.631; 95 % CI 1.432–14.977; p = 0.010). Moreover, previous cerebral ischemia and atrial fibrillation were positively associated with ischemic events in univariate analysis; however, only atrial fibrillation demonstrated a significant correlation in multivariate analysis (HR, 4.309; 95 % CI 1.383–13.426; p = 0.012). APT resumption had a significant prevention effect on recurrent ICH (HR, 0.180; 95 % CI 0.055–0.586; p = 0.004) and ischemic vascular events (HR, 0.240; 95 % CI 0.077–0.750; p = 0.014).
Our findings indicated that restarting APT in patients with ICH was not associated with an increased risk of recurrent ICH. APT can be safely restarted to prevent major thromboembolic complications in patients on previous antithrombotic treatment.
The role of monitoring platelet function perioperatively and platelet transfusion for operated spontaneous intracerebral hemorrhage patients with long-term oral antiplatelet therapy: A case report
2021, International Journal of Surgery Case Reports
Spontaneous intracerebral hemorrhage (SICH) with long-term oral antiplatelet therapy (LOAPT) is known as a dilemma in balancing the risk of postoperative rebleeding and ischemic events because of confused coagulation function. We herein describe a report of perioperative management of spontaneous intracerebral hemorrhage patient on long-term oral antiplatelet therapy.
A 42-year-old male patient on long-term oral antiplatelet therapy presented with coma, and he was diagnosed with spontaneous intracerebral hemorrhage. Considering the patient's clinical condition, despite the thromboelastography suggested that the inhibition of platelet function was high preoperatively, an emergency craniectomy were underwent. After platelet transfusion during surgery and taking control of the clotting and platelet function postoperatively, the patient was stable without rebleeding and new ischemic events in perioperative period and recovered satisfactorily.
Rare studies have provided evidence for managing operated spontaneous intracerebral hemorrhage patients on long-term oral antiplatelet therapy, and whether platelet transfusion is recommended was controversial. In this case, we presented monitoring and taking control of clotting and platelet function postoperatively would help in preventing rebleeding and ischemic events in such patients; moreover, platelet transfusion may quickly and safely reverse platelet dysfunction for emergency surgery. This case was the first to report platelet function and coagulation function management in spontaneous intracerebral hemorrhage patients with long-term oral antiplatelet therapy.
Monitoring and maintaining coagulation and platelet function perioperatively are essential to balance the risk of postoperative rebleeding and ischemic events.
Platelet Transfusion: An Update on Indications and Guidelines
2021, Clinics in Laboratory Medicine
The effect of platelet transfusion on functional independence and mortality after antiplatelet therapy associated spontaneous intracerebral hemorrhage: A systematic review and meta-analysis
2020, Journal of the Neurological Sciences
Citation Excerpt :
Only one study considered antiplatelet sensitivity as an indication for transfusion [19]. Two studies included outcomes at 90 days [12,14], while the others only included outcomes at hospital discharge [10,11,19]. Functional outcomes were defined by modified Rankin Scale of ≤ three in three studies [10,14,19], and simplified to death / dependently alive / or independently alive in the fifth [12].
The practice of platelet transfusion to mitigate the deleterious effects of antiplatelet agents on spontaneous intracerebral hemorrhage (ICH) remains common. However, the effect of antiplatelet agents on patients with ICH is still controversial and transfusing platelets is not without risk. We performed a meta-analysis in order to determine the effect of platelet transfusion on antiplatelet agent associated ICH.
We queried PubMed, Embase, and Scopus databases to identify cohort studies, case-control studies, and randomized control trials. Study quality was graded by the Newcastle-Ottawa Scale and Cochrane Risk of Bias tool, as appropriate. Outcomes of interest included functional independence as measured by the modified Rankin Scale and mortality. We compared patients with antiplatelet agent associated ICH who received platelet transfusion to those that did not.
We identified 625 articles. After reviewing 44 full text articles, 5 were deemed appropriate for meta-analysis, including 4 cohort studies and one randomized control trial. Considerable heterogeneity was present among the studies (I² > 81% for all analyses). We did not find a significant effect of platelet transfusions on functional independence (Odds Ratio [OR] 1.3, 95% CI.0.45–3.9) or mortality (OR 0.58, 95% Confidence Interval [CI] 0.12–2.6).
We found no evidence for an effect of platelet transfusions on functional independence or mortality following antiplatelet associated ICH. More randomized trials are needed to evaluate platelet transfusion in patients with ICH and proven reduced platelet activity or those requiring neurosurgical intervention.
The Role of Platelet Transfusions After Intracranial Hemorrhage in Patients on Antiplatelet Agents: A Systematic Review and Meta-Analysis
2020, World Neurosurgery
Citation Excerpt :
Even if statistically significant, a difference of 0.06 points cannot be considered of clinical relevance. Seven studies reported severe neurologic disability defined as modified Rankin Scale score at discharge,12,26,28 modified Rankin Scale score at 3 months,25,34 Glasgow Outcome Scale at hospital discharge,35 and Activities of Daily Living Scale at 6 months.32 There was no significant difference between the 2 groups; RD was –0.10 (10%; 95% CI, –0.26 to 0.07; P = 0.27; Figure 3).
The evidence suggests that antiplatelet agents (APA) slightly increase the risk of death and disease progression in patients with traumatic brain injury or spontaneous intracranial hemorrhage (ICH). There is little evidence that APA reversal with platelet (PLT) transfusion may improve the outcome. In this systematic review and meta-analysis, our goal was to evaluate the differences in mortality, severe disability, and hematoma expansion related to PLT transfusion. We retrieved randomized or cohort studies comparing adult patients on APA with traumatic brain injury or ICH who were treated with PLT or not. We calculated the standardized risk difference and 95% confidence interval. A random-effects model was applied to analyze the data. The heterogeneity of the retrieved trials was evaluated through the I² statistic. Our review included 16 clinical trials. We observed a significant difference between the 2 groups only for hematoma expansion: risk difference was –0.10 (10%; 95% confidence interval, –0.14 to –0.05; P < 0.0001; I² = 0.90) in favor of PLT transfusion. Performing subgroups analyses according to the type of bleeding mechanism, we observed the same results. The use of PLT in patients on APA affected by ICH seemed to have no clear beneficial effect for the outcomes evaluated; conversely, PLT seemed to slightly increase the odds for adverse events of thromboembolic origin, even although not significantly.

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Original ArticlePrior Antiplatelet Therapy, Platelet Infusion Therapy, and Outcome after Intracerebral Hemorrhage

Background

Methods

Results

Conclusions

Section snippets

Methods

Results

Discussion

Conclusions

Pretreatment with antiplatelet agents is not independently associated with unfavorable outcome in intracerebral hemorrhage

Stroke

Risk factors for early death in acute ischemic stroke and intracerebral hemorrhage: A prospective hospital-based study in Asia; Asian acute stroke advisory panel

Stroke

Prediction of death in patients with primary intracerebral hemorrhage: A prospective study of a defined population

J Neurosurg

The effect of warfarin and intensity of anticoagulation on outcome of intracerebral hemorrhage

Arch Intern Med

Previous antiplatelet therapy is an independent predictor of 30-day mortality after spontaneous supratentorial intracerebral hemorrhage

J Neurol

Antiplatelet therapy contributes to acute deterioration of intracerebral hemorrhage

Neurology

Regular aspirin-use preceding the onset of primary intracerebral hemorrhage is an independent predictor for death

Stroke

Antiplatelet drug use preceding the onset of intracerebral hemorrhage is associated with increased mortality

Fundam Clin Pharmacol

Original Article
Prior Antiplatelet Therapy, Platelet Infusion Therapy, and Outcome after Intracerebral Hemorrhage