- Email: [email protected]
Antiplatelet Medication Reversal Strategies in Operative Intracranial Hemorrhage: A Survey of Practicing Neurosurgeons
Original Article
Antiplatelet Medication Reversal Strategies in Operative Intracranial Hemorrhage: A Survey of Practicing Neurosurgeons Paul M. Foreman1, Adeel Ilyas1, James Mooney1, Philip G.R. Schmalz1, Beverly C. Walters1, Christoph J. Griessenauer2,3
BACKGROUND: Antiplatelet therapy is common and complicates operative management of acute intracranial hemorrhage. Few data exist to guide antiplatelet reversal strategies.
-
METHODS: An online survey detailing antiplatelet reversal strategies in patients presenting with acute operative intracranial hemorrhage (subdural hematoma, epidural hematoma, and intracerebral hemorrhage) was distributed to board-certified neurosurgeons in North America.
-
RESULTS: From 2782 functional e-mail addresses, there were 493 (17.7%) responses to question 1 and 429 (15.4%) completed surveys. Most respondents chose to perform no additional laboratory testing before surgical intervention, regardless of hemorrhage type. The most common antiplatelet reversal strategy in the presence of aspirin was platelet transfusion (subdural hematoma and intracerebral hemorrhage) or no intervention (epidural hematoma). The most common antiplatelet reversal strategy in the presence of an adenosine diphosphate antagonist or dual antiplatelet therapy was platelet transfusion or platelet transfusion with desmopressin acetate administration. There was a statistically significant difference in management strategy depending on the antiplatelet therapy (P < 0.001).
-
CONCLUSIONS: When patients on antiplatelet medication present with operative intracranial hemorrhage, the
-
Key words Antiplatelet - Antiplatelet reversal - Epidural hematoma - Intracerebral hemorrhage - Intracranial hemorrhage - Subdural hematoma -
Abbreviations and Acronyms AANS: American Association of Neurological Surgeons ABNS: American Board of Neurological Surgery ADP: Adenosine diphosphate DAPT: Dual antiplatelet therapy DDAVP: Desmopressin acetate EDH: Epidural hematoma ICH: Intracerebral hemorrhage
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majority of neurosurgeons do not perform qualitative platelet testing. Antiplatelet reversal strategies are significantly influenced by the antiplatelet therapy with more aggressive reversal strategies employed in the presence of ADP antagonists.
INTRODUCTION
A
ntiplatelet therapy is widely used for prevention and treatment of ischemic vascular disease, with more than a third of American adults >35 years old taking aspirin.1 Commonly used medications include aspirin, an irreversible cyclooxygenase inhibitor, and clopidogrel, an irreversible adenosine diphosphate (ADP) receptor inhibitor. Generally, ADP receptor inhibitors produce more potent antiplatelet effects than cyclooxygenase inhibitors,2 and the 2 are often used in combination. The impact of antiplatelet therapy on intracranial hemorrhage is controversial, with some studies reporting increased rates of hematoma expansion and worse outcome,3-6 whereas others have found no difference.7-9 However, antiplatelet medication is a known risk factor for subdural hematoma (SDH) development10,11 and can complicate surgical management of all forms of intracranial hemorrhage. Strategies to reduce the risk of surgical intervention in the face of antiplatelet therapy include platelet transfusion, desmopressin acetate (DDAVP), recombinant factor VII, and fibrinogen supplementation, or a
SDH: Subdural hematoma TEG: Thromboelastography From the 1Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama, USA; 2Department of Neurosurgery, Geisinger Medical Center, Danville, Pennsylvania, USA; and 3Research Institute of Neurointervention, Paracelsus Medical University, Salzburg, Austria To whom correspondence should be addressed: Paul M. Foreman, M.D. [E-mail: [email protected]] Citation: World Neurosurg. (2018). https://doi.org/10.1016/j.wneu.2018.05.064 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2018 Elsevier Inc. All rights reserved.
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ORIGINAL ARTICLE PAUL M. FOREMAN ET AL.
ANTIPLATELETS AND INTRACRANIAL HEMORRHAGE
combination of these.2 The safety and efficacy of these strategies in the setting of operative intervention are largely unknown. Given the lack of quality data to guide treatment decisions, the management of acute operative intracranial hemorrhage in the setting of antiplatelet therapy is hypothesized to vary widely. We performed a survey of practicing neurosurgeons in an effort to elucidate therapeutic strategies.
3. The patient takes an ADP antagonist (i.e., clopidogrel, ticagrelor, prasugrel) daily. You decide to: B
transfuse platelets before/during surgery
B
give DDAVP before/during surgery
B
transfuse platelets AND give DDAVP before/during surgery
B
proceed to surgery without platelet transfusion or DDAVP administration
MATERIALS AND METHODS An online survey development software, SurveyMonkey (Palo Alto, California, USA), was used to create and distribute an online survey detailing the management of operative acute SDH, acute epidural hematoma (EDH), and acute intracerebral hemorrhage (ICH) in the setting of antiplatelet medication. The survey assessed preoperative laboratory work-up of the patient and antiplatelet reversal strategies before or during operative intervention. Using the modified Dillman technique,12 the survey was distributed to American Association of Neurological Surgeons (AANS) members who were board certified; residing in North America; and certified by the American Board of Neurological Surgery (ABNS), the Royal College of Surgeons of Canada, or the Mexican Council of Neurological Surgery. The AANS e-mail registry was selected as a representative sample of practicing neurosurgeons in North America. Board certification was required because it represents completion of educational, peer review, and examination processes and serves as a voluntary quality benchmark. The survey was sent to potential respondents 5 times (initial send, 1 week, 3 weeks, 7 weeks, and 10 weeks) between October and December 2017. The survey consisted of 3 distinct clinical scenarios: 1) acute SDH that required craniotomy for evacuation, 2) acute EDH that required craniotomy for evacuation, and 3) acute ICH that required craniotomy for evacuation. The platelet count and coagulation parameters were reportedly normal. No information was given regarding the clinical status or medical history of the patient. The respondent was then asked the following 4 questions: 1. The patient takes some form of antiplatelet therapy daily. In addition to routine laboratory evaluation (basic metabolic profile, complete blood count, prothrombin time, partial thromboplastin time), you perform: B
thromboelastography (TEG)
B
platelet function testing
B
other functional platelet testing (i.e., platelet mapping TEG)
B none 2. The patient takes aspirin daily. You decide to:
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B
transfuse platelets before/during surgery
B
give DDAVP before/during surgery
B
transfuse platelets AND give DDAVP before/during surgery
B
proceed to surgery without platelet transfusion or DDAVP administration
B
decision is based on laboratory testing from question 1
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B decision is based on laboratory testing from question 1 4. The patient is on dual antiplatelet therapy (DAPT) (i.e., aspirin and ADP antagonist). You decide to: B
transfuse platelets before/during surgery
B
give DDAVP before/during surgery
B
transfuse platelets AND give DDAVP before/during surgery
B
proceed to surgery without platelet transfusion or DDAVP administration
B
decision is based on laboratory testing from question 1
Statistics Descriptive statistics were computed using MATLAB Version R2017a (The MathWorks, Inc., Natick, Massachusetts, USA). c2 tests were performed 1) on the pooled responses to question 1 to determine whether the specific laboratory test obtained was independently associated with the underlying pathology of intracranial hemorrhage and 2) on pooled responses to questions 2e4, grouped by underlying pathology, to determine whether treatment was independently associated with the patient’s use of certain antithrombotic medication. P values of < 0.05 were considered significant. RESULTS The survey was e-mailed to 3104 potential respondents; 322 (10.4%) e-mail addresses had either opted out of survey e-mails or the e-mail was nonfunctional. Of the 2782 functional e-mail addresses, there were 493 (17.7%) responses to question 1 and 429 (15.4%) completed surveys. Subdural Hematoma In patients on antiplatelet therapy presenting with operative SDH, respondents chose to perform the following preoperative laboratory testing: 223 (45.2%), no testing; 176 (35.7%), platelet function testing; 66 (13.4%), TEG; and 28 (5.7%), other functional assay (Table 1). In the presence of aspirin, most respondents transfused platelets (33.5%) or proceeded to surgery without specific reversal agents (29%) (Table 2 and Figure 1). Of respondents, 21.6% said their actions would depend on results of laboratory testing. In the presence of an ADP antagonist, most respondents transfused platelets (44%) or transfused platelets and administered DDAVP (29.1%). Of respondents, 18.4% said their actions would depend on results of laboratory testing. In the presence of DAPT, most respondents transfused platelets (37.9%) or transfused platelets and administered DDAVP (37.2%). Of respondents, 18.2% said their actions would depend on results of laboratory testing.
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ORIGINAL ARTICLE PAUL M. FOREMAN ET AL.
ANTIPLATELETS AND INTRACRANIAL HEMORRHAGE
Table 1. Pooled Responses for Various Laboratory Tests Obtained in Patients with Intracranial Hemorrhage Undergoing Surgical Intervention TEG
Platelet Function
Other Functional Assay
None
Total
SDH
66 (13.4%)
176 (35.7%)
28 (5.7%)
223 (45.2%)
493 (100.0%)
EDH
58 (12.6%)
146 (31.6%)
23 (5.0%)
235 (50.9%)
462 (100.0%)
ICH
65 (14.2%)
166 (36.2%)
29 (6.3%)
199 (43.4%)
459 (100.0%)
c2 P value ¼ 0.433. SDH, subdural hematoma; EDH, epidural hematoma; ICH, intracerebral hemorrhage.
There was a statistically significant difference (P < 0.001) in management strategy depending on the antiplatelet therapy.
statistically significant difference (P < 0.001) in management strategy depending on the antiplatelet therapy.
Epidural Hematoma In patients on antiplatelet therapy presenting with operative EDH, respondents chose to perform the following preoperative laboratory testing: 235 (50.9%), no testing; 146 (31.6%), platelet function testing; 58 (12.6%), TEG; and 23 (5.0%), other functional assay. In the presence of aspirin, most respondents transfused platelets (31.9%) or proceeded to surgery without specific reversal agents (32.8%). Of respondents, 17.4% said their actions would depend on results of laboratory testing. In the presence of an ADP antagonist, most respondents transfused platelets (44.2%) or transfused platelets and administered DDAVP (27.3%). Of respondents, 14.4% said their actions would depend on results of laboratory testing. In the presence of DAPT, most respondents transfused platelets (38.6%) or transfused platelets and administered DDAVP (38.3%). Of respondents, 12.9% said their actions would depend on results of laboratory testing. There was a
Intracerebral Hemorrhage In patients on antiplatelet therapy presenting with operative ICH, respondents chose to perform the following preoperative laboratory testing: 199 (43.4%), no testing; 166 (36.2%), platelet function testing; 65 (14.2%), TEG; and 29 (6.3%), other functional assay. There was no significant difference (P ¼ 0.433) in preoperative laboratory testing among SDH, EDH, and ICH. In the presence of aspirin, most respondents transfused platelets (33.6%) or proceeded to surgery without specific reversal agents (24.2%). Of respondents, 20.4% said their actions would depend on results of laboratory testing. In the presence of an ADP antagonist, most respondents transfused platelets (41.5%) or transfused platelets and administered DDAVP (31.4%). Of respondents, 19.1% said their actions would depend on results of laboratory testing. In the presence of DAPT, most respondents transfused platelets (35.6%) or transfused platelets and administered DDAVP (40.8%). Of
Table 2. Pooled Responses for Various Treatment Options in Patients with Intracranial Hemorrhage Who Are on Aspirin, Adenosine Diphosphate Antagonist, or Dual Antiplatelet Therapy Transfuse Platelets
DDAVP
Platelets and DDAVP
Neither
Depends on Laboratory Results
Total
Aspirin
155 (33.5%)
19 (4.1%)
54 (11.7%)
134 (29.0%)
100 (21.6%)
462 (100.0%)
ADP antagonist
201 (44.0%)
9 (2.0%)
133 (29.1%)
30 (6.6%)
84 (18.4%)
457 (100.0%)
DAPT
173 (37.9%)
8 (1.8%)
170 (37.2%)
23 (5.0%)
83 (18.2%)
457 (100.0%)
SDH
EDH Aspirin
139 (31.9%)
21 (4.8%)
57 (13.1%)
143 (32.8%)
76 (17.4%)
436 (100.0%)
ADP antagonist
191 (44.2%)
14 (3.2%)
118 (27.3%)
47 (10.9%)
62 (14.4%)
432 (100.0%)
DAPT
167 (38.6%)
7 (1.6%)
166 (38.3%)
37 (8.5%)
56 (12.9%)
433 (100.0%)
Aspirin
143 (33.6%)
15 (3.5%)
78 (18.3%)
103 (24.2%)
87 (20.4%)
426 (100.0%)
ADP antagonist
176 (41.5%)
9 (2.1%)
133 (31.4%)
25 (5.9%)
81 (19.1%)
424 (100.0%)
DAPT
151 (35.6%)
7 (1.7%)
173 (40.8%)
18 (4.2%)
75 (17.7%)
424 (100.0%)
ICH
c2 P value < 0.001 for all. DDAVP, desmopressin acetate; SDH, subdural hematoma; ADP, adenosine diphosphate; DAPT, dual antiplatelet therapy; EDH, epidural hematoma; ICH, intracerebral hemorrhage.
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ORIGINAL ARTICLE PAUL M. FOREMAN ET AL.
ANTIPLATELETS AND INTRACRANIAL HEMORRHAGE
Figure 1. Antiplatelet reversal strategies in the management of operative intracranial hemorrhage.
respondents, 17.7% said their actions would depend on results of laboratory testing. There was a statistically significant difference (P < 0.001) in management strategy depending on the antiplatelet therapy.
DDAVP, desmopressin acetate; ADP, adenosine diphosphate.
made by clinicians between aspirin and an ADP antagonist in a patient presenting with an operative intracranial hemorrhage. Surgeons were notably more aggressive in their reversal strategies (i.e., platelet transfusion with or without DDAVP) when an ADP antagonist was present.
DISCUSSION Operative intracranial hemorrhage in patients on antiplatelet medications presents a common therapeutic challenge to the treating physician. A dearth of data regarding optimal work-up and antiplatelet reversal strategy (to include no reversal) has led to variability in management. This variability is highlighted in the present survey, with only a single response (the decision not to perform laboratory testing in a patient presenting with an operative EDH) receiving a majority vote. There is a clear distinction
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Platelet Transfusion Transfusing platelets was the most popular reversal strategy in the current survey and was influenced by the antiplatelet agent being taken. Respondents were more likely to transfuse platelets (with or without the addition of DDAVP) when patients were taking ADP inhibitors or DAPT rather than aspirin alone. The practice of platelet transfusion in the setting of operative intracranial hematoma evacuation is supported by a single prospective randomized
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ORIGINAL ARTICLE PAUL M. FOREMAN ET AL.
ANTIPLATELETS AND INTRACRANIAL HEMORRHAGE
controlled trial.13 This trial enrolled 780 patients with acute hypertensive basal ganglia hemorrhages. Patients reportedly on aspirin were tested using platelet aggregation, and aspirinsensitive patients were then randomly assigned to platelet transfusion or no transfusion. The platelet transfusion group experienced a significantly reduced rate of postoperative hemorrhage, disability, and mortality. However, methodologic limitations, including small sample sizes per group, an ethnically homogeneous patient population, and a controversial indication for surgery, limit the generalizability of these findings. Another small prospective study also lent support to early platelet transfusion in the setting of ICH and reduced platelet activity.14 This study enrolled 45 patients and found improved platelet activity, smaller final hemorrhage size, and improved functional outcome in patients treated with early (<12 hours) versus late (>12 hours) platelet transfusion. Adverse events related to the transfusion occurred in 16% (hypotension and fever). The study was limited by small numbers, heterogeneous transfusions, and a lack of a control group. The PATCH trial was a multicenter, randomized controlled trial that enrolled 190 patients with ICH on antiplatelet medication and randomly assigned them to platelet transfusion with standard of care or standard of care alone.15 The odds of death or dependence at 3 months were significantly higher in the platelet transfusion group, and 42% of patients receiving transfusion had a serious adverse event during hospitalization. This led to a conclusion against platelet transfusion in the setting of antiplatelet-related ICH. It should be noted that patients with planned surgical evacuation of ICH within 24 hours were excluded. Platelet transfusion in the setting of traumatic intracranial hemorrhage has also failed to demonstrate benefit. A retrospective study of patients with mild traumatic brain injury and intracranial hemorrhage found no difference in short-term outcome after platelet transfusion.16 A 2013 prospective study enrolled patients with traumatic intracranial hemorrhage on high-dose aspirin therapy.17 Transfusion of 1 unit of apheresis platelets did not improve platelet function. Additionally, progression of intracranial hemorrhage and need for neurosurgical intervention were independent of platelet function. Guidelines from the Neurocritical Care Society and the Society of Critical Care Medicine recommend against platelet transfusion in patients with intracranial hemorrhage on antiplatelet medication in the absence of a planned neurosurgical procedure.2 However, they recommend transfusion in patients undergoing a neurosurgical procedure, the topic of the survey. Additional recommendations are made for platelet function testing before transfusion to identify patients with normal platelet function unlikely to benefit from transfusion.
antagonist. DDAVP has been shown to reduce bleeding time in uremic patients18 and improve platelet function in uremic patients who require emergent operative intervention.19 DDAVP has also demonstrated efficacy in restoring platelet function in patients taking antiplatelet medications.20-23 Two small studies investigating the effect of DDAVP in the setting of intracranial hemorrhage have been performed. A prospective study of 14 patients presenting with acute ICH and abnormal platelet function reported improved platelet activity concluding that it was an attractive pharmacologic treatment option.22 Another small study, including both traumatic and spontaneous intracranial hemorrhage, reported similar findings and noted that the effect appeared transient (3 hours) and influenced by dosing frequency.24 Small numbers limited the ability of these studies to evaluate the clinical impact of DDAVP in this setting. DDAVP given in combination with platelet transfusion failed to reduce the risk of early radiographic hemorrhage progression and mortality in a recent retrospective study of traumatic intracranial hemorrhage.25 Given the low risk of serious side effects and the suggestion of benefit, published guidelines have recommended consideration of DDAVP for patients taking antiplatelet medication presenting with intracranial hemorrhage.2 A dearth of data on the management of intracranial hemorrhage in the face of antiplatelet medication has led to wide variability in practice. This has led some surgeons to pursue a conservative approach, potentially increasing hemorrhage risk, whereas others pursue a more aggressive strategy that exposes patients to allogeneic blood products while using limited resources. Clinical investigation will be required to elucidate the optimal management strategy with consideration for the cost and availability of unconventional laboratory testing and blood products.
Desmopressin Acetate DDAVP is a synthetic analogue of arginine vasopressin and increases plasma levels of factor VIII and von Willebrand factor, shortening bleeding time. Although its use as a single agent was uncommon among respondents, the decision to give DDAVP with platelets was relatively common when patients were taking an ADP
When patients on antiplatelet medication present with operative intracranial hemorrhage, the majority of neurosurgeons do not perform qualitative platelet testing. Antiplatelet reversal strategies are significantly influenced by the antiplatelet therapy with more aggressive reversal strategies employed in the presence of ADP antagonists.
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Limitations The current survey is limited by the relatively low overall complete response rate of 15.4% and lack of respondent demographic information. However, the response rate was not unexpected given the target audience, and the gross complete response number of 429 was thought to be robust enough to provide representative responses. The survey was also limited by its multiple-choice format. This could misrepresent or exclude individual management paradigms not included in the available choices (i.e., use of prothrombin complex concentrate, tranexamic acid, or recombinant factor VII). These management strategies were thought to lie outside the mainstream based on literature review and thus comprise only a small fraction of current practice.
CONCLUSIONS
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REFERENCES 1. Ajani UA, Ford ES, Greenland KJ, Giles WH, Mokdad AH. Aspirin use among U.S. adults: Behavioral Risk Factor Surveillance System. Am J Prev Med. 2006;30:74-77. 2. Frontera JA, Lewin JJ 3rd, Rabinstein AA, Aisiku IP, Alexandrov AW, Cook AM, 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. 3. Ivascu FA, Howells GA, Junn FS, Bair HA, Bendick PJ, Janczyk RJ. Predictors of mortality in trauma patients with intracranial hemorrhage on preinjury aspirin or clopidogrel. J Trauma. 2008;65: 785-788. 4. Roquer J, Rodriguez Campello A, Gomis M, Ois A, Puente V, Munteis E. Previous antiplatelet therapy is an independent predictor of 30-day mortality after spontaneous supratentorial intracerebral hemorrhage. J Neurol. 2005;252:412-416. 5. Saloheimo P, Ahonen M, Juvela S, Pyhtinen J, Savolainen ER, Hillbom M. Regular aspirin-use preceding the onset of primary intracerebral hemorrhage is an independent predictor for death. Stroke. 2006;37:129-133. 6. Wong DK, Lurie F, Wong LL. The effects of clopidogrel on elderly traumatic brain injured patients. J Trauma. 2008;65:1303-1308. 7. Fortuna GR, Mueller EW, James LE, Shutter LA, Butler KL. The impact of preinjury antiplatelet and anticoagulant pharmacotherapy on outcomes in elderly patients with hemorrhagic brain injury. Surgery. 2008;144:598-603 [discussion: 605]. 8. Sansing LH, Messe SR, Cucchiara BL, Cohen SN, Lyden PD, Kasner SE, et al. Prior antiplatelet use does not affect hemorrhage growth or outcome after ICH. Neurology. 2009;72:1397-1402. 9. Moussouttas M, Malhotra R, Fernandez L, Maltenfort M, Holowecki M, Delgado J, et al. Role of antiplatelet agents in hematoma expansion during the acute period of intracerebral hemorrhage. Neurocrit Care. 2010;12:24-29.
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ANTIPLATELETS AND INTRACRANIAL HEMORRHAGE
10. Gaist D, Garcia Rodriguez LA, Hellfritzsch M, Poulsen FR, Halle B, Hallas J, et al. Association of antithrombotic drug use with subdural hematoma risk. JAMA. 2017;317:836-846. 11. Bakheet MF, Pearce LA, Hart RG. Effect of addition of clopidogrel to aspirin on subdural hematoma: meta-analysis of randomized clinical trials. Int J Stroke. 2015;10:501-505.
require emergent invasive procedures. Ann Hematol. 2015;94:1457-1461. 20. Flordal PA, Sahlin S. Use of desmopressin to prevent bleeding complications in patients treated with aspirin. Br J Surg. 1993;80:723-724.
12. Hoddinott SN, Bass MJ. The Dillman total design survey method. Can Fam Physician. 1986;32:2366-2368.
21. Reiter RA, Mayr F, Blazicek H, Galehr E, JilmaStohlawetz P, Domanovits H, et al. Desmopressin antagonizes the in vitro platelet dysfunction induced by GPIIb/IIIa inhibitors and aspirin. Blood. 2003;102:4594-4599.
13. Li X, Sun Z, Zhao W, Zhang J, Chen J, Li Y, et al. Effect of acetylsalicylic acid usage and platelet transfusion on postoperative hemorrhage and activities of daily living in patients with acute intracerebral hemorrhage. J Neurosurg. 2013;118:94-103.
22. Leithauser B, Zielske D, Seyfert UT, Jung F. Effects of desmopressin on platelet membrane glycoproteins and platelet aggregation in volunteers on clopidogrel. Clin Hemorheol Microcirc. 2008;39: 293-302.
14. Naidech AM, Liebling SM, Rosenberg NF, Lindholm PF, Bernstein RA, Batjer HH, et al. Early platelet transfusion improves platelet activity and may improve outcomes after intracerebral hemorrhage. Neurocrit Care. 2012;16:82-87.
23. Naidech AM, Maas MB, Levasseur-Franklin KE, Liotta EM, Guth JC, Berman M, et al. Desmopressin improves platelet activity in acute intracerebral hemorrhage. Stroke. 2014;45:2451-2453.
15. Baharoglu MI, Cordonnier C, Al-Shahi Salman R, de Gans K, Koopman MM, Brand A, 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: 2605-2613. 16. Washington CW, Schuerer DJ, Grubb RL Jr. Platelet transfusion: an unnecessary risk for mild traumatic brain injury patients on antiplatelet therapy. J Trauma. 2011;71:358-363. 17. Joseph B, Pandit V, Sadoun M, Larkins CG, Kulvatunyou N, Tang A, et al. A prospective evaluation of platelet function in patients on antiplatelet therapy with traumatic intracranial hemorrhage. J Trauma Acute Care Surg. 2013;75: 990-994. 18. Mannucci PM, Remuzzi G, Pusineri F, Lombardi R, Valsecchi C, Mecca G, et al. Deamino-8-D-arginine vasopressin shortens the bleeding time in uremia. N Engl J Med. 1983;308:8-12.
24. Kapapa T, Rohrer S, Struve S, Petscher M, Konig R, Wirtz CR, et al. Desmopressin acetate in intracranial haemorrhage. Neurol Res Int. 2014; 2014:298767. 25. Kim DY, O’Leary M, Nguyen A, Kaji A, Bricker S, Neville A, et al. The effect of platelet and desmopressin administration on early radiographic progression of traumatic intracranial hemorrhage. J Neurotrauma. 2015;32:1815-1821.
Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Received 28 February 2018; accepted 11 May 2018 Citation: World Neurosurg. (2018). https://doi.org/10.1016/j.wneu.2018.05.064 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2018 Elsevier Inc. All rights reserved.
19. Kim JH, Baek CH, Min JY, Kim JS, Kim SB, Kim H. Desmopressin improves platelet function in uremic patients taking antiplatelet agents who
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2018.05.064
Antiplatelet Medication Reversal Strategies in Operative Intracranial Hemorrhage: A Survey of Practicing Neurosurgeons Paul M. Foreman1, Adeel Ilyas1, James Mooney1, Philip G.R. Schmalz1, Beverly C. Walters1, Christoph J. Griessenauer2,3
BACKGROUND: Antiplatelet therapy is common and complicates operative management of acute intracranial hemorrhage. Few data exist to guide antiplatelet reversal strategies.
-
METHODS: An online survey detailing antiplatelet reversal strategies in patients presenting with acute operative intracranial hemorrhage (subdural hematoma, epidural hematoma, and intracerebral hemorrhage) was distributed to board-certified neurosurgeons in North America.
-
RESULTS: From 2782 functional e-mail addresses, there were 493 (17.7%) responses to question 1 and 429 (15.4%) completed surveys. Most respondents chose to perform no additional laboratory testing before surgical intervention, regardless of hemorrhage type. The most common antiplatelet reversal strategy in the presence of aspirin was platelet transfusion (subdural hematoma and intracerebral hemorrhage) or no intervention (epidural hematoma). The most common antiplatelet reversal strategy in the presence of an adenosine diphosphate antagonist or dual antiplatelet therapy was platelet transfusion or platelet transfusion with desmopressin acetate administration. There was a statistically significant difference in management strategy depending on the antiplatelet therapy (P < 0.001).
-
CONCLUSIONS: When patients on antiplatelet medication present with operative intracranial hemorrhage, the
-
Key words Antiplatelet - Antiplatelet reversal - Epidural hematoma - Intracerebral hemorrhage - Intracranial hemorrhage - Subdural hematoma -
Abbreviations and Acronyms AANS: American Association of Neurological Surgeons ABNS: American Board of Neurological Surgery ADP: Adenosine diphosphate DAPT: Dual antiplatelet therapy DDAVP: Desmopressin acetate EDH: Epidural hematoma ICH: Intracerebral hemorrhage
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majority of neurosurgeons do not perform qualitative platelet testing. Antiplatelet reversal strategies are significantly influenced by the antiplatelet therapy with more aggressive reversal strategies employed in the presence of ADP antagonists.
INTRODUCTION
A
ntiplatelet therapy is widely used for prevention and treatment of ischemic vascular disease, with more than a third of American adults >35 years old taking aspirin.1 Commonly used medications include aspirin, an irreversible cyclooxygenase inhibitor, and clopidogrel, an irreversible adenosine diphosphate (ADP) receptor inhibitor. Generally, ADP receptor inhibitors produce more potent antiplatelet effects than cyclooxygenase inhibitors,2 and the 2 are often used in combination. The impact of antiplatelet therapy on intracranial hemorrhage is controversial, with some studies reporting increased rates of hematoma expansion and worse outcome,3-6 whereas others have found no difference.7-9 However, antiplatelet medication is a known risk factor for subdural hematoma (SDH) development10,11 and can complicate surgical management of all forms of intracranial hemorrhage. Strategies to reduce the risk of surgical intervention in the face of antiplatelet therapy include platelet transfusion, desmopressin acetate (DDAVP), recombinant factor VII, and fibrinogen supplementation, or a
SDH: Subdural hematoma TEG: Thromboelastography From the 1Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama, USA; 2Department of Neurosurgery, Geisinger Medical Center, Danville, Pennsylvania, USA; and 3Research Institute of Neurointervention, Paracelsus Medical University, Salzburg, Austria To whom correspondence should be addressed: Paul M. Foreman, M.D. [E-mail: [email protected]] Citation: World Neurosurg. (2018). https://doi.org/10.1016/j.wneu.2018.05.064 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2018 Elsevier Inc. All rights reserved.
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ORIGINAL ARTICLE PAUL M. FOREMAN ET AL.
ANTIPLATELETS AND INTRACRANIAL HEMORRHAGE
combination of these.2 The safety and efficacy of these strategies in the setting of operative intervention are largely unknown. Given the lack of quality data to guide treatment decisions, the management of acute operative intracranial hemorrhage in the setting of antiplatelet therapy is hypothesized to vary widely. We performed a survey of practicing neurosurgeons in an effort to elucidate therapeutic strategies.
3. The patient takes an ADP antagonist (i.e., clopidogrel, ticagrelor, prasugrel) daily. You decide to: B
transfuse platelets before/during surgery
B
give DDAVP before/during surgery
B
transfuse platelets AND give DDAVP before/during surgery
B
proceed to surgery without platelet transfusion or DDAVP administration
MATERIALS AND METHODS An online survey development software, SurveyMonkey (Palo Alto, California, USA), was used to create and distribute an online survey detailing the management of operative acute SDH, acute epidural hematoma (EDH), and acute intracerebral hemorrhage (ICH) in the setting of antiplatelet medication. The survey assessed preoperative laboratory work-up of the patient and antiplatelet reversal strategies before or during operative intervention. Using the modified Dillman technique,12 the survey was distributed to American Association of Neurological Surgeons (AANS) members who were board certified; residing in North America; and certified by the American Board of Neurological Surgery (ABNS), the Royal College of Surgeons of Canada, or the Mexican Council of Neurological Surgery. The AANS e-mail registry was selected as a representative sample of practicing neurosurgeons in North America. Board certification was required because it represents completion of educational, peer review, and examination processes and serves as a voluntary quality benchmark. The survey was sent to potential respondents 5 times (initial send, 1 week, 3 weeks, 7 weeks, and 10 weeks) between October and December 2017. The survey consisted of 3 distinct clinical scenarios: 1) acute SDH that required craniotomy for evacuation, 2) acute EDH that required craniotomy for evacuation, and 3) acute ICH that required craniotomy for evacuation. The platelet count and coagulation parameters were reportedly normal. No information was given regarding the clinical status or medical history of the patient. The respondent was then asked the following 4 questions: 1. The patient takes some form of antiplatelet therapy daily. In addition to routine laboratory evaluation (basic metabolic profile, complete blood count, prothrombin time, partial thromboplastin time), you perform: B
thromboelastography (TEG)
B
platelet function testing
B
other functional platelet testing (i.e., platelet mapping TEG)
B none 2. The patient takes aspirin daily. You decide to:
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B
transfuse platelets before/during surgery
B
give DDAVP before/during surgery
B
transfuse platelets AND give DDAVP before/during surgery
B
proceed to surgery without platelet transfusion or DDAVP administration
B
decision is based on laboratory testing from question 1
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B decision is based on laboratory testing from question 1 4. The patient is on dual antiplatelet therapy (DAPT) (i.e., aspirin and ADP antagonist). You decide to: B
transfuse platelets before/during surgery
B
give DDAVP before/during surgery
B
transfuse platelets AND give DDAVP before/during surgery
B
proceed to surgery without platelet transfusion or DDAVP administration
B
decision is based on laboratory testing from question 1
Statistics Descriptive statistics were computed using MATLAB Version R2017a (The MathWorks, Inc., Natick, Massachusetts, USA). c2 tests were performed 1) on the pooled responses to question 1 to determine whether the specific laboratory test obtained was independently associated with the underlying pathology of intracranial hemorrhage and 2) on pooled responses to questions 2e4, grouped by underlying pathology, to determine whether treatment was independently associated with the patient’s use of certain antithrombotic medication. P values of < 0.05 were considered significant. RESULTS The survey was e-mailed to 3104 potential respondents; 322 (10.4%) e-mail addresses had either opted out of survey e-mails or the e-mail was nonfunctional. Of the 2782 functional e-mail addresses, there were 493 (17.7%) responses to question 1 and 429 (15.4%) completed surveys. Subdural Hematoma In patients on antiplatelet therapy presenting with operative SDH, respondents chose to perform the following preoperative laboratory testing: 223 (45.2%), no testing; 176 (35.7%), platelet function testing; 66 (13.4%), TEG; and 28 (5.7%), other functional assay (Table 1). In the presence of aspirin, most respondents transfused platelets (33.5%) or proceeded to surgery without specific reversal agents (29%) (Table 2 and Figure 1). Of respondents, 21.6% said their actions would depend on results of laboratory testing. In the presence of an ADP antagonist, most respondents transfused platelets (44%) or transfused platelets and administered DDAVP (29.1%). Of respondents, 18.4% said their actions would depend on results of laboratory testing. In the presence of DAPT, most respondents transfused platelets (37.9%) or transfused platelets and administered DDAVP (37.2%). Of respondents, 18.2% said their actions would depend on results of laboratory testing.
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ANTIPLATELETS AND INTRACRANIAL HEMORRHAGE
Table 1. Pooled Responses for Various Laboratory Tests Obtained in Patients with Intracranial Hemorrhage Undergoing Surgical Intervention TEG
Platelet Function
Other Functional Assay
None
Total
SDH
66 (13.4%)
176 (35.7%)
28 (5.7%)
223 (45.2%)
493 (100.0%)
EDH
58 (12.6%)
146 (31.6%)
23 (5.0%)
235 (50.9%)
462 (100.0%)
ICH
65 (14.2%)
166 (36.2%)
29 (6.3%)
199 (43.4%)
459 (100.0%)
c2 P value ¼ 0.433. SDH, subdural hematoma; EDH, epidural hematoma; ICH, intracerebral hemorrhage.
There was a statistically significant difference (P < 0.001) in management strategy depending on the antiplatelet therapy.
statistically significant difference (P < 0.001) in management strategy depending on the antiplatelet therapy.
Epidural Hematoma In patients on antiplatelet therapy presenting with operative EDH, respondents chose to perform the following preoperative laboratory testing: 235 (50.9%), no testing; 146 (31.6%), platelet function testing; 58 (12.6%), TEG; and 23 (5.0%), other functional assay. In the presence of aspirin, most respondents transfused platelets (31.9%) or proceeded to surgery without specific reversal agents (32.8%). Of respondents, 17.4% said their actions would depend on results of laboratory testing. In the presence of an ADP antagonist, most respondents transfused platelets (44.2%) or transfused platelets and administered DDAVP (27.3%). Of respondents, 14.4% said their actions would depend on results of laboratory testing. In the presence of DAPT, most respondents transfused platelets (38.6%) or transfused platelets and administered DDAVP (38.3%). Of respondents, 12.9% said their actions would depend on results of laboratory testing. There was a
Intracerebral Hemorrhage In patients on antiplatelet therapy presenting with operative ICH, respondents chose to perform the following preoperative laboratory testing: 199 (43.4%), no testing; 166 (36.2%), platelet function testing; 65 (14.2%), TEG; and 29 (6.3%), other functional assay. There was no significant difference (P ¼ 0.433) in preoperative laboratory testing among SDH, EDH, and ICH. In the presence of aspirin, most respondents transfused platelets (33.6%) or proceeded to surgery without specific reversal agents (24.2%). Of respondents, 20.4% said their actions would depend on results of laboratory testing. In the presence of an ADP antagonist, most respondents transfused platelets (41.5%) or transfused platelets and administered DDAVP (31.4%). Of respondents, 19.1% said their actions would depend on results of laboratory testing. In the presence of DAPT, most respondents transfused platelets (35.6%) or transfused platelets and administered DDAVP (40.8%). Of
Table 2. Pooled Responses for Various Treatment Options in Patients with Intracranial Hemorrhage Who Are on Aspirin, Adenosine Diphosphate Antagonist, or Dual Antiplatelet Therapy Transfuse Platelets
DDAVP
Platelets and DDAVP
Neither
Depends on Laboratory Results
Total
Aspirin
155 (33.5%)
19 (4.1%)
54 (11.7%)
134 (29.0%)
100 (21.6%)
462 (100.0%)
ADP antagonist
201 (44.0%)
9 (2.0%)
133 (29.1%)
30 (6.6%)
84 (18.4%)
457 (100.0%)
DAPT
173 (37.9%)
8 (1.8%)
170 (37.2%)
23 (5.0%)
83 (18.2%)
457 (100.0%)
SDH
EDH Aspirin
139 (31.9%)
21 (4.8%)
57 (13.1%)
143 (32.8%)
76 (17.4%)
436 (100.0%)
ADP antagonist
191 (44.2%)
14 (3.2%)
118 (27.3%)
47 (10.9%)
62 (14.4%)
432 (100.0%)
DAPT
167 (38.6%)
7 (1.6%)
166 (38.3%)
37 (8.5%)
56 (12.9%)
433 (100.0%)
Aspirin
143 (33.6%)
15 (3.5%)
78 (18.3%)
103 (24.2%)
87 (20.4%)
426 (100.0%)
ADP antagonist
176 (41.5%)
9 (2.1%)
133 (31.4%)
25 (5.9%)
81 (19.1%)
424 (100.0%)
DAPT
151 (35.6%)
7 (1.7%)
173 (40.8%)
18 (4.2%)
75 (17.7%)
424 (100.0%)
ICH
c2 P value < 0.001 for all. DDAVP, desmopressin acetate; SDH, subdural hematoma; ADP, adenosine diphosphate; DAPT, dual antiplatelet therapy; EDH, epidural hematoma; ICH, intracerebral hemorrhage.
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ANTIPLATELETS AND INTRACRANIAL HEMORRHAGE
Figure 1. Antiplatelet reversal strategies in the management of operative intracranial hemorrhage.
respondents, 17.7% said their actions would depend on results of laboratory testing. There was a statistically significant difference (P < 0.001) in management strategy depending on the antiplatelet therapy.
DDAVP, desmopressin acetate; ADP, adenosine diphosphate.
made by clinicians between aspirin and an ADP antagonist in a patient presenting with an operative intracranial hemorrhage. Surgeons were notably more aggressive in their reversal strategies (i.e., platelet transfusion with or without DDAVP) when an ADP antagonist was present.
DISCUSSION Operative intracranial hemorrhage in patients on antiplatelet medications presents a common therapeutic challenge to the treating physician. A dearth of data regarding optimal work-up and antiplatelet reversal strategy (to include no reversal) has led to variability in management. This variability is highlighted in the present survey, with only a single response (the decision not to perform laboratory testing in a patient presenting with an operative EDH) receiving a majority vote. There is a clear distinction
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Platelet Transfusion Transfusing platelets was the most popular reversal strategy in the current survey and was influenced by the antiplatelet agent being taken. Respondents were more likely to transfuse platelets (with or without the addition of DDAVP) when patients were taking ADP inhibitors or DAPT rather than aspirin alone. The practice of platelet transfusion in the setting of operative intracranial hematoma evacuation is supported by a single prospective randomized
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ANTIPLATELETS AND INTRACRANIAL HEMORRHAGE
controlled trial.13 This trial enrolled 780 patients with acute hypertensive basal ganglia hemorrhages. Patients reportedly on aspirin were tested using platelet aggregation, and aspirinsensitive patients were then randomly assigned to platelet transfusion or no transfusion. The platelet transfusion group experienced a significantly reduced rate of postoperative hemorrhage, disability, and mortality. However, methodologic limitations, including small sample sizes per group, an ethnically homogeneous patient population, and a controversial indication for surgery, limit the generalizability of these findings. Another small prospective study also lent support to early platelet transfusion in the setting of ICH and reduced platelet activity.14 This study enrolled 45 patients and found improved platelet activity, smaller final hemorrhage size, and improved functional outcome in patients treated with early (<12 hours) versus late (>12 hours) platelet transfusion. Adverse events related to the transfusion occurred in 16% (hypotension and fever). The study was limited by small numbers, heterogeneous transfusions, and a lack of a control group. The PATCH trial was a multicenter, randomized controlled trial that enrolled 190 patients with ICH on antiplatelet medication and randomly assigned them to platelet transfusion with standard of care or standard of care alone.15 The odds of death or dependence at 3 months were significantly higher in the platelet transfusion group, and 42% of patients receiving transfusion had a serious adverse event during hospitalization. This led to a conclusion against platelet transfusion in the setting of antiplatelet-related ICH. It should be noted that patients with planned surgical evacuation of ICH within 24 hours were excluded. Platelet transfusion in the setting of traumatic intracranial hemorrhage has also failed to demonstrate benefit. A retrospective study of patients with mild traumatic brain injury and intracranial hemorrhage found no difference in short-term outcome after platelet transfusion.16 A 2013 prospective study enrolled patients with traumatic intracranial hemorrhage on high-dose aspirin therapy.17 Transfusion of 1 unit of apheresis platelets did not improve platelet function. Additionally, progression of intracranial hemorrhage and need for neurosurgical intervention were independent of platelet function. Guidelines from the Neurocritical Care Society and the Society of Critical Care Medicine recommend against platelet transfusion in patients with intracranial hemorrhage on antiplatelet medication in the absence of a planned neurosurgical procedure.2 However, they recommend transfusion in patients undergoing a neurosurgical procedure, the topic of the survey. Additional recommendations are made for platelet function testing before transfusion to identify patients with normal platelet function unlikely to benefit from transfusion.
antagonist. DDAVP has been shown to reduce bleeding time in uremic patients18 and improve platelet function in uremic patients who require emergent operative intervention.19 DDAVP has also demonstrated efficacy in restoring platelet function in patients taking antiplatelet medications.20-23 Two small studies investigating the effect of DDAVP in the setting of intracranial hemorrhage have been performed. A prospective study of 14 patients presenting with acute ICH and abnormal platelet function reported improved platelet activity concluding that it was an attractive pharmacologic treatment option.22 Another small study, including both traumatic and spontaneous intracranial hemorrhage, reported similar findings and noted that the effect appeared transient (3 hours) and influenced by dosing frequency.24 Small numbers limited the ability of these studies to evaluate the clinical impact of DDAVP in this setting. DDAVP given in combination with platelet transfusion failed to reduce the risk of early radiographic hemorrhage progression and mortality in a recent retrospective study of traumatic intracranial hemorrhage.25 Given the low risk of serious side effects and the suggestion of benefit, published guidelines have recommended consideration of DDAVP for patients taking antiplatelet medication presenting with intracranial hemorrhage.2 A dearth of data on the management of intracranial hemorrhage in the face of antiplatelet medication has led to wide variability in practice. This has led some surgeons to pursue a conservative approach, potentially increasing hemorrhage risk, whereas others pursue a more aggressive strategy that exposes patients to allogeneic blood products while using limited resources. Clinical investigation will be required to elucidate the optimal management strategy with consideration for the cost and availability of unconventional laboratory testing and blood products.
Desmopressin Acetate DDAVP is a synthetic analogue of arginine vasopressin and increases plasma levels of factor VIII and von Willebrand factor, shortening bleeding time. Although its use as a single agent was uncommon among respondents, the decision to give DDAVP with platelets was relatively common when patients were taking an ADP
When patients on antiplatelet medication present with operative intracranial hemorrhage, the majority of neurosurgeons do not perform qualitative platelet testing. Antiplatelet reversal strategies are significantly influenced by the antiplatelet therapy with more aggressive reversal strategies employed in the presence of ADP antagonists.
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Limitations The current survey is limited by the relatively low overall complete response rate of 15.4% and lack of respondent demographic information. However, the response rate was not unexpected given the target audience, and the gross complete response number of 429 was thought to be robust enough to provide representative responses. The survey was also limited by its multiple-choice format. This could misrepresent or exclude individual management paradigms not included in the available choices (i.e., use of prothrombin complex concentrate, tranexamic acid, or recombinant factor VII). These management strategies were thought to lie outside the mainstream based on literature review and thus comprise only a small fraction of current practice.
CONCLUSIONS
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REFERENCES 1. Ajani UA, Ford ES, Greenland KJ, Giles WH, Mokdad AH. Aspirin use among U.S. adults: Behavioral Risk Factor Surveillance System. Am J Prev Med. 2006;30:74-77. 2. Frontera JA, Lewin JJ 3rd, Rabinstein AA, Aisiku IP, Alexandrov AW, Cook AM, 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. 3. Ivascu FA, Howells GA, Junn FS, Bair HA, Bendick PJ, Janczyk RJ. Predictors of mortality in trauma patients with intracranial hemorrhage on preinjury aspirin or clopidogrel. J Trauma. 2008;65: 785-788. 4. Roquer J, Rodriguez Campello A, Gomis M, Ois A, Puente V, Munteis E. Previous antiplatelet therapy is an independent predictor of 30-day mortality after spontaneous supratentorial intracerebral hemorrhage. J Neurol. 2005;252:412-416. 5. Saloheimo P, Ahonen M, Juvela S, Pyhtinen J, Savolainen ER, Hillbom M. Regular aspirin-use preceding the onset of primary intracerebral hemorrhage is an independent predictor for death. Stroke. 2006;37:129-133. 6. Wong DK, Lurie F, Wong LL. The effects of clopidogrel on elderly traumatic brain injured patients. J Trauma. 2008;65:1303-1308. 7. Fortuna GR, Mueller EW, James LE, Shutter LA, Butler KL. The impact of preinjury antiplatelet and anticoagulant pharmacotherapy on outcomes in elderly patients with hemorrhagic brain injury. Surgery. 2008;144:598-603 [discussion: 605]. 8. Sansing LH, Messe SR, Cucchiara BL, Cohen SN, Lyden PD, Kasner SE, et al. Prior antiplatelet use does not affect hemorrhage growth or outcome after ICH. Neurology. 2009;72:1397-1402. 9. Moussouttas M, Malhotra R, Fernandez L, Maltenfort M, Holowecki M, Delgado J, et al. Role of antiplatelet agents in hematoma expansion during the acute period of intracerebral hemorrhage. Neurocrit Care. 2010;12:24-29.
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10. Gaist D, Garcia Rodriguez LA, Hellfritzsch M, Poulsen FR, Halle B, Hallas J, et al. Association of antithrombotic drug use with subdural hematoma risk. JAMA. 2017;317:836-846. 11. Bakheet MF, Pearce LA, Hart RG. Effect of addition of clopidogrel to aspirin on subdural hematoma: meta-analysis of randomized clinical trials. Int J Stroke. 2015;10:501-505.
require emergent invasive procedures. Ann Hematol. 2015;94:1457-1461. 20. Flordal PA, Sahlin S. Use of desmopressin to prevent bleeding complications in patients treated with aspirin. Br J Surg. 1993;80:723-724.
12. Hoddinott SN, Bass MJ. The Dillman total design survey method. Can Fam Physician. 1986;32:2366-2368.
21. Reiter RA, Mayr F, Blazicek H, Galehr E, JilmaStohlawetz P, Domanovits H, et al. Desmopressin antagonizes the in vitro platelet dysfunction induced by GPIIb/IIIa inhibitors and aspirin. Blood. 2003;102:4594-4599.
13. Li X, Sun Z, Zhao W, Zhang J, Chen J, Li Y, et al. Effect of acetylsalicylic acid usage and platelet transfusion on postoperative hemorrhage and activities of daily living in patients with acute intracerebral hemorrhage. J Neurosurg. 2013;118:94-103.
22. Leithauser B, Zielske D, Seyfert UT, Jung F. Effects of desmopressin on platelet membrane glycoproteins and platelet aggregation in volunteers on clopidogrel. Clin Hemorheol Microcirc. 2008;39: 293-302.
14. Naidech AM, Liebling SM, Rosenberg NF, Lindholm PF, Bernstein RA, Batjer HH, et al. Early platelet transfusion improves platelet activity and may improve outcomes after intracerebral hemorrhage. Neurocrit Care. 2012;16:82-87.
23. Naidech AM, Maas MB, Levasseur-Franklin KE, Liotta EM, Guth JC, Berman M, et al. Desmopressin improves platelet activity in acute intracerebral hemorrhage. Stroke. 2014;45:2451-2453.
15. Baharoglu MI, Cordonnier C, Al-Shahi Salman R, de Gans K, Koopman MM, Brand A, 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: 2605-2613. 16. Washington CW, Schuerer DJ, Grubb RL Jr. Platelet transfusion: an unnecessary risk for mild traumatic brain injury patients on antiplatelet therapy. J Trauma. 2011;71:358-363. 17. Joseph B, Pandit V, Sadoun M, Larkins CG, Kulvatunyou N, Tang A, et al. A prospective evaluation of platelet function in patients on antiplatelet therapy with traumatic intracranial hemorrhage. J Trauma Acute Care Surg. 2013;75: 990-994. 18. Mannucci PM, Remuzzi G, Pusineri F, Lombardi R, Valsecchi C, Mecca G, et al. Deamino-8-D-arginine vasopressin shortens the bleeding time in uremia. N Engl J Med. 1983;308:8-12.
24. Kapapa T, Rohrer S, Struve S, Petscher M, Konig R, Wirtz CR, et al. Desmopressin acetate in intracranial haemorrhage. Neurol Res Int. 2014; 2014:298767. 25. Kim DY, O’Leary M, Nguyen A, Kaji A, Bricker S, Neville A, et al. The effect of platelet and desmopressin administration on early radiographic progression of traumatic intracranial hemorrhage. J Neurotrauma. 2015;32:1815-1821.
Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Received 28 February 2018; accepted 11 May 2018 Citation: World Neurosurg. (2018). https://doi.org/10.1016/j.wneu.2018.05.064 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2018 Elsevier Inc. All rights reserved.
19. Kim JH, Baek CH, Min JY, Kim JS, Kim SB, Kim H. Desmopressin improves platelet function in uremic patients taking antiplatelet agents who
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