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ARTICLES: L. H. Sansing, S. R. Messe, B. L. Cucchiara, S. N. Cohen, P. D. Lyden, S. E. Kasner For the CHANT Investigators Prior antiplatelet use does not affect hemorrhage growth or outcome after ICH Neurology 2009; 72: 1397-1402 [Abstract] [Full text] [PDF]

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Prior antiplatelet use does not affect hemorrhage growth or outcome after ICH

Andrew M. Naidech, Richard A. Bernstein, Mark J. Alberts, Thomas P. Bleck   (2 September 2009)

Reply from the authors

Lauren H. Sansing, Brett L. Cucchiara, Steven R. Messe, Patrick D. Lyden and Scott E. Kasner   (2 September 2009)

Prior antiplatelet use does not affect hemorrhage growth or outcome after ICH 2 September 2009
Andrew M. Naidech, Northwestern University 710 N. Lake Shore Drive, 11th Floor, Chicago, IL 60611, Richard A. Bernstein, Mark J. Alberts, Thomas P. Bleck Send Correspondence to journal: Re: Prior antiplatelet use does not affect hemorrhage growth or outcome after ICH a-naidech{at}northwestern.edu Andrew M. Naidech, et al.	We were intrigued by the recent article and editorial regarding anti-platelet medication and outcome after intracerebral hemorrhage (ICH). [1,2] The analysis presumes that a history of aspirin use obtained from the patient or surrogate is a reliable indicator of platelet activity but this may be inaccurate. We have found that a substantial number of patients not known to take aspirin have reduced platelet activity on admission when tested. [3] Because the presumed mechanism of aspirin's effect on outcome after ICH would be reduced platelet activity, the important question is not whether reported aspirin use is related to ICH volume growth and outcomes, but whether platelet activity is. Reduced measured platelet activity on admission—usually but not always related to clinically verifiable aspirin use—is associated with ICH volume growth and worse outcomes. [4] Aspirin use alone is not. This may be due to the significant number of patients with reduced platelet activity without known aspirin use, the variable effect of aspirin on platelet activity, and the potential unreliability of the medication history. Why would patients have reduced platelet activity without aspirin use? We suspect this is because patients often take an anti-platelet agent at the onset of headache but are unable to relate this history because of aphasia or depressed mental status. We have since identified one patient admitted with an ICH who was alert and able to relate she took ibuprofen for headache, but not aspirin, and had reduced platelet activity on admission. The inability to detect therapeutic anti-platelet medication by routine toxicology screens compounds the problem. It may be premature to say platelet-activating therapy will be ineffective for acute ICH. Rather, the key may be to target therapy to patients who actually have reduced platelet activity, known to take aspirin or not. References 1. Sansing LH, Messe SR, Cucchiara BL, Cohen SN, Lyden PD, Kasner SE. CHANT Investigators. Prior antiplatelet use does not affect hemorrhage growth or outcome after ICH Neurology 2009;72:1397-1402. 2. Broderick JP. Evidence against rapid reversal of antiplatelet medications in acute intracerebral hemorrhage. Neurology 2009;72:1376-1377. 3. Naidech AM, Bassin SL, Bernstein RA, et al. Reduced platelet activity is more common than reported anti-platelet medication use in patients with intracerebral hemorrhage. Neurocrit Care 2009;11:307–310. 4. Naidech AM, Jovanovic B, Liebling S, et al. Reduced platelet activity is associated with early clot growth and worse 3-month outcome after intracerebral hemorrhage. Stroke 2009;40:2398-2401. Epub 2009 May 14. Disclosures: Dr. Naidech received research funding from NovoNordisk, the Neurocritical Care Society and the Northwestern Memorial Foundation; received personal compensation from EKR Therapeutics; receives research support from Astellas Pharma US and Gaymar Inc.; received research support from NovoNordisk, the Northwestern Memorial Foundation, the Neurocritical Care Society, Gaymar Inc., and Astellas Pharma US; and received personal compensation from EKR Therapeutics. Dr. Bernstein and Dr. Alberts report no disclosures. Dr. Bleck received support from NovoNordisk.
Reply from the authors 2 September 2009
Lauren H. Sansing, University of Pennsylvania 3400 Spruce St, 3 W Gates, Philadelphia, PA 19104, Brett L. Cucchiara, Steven R. Messe, Patrick D. Lyden and Scott E. Kasner Send Correspondence to journal: Re: Reply from the authors lauren.sansing{at}uphs.upenn.edu Lauren H. Sansing, et al.	We thank Naidech et al. for their interest in our article. We agree that the report of antiplatelet medication use is imperfect. Using patient or surrogate reporting may fail to identify some patients who have taken an aspirin for pain relief and may falsely classify some patients who report being on an antiplatelet medication but have been noncompliant. However, bedside measures of platelet inhibition have been historically unreliable due to poor correlation with the gold standard of light transmission aggregometry (LTA) [5] and are not routinely used in most hospitals. Therefore, the majority of neurologists and emergency room physicians decide whether to give a platelet transfusion to patients with ICH based on the patient/surrogate report of antiplatelet medication use. This is the common clinical scenario we addressed and we found no association of antiplatelet medication use with hemorrhage enlargement (by any of the commonly used definitions) or clinical outcome. [1] Naidech et al. recently found that reduced measured platelet activity on admission was associated with ICH volume growth and worse outcomes. [4] However, their analysis had many of the same potential confounders as other conflicting studies on antiplatelet medication use and ICH. These confounders include: small sample size; non-standardized timing of follow-up neuroimaging; the potential for preferential reimaging of patients who had either reported antiplatelet medications or were found to have reduced platelet activity; the preferential use of platelet transfusions in patients found to have reduced platelet activity; and the lack of blinding in outcome assessments. Furthermore, the device used (VerifyNow Aspirin Assay, Accumetrics, San Diego, CA) has a specific indication only for assessment of the impact of aspirin on platelet function. [6] Its use for assessing platelet function in patients not taking aspirin is still unclear. Finally, while it was the best of those tested, this device still had a poor correlation (r=0.13) and only poor-to-fair agreement (ê=0.247) with LTA when tested in a larger sample of patients on aspirin for cardiovascular disease.[5] This adds to the concern for systemic or random misclassification of platelet activity. Further research is needed on the predictive utility of bedside measures of platelet activity on hemorrhage enlargement and this investigation must adhere to the rigors of standardized and blinded follow-up neuroimaging and clinical outcome assessments. References 5. Lordkipanidze, M, Pharand C, Schampaert E, Turgeon J, Palisaitis DA, Diodati JG. A comparison of six major platelet function tests to determine the prevalence of aspirin resistance in patients with stable coronary artery disease. Eur Heart J 2007;28:1702-1708. 6. VerifyNow Aspirin Assay package insert. Accumetrics, San Diego, CA. Disclosures: Dr. Sansing received research support from NIH 5T32HL007954-08; and provided an expert opinion in Saunders v. Paris et al. Dr. Messe receives research support from NIH DK60990, NS40406-04, and AHA Beginning Grant-in-Aid; serves on the speakers’ bureau of Boehringer-Ingleheim; and provides expert testimony in several cases involving strokes. Dr. Cucchiara receives research support from NIH 5R01NS061572-03 and R43 NS061566-01; received research funding from an AHA Fellow-to-Faculty Award; serves on a stroke endpoint adjudication committee for Wyeth; has received honoraria from various hospitals for lectures on stroke; and served as a consultant for several legal cases involving stroke. Dr. Lyden receives research support from NIH NS44148 and a research grant from PhotoThera; serves on the editorial boards of Stroke, Journal of Stroke and Cerebrovascular Disease, and the International Journal of Stroke; serves on the advisory board of CoAxia; receives royalties from the book Thrombolytic Therapy in Acute Stroke; acts as a consultant to PhotoThera, CoAxia, BeneChill, and Mitsubishi; received honoraria for a lecture from Bayer; received travel funding for a trip from PhotoThera; and served as an expert witness. Dr. Kasner serves as the Stroke section editor for UpToDate; receives royalties from the book Prevention and Treatment of Ischemic Stroke; serves on the scientific advisory board of CardioNet; serves on stroke endpoint adjudication committees for Wyeth, Merck, and Novartis; serves as chair of a DSMB for BrainsGate; serves on the steering committee of an anticoagulation trial for AstraZeneca; is principal investigator for a PFO closure trial sponsored by Gore; and provides expert opinion in Dell v. Tausch.