Journal of the Neurological Sciences 338 (2014) 236
Contents lists available at ScienceDirect
Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns
Letter to the Editor Molecular insights into aneurysmal subarachnoid hemorrhage and cerebral vasospasm from analysis of coated-platelets I have read, with great interest, a recently published article in the Journal of Neurological Sciences by Prodan et al. titled ‘Higher levels of coated-platelets are observed in patients with subarachnoid hemorrhage but lower levels are associated with increased mortality at 30 days’ [1]. In this case–control study, the authors sought to identify an association between serum levels of coated-platelets (CPs) and subarachnoid hemorrhage (SAH) and between CP levels and postSAH clinical outcomes. Both cohorts were comprised of 40 patients each without any statistically significant differences in baseline demographics, smoking status, or medical comorbidities. CP levels were significantly higher in the SAH cohort (mean 42%) compared to the control cohort (31%, p b 0.0001). The patients in the SAH cohort were then evenly divided in to tertiles, lowest, middle, and highest, based on CP level. The patients in the middle and highest tertiles had significantly higher rates of vasospasm than those in the lowest tertile (p = 0.03) but the rates of post-SAH infarction were similar across tertiles (p = 0.22). However, the mortality rate at 30 days was significantly higher for patients in the lowest tertile compared to those in the middle or highest tertiles (p = 0.01). In their discussion, the authors postulate that higher levels of CPs in the SAH cohort are secondary to the inflammatory process which is known to underlie the pathogenesis of intracranial aneurysms [2]. While aneurysm formation and progression are a chronic inflammatory process, aneurysm rupture results in a tremendous acute inflammatory response. Since the serum CP levels were drawn after the ictus of SAH, the rise in CP level in the SAH cohort was more likely representative of the hematologic response to aneurysm rupture rather than the degree of chronic inflammation. Furthermore, 20% of the patients presented with non-aneurysmal SAH which is generally considered to be a separate pathological entity from aneurysmal SAH with disparate clinical outcomes [3]. Based on the results of this series alone, one cannot infer a correlation between CPs and the inflammatory cascade underlying aneurysm pathogenesis. A study with the potential for significant impact would be evaluation of CP levels in patients with conservatively managed unruptured aneurysms and identification of an association between CP levels and subsequent rupture risk after longitudinal follow-up. Even in the current study, it would have been interesting for the authors to note if there was any correlation between aneurysm size and CP level given that maximal diameter of the dome is the single most powerful predictor of aneurysm rupture risk [4,5]. The association between higher CP levels and increased incidence of vasospasm may support the authors' claim that CP levels are linked to the degree of systemic inflammation given the contribution of proinflammatory cascades to the development of post-SAH vasospasm [6].
0022-510X/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.jns.2013.12.036
The lack of correlation between CP levels and post-SAH infarction is consistent with prior large clinical trials demonstrating a dissociation between successful treatment of radiographic vasospasm and good clinical outcome [7]. The contributing role of impaired cerebral autoregulation to secondary cerebral ischemia following aneurysmal SAH has recently emerged and supports the long held notion that vasospasm alone was inadequate to account for post-SAH delayed neurological morbidity [8]. The same group reported significantly lower CP levels in patients with spontaneous intracerebral hemorrhage compared to controls (25% versus 33%, p = 0.0035) [9]. Along with prior studies, these results appear to support a hemostatic role of CPs [10]. Perhaps the most interesting molecular insight provided by the current study is the suggestion that the balance of hemostatic and inflammatory pathways is severely disturbed during SAH and vasospasm. Future research targeting these closely related but distinct cerebrovascular pathologies should seek to restore a healthy equilibrium to these two interrelated biological cascades. References [1] Prodan CI, Vincent AS, Kirkpatrick AC, Hoover SL, Dale GL. Higher levels of coatedplatelets are observed in patients with subarachnoid hemorrhage but lower levels are associated with increased mortality at 30 days. J Neurol Sci 2013;334(1–2):126–9. [2] Chalouhi N, Ali MS, Jabbour PM, Tjoumakaris SI, Gonzalez LF, Rosenwasser RH, et al. Biology of intracranial aneurysms: role of inflammation. J Cereb Blood Flow Metab 2012;32(9):1659–76. [3] Dalyai R, Chalouhi N, Theofanis T, Jabbour PM, Dumont AS, Gonzalez LF, et al. Subarachnoid hemorrhage with negative initial catheter angiography: a review of 254 cases evaluating patient clinical outcome and efficacy of short- and long-term repeat angiography. Neurosurgery 2013;72(4):646–52 [discussion 651–2]. [4] Wiebers DO, Whisnant JP, Huston III J, Meissner I, Brown Jr RD, Piepgras DG, et al. Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment. Lancet 2003;362(9378):103–10. [5] Morita A, Kirino T, Hashi K, Aoki N, Fukuhara S, Hashimoto N, et al. The natural course of unruptured cerebral aneurysms in a Japanese cohort. N Engl J Med 2012;366(26):2474–82. [6] Dumont AS, Dumont RJ, Chow MM, Lin CL, Calisaneller T, Ley KF, et al. Cerebral vasospasm after subarachnoid hemorrhage: putative role of inflammation. Neurosurgery 2003;53(1):123–33 [discussion 133–5]. [7] Macdonald RL, Higashida RT, Keller E, Mayer SA, Molyneux A, Raabe A, et al. Randomized trial of clazosentan in patients with aneurysmal subarachnoid hemorrhage undergoing endovascular coiling. Stroke 2012;43(6):1463–9. [8] Budohoski KP, Czosnyka M, Kirkpatrick PJ, Smielewski P, Steiner LA, Pickard JD. Clinical relevance of cerebral autoregulation following subarachnoid haemorrhage. Nat Rev Neurol 2013;9(3):152–63. [9] Prodan CI, Vincent AS, Padmanabhan R, Dale GL. Coated-platelet levels are low in patients with spontaneous intracerebral hemorrhage. Stroke 2009;40(7):2578–80. [10] Dale GL. Coated-platelets: an emerging component of the procoagulant response. J Thromb Haemost 2005;3(10):2185–92.
Dale Ding University of Virginia, Department of Neurological Surgery, P.O. Box 800212, Charlottesville, VA 22908, United States Tel.: +1 434 924 2203; fax: +1 434 243 6726. E-mail address: [email protected]. 21 November 2013
Contents lists available at ScienceDirect
Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns
Letter to the Editor Molecular insights into aneurysmal subarachnoid hemorrhage and cerebral vasospasm from analysis of coated-platelets I have read, with great interest, a recently published article in the Journal of Neurological Sciences by Prodan et al. titled ‘Higher levels of coated-platelets are observed in patients with subarachnoid hemorrhage but lower levels are associated with increased mortality at 30 days’ [1]. In this case–control study, the authors sought to identify an association between serum levels of coated-platelets (CPs) and subarachnoid hemorrhage (SAH) and between CP levels and postSAH clinical outcomes. Both cohorts were comprised of 40 patients each without any statistically significant differences in baseline demographics, smoking status, or medical comorbidities. CP levels were significantly higher in the SAH cohort (mean 42%) compared to the control cohort (31%, p b 0.0001). The patients in the SAH cohort were then evenly divided in to tertiles, lowest, middle, and highest, based on CP level. The patients in the middle and highest tertiles had significantly higher rates of vasospasm than those in the lowest tertile (p = 0.03) but the rates of post-SAH infarction were similar across tertiles (p = 0.22). However, the mortality rate at 30 days was significantly higher for patients in the lowest tertile compared to those in the middle or highest tertiles (p = 0.01). In their discussion, the authors postulate that higher levels of CPs in the SAH cohort are secondary to the inflammatory process which is known to underlie the pathogenesis of intracranial aneurysms [2]. While aneurysm formation and progression are a chronic inflammatory process, aneurysm rupture results in a tremendous acute inflammatory response. Since the serum CP levels were drawn after the ictus of SAH, the rise in CP level in the SAH cohort was more likely representative of the hematologic response to aneurysm rupture rather than the degree of chronic inflammation. Furthermore, 20% of the patients presented with non-aneurysmal SAH which is generally considered to be a separate pathological entity from aneurysmal SAH with disparate clinical outcomes [3]. Based on the results of this series alone, one cannot infer a correlation between CPs and the inflammatory cascade underlying aneurysm pathogenesis. A study with the potential for significant impact would be evaluation of CP levels in patients with conservatively managed unruptured aneurysms and identification of an association between CP levels and subsequent rupture risk after longitudinal follow-up. Even in the current study, it would have been interesting for the authors to note if there was any correlation between aneurysm size and CP level given that maximal diameter of the dome is the single most powerful predictor of aneurysm rupture risk [4,5]. The association between higher CP levels and increased incidence of vasospasm may support the authors' claim that CP levels are linked to the degree of systemic inflammation given the contribution of proinflammatory cascades to the development of post-SAH vasospasm [6].
0022-510X/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.jns.2013.12.036
The lack of correlation between CP levels and post-SAH infarction is consistent with prior large clinical trials demonstrating a dissociation between successful treatment of radiographic vasospasm and good clinical outcome [7]. The contributing role of impaired cerebral autoregulation to secondary cerebral ischemia following aneurysmal SAH has recently emerged and supports the long held notion that vasospasm alone was inadequate to account for post-SAH delayed neurological morbidity [8]. The same group reported significantly lower CP levels in patients with spontaneous intracerebral hemorrhage compared to controls (25% versus 33%, p = 0.0035) [9]. Along with prior studies, these results appear to support a hemostatic role of CPs [10]. Perhaps the most interesting molecular insight provided by the current study is the suggestion that the balance of hemostatic and inflammatory pathways is severely disturbed during SAH and vasospasm. Future research targeting these closely related but distinct cerebrovascular pathologies should seek to restore a healthy equilibrium to these two interrelated biological cascades. References [1] Prodan CI, Vincent AS, Kirkpatrick AC, Hoover SL, Dale GL. Higher levels of coatedplatelets are observed in patients with subarachnoid hemorrhage but lower levels are associated with increased mortality at 30 days. J Neurol Sci 2013;334(1–2):126–9. [2] Chalouhi N, Ali MS, Jabbour PM, Tjoumakaris SI, Gonzalez LF, Rosenwasser RH, et al. Biology of intracranial aneurysms: role of inflammation. J Cereb Blood Flow Metab 2012;32(9):1659–76. [3] Dalyai R, Chalouhi N, Theofanis T, Jabbour PM, Dumont AS, Gonzalez LF, et al. Subarachnoid hemorrhage with negative initial catheter angiography: a review of 254 cases evaluating patient clinical outcome and efficacy of short- and long-term repeat angiography. Neurosurgery 2013;72(4):646–52 [discussion 651–2]. [4] Wiebers DO, Whisnant JP, Huston III J, Meissner I, Brown Jr RD, Piepgras DG, et al. Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment. Lancet 2003;362(9378):103–10. [5] Morita A, Kirino T, Hashi K, Aoki N, Fukuhara S, Hashimoto N, et al. The natural course of unruptured cerebral aneurysms in a Japanese cohort. N Engl J Med 2012;366(26):2474–82. [6] Dumont AS, Dumont RJ, Chow MM, Lin CL, Calisaneller T, Ley KF, et al. Cerebral vasospasm after subarachnoid hemorrhage: putative role of inflammation. Neurosurgery 2003;53(1):123–33 [discussion 133–5]. [7] Macdonald RL, Higashida RT, Keller E, Mayer SA, Molyneux A, Raabe A, et al. Randomized trial of clazosentan in patients with aneurysmal subarachnoid hemorrhage undergoing endovascular coiling. Stroke 2012;43(6):1463–9. [8] Budohoski KP, Czosnyka M, Kirkpatrick PJ, Smielewski P, Steiner LA, Pickard JD. Clinical relevance of cerebral autoregulation following subarachnoid haemorrhage. Nat Rev Neurol 2013;9(3):152–63. [9] Prodan CI, Vincent AS, Padmanabhan R, Dale GL. Coated-platelet levels are low in patients with spontaneous intracerebral hemorrhage. Stroke 2009;40(7):2578–80. [10] Dale GL. Coated-platelets: an emerging component of the procoagulant response. J Thromb Haemost 2005;3(10):2185–92.
Dale Ding University of Virginia, Department of Neurological Surgery, P.O. Box 800212, Charlottesville, VA 22908, United States Tel.: +1 434 924 2203; fax: +1 434 243 6726. E-mail address: [email protected]. 21 November 2013
