Skip to main content
SpringerLink
Log in

Intracerebral Hemorrhage

  • Chapter
  • First Online:
Book cover Handbook of Cerebrovascular Disease and Neurointerventional Technique

Part of the book series: Contemporary Medical Imaging ((CMI))

  • 2292 Accesses

Abstract

This chapter discusses intracerebral hemorrhage (ICH) in general and specific circumstances, including intraventricular hemorrhage, posterior fossa hemorrhage, and anticoagulant-related hemorrhage.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

References

  1. Kase CS, Shoamanesh A, Greenberg SM, Caplan LR. Intracerebral hemorrhage. In: Grotta JC, Albers GW, Broderick JP, et al., editors. Stroke: pathophysiology, diagnosis and management. 6th ed. Philadelphia: Elsevier; 2016. p. 466–515.

    Google Scholar 

  2. Hemphill JC 3rd, Greenberg SM, Anderson CS, et al. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2015;46:2032–60.

    Google Scholar 

  3. Steiner T, Al-Shahi Salman R, Beer R, et al. European Stroke Organisation (ESO) guidelines for the management of spontaneous intracerebral hemorrhage. Int J Stroke. 2014;9:840–55.

    Google Scholar 

  4. Feigin VL, Krishnamurthi RV. Global burden of stroke. In: Grotta JC, Albers GW, Broderick JP, et al., editors. Stroke: pathophysiology, diagnosis and management. Philadelphia: Elsevier; 2016. p. 165–206.

    Google Scholar 

  5. van Asch CJ, Luitse MJ, Rinkel GJ, van der Tweel I, Algra A, Klijn CJ. Incidence, case fatality, and functional outcome of intracerebral haemorrhage over time, according to age, sex, and ethnic origin: a systematic review and meta-analysis. Lancet Neurol. 2010;9:167–76.

    Google Scholar 

  6. Howard G, Cushman M, Howard VJ, et al. Risk factors for intracerebral hemorrhage: the REasons for geographic and racial differences in stroke (REGARDS) study. Stroke. 2013;44:1282–7.

    PubMed Central  Google Scholar 

  7. Sturgeon JD, Folsom AR, Longstreth WT Jr, Shahar E, Rosamond WD, Cushman M. Risk factors for intracerebral hemorrhage in a pooled prospective study. Stroke. 2007;38:2718–25.

    Google Scholar 

  8. Devan WJ, Falcone GJ, Anderson CD, et al. Heritability estimates identify a substantial genetic contribution to risk and outcome of intracerebral hemorrhage. Stroke. 2013;44:1578–83.

    CAS  PubMed Central  Google Scholar 

  9. Feldmann E, Broderick JP, Kernan WN, et al. Major risk factors for intracerebral hemorrhage in the young are modifiable. Stroke. 2005;36:1881–5.

    Google Scholar 

  10. van Walraven C, Hart RG, Singer DE, et al. Oral anticoagulants vs aspirin in nonvalvular atrial fibrillation: an individual patient meta-analysis. JAMA. 2002;288:2441–8.

    Google Scholar 

  11. He J, Whelton PK, Vu B, Klag MJ. Aspirin and risk of hemorrhagic stroke: a meta-analysis of randomized controlled trials. JAMA. 1998;280:1930–5.

    CAS  Google Scholar 

  12. Palacio S, Hart RG, Pearce LA, Benavente OR. Effect of addition of clopidogrel to aspirin on mortality: systematic review of randomized trials. Stroke. 2012;43:2157–62.

    CAS  PubMed Central  Google Scholar 

  13. Sacco S, Ornello R, Ripa P, Pistoia F, Carolei A. Migraine and hemorrhagic stroke: a meta-analysis. Stroke. 2013;44:3032–8.

    Google Scholar 

  14. O’Donnell MJ, Xavier D, Liu L, et al. Risk factors for ischaemic and intracerebral haemorrhagic stroke in 22 countries (the INTERSTROKE study): a case-control study. Lancet. 2010;376:112–23.

    Google Scholar 

  15. Tsai CF, Thomas B, Sudlow CL. Epidemiology of stroke and its subtypes in Chinese vs white populations: a systematic review. Neurology. 2013;81:264–72.

    PubMed Central  Google Scholar 

  16. Johnston SC, Mendis S, Mathers CD. Global variation in stroke burden and mortality: estimates from monitoring, surveillance, and modelling. Lancet Neurol. 2009;8:345–54.

    Google Scholar 

  17. Andersen KK, Olsen TS, Dehlendorff C, Kammersgaard LP. Hemorrhagic and ischemic strokes compared: stroke severity, mortality, and risk factors. Stroke. 2009;40:2068–72.

    Google Scholar 

  18. Paolucci S, Antonucci G, Grasso MG, et al. Functional outcome of ischemic and hemorrhagic stroke patients after inpatient rehabilitation: a matched comparison. Stroke. 2003;34:2861–5.

    Google Scholar 

  19. Kelly PJ, Furie KL, Shafqat S, Rallis N, Chang Y, Stein J. Functional recovery following rehabilitation after hemorrhagic and ischemic stroke. Arch Phys Med Rehabil. 2003;84:968–72.

    Google Scholar 

  20. Katrak PH, Black D, Peeva V. Do stroke patients with intracerebral hemorrhage have a better functional outcome than patients with cerebral infarction? PM R. 2009;1:427–33.

    Google Scholar 

  21. Bhalla A, Wang Y, Rudd A, Wolfe CD. Differences in outcome and predictors between ischemic and intracerebral hemorrhage: the South London Stroke Register. Stroke. 2013;44:2174–81.

    Google Scholar 

  22. Poon MT, Fonville AF, Al-Shahi Salman R. Long-term prognosis after intracerebral haemorrhage: systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2014;85:660–7.

    Google Scholar 

  23. Hemphill JC 3rd, Bonovich DC, Besmertis L, Manley GT, Johnston SC. The ICH score: a simple, reliable grading scale for intracerebral hemorrhage. Stroke. 2001;32:891–7.

    Google Scholar 

  24. Hemphill JC 3rd, Farrant M, Neill TA Jr. Prospective validation of the ICH score for 12-month functional outcome. Neurology. 2009;73:1088–94.

    PubMed Central  Google Scholar 

  25. Aysenne AM, Albright KC, Mathias T, et al. 24-hour ICH score is a better predictor of outcome than admission ICH score. ISRN Stroke. 2013;2013. https://doi.org/10.1155/2013/605286.

  26. Sato S, Heeley E, Arima H, et al. Higher mortality in patients with right hemispheric intracerebral haemorrhage: INTERACT1 and 2. J Neurol Neurosurg Psychiatry. 2015;86:1319–23.

    Google Scholar 

  27. Murthy SB, Merkler AE, Omran SS, et al. Outcomes after intracerebral hemorrhage from arteriovenous malformations. Neurology. 2017;88:1882–8.

    PubMed Central  Google Scholar 

  28. Fisher CM. Pathological observations in hypertensive cerebral hemorrhage. J Neuropathol Exp Neurol. 1971;30:536–50.

    CAS  Google Scholar 

  29. Keep RF, Hua Y, Xi G. Intracerebral haemorrhage: mechanisms of injury and therapeutic targets. Lancet Neurol. 2012;11:720–31.

    CAS  Google Scholar 

  30. TY W, Yassi N, Shah DG, et al. Simultaneous multiple intracerebral hemorrhages (SMICH). Stroke. 2017;48:581–6.

    Google Scholar 

  31. Davis SM, Broderick J, Hennerici M, et al. Hematoma growth is a determinant of mortality and poor outcome after intracerebral hemorrhage. Neurology. 2006;66:1175–81.

    CAS  Google Scholar 

  32. Dowlatshahi D, Demchuk AM, Flaherty ML, et al. Defining hematoma expansion in intracerebral hemorrhage: relationship with patient outcomes. Neurology. 2011;76:1238–44.

    CAS  PubMed Central  Google Scholar 

  33. Ovesen C, Christensen AF, Krieger DW, Rosenbaum S, Havsteen I, Christensen H. Time course of early postadmission hematoma expansion in spontaneous intracerebral hemorrhage. Stroke. 2014;45:994–9.

    Google Scholar 

  34. Sporns PB, Schwake M, Schmidt R, et al. Computed tomographic blend sign is associated with computed tomographic angiography spot sign and predicts secondary neurological deterioration after intracerebral hemorrhage. Stroke. 2017;48:131–5.

    Google Scholar 

  35. Gebel JM Jr, Jauch EC, Brott TG, et al. Natural history of perihematomal edema in patients with hyperacute spontaneous intracerebral hemorrhage. Stroke. 2002;33:2631–5.

    Google Scholar 

  36. Staykov D, Wagner I, Volbers B, et al. Natural course of perihemorrhagic edema after intracerebral hemorrhage. Stroke. 2011;42(9):2625.

    Google Scholar 

  37. Butcher KS, Baird T, MacGregor L, Desmond P, Tress B, Davis S. Perihematomal edema in primary intracerebral hemorrhage is plasma derived. Stroke. 2004;35:1879–85.

    Google Scholar 

  38. Xi G, Reiser G, Keep RF. The role of thrombin and thrombin receptors in ischemic, hemorrhagic and traumatic brain injury: deleterious or protective? J Neurochem. 2003;84:3–9.

    CAS  Google Scholar 

  39. Striggow F, Riek M, Breder J, Henrich-Noack P, Reymann KG, Reiser G. The protease thrombin is an endogenous mediator of hippocampal neuroprotection against ischemia at low concentrations but causes degeneration at high concentrations. Proc Natl Acad Sci U S A. 2000;97:2264–9.

    CAS  PubMed Central  Google Scholar 

  40. Huang FP, Xi G, Keep RF, Hua Y, Nemoianu A, Hoff JT. Brain edema after experimental intracerebral hemorrhage: role of hemoglobin degradation products. J Neurosurg. 2002;96:287–93.

    Google Scholar 

  41. Xi G, Keep RF, Hoff JT. Erythrocytes and delayed brain edema formation following intracerebral hemorrhage in rats. J Neurosurg. 1998;89(6):991.

    CAS  Google Scholar 

  42. Wu J, Hua Y, Keep RF, Nakamura T, Hoff JT, Xi G. Iron and iron-handling proteins in the brain after intracerebral hemorrhage. Stroke. 2003;34:2964–9.

    CAS  Google Scholar 

  43. Righy C, Bozza MT, Oliveira MF, Bozza FA. Molecular, cellular and clinical aspects of intracerebral hemorrhage: are the enemies within? Curr Neuropharmacol. 2016;14:392–402.

    CAS  PubMed Central  Google Scholar 

  44. Yeatts SD, Palesch YY, Moy CS, Selim M. High dose deferoxamine in intracerebral hemorrhage (HI-DEF) trial: rationale, design, and methods. Neurocrit Care. 2013;19:257–66.

    CAS  PubMed Central  Google Scholar 

  45. Aronowski J, Zhao X. Molecular pathophysiology of cerebral hemorrhage: secondary brain injury. Stroke. 2011;42(6):1781.

    PubMed Central  Google Scholar 

  46. McCourt R, Gould B, Gioia L, et al. Cerebral perfusion and blood pressure do not affect perihematoma edema growth in acute intracerebral hemorrhage. Stroke. 2014;45:1292–8.

    Google Scholar 

  47. Schellinger PD, Fiebach JB, Hoffmann K, et al. Stroke MRI in intracerebral hemorrhage: is there a perihemorrhagic penumbra? Stroke. 2003;34:1674–9.

    Google Scholar 

  48. Olivot JM, Mlynash M, Kleinman JT, et al. MRI profile of the perihematomal region in acute intracerebral hemorrhage. Stroke. 2010;41:2681–3.

    PubMed Central  Google Scholar 

  49. Mayer SA, Lignelli A, Fink ME, et al. Perilesional blood flow and edema formation in acute intracerebral hemorrhage: a SPECT study. Stroke. 1998;29:1791–8.

    CAS  Google Scholar 

  50. Carhuapoma JR, Wang PY, Beauchamp NJ, Keyl PM, Hanley DF, Barker PB. Diffusion-weighted MRI and proton MR spectroscopic imaging in the study of secondary neuronal injury after intracerebral hemorrhage. Stroke. 2000;31:726–32.

    CAS  Google Scholar 

  51. Powers WJ, Zazulia AR, Videen TO, et al. Autoregulation of cerebral blood flow surrounding acute (6 to 22 hours) intracerebral hemorrhage. Neurology. 2001;57:18–24.

    CAS  Google Scholar 

  52. Anderson CS, Heeley E, Huang Y, et al. Rapid blood-pressure lowering in patients with acute intracerebral hemorrhage. N Engl J Med. 2013;368:2355–65.

    CAS  Google Scholar 

  53. Qureshi AI, Palesch YY, Barsan WG, et al. Intensive blood-pressure lowering in patients with acute cerebral hemorrhage. N Engl J Med. 2016;375:1033–43.

    PubMed Central  Google Scholar 

  54. Gould B, McCourt R, Gioia LC, et al. Acute blood pressure reduction in patients with intracerebral hemorrhage does not result in borderzone region hypoperfusion. Stroke. 2014;45:2894–9.

    CAS  Google Scholar 

  55. Runchey S, McGee S. Does this patient have a hemorrhagic stroke?: clinical findings distinguishing hemorrhagic stroke from ischemic stroke. JAMA. 2010;303:2280–6.

    CAS  Google Scholar 

  56. Melo TP, Pinto AN, Ferro JM. Headache in intracerebral hematomas. Neurology. 1996;47:494–500.

    CAS  Google Scholar 

  57. Tatu L, Moulin T, El Mohamad R, Vuillier F, Rumbach L, Czorny A. Primary intracerebral hemorrhages in the Besancon stroke registry. Initial clinical and CT findings, early course and 30-day outcome in 350 patients. Eur Neurol. 2000;43:209–14.

    CAS  Google Scholar 

  58. Haapaniemi E, Strbian D, Rossi C, et al. The CAVE score for predicting late seizures after intracerebral hemorrhage. Stroke. 2014;45:1971–6.

    Google Scholar 

  59. Conrad J, Pawlowski M, Dogan M, Kovac S, Ritter MA, Evers S. Seizures after cerebrovascular events: risk factors and clinical features. Seizure. 2013;22:275–82.

    Google Scholar 

  60. Meretoja A, Strbian D, Putaala J, et al. SMASH-U: a proposal for etiologic classification of intracerebral hemorrhage. Stroke. 2012;43:2592–7.

    Google Scholar 

  61. Mehndiratta P, Manjila S, Ostergard T, et al. Cerebral amyloid angiopathy-associated intracerebral hemorrhage: pathology and management. Neurosurg Focus. 2012;32:E7.

    Google Scholar 

  62. van Etten ES, Auriel E, Haley KE, et al. Incidence of symptomatic hemorrhage in patients with lobar microbleeds. Stroke. 2014;45:2280–5.

    PubMed Central  Google Scholar 

  63. Yeh SJ, Tang SC, Tsai LK, Jeng JS. Pathogenetical subtypes of recurrent intracerebral hemorrhage: designations by SMASH-U classification system. Stroke. 2014;45:2636–42.

    Google Scholar 

  64. Plesea IE, Camenita A, Georgescu CC, et al. Study of cerebral vascular structures in hypertensive intracerebral haemorrhage. Romanian J Morphol Embryol. 2005;46:249–56.

    CAS  Google Scholar 

  65. Lang EW, Ren Ya Z, Preul C, et al. Stroke pattern interpretation: the variability of hypertensive versus amyloid angiopathy hemorrhage. Cerebrovasc Dis. 2001;12:121–30.

    CAS  Google Scholar 

  66. Yen CP, Lin CL, Kwan AL, et al. Simultaneous multiple hypertensive intracerebral haemorrhages. Acta Neurochir. 2005;147:393–9; discussion 9.

    CAS  Google Scholar 

  67. Vonsattel JP, Myers RH, Hedley-Whyte ET, Ropper AH, Bird ED, Richardson EP Jr. Cerebral amyloid angiopathy without and with cerebral hemorrhages: a comparative histological study. Ann Neurol. 1991;30:637–49.

    CAS  Google Scholar 

  68. Gurol ME, Viswanathan A, Gidicsin C, et al. Cerebral amyloid angiopathy burden associated with leukoaraiosis: a positron emission tomography/magnetic resonance imaging study. Ann Neurol. 2013;73:529–36.

    PubMed Central  Google Scholar 

  69. Wisniewski HM, Wegiel J. Beta-amyloid formation by myocytes of leptomeningeal vessels. Acta Neuropathol. 1994;87:233–41.

    CAS  Google Scholar 

  70. Jung SS, Zhang W, Van Nostrand WE. Pathogenic A beta induces the expression and activation of matrix metalloproteinase-2 in human cerebrovascular smooth muscle cells. J Neurochem. 2003;85:1208–15.

    CAS  Google Scholar 

  71. Mendel TA, Wierzba-Bobrowicz T, Lewandowska E, Stepien T, Szpak GM. The development of cerebral amyloid angiopathy in cerebral vessels. A review with illustrations based upon own investigated post mortem cases. Pol J Pathol. 2013;64:260–7.

    CAS  Google Scholar 

  72. McCarron MO, Nicoll JA, Stewart J, et al. The apolipoprotein E epsilon2 allele and the pathological features in cerebral amyloid angiopathy-related hemorrhage. J Neuropathol Exp Neurol. 1999;58:711–8.

    CAS  Google Scholar 

  73. Walker LC, Pahnke J, Madauss M, et al. Apolipoprotein E4 promotes the early deposition of Abeta42 and then Abeta40 in the elderly. Acta Neuropathol. 2000;100:36–42.

    CAS  Google Scholar 

  74. Greenberg SM, Briggs ME, Hyman BT, et al. Apolipoprotein E epsilon 4 is associated with the presence and earlier onset of hemorrhage in cerebral amyloid angiopathy. Stroke. 1996;27:1333–7.

    CAS  Google Scholar 

  75. O’Donnell HC, Rosand J, Knudsen KA, et al. Apolipoprotein E genotype and the risk of recurrent lobar intracerebral hemorrhage. N Engl J Med. 2000;342:240–5.

    Google Scholar 

  76. Selkoe DJ. The origins of Alzheimer disease: a is for amyloid. JAMA. 2000;283:1615–7.

    CAS  Google Scholar 

  77. Levy E, Lopez-Otin C, Ghiso J, Geltner D, Frangione B. Stroke in Icelandic patients with hereditary amyloid angiopathy is related to a mutation in the cystatin C gene, an inhibitor of cysteine proteases. J Exp Med. 1989;169:1771–8.

    CAS  Google Scholar 

  78. Vidal R, Frangione B, Rostagno A, et al. A stop-codon mutation in the BRI gene associated with familial British dementia. Nature. 1999;399:776–81.

    CAS  Google Scholar 

  79. Knudsen KA, Rosand J, Karluk D, Greenberg SM. Clinical diagnosis of cerebral amyloid angiopathy: validation of the Boston criteria. Neurology. 2001;56:537–9.

    CAS  Google Scholar 

  80. Rosand J, Muzikansky A, Kumar A, et al. Spatial clustering of hemorrhages in probable cerebral amyloid angiopathy. Ann Neurol. 2005;58:459–62.

    Google Scholar 

  81. Attems J, Quass M, Jellinger KA, Lintner F. Topographical distribution of cerebral amyloid angiopathy and its effect on cognitive decline are influenced by Alzheimer disease pathology. J Neurol Sci. 2007;257:49–55.

    Google Scholar 

  82. Fazekas F, Kleinert R, Roob G, et al. Histopathologic analysis of foci of signal loss on gradient-echo T2*-weighted MR images in patients with spontaneous intracerebral hemorrhage: evidence of microangiopathy-related microbleeds. AJNR Am J Neuroradiol. 1999;20:637–42.

    CAS  PubMed Central  Google Scholar 

  83. Martinez-Ramirez S, Greenberg SM, Viswanathan A. Cerebral microbleeds: overview and implications in cognitive impairment. Alzheimers Res Ther. 2014;6:33.

    PubMed Central  Google Scholar 

  84. Greenberg SM, Nandigam RN, Delgado P, et al. Microbleeds versus macrobleeds: evidence for distinct entities. Stroke. 2009;40:2382–6.

    PubMed Central  Google Scholar 

  85. Cordonnier C, Al-Shahi Salman R, Wardlaw J. Spontaneous brain microbleeds: systematic review, subgroup analyses and standards for study design and reporting. Brain. 2007;130:1988–2003.

    Google Scholar 

  86. Wang Z, Soo YO, Mok VC. Cerebral microbleeds: is antithrombotic therapy safe to administer? Stroke. 2014;45:2811–7.

    Google Scholar 

  87. Greenberg SM, Vonsattel JP, Stakes JW, Gruber M, Finklestein SP. The clinical spectrum of cerebral amyloid angiopathy: presentations without lobar hemorrhage. Neurology. 1993;43:2073–9.

    CAS  Google Scholar 

  88. Hirohata M, Yoshita M, Ishida C, et al. Clinical features of non-hypertensive lobar intracerebral hemorrhage related to cerebral amyloid angiopathy. Eur J Neurol. 2010;17:823–9.

    CAS  Google Scholar 

  89. Cordonnier C, Leys D, Dumont F, et al. What are the causes of pre-existing dementia in patients with intracerebral haemorrhages? Brain. 2010;133:3281–9.

    Google Scholar 

  90. Bekelis K, Desai A, Zhao W, et al. Computed tomography angiography: improving diagnostic yield and cost effectiveness in the initial evaluation of spontaneous nonsubarachnoid intracerebral hemorrhage. J Neurosurg. 2012;117:761–6.

    Google Scholar 

  91. van Asch CJ, Velthuis BK, Rinkel GJ, et al. Diagnostic yield and accuracy of CT angiography, MR angiography, and digital subtraction angiography for detection of macrovascular causes of intracerebral haemorrhage: prospective, multicentre cohort study. BMJ. 2015;351:h5762.

    PubMed Central  Google Scholar 

  92. Gazzola S, Aviv RI, Gladstone DJ, et al. Vascular and nonvascular mimics of the CT angiography “spot sign” in patients with secondary intracerebral hemorrhage. Stroke. 2008;39:1177–83.

    Google Scholar 

  93. Molshatzki N, Orion D, Tsabari R, et al. Chronic kidney disease in patients with acute intracerebral hemorrhage: association with large hematoma volume and poor outcome. Cerebrovasc Dis. 2011;31:271–7.

    Google Scholar 

  94. Webb AJ, Ullman NL, Morgan TC, et al. Accuracy of the ABC/2 score for intracerebral hemorrhage: systematic review and analysis of MISTIE, CLEAR-IVH, and CLEAR III. Stroke. 2015;46:2470–6.

    PubMed Central  Google Scholar 

  95. Pedraza S, Puig J, Blasco G, et al. Reliability of the ABC/2 method in determining acute infarct volume. J Neuroimaging. 2012;22:155–9.

    Google Scholar 

  96. Scherer M, Cordes J, Younsi A, et al. Development and validation of an automatic segmentation algorithm for quantification of intracerebral hemorrhage. Stroke. 2016;47:2776–82.

    CAS  Google Scholar 

  97. Li Q, Zhang G, Huang YJ, et al. Blend sign on computed tomography: novel and reliable predictor for early hematoma growth in patients with intracerebral hemorrhage. Stroke. 2015;46:2119–23.

    Google Scholar 

  98. Li Q, Zhang G, Xiong X, et al. Black hole sign: novel imaging marker that predicts hematoma growth in patients with intracerebral hemorrhage. Stroke. 2016;47:1777–81.

    Google Scholar 

  99. Macellari F, Paciaroni M, Agnelli G, Caso V. Neuroimaging in intracerebral hemorrhage. Stroke. 2014;45:903–8.

    Google Scholar 

  100. Yoon DY, Chang SK, Choi CS, Kim WK, Lee JH. Multidetector row CT angiography in spontaneous lobar intracerebral hemorrhage: a prospective comparison with conventional angiography. AJNR Am J Neuroradiol. 2009;30:962–7.

    CAS  PubMed Central  Google Scholar 

  101. Wong GK, Siu DY, Abrigo JM, et al. Computed tomographic angiography and venography for young or nonhypertensive patients with acute spontaneous intracerebral hemorrhage. Stroke. 2011;42:211–3.

    Google Scholar 

  102. Wada R, Aviv RI, Fox AJ, et al. CT angiography “spot sign” predicts hematoma expansion in acute intracerebral hemorrhage. Stroke. 2007;38:1257–62.

    Google Scholar 

  103. Brott T, Broderick J, Kothari R, et al. Early hemorrhage growth in patients with intracerebral hemorrhage. Stroke. 1997;28:1–5.

    CAS  Google Scholar 

  104. Demchuk AM, Dowlatshahi D, Rodriguez-Luna D, et al. Prediction of haematoma growth and outcome in patients with intracerebral haemorrhage using the CT-angiography spot sign (PREDICT): a prospective observational study. Lancet Neurol. 2012;11:307–14.

    Google Scholar 

  105. Delgado Almandoz JE, Yoo AJ, Stone MJ, et al. The spot sign score in primary intracerebral hemorrhage identifies patients at highest risk of in-hospital mortality and poor outcome among survivors. Stroke. 2010;41:54–60.

    Google Scholar 

  106. Dowlatshahi D, Brouwers HB, Demchuk AM, et al. Predicting intracerebral hemorrhage growth with the spot sign: the effect of onset-to-scan time. Stroke. 2016;47:695–700.

    CAS  PubMed Central  Google Scholar 

  107. Kamel H, Navi BB, Hemphill JC 3rd. A rule to identify patients who require magnetic resonance imaging after intracerebral hemorrhage. Neurocrit Care. 2013;18:59–63.

    Google Scholar 

  108. Wintermark M, Fiebach J. Imaging of brain parenchyma in stroke. Handb Clin Neurol. 2009;94:1011–9.

    Google Scholar 

  109. Fiebach JB, Schellinger PD, Gass A, et al. Stroke magnetic resonance imaging is accurate in hyperacute intracerebral hemorrhage: a multicenter study on the validity of stroke imaging. Stroke. 2004;35:502–6.

    Google Scholar 

  110. Schindlbeck KA, Santaella A, Galinovic I, et al. Spot sign in acute intracerebral hemorrhage in dynamic T1-weighted magnetic resonance imaging. Stroke. 2016;47:417–23.

    Google Scholar 

  111. Jeon SB, Kang DW, Cho AH, et al. Initial microbleeds at MR imaging can predict recurrent intracerebral hemorrhage. J Neurol. 2007;254:508–12.

    Google Scholar 

  112. Wilson D, Adams ME, Robertson F, Murphy M, Werring DJ. Investigating intracerebral haemorrhage. BMJ. 2015;350:h2484.

    Google Scholar 

  113. Delgado Almandoz JE, Schaefer PW, Goldstein JN, et al. Practical scoring system for the identification of patients with intracerebral hemorrhage at highest risk of harboring an underlying vascular etiology: the Secondary Intracerebral Hemorrhage Score. AJNR Am J Neuroradiol. 2010;31:1653–60.

    CAS  PubMed Central  Google Scholar 

  114. Kadkhodayan Y, Delgado Almandoz JE, Kelly JE, et al. Yield of catheter angiography in patients with intracerebral hemorrhage with and without intraventricular extension. J Neurointerv Surg. 2012;4:358–63.

    Google Scholar 

  115. Hino A, Fujimoto M, Yamaki T, Iwamoto Y, Katsumori T. Value of repeat angiography in patients with spontaneous subcortical hemorrhage. Stroke. 1998;29:2517–21.

    CAS  Google Scholar 

  116. Qureshi AI, Safdar K, Weil J, et al. Predictors of early deterioration and mortality in black Americans with spontaneous intracerebral hemorrhage. Stroke. 1995;26:1764–7.

    CAS  Google Scholar 

  117. Gujjar AR, Deibert E, Manno EM, Duff S, Diringer MN. Mechanical ventilation for ischemic stroke and intracerebral hemorrhage: indications, timing, and outcome. Neurology. 1998;51:447–51.

    CAS  Google Scholar 

  118. Sykora M, Schönenberger S, Bösel S. Critical care of the patient with acute stroke. In: Grotta JC, Albers GW, Broderick JP, et al., editors. Stroke: pathophysiology, diagnosis and management. 6th ed. Philadelphia: Elsevier; 2016. p. 885–915.

    Google Scholar 

  119. Gensic A, Pancioli A. Prehospital and emergency department care of the patient with acute stroke. In: Grotta JC, Albers GW, Broderick JP, et al., editors. Stroke: pathophysiology, diagnosis and management. 6th ed. Philadelphia: Elsevier; 2016. p. 809–25.

    Google Scholar 

  120. Stroke Unit Trialists’ Collaboration. Organised inpatient (stroke unit) care for stroke. Cochrane Database Syst Rev. 2013;9:CD000197.

    Google Scholar 

  121. Mohr JP, Caplan LR, Melski JW, et al. The Harvard Cooperative Stroke Registry: a prospective registry. Neurology. 1978;28:754–62.

    CAS  Google Scholar 

  122. Butcher KS, Jeerakathil T, Hill M, et al. The intracerebral hemorrhage acutely decreasing arterial pressure trial. Stroke. 2013;44:620–6.

    Google Scholar 

  123. Chan E, Anderson CS, Wang X, et al. Early blood pressure lowering does not reduce growth of intraventricular hemorrhage following acute intracerebral hemorrhage: results of the INTERACT studies. Cerebrovasc Dis Extra. 2016;6:71–5.

    PubMed Central  Google Scholar 

  124. Vemmos KN, Tsivgoulis G, Spengos K, et al. U-shaped relationship between mortality and admission blood pressure in patients with acute stroke. J Intern Med. 2004;255:257–65.

    CAS  Google Scholar 

  125. Gilmore EJ, Maciel CB, Hirsch LJ, Sheth KN. Review of the utility of prophylactic anticonvulsant use in critically ill patients with intracerebral hemorrhage. Stroke. 2016;47:2666–72.

    Google Scholar 

  126. Bladin CF, Alexandrov AV, Bellavance A, et al. Seizures after stroke: a prospective multicenter study. Arch Neurol. 2000;57:1617–22.

    CAS  Google Scholar 

  127. Szaflarski JP, Rackley AY, Kleindorfer DO, et al. Incidence of seizures in the acute phase of stroke: a population-based study. Epilepsia. 2008;49:974–81.

    PubMed Central  Google Scholar 

  128. De Reuck J, Hemelsoet D, Van Maele G. Seizures and epilepsy in patients with a spontaneous intracerebral haematoma. Clin Neurol Neurosurg. 2007;109:501–4.

    Google Scholar 

  129. De Herdt V, Dumont F, Henon H, et al. Early seizures in intracerebral hemorrhage: incidence, associated factors, and outcome. Neurology. 2011;77:1794–800.

    Google Scholar 

  130. Claassen J, Jette N, Chum F, et al. Electrographic seizures and periodic discharges after intracerebral hemorrhage. Neurology. 2007;69:1356–65.

    CAS  Google Scholar 

  131. Vespa PM, O’Phelan K, Shah M, et al. Acute seizures after intracerebral hemorrhage: a factor in progressive midline shift and outcome. Neurology. 2003;60:1441–6.

    CAS  Google Scholar 

  132. Mecarelli O, Pro S, Randi F, et al. EEG patterns and epileptic seizures in acute phase stroke. Cerebrovasc Dis. 2011;31:191–8.

    CAS  Google Scholar 

  133. Fisher RS, Acevedo C, Arzimanoglou A, et al. ILAE official report: a practical clinical definition of epilepsy. Epilepsia. 2014;55:475–82.

    Google Scholar 

  134. Krakow K, Sitzer M, Rosenow F, Steinmetz H, Foerch C, Arbeitsgruppe Schlaganfall H. Predictors of acute poststroke seizures. Cerebrovasc Dis. 2010;30:584–9.

    Google Scholar 

  135. Szaflarski JP, Sangha KS, Lindsell CJ, Shutter LA. Prospective, randomized, single-blinded comparative trial of intravenous levetiracetam versus phenytoin for seizure prophylaxis. Neurocrit Care. 2010;12:165–72.

    CAS  Google Scholar 

  136. Szaflarski JP, Meckler JM, Szaflarski M, Shutter LA, Privitera MD, Yates SL. Levetiracetam use in critically ill patients. Neurocrit Care. 2007;7:140–7.

    Google Scholar 

  137. Taylor S, Heinrichs RJ, Janzen JM, Ehtisham A. Levetiracetam is associated with improved cognitive outcome for patients with intracranial hemorrhage. Neurocrit Care. 2011;15:80–4.

    CAS  Google Scholar 

  138. Messe SR, Sansing LH, Cucchiara BL, et al. Prophylactic antiepileptic drug use is associated with poor outcome following ICH. Neurocrit Care. 2009;11:38–44.

    CAS  Google Scholar 

  139. Consoli D, Bosco D, Postorino P, et al. Levetiracetam versus carbamazepine in patients with late poststroke seizures: a multicenter prospective randomized open-label study (EpIC Project). Cerebrovasc Dis. 2012;34:282–9.

    CAS  Google Scholar 

  140. Klein P, Herr D, Pearl PL, et al. Results of phase 2 safety and feasibility study of treatment with levetiracetam for prevention of posttraumatic epilepsy. Arch Neurol. 2012;69:1290–5.

    PubMed Central  Google Scholar 

  141. Naidech AM, Garg RK, Liebling S, et al. Anticonvulsant use and outcomes after intracerebral hemorrhage. Stroke. 2009;40:3810–5.

    CAS  Google Scholar 

  142. Sheth KN, Martini SR, Moomaw CJ, et al. Prophylactic antiepileptic drug use and outcome in the ethnic/racial variations of intracerebral hemorrhage study. Stroke. 2015;46:3532–5.

    CAS  PubMed Central  Google Scholar 

  143. Kamel H, Hemphill JC 3rd. Characteristics and sequelae of intracranial hypertension after intracerebral hemorrhage. Neurocrit Care. 2012;17:172–6.

    CAS  Google Scholar 

  144. Fernandes HM, Siddique S, Banister K, et al. Continuous monitoring of ICP and CPP following ICH and its relationship to clinical, radiological and surgical parameters. Acta Neurochir Suppl. 2000;76:463–6.

    CAS  Google Scholar 

  145. American Heart Association News. Head position after stroke: up or down? American Heart Association: Houston, TX; 2017.

    Google Scholar 

  146. Rincon F, Mayer SA. Clinical review: critical care management of spontaneous intracerebral hemorrhage. Crit Care. 2008;12:237.

    PubMed Central  Google Scholar 

  147. Passero S, Ciacci G, Ulivelli M. The influence of diabetes and hyperglycemia on clinical course after intracerebral hemorrhage. Neurology. 2003;61:1351–6.

    Google Scholar 

  148. Qureshi AI, Geocadin RG, Suarez JI, Ulatowski JA. Long-term outcome after medical reversal of transtentorial herniation in patients with supratentorial mass lesions. Crit Care Med. 2000;28:1556–64.

    CAS  Google Scholar 

  149. Kamel H, Navi BB, Nakagawa K, Hemphill JC 3rd, Ko NU. Hypertonic saline versus mannitol for the treatment of elevated intracranial pressure: a meta-analysis of randomized clinical trials. Crit Care Med. 2011;39:554–9.

    CAS  Google Scholar 

  150. Wei JW, Huang Y, Wang JG, et al. Current management of intracerebral haemorrhage in China: a national, multi-centre, hospital register study. BMC Neurol. 2011;11:16.

    PubMed Central  Google Scholar 

  151. Kalita J, Misra UK, Ranjan P. Prescribing pattern of antiedema therapy in stroke by neurologists and general physicians. Neurol India. 2004;52:191–3.

    CAS  Google Scholar 

  152. Misra UK, Kalita J, Ranjan P, Mandal SK. Mannitol in intracerebral hemorrhage: a randomized controlled study. J Neurol Sci. 2005;234:41–5.

    CAS  Google Scholar 

  153. Kalita J, Misra UK, Ranjan P, Pradhan PK, Das BK. Effect of mannitol on regional cerebral blood flow in patients with intracerebral hemorrhage. J Neurol Sci. 2004;224:19–22.

    CAS  Google Scholar 

  154. Wang X, Arima H, Yang J, et al. Mannitol and outcome in intracerebral hemorrhage: propensity score and multivariable intensive blood pressure reduction in acute cerebral hemorrhage trial 2 results. Stroke. 2015;46:2762–7.

    CAS  Google Scholar 

  155. Staykov D, Wagner I, Volbers B, Doerfler A, Schwab S, Kollmar R. Mild prolonged hypothermia for large intracerebral hemorrhage. Neurocrit Care. 2013;18:178–83.

    Google Scholar 

  156. Han Y, Sheng K, Su M, Yang N, Wan D. Local mild hypothermia therapy as an augmentation strategy for minimally invasive surgery of hypertensive intracerebral hemorrhage: a meta-analysis of randomized clinical trials. Neuropsychiatr Dis Treat. 2017;13:41–9.

    Google Scholar 

  157. Poungvarin N, Bhoopat W, Viriyavejakul A, et al. Effects of dexamethasone in primary supratentorial intracerebral hemorrhage. N Engl J Med. 1987;316:1229–33.

    CAS  Google Scholar 

  158. Kuramatsu JB, Bobinger T, Volbers B, et al. Hyponatremia is an independent predictor of in-hospital mortality in spontaneous intracerebral hemorrhage. Stroke. 2014;45:1285–91.

    Google Scholar 

  159. Gray JR, Morbitzer KA, Liu-DeRyke X, Parker D, Zimmerman LH, Rhoney DH. Hyponatremia in patients with spontaneous intracerebral hemorrhage. J Clin Med. 2014;3:1322–32.

    Google Scholar 

  160. Carcel C, Sato S, Zheng D, et al. Prognostic significance of hyponatremia in acute intracerebral hemorrhage: pooled analysis of the intensive blood pressure reduction in acute cerebral hemorrhage trial studies. Crit Care Med. 2016;44:1388–94.

    CAS  Google Scholar 

  161. Kalita J, Singh RK, Misra UK. Cerebral salt wasting is the most common cause of hyponatremia in stroke. J Stroke Cerebrovasc Dis. 2017;26(5):1026–32.

    Google Scholar 

  162. Broderick JP, Brott TG, Duldner JE, Tomsick T, Huster G. Volume of intracerebral hemorrhage. A powerful and easy-to-use predictor of 30-day mortality. Stroke. 1993;24:987–93.

    CAS  Google Scholar 

  163. Mendelow AD, Gregson BA, Fernandes HM, et al. Early surgery versus initial conservative treatment in patients with spontaneous supratentorial intracerebral haematomas in the International Surgical Trial in Intracerebral Haemorrhage (STICH): a randomised trial. Lancet. 2005;365:387–97.

    Google Scholar 

  164. Mendelow AD, Gregson BA, Rowan EN, et al. Early surgery versus initial conservative treatment in patients with spontaneous supratentorial lobar intracerebral haematomas (STICH II): a randomised trial. Lancet. 2013;382:397–408.

    PubMed Central  Google Scholar 

  165. Mendelow AD, Gregson BA, Rowan EN, et al. Early surgery versus initial conservative treatment in patients with traumatic intracerebral hemorrhage (STITCH[Trauma]): the first randomized trial. J Neurotrauma. 2015;32:1312–23.

    PubMed Central  Google Scholar 

  166. Gautschi OP, Schaller K. Surgery or conservative therapy for cerebral haemorrhage? Lancet. 2013;382:377–8.

    Google Scholar 

  167. Zhou X, Chen J, Li Q, et al. Minimally invasive surgery for spontaneous supratentorial intracerebral hemorrhage: a meta-analysis of randomized controlled trials. Stroke. 2012;43:2923–30.

    Google Scholar 

  168. Mould WA, Carhuapoma JR, Muschelli J, et al. Minimally invasive surgery plus recombinant tissue-type plasminogen activator for intracerebral hemorrhage evacuation decreases perihematomal edema. Stroke. 2013;44:627–34.

    CAS  PubMed Central  Google Scholar 

  169. Vespa P, Hanley D, Betz J, et al. ICES (Intraoperative Stereotactic Computed Tomography-Guided Endoscopic Surgery) for brain hemorrhage: a multicenter randomized controlled trial. Stroke. 2016;47:2749–55.

    PubMed Central  Google Scholar 

  170. Spiotta AM, Fiorella D, Vargas J, et al. Initial multicenter technical experience with the Apollo device for minimally invasive intracerebral hematoma evacuation. Neurosurgery. 2015;11(Suppl 2):243–51; discussion 51.

    Google Scholar 

  171. Da Pian R, Bazzan A, Pasqualin A. Surgical versus medical treatment of spontaneous posterior fossa haematomas: a cooperative study on 205 cases. Neurol Res. 1984;6:145–51.

    Google Scholar 

  172. van Loon J, Van Calenbergh F, Goffin J, Plets C. Controversies in the management of spontaneous cerebellar haemorrhage. A consecutive series of 49 cases and review of the literature. Acta Neurochir. 1993;122:187–93.

    Google Scholar 

  173. Leira R, Davalos A, Silva Y, et al. Early neurologic deterioration in intracerebral hemorrhage: predictors and associated factors. Neurology. 2004;63:461–7.

    CAS  Google Scholar 

  174. Chan E, Anderson CS, Wang X, et al. Significance of intraventricular hemorrhage in acute intracerebral hemorrhage: intensive blood pressure reduction in acute cerebral hemorrhage trial results. Stroke. 2015;46:653–8.

    Google Scholar 

  175. Huttner HB, Kohrmann M, Berger C, Georgiadis D, Schwab S. Influence of intraventricular hemorrhage and occlusive hydrocephalus on the long-term outcome of treated patients with basal ganglia hemorrhage: a case-control study. J Neurosurg. 2006;105:412–7.

    Google Scholar 

  176. Hanley DF, Lane K, McBee N, et al. Thrombolytic removal of intraventricular haemorrhage in treatment of severe stroke: results of the randomised, multicentre, multiregion, placebo-controlled CLEAR III trial. Lancet. 2017;389:603–11.

    CAS  PubMed Central  Google Scholar 

  177. Chen CC, Liu CL, Tung YN, et al. Endoscopic surgery for intraventricular hemorrhage (IVH) caused by thalamic hemorrhage: comparisons of endoscopic surgery and external ventricular drainage (EVD) surgery. World Neurosurg. 2011;75:264–8.

    Google Scholar 

  178. Fiorella D, Gutman F, Woo H, Arthur A, Aranguren R, Davis R. Minimally invasive evacuation of parenchymal and ventricular hemorrhage using the Apollo system with simultaneous neuronavigation, neuroendoscopy and active monitoring with cone beam CT. J Neurointerv Surg. 2015;7:752–7.

    Google Scholar 

  179. Meyer-Heim AD, Boltshauser E. Spontaneous intracranial haemorrhage in children: aetiology, presentation and outcome. Brain Dev. 2003;25:416–21.

    Google Scholar 

  180. Srinivasan VM, Gressot LV, Daniels BS, Jones JY, Jea A, Lam S. Management of intracerebral hemorrhage in pediatric neurosurgery. Surg Neurol Int. 2016;7:S1121–S6.

    PubMed Central  Google Scholar 

  181. Huhtakangas J, Tetri S, Juvela S, Saloheimo P, Bode MK, Hillbom M. Effect of increased warfarin use on warfarin-related cerebral hemorrhage: a longitudinal population-based study. Stroke. 2011;42:2431–5.

    CAS  Google Scholar 

  182. Nilsson OG, Lindgren A, Stahl N, Brandt L, Saveland H. Incidence of intracerebral and subarachnoid haemorrhage in southern Sweden. J Neurol Neurosurg Psychiatry. 2000;69:601–7.

    CAS  PubMed Central  Google Scholar 

  183. Sjoblom L, Hardemark HG, Lindgren A, et al. Management and prognostic features of intracerebral hemorrhage during anticoagulant therapy: a Swedish multicenter study. Stroke. 2001;32:2567–74.

    CAS  Google Scholar 

  184. Flibotte JJ, Hagan N, O’Donnell J, Greenberg SM, Rosand J. Warfarin, hematoma expansion, and outcome of intracerebral hemorrhage. Neurology. 2004;63:1059–64.

    CAS  Google Scholar 

  185. Frontera JA, Lewin JJ 3rd, Rabinstein AA, 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.

    CAS  Google Scholar 

  186. de Oliveira Manoel AL, Goffi A, Zampieri FG, et al. The critical care management of spontaneous intracranial hemorrhage: a contemporary review. Crit Care. 2016;20:272.

    PubMed Central  Google Scholar 

  187. Holbrook A, Schulman S, Witt DM, et al. Evidence-based management of anticoagulant therapy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141:e152S–84S.

    CAS  PubMed Central  Google Scholar 

  188. Dentali F, Ageno W, Crowther M. Treatment of coumarin-associated coagulopathy: a systematic review and proposed treatment algorithms. J Thromb Haemost. 2006;4:1853–63.

    CAS  Google Scholar 

  189. Goldstein JN, Thomas SH, Frontiero V, et al. Timing of fresh frozen plasma administration and rapid correction of coagulopathy in warfarin-related intracerebral hemorrhage. Stroke. 2006;37:151–5.

    Google Scholar 

  190. Boulis NM, Bobek MP, Schmaier A, Hoff JT. Use of factor IX complex in warfarin-related intracranial hemorrhage. Neurosurgery. 1999;45:1113–8; discussion 8–9.

    CAS  Google Scholar 

  191. Huttner HB, Schellinger PD, Hartmann M, et al. Hematoma growth and outcome in treated neurocritical care patients with intracerebral hemorrhage related to oral anticoagulant therapy: comparison of acute treatment strategies using vitamin K, fresh frozen plasma, and prothrombin complex concentrates. Stroke. 2006;37:1465–70.

    CAS  Google Scholar 

  192. Awad NI, Cocchio C. Activated prothrombin complex concentrates for the reversal of anticoagulant-associated coagulopathy. P T. 2013;38:696–701.

    PubMed Central  Google Scholar 

  193. Tanaka KA, Szlam F, Dickneite G, Levy JH. Effects of prothrombin complex concentrate and recombinant activated factor VII on vitamin K antagonist induced anticoagulation. Thromb Res. 2008;122:117–23.

    CAS  Google Scholar 

  194. Rosovsky RP, Crowther MA. What is the evidence for the off-label use of recombinant factor VIIa (rFVIIa) in the acute reversal of warfarin? ASH evidence-based review 2008. Hematology Am Soc Hematol Educ Program. 2008:36–8. https://doi.org/10.1182/asheducation-2008.1.36.

  195. Mayer SA, Brun NC, Begtrup K, et al. Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med. 2008;358:2127–37.

    CAS  Google Scholar 

  196. Chatterjee S, Sardar P, Biondi-Zoccai G, Kumbhani DJ. New oral anticoagulants and the risk of intracranial hemorrhage: traditional and Bayesian meta-analysis and mixed treatment comparison of randomized trials of new oral anticoagulants in atrial fibrillation. JAMA Neurol. 2013;70:1486–90.

    Google Scholar 

  197. Tran H, Joseph J, Young L, et al. New oral anticoagulants: a practical guide on prescription, laboratory testing and peri-procedural/bleeding management. Australasian Society of Thrombosis and Haemostasis. Intern Med J. 2014;44:525–36.

    CAS  Google Scholar 

  198. Connolly SJ, Milling TJ Jr, Eikelboom JW, et al. Andexanet alfa for acute major bleeding associated with factor Xa inhibitors. N Engl J Med. 2016;375:1131–41.

    CAS  PubMed Central  Google Scholar 

  199. Stangier J, Rathgen K, Stahle H, Mazur D. Influence of renal impairment on the pharmacokinetics and pharmacodynamics of oral dabigatran etexilate: an open-label, parallel-group, single-centre study. Clin Pharmacokinet. 2010;49:259–68.

    CAS  Google Scholar 

  200. Marlu R, Hodaj E, Paris A, Albaladejo P, Cracowski JL, Pernod G. Effect of non-specific reversal agents on anticoagulant activity of dabigatran and rivaroxaban: a randomised crossover ex vivo study in healthy volunteers. Thromb Haemost. 2012;108:217–24.

    CAS  Google Scholar 

  201. Eerenberg ES, Kamphuisen PW, Sijpkens MK, Meijers JC, Buller HR, Levi M. Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a randomized, placebo-controlled, crossover study in healthy subjects. Circulation. 2011;124:1573–9.

    CAS  Google Scholar 

  202. Wang X, Mondal S, Wang J, et al. Effect of activated charcoal on apixaban pharmacokinetics in healthy subjects. Am J Cardiovasc Drugs. 2014;14:147–54.

    Google Scholar 

  203. Majeed A, Kim YK, Roberts RS, Holmstrom M, Schulman S. Optimal timing of resumption of warfarin after intracranial hemorrhage. Stroke. 2010;41:2860–6.

    CAS  Google Scholar 

  204. Antithrombotic Trialists C, Baigent C, Blackwell L, et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet. 2009;373:1849–60.

    Google Scholar 

  205. Lovelock CE, Molyneux AJ, Rothwell PM, Oxford Vascular S. Change in incidence and aetiology of intracerebral haemorrhage in Oxfordshire, UK, between 1981 and 2006: a population-based study. Lancet Neurol. 2007;6:487–93.

    CAS  Google Scholar 

  206. Thompson BB, Bejot Y, Caso V, et al. Prior antiplatelet therapy and outcome following intracerebral hemorrhage: a systematic review. Neurology. 2010;75:1333–42.

    CAS  PubMed Central  Google Scholar 

  207. 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;40:2398–401.

    Google Scholar 

  208. Baharoglu MI, Cordonnier C, Al-Shahi Salman R, 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;387:2605–13.

    Google Scholar 

  209. Naidech AM, Maas MB, Levasseur-Franklin KE, et al. Desmopressin improves platelet activity in acute intracerebral hemorrhage. Stroke. 2014;45:2451–3.

    CAS  PubMed Central  Google Scholar 

  210. Kapapa T, Rohrer S, Struve S, et al. Desmopressin acetate in intracranial haemorrhage. Neurol Res Int. 2014;2014:298767.

    PubMed Central  Google Scholar 

  211. Galbusera M, Remuzzi G, Boccardo P. Treatment of bleeding in dialysis patients. Semin Dial. 2009;22:279–86.

    Google Scholar 

  212. Fullerton HJ, YW W, Zhao S, Johnston SC. Risk of stroke in children: ethnic and gender disparities. Neurology. 2003;61:189–94.

    Google Scholar 

  213. Lo WD, Lee J, Rusin J, Perkins E, Roach ES. Intracranial hemorrhage in children: an evolving spectrum. Arch Neurol. 2008;65:1629–33.

    Google Scholar 

  214. Jordan LC, Hillis AE. Hemorrhagic stroke in children. Pediatr Neurol. 2007;36:73–80.

    Google Scholar 

  215. Al-Jarallah A, Al-Rifai MT, Riela AR, Roach ES. Nontraumatic brain hemorrhage in children: etiology and presentation. J Child Neurol. 2000;15:284–9.

    CAS  Google Scholar 

  216. Abbas Q, Merchant QU, Nasir B, Haque AU, Salam B, Javed G. Spectrum of intracerebral hemorrhage in children: a report from PICU of a Resource Limited Country. Crit Care Res Pract. 2016;2016:9124245.

    PubMed Central  Google Scholar 

  217. Beslow LA, Ichord RN, Gindville MC, et al. Pediatric intracerebral hemorrhage score: a simple grading scale for intracerebral hemorrhage in children. Stroke. 2014;45:66–70.

    Google Scholar 

  218. Lynch JK, Han CJ. Pediatric stroke: what do we know and what do we need to know? Semin Neurol. 2005;25:410–23.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Neurosurgery, Neurology and Radiology, University of Alabama at Birmingham, Birmingham, Alabama, USA

    Mark R. Harrigan

  2. Department of Neurosurgery and Radiology, University of Alabama at Birmingham, Birmingham, Alabama, USA

    John P. Deveikis

Authors
  1. Mark R. Harrigan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. John P. Deveikis
    View author publications

    You can also search for this author in PubMed Google Scholar

Appendix 17.1: Essential Reversal Techniques

Appendix 17.1: Essential Reversal Techniques

Summary of eliminations, removals, and reversals of common anticoagulants and thrombolyticsa

Drug

Elimination half-life (T1/2)

Removal by hemodialysis (HD)?

Reversal approach

Direct factor Xa inhibitors, oral

Apixaban (Eliquis®)

– 12 h (range 7–15)

No

– Activated charcoal:

– Prolonged in renal impairment

 • Apixaban—In healthy subjects administered 2–6 h after ingestion of a 20 mg dose reduced AUC by 50% and 27%, respectively

Edoxaban (Savaysa®)

– 10–14 h

 • Edoxaban—no information available; could likely be considered if within a few hours of dose

– Prolonged in renal impairment

 • Rivaroxaban—may be considered

Rivaroxaban (Xarelto®)

– Healthy: 5–9 h

– Prothrombin Complex Concentrates (PCCs):

– Elderly: 11–13 h

 • There is insufficient data to recommend use, but may be reasonable approach in dire clinical situations

– Prolonged in renal impairment

 • Options: KCentra 50 U/kg (maximum dose of 5000 units) or activated PCC (FEIBA) 50 U/kg

– Anti-Xa lab assay only useful for detecting presence of drug and cannot be used to accurately quantitate the level of anticoagulation

Factor Xa inhibitors, parenteral

Fondaparinux (Arixtra®)

– 17–21 h

Unlikely to be of value

– For uncontrollable bleeding:

– Prolonged in renal impairment

 • Consider rFVIIa (Novoseven®) 90 mcg/kg

– Anti-Xa lab assay (specific to fondaparinux)

Direct thrombin inhibitors, oral

Dabigatran (Pradaxa®)

– 12–17 h

Yes: ~60% Likely rebound upon cessation

– Activated charcoal:

– Significantly prolonged in renal impairment

 • May be considered if 1–2 h after ingestion

– Specific reversal agent:

 • Idarucizumab (Praxbind®) 5 grams IV × 1 (supplied as two separate 2.5 gram vials)

   Although data is limited, can consider re-dosing at 5 grams for refractory bleeding

– Consider HD for patients with refractory bleeding or especially in those with impaired renal function

– Thrombin time can be used to assess presence of drug in circulation

Direct thrombin inhibitors, parenteral

Bivalirudin (Angiomax®)

– 25 min

Yes: 25%; HD is generally not practical

– Turn off the infusion

– Significantly prolonged in renal impairment

– aPTT lab assay is used to assess the degree of anticoagulation

Argatroban

– 30–51 min

Yes: 20%; HD is generally not practical

– No specific reversal agent available and no factor product administration recommended

– Prolonged in hepatic impairment

Heparins/low molecular weight heparins (LMWH)

Enoxaparin (Lovenox®)

– 4.5–7 h

Unlikely to be of value

– Protamine partially neutralizes anti-Xa activity (~60%)

– Prolonged in renal impairment

Time since last dose

Dose of protamine for each 1 mg of enoxaparin or 100 units of dalteparin

Dalteparin (Fragmin®)

– 3–5 h

≤ 8 h

1 mg

Maximum of 50 mg in 10 min period

– Prolonged in renal impairment

8–12 h

0.5 mg

>12 h

Not likely to be useful

Unfractionated heparin

– ~1.5 h

No

– Protamine provides rapid reversal of anticoagulant effects (measured by aPTT or anti-Xa activity)

 • Only heparin given in the preceding several hours needs to be considered when calculating dose of protamine (e.g. the previous 2–2.5 h if given as continuous infusion)

Time since last dose

Dose of protamine for each 100 units of heparin

Immediate

1 mg

Maximum of 50 mg in a 10 min period

30 min—2 h

0.5 mg

>2 h

0.25 mg

Vitamin K antagonists

Warfarin (Coumadin®)

 –~ 1 week

No

– Any major/life-threatening bleeding

 • 4-factor PCC (KCentra) AND Vitamin K 10 mg by slow IV injection (mixed in minimum 50 mL and given over at a rate not exceeding 1 mg/min)

Pretreatment INRb

KCentra dose

2 to <4

25 units/kg (Maximum 2500 units)

4–6

35 units/kg (Maximum 3500 units)

>6

50 units/kg (Maximum 5000 units)

– INR > 4.5 and no evidence of bleeding: Vitamin K PO 1–2.5 mg

– Minor bleeding: Vitamin K PO 2.5–5 mg (with possible repeat dose at 24 h)

Thrombolytics

Alteplase

– Initial: ~5 min

No

– Discontinue thrombolytic agent

– Following 90 min infusion: 27–46 min

– Thrombolytic-associated symptomatic intracranial hemorrhage

Tenecteplase

– Initial: 20–24 min

 • Consider cryoprecipitate (10 units initial dose) to a goal fibrinogen >150 mg/dL in patients who have received thrombolytic agent in the previous 24 h

– Terminal: 115 min

 • If cryoprecipitate is contraindicated, consider aminocaproic acid 4–5 g IV over 1 h or tranexamic acid 10–15 mg/kg IV over 20 mins

 • Consider platelet transfusion for platelet count <100,000

  1. aThe authors thank Casey C. May, PharmD, for the preparation of this table
  2. bFor emergent reversal of an INR < 2, a typical dose of 15 units/kg may be used
  3. Sources:
  4. 1. Apixaban; Rivaroxaban; Edoxaban; Fondaparinux, Dabigatran; Bivalirudin; Argatroban; Enoxaparin; Dalteparin; Heparin; Alteplase; Tenecteplase; Protamine; Phytonadione; Warfarin. Micromedex Solutions. Truven Health Analytics, Inc. Ann Arbor, MI. Available at: http://www.micromedexsolutions.com. Accessed November 2, 2016.
  5. 2. Apixaban (Eliquis®) [package insert]. Princeton, New Jersey: Bristol-Myers Squibb Company. 2012
  6. 3. Rivaroxaban (Xarelto®) [package insert]. Titusville, New Jersey: Janssen Pharmaceuticals. 2011
  7. 4. Fondaparinux (Arixtra®) [package insert]. Research Triangle Park, NC: GlaxoSmithKline. 2008
  8. 5. Dabigatran (Pradaxa®) [package insert]. Ridgefield, CT. Boehringer Ingelheim Pharmaceuticals, Inc. 2010
  9. 6. Edoxaban (Savaysa®) [package insert]. Tokyo, Japan. Daiichi Sankyo co., LTD 2015
  10. 7. Kcentra [package insert]. Marburg, Germany. CSL Behring GmbH. 2013
  11. 8. FEIBA NF [package insert]. Deerfield, IL. Baxter Healthcare Corporation. 1986
  12. 9. Idarucizumab (Praxbind®) [package insert]. Ridgefield, CT. Boehringer Ingelheim Pharmaceuticals, Inc. 2015
  13. 10. Dzik WH. Reversal of oral factor Xa inhibitors by prothrombin complex concentrates: a re-appraisal [205]
  14. 11. Kaatz S, Kouides PA, Garcia DA, et al. Guidance on the emergent reversal of oral thrombin and factor Xa inhibitors [206]
  15. 12. Bijsterveld NR, Moons AH, Boekholdt SM, et al. Ability of recombinant factor VIIa to reverse the anticoagulant effect of pentasaccharide Fondaparinux in healthy volunteers [207]
  16. 13. Frontera JA, Lewin JJ, Rabinstein AA, et al. Guideline for reversal of antithrombotics in intracranial hemorrhage. A Statement for Healthcare Professionals From the Neurocritical Care Society and the Society of Critical Care Medicine [169]
  17. 14. Holbrook A, Schulman S, Witt DM, et al. Evidence-Based Management of Anticoagulant Therapy. Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines [171]
  18. 15. Garcia DA, Baglin, TP, Weitz JI, Samama MM. Parenteral Anticoagulants. Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines [208]
  19. 16. Ageno W, Gallus AS, Wittkowsky A, et al. Oral anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines [209]
  20. 17. Patriquin C, Crowther M. Treatment of warfarin-associated coagulopathy with vitamin K [210]

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Harrigan, M.R., Deveikis, J.P. (2018). Intracerebral Hemorrhage. In: Handbook of Cerebrovascular Disease and Neurointerventional Technique. Contemporary Medical Imaging. Humana, Cham. https://doi.org/10.1007/978-3-319-66779-9_17

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-66779-9_17

  • Published:

  • Publisher Name: Humana, Cham

  • Print ISBN: 978-3-319-66777-5

  • Online ISBN: 978-3-319-66779-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation