Intracranial Hemorrhage Focused on Cancer and Hemato-Oncologic Patients

  • Yasser Mohamad KhorchidEmail author
  • Marc Malkoff
Living reference work entry


Intracranial hemorrhage (ICH) is the most fatal type of stroke and has the highest rate of disability. It is seen in less than 10% of cancer patients, including known intracranial neoplasms. Intratumoral hemorrhage and coagulopathy are the most common etiologies. ICH most commonly occurs supratentorially, in the cerebral parenchyma. The most common cancers associated with ICH are intracranial metastases, followed by glioblastoma multiforme and hematologic malignancies. Among hemorrhagic metastases, melanoma, lung, and breast cancers are the most common primary tumors. The exact mechanism of intratumoral hemorrhage is unknown, although vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMP) appear to play an important role. Most cancer patients with ICH are symptomatic. Change in mental status, hemiparesis, and headaches are the most common clinical presentations. A non-contrast head computed tomography (CT) scan is the initial diagnostic step if ICH is suspected. There are no specific guidelines for ICH management in cancer patients. Blood pressure needs to be controlled, and coagulopathy has to be corrected. Surgical interventions might be life-saving, especially in large hemorrhages in the posterior fossa. Overall, cancer patients have worse clinical outcomes than the general population when they develop ICH. Patients with coagulopathy have the poorest prognosis.


Intracranial hemorrhage Cancer Brain tumor Glioblastoma multiforme Brain metastases Intratumoral hemorrhage Coagulopathy Thrombocytopenia 


  1. 1.
    Minimally invasive surgery plus Rt-PA for ICH evacuation phase III (MISTIE III). Clinical Trials. gov Identifier: NCT 01827046Google Scholar
  2. 2.
    Abrahams NA, Prayson R. The role of histopathologic examination of intracranial blood clots removed for hemorrhage of unknown etiology: a clinical pathologic analysis of 31 cases. Ann Diagn Pathol. 2000;4:361–6.CrossRefGoogle Scholar
  3. 3.
    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.CrossRefGoogle Scholar
  4. 4.
    Atlas SW, Grossman RI, Gomori JM, et al. Hemorrhagic intracranial malignant neoplasms: spin-echo MR imaging. Radiology. 1987;164:71–7.CrossRefGoogle Scholar
  5. 5.
    Barnholtz-Sloan JS, Sloan A, Davis FG, et al. Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System. J Clin Oncol. 2004;22:2865–72.CrossRefGoogle Scholar
  6. 6.
    Boulouis G, Morotti A, Goldstein JN, Charidimou A. Intensive blood pressure lowering in patients with acute intracerebral haemorrhage: clinical outcomes and haemorrhage expansion systematic review and meta-analysis of randomised trials. J Neurol Neurosurg Psychiatry. 2017;88:339–45.CrossRefGoogle Scholar
  7. 7.
    Brophy GM, Bell R, Claassen J, Neurocritical Care Society Status Epilepticus Guideline Writing Committee, et al. Guidelines for the evaluation and management of status epilepticus. Neurocrit Care. 2012;17:3.CrossRefGoogle Scholar
  8. 8.
    Brouwers HB, Chang Y, Falcone GJ, et al. Predicting hematoma expansion after primary intracerebral hemorrhage. JAMA Neurol. 2014;71:158–64.CrossRefGoogle Scholar
  9. 9.
    Bug G, Anargyrou K, Tonn T, et al. Impact of leukapheresis on early death rate in adult acute myeloid leukemia presenting with hyperleukocytosis. Transfusion. 2007;47:1843–50.CrossRefGoogle Scholar
  10. 10.
    Cao R, Eriksson A, Kubo H, Alitalo K, Cao Y, Thyberg J. Comparative evaluation of FGF-2-, VEGF-A-, and VEGF-C-induced angiogenesis, lymphangiogenesis, vascular fenestrations, and permeability. Circ Res. 2004;94:664–70.CrossRefGoogle Scholar
  11. 11.
    Chang L, Chen Y-L, Kao M-CC. Intracranial metastasis of hepatocellular carcinoma: review of 45 cases. Surg Neurol. 2004;62:172–7.CrossRefGoogle Scholar
  12. 12.
    Chang MC, Chen T, Tang JL, et al. Leukapheresis and cranial irradiation in patients with hyperleukocytic acute myeloid leukemia: no impact on early mortality and intracranial hemorrhage. Am J Hematol. 2007;82:976–80.CrossRefGoogle Scholar
  13. 13.
    Connolly ES Jr, Rabinstein A, Carhuapoma JR, Derdeyn CP, Dion J, Higashida RT, Hoh BL, Kirkness CJ, Naidech AM, Ogilvy CS, Patel AB, Thompson BG, Vespa P, American Heart Association Stroke Council, Council on Cardiovascular Radiology and Intervention, Council on Cardiovascular Nursing, Council on Cardiovascular Surgery and Anesthesia, Council on Clinical Cardiology. Guidelines for the management of aneurysmal subarachnoid hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2012;43:1711–37.CrossRefGoogle Scholar
  14. 14.
    Connolly SJ, Milling TJ, Eikelboom JW, ANNEXA-4 Investigators, et al. Andexanet alfa for acute major bleeding associated with factor Xa inhibitors. N Engl J Med. 2016;375:1131–41.CrossRefGoogle Scholar
  15. 15.
    Coussens LM, Fingleton B, Matrisian LM. Matrix metalloproteinase inhibitors and cancer: trials and tribulations. Science. 2002;295:2387–92.CrossRefGoogle Scholar
  16. 16.
    Croce MA, Dent D, Menke PG, Robertson JT, Hinson MS, Young BH, Donovan TB, Pritchard FE, Minard G, Kudsk KA, et al. Acute subdural hematoma: nonsurgical management of selected patients. J Trauma. 1994;36:820–6.CrossRefGoogle Scholar
  17. 17.
    Dammann P, Asgari S, Bassiouni H, et al. Spontaneous cerebellar hemorrhage: experience with 57 surgically treated patients and review of the literature. Neurosurg Rev. 2011;34:77–86.CrossRefGoogle Scholar
  18. 18.
    Diringer MN, Edwards D. Admission to a neurologic/neurosurgical intensive care unit is associated with reduced mortality rate after intracerebral hemorrhage. Crit Care Med. 2001;29:635–40.CrossRefGoogle Scholar
  19. 19.
    Ducruet AF, Grobelny B, Zacharia BE, Hickman ZL, DeRosa PL, Anderson K, Sussman E, Carpenter A, Connolly ES Jr. The surgical management of chronic subdural hematoma. Neurosurg Rev. 2012;35:155–69.CrossRefGoogle Scholar
  20. 20.
    Fidler IJ. The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited. Nat Rev Cancer. 2003;3:453–8.CrossRefGoogle Scholar
  21. 21.
    Flibotte JJ, Hagan N, O’Donnell J, et al. Warfarin, hematoma expansion, and outcome of intracerebral hemorrhage. Neurology. 2004;63:1059–64.CrossRefGoogle Scholar
  22. 22.
    Freeman WD. Management of intracranial pressure. Continuum (Minneap Minn). 2015;21:1299–323.Google Scholar
  23. 23.
    Golash A, Thorne J, West CG. Low grade pilocytic astrocytoma presenting as a spontaneous intracerebral haemorrhage in a child. Br J Neurosurg. 1998;12:59–62.CrossRefGoogle Scholar
  24. 24.
    Graus F, Rogers L, Posner JB. Cerebrovascular complications in patients with cancer. Medicine (Baltimore). 1985;64:16–35.CrossRefGoogle Scholar
  25. 25.
    Hanley DF, Lane K, McBee N, CLEAR III Investigators, 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.CrossRefGoogle Scholar
  26. 26.
    Hemphill JC 3rd, Greenberg S, Anderson CS, Becker K, Bendok BR, Cushman M, Fung GL, Goldstein JN, Macdonald RL, Mitchell PH, Scott PA, Selim MH, Woo D, American Heart Association Stroke Council, Council on Cardiovascular and Stroke Nursing, Council on Clinical Cardiology. 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.CrossRefGoogle Scholar
  27. 27.
    Jin Kim Y, Hyun Kim C, Hwan Cheong J, Min Kim J. Relationship between expression of vascular endothelial growth factor and intratumoral hemorrhage in human pituitary adenomas. Tumori. 2011;97:639–46.CrossRefGoogle Scholar
  28. 28.
    Joseph DM, O’Neill A, Chandra RV, Lai LT. Glioblastoma presenting as spontaneous intracranial haemorrhage: case report and review of the literature. J Clin Neurosci. 2017;40:1–5.CrossRefGoogle Scholar
  29. 29.
    Jung S, Moon K, Jung TY, Kim IY, Lee YH, Rhu HH, et al. Possible pathophysiological role of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) in metastatic brain tumor-associated intracerebral hemorrhage. J Neuro-Oncol. 2006;76:257–63.CrossRefGoogle Scholar
  30. 30.
    Kamel H, Navi B, Hemphill JC. A rule to identify patients who require magnetic resonance imaging after intracerebral hemorrhage. Neurocrit Care. 2013;18:59–63.CrossRefGoogle Scholar
  31. 31.
    Kondziolka D, Bernstein M, Resch L, et al. Significance of hemorrhage into brain tumors: clinicopathological study. J Neurosurg. 1987;67:852–7.CrossRefGoogle Scholar
  32. 32.
    Kothbauer P, Jellinger K, Falment H. Primary brain tumour presenting as spontaneous intracerebral haemorrhage. Acta Neurochir. 1979;49:35–45.CrossRefGoogle Scholar
  33. 33.
    Laigle-Donadey F, Taillibert S, Mokhtari K, et al. Dural metastases. J Neuro-Oncol. 2005;75:57–61.CrossRefGoogle Scholar
  34. 34.
    Licata B, Turazzi S. Bleeding cerebral neoplasms with symptomatic hematoma. J Neurosurg Sci. 2003;47:201–10.PubMedGoogle Scholar
  35. 35.
    Lieu AS, Hwang S, Howng SL, Chai CY. Brain tumors with hemorrhage. J Formos Med Assoc. 1999;98:365–7.PubMedGoogle Scholar
  36. 36.
    Little JR, Dial B, Bélanger G, Carpenter S. Brain hemorrhage from intracranial tumor. Stroke. 1979;10:283–8.CrossRefGoogle Scholar
  37. 37.
    Liwnicz BH, Wu S, Tew JM Jr. The relationship between the capillary structure and haemorrhage in gliomas. J Neurosurg. 1987;66:536–41.CrossRefGoogle Scholar
  38. 38.
    Maiuri F, D’Andrea F, Gallicchio B, Carandente M. Intracranial haemorrhages in metastatic brain tumours. J Neurosurg Sci. 1985;29:37–41.PubMedGoogle Scholar
  39. 39.
    Mandybur TI. Intracranial hemorrhage caused by metastatic tumors. Neurology (Minneap). 1977;27:650–5.CrossRefGoogle Scholar
  40. 40.
    Marneros AG. Tumor angiogenesis in melanoma. Hematol Oncol Clin North Am. 2009;23:431–46.CrossRefGoogle Scholar
  41. 41.
    Mayer SA, Brun N, Begtrup K, Broderick J, Davis S, Diringer MN, et al. Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med. 2008;358:2127–37.CrossRefGoogle Scholar
  42. 42.
    McCormick WF, Rosenfield D. Massive brain hemorrhage: a review of 144 cases and an examination of their causes. Stroke. 1973;4:946–54.CrossRefGoogle Scholar
  43. 43.
    McIver JI, Scheithauer B, Rydberg CH, et al. Metastatic hepatocellular carcinoma presenting as epidural hematoma: case report. Neurosurgery. 2001;49:447–9.PubMedGoogle Scholar
  44. 44.
    Mendelow AD, Gregson B, 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 Neurol. 2005;365:387–97.CrossRefGoogle Scholar
  45. 45.
    Mendelow AD, Gregson B, Fernanades HM, et al. Early surgery versus initial conservative treatment in patients with spontaneous supratentorial lobar intracerebral haematoma in the international surgical trial in intracerebral hemorrhage (STICH II): a randomised clinical trial. Lancet. 2013;382:397–408.CrossRefGoogle Scholar
  46. 46.
    Minette SE, Kimmel D. Subdural hematoma in patients with systemic cancer. Mayo Clin Proc. 1989;64:637–42.CrossRefGoogle Scholar
  47. 47.
    Murthy SB, Shastri A, Merkler AE, Hanley DF, Ziai WC, Fink ME, Iadecola C, Kamel H, Navi BB. Intracerebral hemorrhage outcomes in patients with systemic cancer. J Stroke Cerebrovasc Dis. 2016;25:2918–24.CrossRefGoogle Scholar
  48. 48.
    Navi BB, Reichman J, Berlin D, Reiner AS, Panageas KS, Segal AZ, DeAngelis LM. Intracerebral and subarachnoid hemorrhage in patients with cancer. Neurology. 2010;74:494–501.CrossRefGoogle Scholar
  49. 49.
    Omofoye OA, Barnett R., Lau W, Trembath D, Jordan JD, Sasaki-Adams DM. Neoplastic cerebral aneurysm from metastatic non-small cell lung carcinoma: case report and literature review. Neurosurgery. 2018;83:E221–25.CrossRefGoogle Scholar
  50. 50.
    Openshaw H, Ressler J, Snyder DS. Lumbar puncture and subdural hygroma and hematomas in hematopoietic cell transplant patients. Bone Marrow Transplant. 2008;41:791–5.CrossRefGoogle Scholar
  51. 51.
    Pantuck AJ, Zeng G, Belldegrun AS, Figlin RA. Pathobiology, prognosis, and targeted therapy for renal cell carcinoma: exploiting the hypoxia-induced pathway. Clin Cancer Res. 2003;9:4641–52.PubMedGoogle Scholar
  52. 52.
    Pollack CV Jr, Reilly P, van Ryn J, et al. Idarucizumab for dabigatran reversal – full cohort analysis. N Engl J Med. 2017;377:431–41.CrossRefGoogle Scholar
  53. 53.
    Qureshi AI, et al. Isolated and borderline isolated systolic hypertension relative to long-term risk and type of stroke: a 20-year follow-up of the national health and nutrition survey. Stroke. 2002;33:2781–8.CrossRefGoogle Scholar
  54. 54.
    Qureshi AI, Palesch Y, Barsan WG, Hanley DF, Hsu CY, Martin RL, Moy CS, Silbergleit R, Steiner T, Suarez JI, Toyoda K, Wang Y, Yamamoto H, Yoon BW, ATACH-2 Trial Investigators and the Neurological Emergency Treatment Trials Network. Intensive blood-pressure lowering in patients with acute cerebral hemorrhage. N Engl J Med. 2016;375:1033–43.CrossRefGoogle Scholar
  55. 55.
    Reichman J, Singer S, Navi B, Reiner A, Panageas K, Gutin PH, DeAngelis LM. Subdural hematoma in patients with cancer. Neurosurgery. 2012;71:74–9.CrossRefGoogle Scholar
  56. 56.
    Rogers LR. Cerebrovascular complications in cancer patients. Neurol Clin. 2003;21:167–92.CrossRefGoogle Scholar
  57. 57.
    Schouten LJ, Rutten J, Huveneers HA, Twijnstra A. Incidence of brain metastases in a cohort of patients with carcinoma of the breast, colon, kidney, and lung and melanoma. Cancer. 2002;94:2698–705.CrossRefGoogle Scholar
  58. 58.
    Schrader B, Barth H, Lang EW, Buhl R, Hugo HH, Biederer J, Mehdorn HM. Spontaneous intracranial haematomas caused by neoplasms. Acta Neurochir (Wien). 2000;142:979–85.CrossRefGoogle Scholar
  59. 59.
    Scott M. Spontaneous intracerebral hematoma caused by cerebral neoplasms. Report of eight verified cases. J Neurosurg. 1975;42:338–42.CrossRefGoogle Scholar
  60. 60.
    Sessa M. Intracerebral hemorrhage and hypertension. Neurol Sci. 2008;29(Suppl 2):S258–9.CrossRefGoogle Scholar
  61. 61.
    Shuangshoti S, Panyathanya R, Wichienkur P. Intracranial metastases from unsuspected choriocarcinoma. Neurology (Minneap). 1974;24:649–54.CrossRefGoogle Scholar
  62. 62.
    Suarez JI. Diagnosis and management of subarachnoid hemorrhage. Continuum (Minneap Minn). 2015;21:1263–87.Google Scholar
  63. 63.
    Tung GA, Julius B, Rogg JM. MRI of intracerebral hematoma: value of vasogenic edema ratio for predicting the cause. Neuroradiology. 2003;45:357–62.CrossRefGoogle Scholar
  64. 64.
    van Asch CJ, Luitse M, 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.CrossRefGoogle Scholar
  65. 65.
    van den Doel EM, van Merriënboer F, Tulleken CA. Cerebral haemorrhage from unsuspected choriocarcinoma. Clin Neurol Neurosurg. 1985;87:287–90.CrossRefGoogle Scholar
  66. 66.
    Velander AJ, DeAngelis L, Navi BB. Intracranial hemorrhage in patients with Cancer. Curr Atheroscler Rep. 2012;14:373–81.CrossRefGoogle Scholar
  67. 67.
    Wada R, Aviv R, Fox AJ, et al. CT angiography “spot sign” predicts hematoma expansion in acute intracerebral hemorrhage. Stroke. 2007;38:1257–62.CrossRefGoogle Scholar
  68. 68.
    Wakai S, Yamakawa K, Manaka S, Takakura K. Spontaneous intracranial hemorrhage caused by brain tumor: its incidence and clinical significance. Neurosurgery. 1982;10:437–44.CrossRefGoogle Scholar
  69. 69.
    Woo D, et al. Effect of untreated hypertension on hemorrhagic stroke. Stroke. 2004;35:1703–8.CrossRefGoogle Scholar
  70. 70.
    Wűrthner JU, Köhler G, Behringer D, Lindemann A, Mertelsmann R, Lűbbert M. Leukostasis followed by hemorrhage complicating the initiation of chemotherapy in patients with acute myeloid leukemia and hyperleukocytosis: a clinicopathologic report of four cases. Cancer. 1999;85:368–74.CrossRefGoogle Scholar
  71. 71.
    Yamauchi K, Umeda Y. Symptomatic intracranial haemorrhage in acute non-lymphoblastic leukaemia: analysis of CT and autopsy findings. J Neurol. 1997;244:94–100.CrossRefGoogle Scholar
  72. 72.
    Yuguang L, Meng L, Shugan Z, et al. Intracranial tumoural haemorrhage-a report of 58 cases. J Clin Neurosci. 2002;9:637–9.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of NeurologyUniversity of Tennessee Health Science CenterMemphisUSA

Section editors and affiliations

  • Yenny Cardenas
    • 1
  1. 1.Critical Care DepartmentUniversidad del Rosario Hospital Universitario Fundacion Santa Fe deBogotaColombia

Personalised recommendations