Advertisement

Mechanisms of Fibrinolysis-Associated Hemorrhagic Transformation

  • G. J. del Zoppo
  • Y. Okada
  • G. F. Hamann
  • R. Fitridge
  • M. S. Pessin

Abstract

Symptomatic intracerebral hemorrhage is an often-feared companion of acute cerebral ischemia treated with plasminogen activators. The pathophysiology of parenchymal hemorrhage is poorly understood and has been the subject of previous treatises in this series [1,2]. Clinical studies of this disorder suggest a spectrum of clinical severity from asymptomatic episodes diagnosed by computed tomographic (CT) scan or magnetic resonance imaging (MRI) to catastrophic events with debilitating or fatal issue [3–13]. The importance of understanding the pathogenesis of hemorrhagic events, particularly in the setting of fibrinolytic intervention, is emphasized by the dilemma that can arise in judging whether a particular hemorrhage may be reasonably attributable to the plasminogen activator the patient has received.

Keywords

Acute Ischemic Stroke Focal Cerebral Ischemia Hemorrhagic Transformation Embolic Stroke Hemorrhagic Event 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Pessin MS (1991) Hemorrhagic transformation in the natural history of acute embolic stroke. In: Hacke W, del Zoppo GJ, Hirschberg M (eds) Thrombolytic therapy in acute ischemic stroke. Springer, Berlin Heidelberg New York, pp 67–74CrossRefGoogle Scholar
  2. 2.
    Molinari GF (1993) Pathogenesis of secondary brain hemorrhage after ischemia: lessons from animal models and a few from man, too. In: del Zoppo GJ, Mori E, Hacke W (eds) Thrombolytic therapy in acute ischemic stroke II. Springer, Berlin Heidelberg New York, pp 29–36CrossRefGoogle Scholar
  3. 3.
    Fisher CM, Adams RD (1951) Observations on brain embolism with special reference to the mechanism of hemorrhagic infarction. J Neuropathol Exp Neurol 10: 92–94PubMedGoogle Scholar
  4. 4.
    Fisher CM, Adams RD (1987) Observations on brain embolism with special reference to hemorrhage infarction. In: Furlan AJ (ed) The heart and stroke. Exploring mutual cerebrovascular and cardiovascular issues. Springer, Berlin Heidelberg New York, pp 17–36Google Scholar
  5. 5.
    Yamaguchi T, Minematsu K, Choki J, Ikeda M (1984) Clinical and neuroradiological analysis of thrombotic and embolic cerebral infarction. Jpn Circ J 48: 50–58PubMedCrossRefGoogle Scholar
  6. 6.
    Okada Y, Yamaguchi T, Minematsu K, Miyashita T, Sawada T, Sadoshima S, Fujishima M, Omae T (1989) Hemorrhagic transformation in cerebral embolism. Stroke 20: 598–603PubMedCrossRefGoogle Scholar
  7. 7.
    Serradimigni A, Bory M, Dijiane P, Mathieu P, Leonetti J, Juhan-Vague I, Sampol J (1978) Treatment of venous thrombosis and pulmonary embolism by streptokinase. Angiology 29: 825–831PubMedCrossRefGoogle Scholar
  8. 8.
    Ott BR, Zamani A, Kleefield J, Funkenstein HH (1986) The clinical spectrum of hemorrhagic infarction. Stroke 17: 630–637PubMedCrossRefGoogle Scholar
  9. 9.
    Hart RG (1986) Cerebral embolism study group: timing of hemorrhagic transformation of cardioembolic stroke. In: Stober T, Schimrigk K, Ganten D, Sherman DG (eds) Central nervous system control of the heart. Nijhoff, Boston, pp 229–232CrossRefGoogle Scholar
  10. 10.
    Lodder J, Krijne-Kubat B, van der Lugt PJM (1988) Timing of autopsy-confirmed hemorrhagic infarction with reference to cardioembolic stroke. Stroke 19: 1482–1484PubMedCrossRefGoogle Scholar
  11. 11.
    Drake ME, Shin C (1983) Conversion of ischemic to hemorrhagic infarction by anticoagulant administration. Report of two cases with evidence from serial computed tomographic brain scans. Arch Neurol 40: 44–46PubMedCrossRefGoogle Scholar
  12. 12.
    Meyer JS, Gilroy J, Barnhart MI, Johnson JF (1963) Therapeutic thrombolysis in cerebral thromboembolism. Neurology 13: 927–937PubMedGoogle Scholar
  13. 13.
    Babikian VL, Kase CS, Pessin MS, Norrving B, Gorelick PB (1989) Intracerebral hemorrhage in stroke patients anticoagulated with heparin. Stroke 29: 1500–1503CrossRefGoogle Scholar
  14. 14.
    Pessin MS, Teal PA, Caplan LR (1991) Hemorrhagic infarction: guilt by association. AJNR 12: 1123–1126PubMedGoogle Scholar
  15. 15.
    del Zoppo GJ, Poeck K, Pessin MS, Wolpert SM, Furlan AJ, Ferbert A, Alberts MJ, Zivin JA, Wechsler L, Busse O, Greenlee R Jr, Brass L, Mohr JP, Feldmann E, Hacke W, Kase CS, Biller J, Gress D, Otis SM (1992) Recombinant tissue plasminogen activator in acute thrombotic and embolic stroke. Ann Neurol 32: 78–86PubMedCrossRefGoogle Scholar
  16. 16.
    Leblanc R, Haddad G, Robitaille Y (1992) Cerebral hemorrhage from amyloid angiopathy and coronary thrombolysis. Neurosurgery 31 (3): 586–590PubMedCrossRefGoogle Scholar
  17. 17.
    Jörgensen L, Torvik A (1969) Ischaemic cerebrovascular diseases in an autopsy series. Part 2. Prevalence, location, pathogenesis, and clinical course of cerebral infarcts. J Neurol Sci 9: 285–320PubMedCrossRefGoogle Scholar
  18. 18.
    Hornig CR, Dorndorf W, Agnoli AL (1986) Hemorrhagic cerebral infarction: a prospective study. Stroke 17: 179–185PubMedCrossRefGoogle Scholar
  19. 19.
    Ogata J, Yutani C, Imakita M, Ishibashi-Ueda H, Saku Y, Minematsu K, Sawada T, Yamaguchi T (1989) Hemorrhagic infarct of the brain without a reopening of the occluded arteries in cardioembolic stroke. Stroke 20: 876–883PubMedCrossRefGoogle Scholar
  20. 20.
    Molinari GF (1988) Why model strokes? Stroke 19: 1195–1197PubMedCrossRefGoogle Scholar
  21. 21.
    Ropper AH, Zervas NT (1980) Temporal patterns of cerebral blood flow in experimental basal ganglia hemorrhage (abstr). Ann Neurol 8: 99CrossRefGoogle Scholar
  22. 22.
    Bullock R, Mendelow AD, Teasdale GM, Graham DI (1988) Intracranial haemorrhage induced at arterial pressure in the rat. Part 1: Description of technique, ICP changes and neuropathological findings. Neurol Res 6: 184–188Google Scholar
  23. 23.
    Nath FP, Jenkins A, Mendelow AD, Graham DI, Teasdale GM (1986) Early hemodynamic changes in experimental intracerebral hemorrhage. J Neurosurg 65: 697–703PubMedCrossRefGoogle Scholar
  24. 24.
    Kaufmann HH, Schochet S, Koss W, Herschberger J, Bernstein D (1987) Efficacy and safety of tissue plasminogen activator. Neurosurgery 20: 403–407CrossRefGoogle Scholar
  25. 25.
    Kaufmann HH, Pruessner JL, Bernstein DP, Borit A, Ostrow PT, Cahall DL (1985) A rabbit model of intracerebral hematoma. Acta Neuropathol (Berl) 65: 318–321CrossRefGoogle Scholar
  26. 26.
    Mohr CP, Lorenz R (1979) The effect of experimentally produced intracerebral hematoma upon ICP (abstr). Neurosurgery 4: 468Google Scholar
  27. 27.
    Hubschmann OR, Kornhauser D (1983) Effects of intraparenchymal hemorrhage on extracellular cortical potassium in experimental head trauma. J Neurosurg 59: 289–293PubMedCrossRefGoogle Scholar
  28. 28.
    Wallenfang T, Fries G, Bayer J, Schurmann K (1986) Immunohistochemical investigation in experimental intracranial hemorrhage (ICH) and its correlation with findings in clinical studies. In: Miller JD, Teasdale GM, Rowan JO, Galbraith SL, Mendelow AD (eds) Intracranial pressure VI. Springer, Berlin, pp 532–537Google Scholar
  29. 29.
    Sussman BJ, Barber JB, Goald H (1974) Experimental intracerebral hematoma: reduction of oxygen tension in brain and cerebrospinal fluid. J Neurosurg 41: 177–186PubMedCrossRefGoogle Scholar
  30. 30.
    Steiner L, Lofgren J, Zwetnow N (1975) Characteristics and limits of tolerance in repeated subarachnoid hemorrhage in dogs. Acta Neurol Scand 52: 241–267PubMedCrossRefGoogle Scholar
  31. 31.
    Kuchiwaki H. Furuse M, Nakaya T, Toyama K, Ikeyama A, Hasuo M, Teraoka M, Kageyama N (1979) Intracranial dynamics associated with experimentally induced pressure waves. Neurosurgery 4: 464Google Scholar
  32. 32.
    Enzmann DR, Britt RH, Lyons BE, Buxton JL, Wilson DA (1981) Natural history of experimental intracerebral hemorrhage: sonography, computed tomography and neuropathology. AJNR 2: 517–626PubMedGoogle Scholar
  33. 33.
    Takasugi S. Ueda S. Matsumoto K (1985) Chronological changes in spontaneous intra-cerebral hematoma—an experimental and clinical study. Stroke 16: 651–658PubMedCrossRefGoogle Scholar
  34. 34.
    Van der Ark GD, Kahn EA (1968) Spontaneous intracerebral hematoma. J Neurosurg 28: 252–256CrossRefGoogle Scholar
  35. 35.
    Laurent JP, Molinari GF, Oakley JC (1976) Primate model of cerebral hematoma. Neuropathol Exp Neurol 35: 560–568CrossRefGoogle Scholar
  36. 36.
    Segal R, Dujovny M, Nelson D, Meyer J (1982) Local urokinase treatment for spontaneous intracerebral hematoma. Clin Res 30: 412AGoogle Scholar
  37. 37.
    Kaufman HH, Schorhet SS (1992) Pathology, pathophysiology and modeling. In: Kaufman HH (ed) Intracerebral hematomas. Raven. New York, pp 13–22Google Scholar
  38. 38.
    Slivka A. Pulsinelli WA (1987) Hemorrhagic complications of thrombolytic therapy in experimental stroke. Neurology 37 (suppl 1): 82Google Scholar
  39. 39.
    Zivin JA, Lyden PD. De Girolami U, Kochbar R, Mazzarella V, Hemenway CC. Johnston P (1988) Tissue plasminogen activator reduction of neurologic damage after experimental embolic stroke. Arch Neurol 45: 387–391PubMedCrossRefGoogle Scholar
  40. 40.
    Lyden PD, Zivin JA, Clark WA, Madden K, Sasse KC, Mazzarella VA, Terry RD, Press GA (1989) Tissue plasminogen activator-mediated thrombolysis of cerebral emboli and its effect on hemorrhagic infarction in rabbits. Neurology 39: 703–708PubMedGoogle Scholar
  41. 41.
    Phillips DA, Fisher M, Smith TW, Davis MA (1988) The safety and angiographie efficacy of tissue plasminogen activator in a cerebral embolization model. Ann Neurol 23: 391–394PubMedCrossRefGoogle Scholar
  42. 42.
    Phillips DA, Fisher M, Davis MA, Smith TW, Pang RHL (1990) Delayed treatment with a t-PA analogue and streptokinase in a rabbit embolic stroke model. Stroke 21: 602–605PubMedCrossRefGoogle Scholar
  43. 43.
    Hirschberg M, Hofferberth B (1987) Rapid fibrinolysis of different time intervals in a canine model at acute stroke (abstr). Stroke 18: 292Google Scholar
  44. 44.
    Hirschberg M, Hofferberth B (1987) Thrombolytic therapy with urokinase and prourokinase in a canine model of acute stroke (abstr). Neurology 37 (suppl 1): 132Google Scholar
  45. 45.
    del Zoppo GJ, Copeland BR, Waltz TA, Zyroff J, Plow EF, Harker LA (1986) The beneficial effect of intracarotid urokinase of acute stroke in a baboon model. Stroke 17: 638–643PubMedCrossRefGoogle Scholar
  46. 46.
    del Zoppo GJ, Copeland BR, Anderchek K, Hacke W, Koziol JA (1990) Hemorrhagic transformation following tissue plasminogen activator in experimental cerebral infarction. Stroke 21: 596–601PubMedCrossRefGoogle Scholar
  47. 47.
    del Zoppo GJ, Pessin MS, Mori E, Hacke W (1991) Thrombolytic intervention in acute thrombotic and embolic stroke. Semin Neurol 11: 368–384PubMedCrossRefGoogle Scholar
  48. 48.
    del Zoppo GJ (1994) Microvascular change during cerebral ischemia and reperfusion. Cerebrovasc Brain Metab Rev 6: 47–96PubMedGoogle Scholar
  49. 49.
    Martinez-Hernandez A, Amenta PS (1983) The basement membrane in pathology. Lab Invest 48: 656–677PubMedGoogle Scholar
  50. 50.
    Mohan PS, Spiro RG (1986) Macromolecular organization of basement membranes. J Biol Chem 261: 4328–4336PubMedGoogle Scholar
  51. 51.
    Yurchenco PD, Schittny JC (1990) Molecular architecture of basement membranes. FASEB J 4: 1577–1590PubMedGoogle Scholar
  52. 52.
    Hynes RO, Yamada KM (1982) Fibronectins: multifunctional modular glycoproteins. J Cell Biol 95: 369–377PubMedCrossRefGoogle Scholar
  53. 53.
    Houdijk WPM, Sixma JJ (1985) Fibronectin in artery subendothelium is important for platelet adhesion. Blood 65 (3): 598–604PubMedGoogle Scholar
  54. 54.
    Bastida E, Escolar G, Ordinas A, Sixma JJ (1987) Fibronectin is required for platelet adhesion and for thrombus formation on subendothelium and collagen surfaces. Blood 70: 1437–1442PubMedGoogle Scholar
  55. 55.
    Forsyth KD, Levinsky RJ (1990) Fibronectin degradation; an in vitro model of neutrophilmediated endothelial cell damage. J Pathol 161: 313–319PubMedCrossRefGoogle Scholar
  56. 56.
    Forsyth KD, Simpson AC, Fitzpatrick MM, Barratt TM, Levinsky RJ (1989) Neutrophilmediated endothelial injury in haemolytic uraemic syndrome. Lancet 19: 411–414CrossRefGoogle Scholar
  57. 57.
    Tryggvason K, Höyhtyä M, Salo T (1987) Proteolytic degradation of extracellular matrix in tumor invasion. Biochim Biophys Acta 907: 191–217PubMedCrossRefGoogle Scholar
  58. 58.
    Saksela O (1985) Plasminogen activation and regulation of pericellular proteolysis. Biochim Biophys Acta 823: 35–65PubMedCrossRefGoogle Scholar
  59. 59.
    Schlechte W, Murano G, Boyd D (1989) Examination of the role of the urokinase receptor in human colon cancer mediated laminin degradation. Cancer Res 49: 6064–6069PubMedGoogle Scholar
  60. 60.
    Shirasuna K, Saka M, Hayashido Y, Yoshioka H, Sugiura T, Matsuya T (1993) Extracellular matrix production and degradation by adenoid cystic carcinoma cells: participation of plasminogen activator and its inhibitor in matrix degradation. Cancer Res 53: 147–152PubMedGoogle Scholar
  61. 61.
    Morrissey JH, Fabhrai H, Edgington TS (1987) Molecular cloning of the cDNA for tissue factor, the cellular receptor for the initiation of the coagulation protease cascade. Cell 50: 129–135PubMedCrossRefGoogle Scholar
  62. 62.
    del Zoppo G, Yu J-Q, Copeland BR, Thomas WS, Schneiderman J, Morrissey J (1992) Tissue factor location in non-human primate cerebral tissue. Thromb Haemostasis 68: 642–647Google Scholar
  63. 63.
    del Zoppo GJ, Schömid-Schönbein GW, Mori E, Copeland BR, Chang C-M (1991) Polymorphonuclear leukocytes occlude capillaries following middle cerebral artery occlusion and reperfusion in baboons. Stroke 22: 1276–1283PubMedCrossRefGoogle Scholar
  64. 64.
    Mori E, del Zoppo GJ, Chambers JD, Copeland BR, Arfors KE (1992) Inhibition of polymorphonuclear leukocyte adherence suppresses no-reflow after focal cerebral ischemia. Stroke 23: 712–718PubMedCrossRefGoogle Scholar
  65. 65.
    Okada Y, Copeland BR, Mori E, Tung M-M, Thomas WS, del Zoppo GJ (1994) P-selectin and intercellular adhesion molecule-1 expression after focal brain ischemia and reperfusion. Stroke 25: 201–210Google Scholar
  66. 66.
    Garcia JH, Liu KF, Yoshida Y, Lian J, Chen S, del Zoppo GJ (1993) The influx of leukocytes and platelets in an evolving brain infarct ( Wistar rat ). Am J Pathol 144: 188–199Google Scholar
  67. 67.
    Garcia JH, Lowry SL, Briggs L, Mitchem HL, Morawetz R, Halsey JH, Conger KA (1983) Brain capillaries expand and rupture in areas of ischemia and reperfusion. In: Reivich M, Hurtig HI (eds) Cerebrovascular diseases. Raven, New York, pp 169–182Google Scholar
  68. 68.
    Okada Y, Copeland BK, Tung M-M, del Zoppo GJ (1994) Fibrin contributes to micro-vascular obstructions and parenchymal changes during early focal cerebral ischemia and reperfusion. Stroke 25: 1847–1854PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Tokyo 1995

Authors and Affiliations

  • G. J. del Zoppo
    • 1
  • Y. Okada
    • 1
  • G. F. Hamann
    • 1
  • R. Fitridge
    • 1
  • M. S. Pessin
    • 2
  1. 1.Department of Molecular and Experimental MedicineThe Scripps Research InstituteLa JollaUSA
  2. 2.Department of NeurologyTufts-New England Medical CenterBostonUSA

Personalised recommendations