Skip to main content
SpringerLink
Log in

Benefits and risks of antifibrinolytic therapy in the management of ruptured intracranial aneurysms

A double-blind placebo-controlled study

  • Clinical Articles
  • Published:
Acta Neurochirurgica Aims and scope Submit manuscript

Summary

One hundred patients with a verified subarachnoid haemorrhage were studied in a double blind, placebo-controlled trial at a single centre to determine the value and relative risks of tranexamic acid (TXA) in the management of ruptured intracranial aneurysms. The incidence of recurrent haemorrhage between active and placebo groups was identical (12%) and the mortality from recurrent haemorrhage was 7% and 5%, respectively. The overall incidence of cerebral infarction before surgery, at discharge and at 6 months follow-up was greater in the TXA group (27%) than in the control group (11%). Post-operative cerebral ischaemia was significantly more frequent in the active, 18 of 29 as compared to 6 of 32 patients, in the placebo group. In a fifth of the patients in whom cerebral blood flow was estimated there was a significant reduction of cerebral blood flow (CBF) on the side of the ruptured aneurysm in the TXA treated group. It is suggested that this may be the cause of the increased incidence of cerebral ischaemia in this group. There was no significant difference in the incidence of cerebral vasospasm, hydrocephalus, visual disturbances and gastrointestinal disturbances.

More fatalities were encountered from ischaemia and recurrent haemorrhage in the TXA group but these differences did not reach statistical significance at the 5% level. Given that disability was due to either vasospasm or recurrent haemorrhage then a patient under TXA treatment was significantly more likely to have disability due to vasospasm (p<0.04); the reverse was true for the placebo patient (p<0.05).

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Adams HP, Nibbelink DW, Torner JC, Sahs AL (1981) Antifibrinolytic therapy in patients with aneurysmal subarachnoid haemorrhage. A report of the co-operative study. Arch Neurol 38: 25–29

    PubMed  Google Scholar 

  2. Alvarez Garijo JA, Vilchez JJ, Aznar JA (1980) Preoperative treatment of ruptured intracranial aneurysms with tranexamic acid and monitoring of fibrinolytic activity. J Neurosurg 52: 453–455

    PubMed  Google Scholar 

  3. Chandra B (1978) Treatment of subarachnoid haemorrhage from ruptured intracranial aneurysm with tranexamic acid; A double-blind clinical trial. Ann Neurol 3: 502–504

    PubMed  Google Scholar 

  4. Chowdhary UM, Carey PC, Hussein MM (1979) Prevention of early recurrence of spontaneous subarachnoid haemorrhage by e-aminocaproic acid. Lancet I: 741–743

    Google Scholar 

  5. Chowdhary UM, Sayed K (1981) Comparative clinical trial of epsilon aminocaproic acid and tranexamic acid in the prevention of early recurrence of subarachnoid haemorrhage. J Neurol Neurosurg Psychiatry 44: 810–813

    PubMed  Google Scholar 

  6. Corkill G (1974) Earlier operation and antifibrinolytic therapy in the management of aneurysmal subarachnoid haemorrhage. Review of recent experience in Tasmania. Med J Aust 1: 468–470

    PubMed  Google Scholar 

  7. Elworthy PM, Tsementzis SA, Westhead R, Hitchcock ER (1985) Determination of plasma tranexamic acid using cation exchange high-performance liquid chromatography with fluorescence detection. J Chromatography 343: 109–117

    Google Scholar 

  8. Filizzolo F, D'Angelo V, Collice M, Ferrara M, Donati MB, Porta M (1978) Fibrinolytic activity in blood and cerebrospinal fluid in subarachnoid haemorrhage from ruptured intracranial saccular aneurysm before and during EACA treatment. Eur Neurol 17: 43–47

    PubMed  Google Scholar 

  9. Fodstad H, Forssell A, Liliequist B, Schannong M (1981) Antifibrinolysis with tranexamic acid in aneurysmal subarachnoid haemorrhage: A consecutive controlled clinical trial. Neurosurg 8: 158–165

    PubMed  Google Scholar 

  10. Gelmers HJ (1980) Prevention of recurrence of spontaneous subarachnoid haemorrhage by tranexamic acid. Acta Neurochir (Wien) 52: 45–50

    Google Scholar 

  11. Gibbs JR, Corkill G (1971) Use of an antifibrinolytic agent (tranexamic acid) in the management of ruptured intracranial aneurysms. Postgrad Med J 47: 199–200

    PubMed  Google Scholar 

  12. Girvin JP (1973) The use of antifibrinolytic agents in the preoperative treatment of ruptured intracranial aneurysms. Trans Am Neurol Assoc 98: 150–152

    PubMed  Google Scholar 

  13. Glick R, Green D, Chung-hsin Ts'ao, Witt WA, Yu Amy TW, Raimondi AJ (1981) High dose e-aminocaproic acid prolongs the bleeding time and increases rebleeding and intraoperative haemorrhage in patients with subarachnoid haemorrhage. Neurosurg 9: 398–401

    Google Scholar 

  14. Gordon-Smith IC, Hickman JA, El Marsi SH (1972) The effect of the fibrinolytic inhibitor epsilon-amino-caproic acid on the incidence of deep vein thrombosis after prostatectomy. Br J Surg 59: 522–524

    PubMed  Google Scholar 

  15. Guidetti B, Spallone A (1981) The role of antifibrinolytic therapy in the preoperative management of recently ruptured intracranial aneurysms. Surg Neurol 15: 239–247

    PubMed  Google Scholar 

  16. Heidrich R, Markwardt F, Endler S, Hindersin P (1978) Antifibrinolytic therapy of subarachnoid haemorrhage by intrathecal administration of p-aminomethylbenzoic acid. J Neurol 219: 83–85

    PubMed  Google Scholar 

  17. Jennet B, Bodn M (1975) Assessment of outcome after severe brain damage. A practical scale. Lancet 1: 480–484

    PubMed  Google Scholar 

  18. Kassell NF, Torner JC, Adams HP (1984) Antifibrinolytic therapy in the acute period following aneurysmal subarachnoid hemorrhage. Preliminary observations from the co-operative aneurysm study. J Neurosurg 61: 225–230

    PubMed  Google Scholar 

  19. Kaste M, Ramsey M (1979) Tranexamic acid in subarachnoid haemorrhage. A double-blind study. Stroke 10: 519–522

    PubMed  Google Scholar 

  20. Kjellman H (1974) Synthetic antifibrinolytics. In: Nilsson Im (ed) Haemorrhagic and thrombotic diseases. John Wiley, London, pp 140–145

    Google Scholar 

  21. Maurice-Williams RS (1978) Prolonged antifibrinolysis: An effective nonsurgical treatment for ruptured intracranial aneurysms? Br Med J I: 945–947

    Google Scholar 

  22. Meyer CHA, Lowe D, Meyer M, Richardson PL, Neil-Dywer G (1983) Progressive change in cerebral blood flow during the first three weeks after subarachnoid haemorrhage. Neurosurg 12: 58–76

    PubMed  Google Scholar 

  23. Mullan S, Dawley J (1968) Antifibrinolytic therapy for intracranial aneurysms. J Neurosurg 28: 21–23

    PubMed  Google Scholar 

  24. Nibbelink DW (1975) Co-operative aneurysm study: Antihypertensive and antifibrinolytic therapy following subarachnoid haemorrhage from ruptured intracranial aneurysm. In: Wishnant JP, Sandok BA (eds) Cerebral vascular diseases. Grune & Stratton, New York San Francisco London, pp 155–173

    Google Scholar 

  25. Nibbelink DW, Torner JC, Henderson WG (1976) Intracranial aneurysms and subarachnoid haemorrhage. A co-operative study. Antifibrinolytic therapy in recent onset subarachnoid haemorrhage. Stroke 6: 622–629

    Google Scholar 

  26. Norlen G, Thulin CA (1969) The use of antifibrinolytic substances in ruptured intracranial aneurysm. Neurochirurgica (Stuttg) 2: 7–8

    Google Scholar 

  27. Park BE (1979) Spontaneous subarachnoid haemorrhage complicated by communicating hydrocephalus. Epsilon-amino-caproic acid as a possible predisposing factor. Surg Neurol 11: 73–80

    PubMed  Google Scholar 

  28. Profeta G, Castellano F, Guarnieri L, Cigliano A, Ambrosio A (1975) Antifibrinolytic therapy in the treatment of subarachnoid haemorrhage caused by arterial aneurysms. J Neurosurg Sci 19: 77–78

    PubMed  Google Scholar 

  29. Ransohoff J, Goodgold A, Benjamin MW (1972) Preoperative management of patients with ruptured intracranial aneurysms. J Neurosurg 36: 525–530

    PubMed  Google Scholar 

  30. Rossum J, van Wintzen AR, Endtz LJ, Schoen JHR, Jonge H (1977) Effect of tranexamic acid on rebleeding after subarachnoid haemorrhage: Double-blind controlled clinical trial. Ann Neurol 2: 238–242

    Google Scholar 

  31. Schisano G (1978) The use of antifibrinolytic drugs in aneurysmal subarachnoid haemorrhage. Surg Neurol 10: 217–222

    PubMed  Google Scholar 

  32. Sengupta RP, So SC, Villarejo-Ortega FJ (1976) Use of epsilon aminocaproic acid (EACA) in the preoperative management of ruptured intracranial aneurysms. J Neurosurg 44: 476–484

    Google Scholar 

  33. Shaw MDM, Miller JD (1974) Epsilon aminocaproic acid and subarachnoid haemorrhage. Lancet II: 847–848

    Google Scholar 

  34. Shucart WA, Hussain Sk, Cooper RP (1980) Epsilon-aminocaproic acid and recurrent subarachnoid haemorrhage. A clinical trial. J Neurosurg 53: 28–31

    PubMed  Google Scholar 

  35. Spallone A (1982) Antifibrinolytics in aneurysmal subarachnoid haemorrhage. A retrospective comparison of two different forms of antifibrinolytic therapy. Acta Neurochir (Wien) 63: 245–250

    Google Scholar 

  36. Tovi D (1972) Studies on fibrinolysis in the central nervous system with special reference to intracranial haemorrhages and to the effect of antifibrinolytic drugs. Umea University Medical Dissertations 8: 1–50

    Google Scholar 

  37. Tsementzis SA, Hitchcock ER (1985) Antifibrinolytics in subarachnoid haemorrhage. Br J Cl Pract 39: 423–425

    Google Scholar 

  38. Tsementzis SA, Honan W, Hitchcock ER, Nightingale S: Fibrinolytic activity after subarachnoid haemorrhage and the effect of tranexamic acid. J Neurosurg (submitted for publication)

  39. Uttley D, Richardson AE (1974) E-aminocaproic acid and subarachnoid haemorrhage. Lancet II: 1080–1081

    Google Scholar 

  40. Vermeulen M, Lindsary KW, Murray GD, Cheah F, Hijdra A, Muizelaar JP, Schannong M, Teasdale GM, van Greuel H (1984) Antifibrinolytic treatment in subarachnoid hemorrhage: A consecutive controlled clinical trial. N Engl J Med 311: 432–437

    PubMed  Google Scholar 

  41. Vinnicombe J, Shuttleworth KED (1966) Aminocaproic acid in the control of haemorrhage after prostatectomy: a controlled trial. Lancet I: 230–234

    Google Scholar 

  42. Wyper DJ, Pickard JD, Acar U (1979) Monitoring cerebral blood flow during intracranial operations: An intravenous injection method. Neurol Res 1: 31–37

    PubMed  Google Scholar 

  43. Wysenbeck AJ, Selia A, Blum I, Yeshurum D (1979) Acute delirious state after e-amino-caproic acid administration. Clin Toxicol 14: 93–95

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University Department of Neurosurgery, Birmingham, UK

    S. A. Tsementzis M.D., E. R. Hitchcock & C. H. A. Meyer

Authors
  1. S. A. Tsementzis M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. R. Hitchcock
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C. H. A. Meyer
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tsementzis, S.A., Hitchcock, E.R. & Meyer, C.H.A. Benefits and risks of antifibrinolytic therapy in the management of ruptured intracranial aneurysms. Acta neurochir 102, 1–10 (1990). https://doi.org/10.1007/BF01402177

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01402177

Keywords

Search

Navigation