A method for monitoring antifibrinolytic therapy in patients with ruptured intracranial aneurysms

Restricted access

✓ A rapid fluorometric assay technique has been utilized to assess the degree of fibrinolytic inhibition in 20 patients with ruptured intracranial aneurysms treated with epsilon-aminocaproic acid (EACA). This method quantitates the available plasminogen activity (APA) of plasma, and has proven to be a reliable means of monitoring antifibrinolytic therapy. Determination of the plasma APA also permits correlation of the level of fibrinolytic activity with putative complications of EACA therapy. Normal control plasma APA was 3.1 ± 0.7 CTA units/ml, but in patients with subarachnoid hemorrhage (SAH), pretreatment fibrinolytic activity was supranormal at 3.78 ± 0.88 CTA units/ml. During continuous intravenous administration of EACA (1.5 gm/hr) in patients with SAH, the plasma fibrinolytic activity was decreased to 0.9 ± 0.31 CTA units/ml. A case is described which exemplifies the use of this assay. In addition, an approach to monitoring antifibrinolytic therapy using the plasma APA is proposed.

Article Information

Address reprint requests to: Kim J. Burchiel, M.D., Department of Neurological Surgery, University of Washington, Seattle, Washington 98195.

© AANS, except where prohibited by US copyright law.

Headings

Figures

  • View in gallery

    Results of monitoring the available plasminogen activity (APA) in a patient with subarachnoid hemorrhage (SAH) treated by the continuous intravenous infusion of epsilon-aminocaproic acid (EACA). On the 1st day of treatment the patient was given 1.5 gm/hr EACA which rapidly decreased plasma APA from the baseline of 2.0 CTA units/ml to 0.5 CTA units/ml, with further inhibition to 0.4 CTA units/ml on the 2nd hospital day. The EACA dose was decreased at this point to 1.25 gm/hr and the APA gradually returned to the range of 1.0 CTA units/ml. A further dose correction to 1.4 gm/hr was performed on the 5th day of treatment. Following this, the APA reached a steady level of 0.7 CTA units/ml for the duration of treatment, with the exception of the 9th day of treatment, at which time the infiltration of the patient's intravenous site occurred in the hours before obtaining blood for the APA determination. This was reflected by an immediate increase in the plasma APA. CTAU = Committee on Thromboplastic Activity (CTA) Units/ml.

References

1.

Alvarez Garijo JAVilches JJAznar JA: Preoperative treatment of ruptured intracranial aneurysms with tranexamic acid and monitoring of fibrinolytic activity. J Neurosurg 52:4534551980Alvarez Garijo JA Vilches JJ Aznar JA: Preoperative treatment of ruptured intracranial aneurysms with tranexamic acid and monitoring of fibrinolytic activity. J Neurosurg 52:453–455 1980

2.

Bergin JJ: The complications of therapy with epsilonaminocaproic acid. Med Clin North Am 50(6): 166916781966Bergin JJ: The complications of therapy with epsilonaminocaproic acid. Med Clin North Am 50(6):1669–1678 1966

3.

Britt CWLight RRPeters BHet al: Rhabdomyolysis during treatment with epsilon-aminocaproic acid. Arch Neurol 37:1871881980Britt CW Light RR Peters BH et al: Rhabdomyolysis during treatment with epsilon-aminocaproic acid. Arch Neurol 37:187–188 1980

4.

Charyton CPurtilo D: Glomerular capillary thrombosis and acute renal failure after epsilon-amino caproic acid therapy. N Engl J Med 280:110211041969Charyton C Purtilo D: Glomerular capillary thrombosis and acute renal failure after epsilon-amino caproic acid therapy. N Engl J Med 280:1102–1104 1969

5.

DADE Protopath Procedure Manual. Miami, FL: American Hospital Supply Corp1979DADE Protopath Procedure Manual. Miami FL: American Hospital Supply Corp 1979

6.

Fearnley GRBalmforth GFearnley E: Evidence of a diurnal fibrinolytic rhythm; with a simple method of measuring natural fibrinolysis. Clin Sci 16:6456501957Fearnley GR Balmforth G Fearnley E: Evidence of a diurnal fibrinolytic rhythm; with a simple method of measuring natural fibrinolysis. Clin Sci 16:645–650 1957

7.

Geronemus RHerz DAShulman K: Streptokinase clot lysis time in patients with ruptured intracranial aneurysms. J Neurosurg 40:4995031974Geronemus R Herz DA Shulman K: Streptokinase clot lysis time in patients with ruptured intracranial aneurysms. J Neurosurg 40:499–503 1974

8.

Gibbs JRO'Gorman P: Fibrinolysis in subarachnoid haemorrhage. Postgrad Med J 43:7797841967Gibbs JR O'Gorman P: Fibrinolysis in subarachnoid haemorrhage. Postgrad Med J 43:779–784 1967

9.

Gralnick HRGreipp P: Thrombosis with epsilon aminocaproic acid therapy. Am J Clin Pathol 56:1511541971Gralnick HR Greipp P: Thrombosis with epsilon aminocaproic acid therapy. Am J Clin Pathol 56:151–154 1971

10.

MacKay ARU HSWeinstein PR: Myopathy associated with epsilon-aminocaproic acid (EACA) therapy. Report of two cases. J Neurosurg 49:5976011978MacKay AR U HS Weinstein PR: Myopathy associated with epsilon-aminocaproic acid (EACA) therapy. Report of two cases. J Neurosurg 49:597–601 1978

11.

McKay DGMüller-Berghaus G: Therapeutic implications of disseminated intravascular coagulation. Am J Cardiol 20:3924101967McKay DG Müller-Berghaus G: Therapeutic implications of disseminated intravascular coagulation. Am J Cardiol 20:392–410 1967

12.

McNicol GPFletcher APAlkjaersig Net al: The absorption, distribution, and excretion of ϵ-aminocaproic acid following oral or intravenous administration to man. J Lab Clin Med 59:15241962McNicol GP Fletcher AP Alkjaersig N et al: The absorption distribution and excretion of ϵ-aminocaproic acid following oral or intravenous administration to man. J Lab Clin Med 59:15–24 1962

13.

McNicol GPFletcher APAlkjaersig Net al: The use of epsilon aminocaproic acid, a potent inhibitor of fibrinolytic activity, in the management of postoperative hematuria. J Urol 86:8298371961McNicol GP Fletcher AP Alkjaersig N et al: The use of epsilon aminocaproic acid a potent inhibitor of fibrinolytic activity in the management of postoperative hematuria. J Urol 86:829–837 1961

14.

Mullan SDawley J: Antifibrinolytic therapy for intracranial aneurysms. J Neurosurg 28:21231968Mullan S Dawley J: Antifibrinolytic therapy for intracranial aneurysms. J Neurosurg 28:21–23 1968

15.

Naeye RL: Thrombotic state after a hemorrhagic diathesis, a possible complication of therapy with epsilon-aminocaproic acid. Blood 19:6947011962Naeye RL: Thrombotic state after a hemorrhagic diathesis a possible complication of therapy with epsilon-aminocaproic acid. Blood 19:694–701 1962

16.

Nibbelink DW: Antifibrinolytic activity during administration of epsilon-aminocaproic acid. Stroke 2:5555581971Nibbelink DW: Antifibrinolytic activity during administration of epsilon-aminocaproic acid. Stroke 2:555–558 1971

17.

Nibbelink DWTorner JCHenderson WG: Intracranial aneurysms and subarachnoid hemorrhage. A cooperative study. Antifibrinolytic therapy in recent onset subarachnoid hemorrhage. Stroke 6:6226291975Nibbelink DW Torner JC Henderson WG: Intracranial aneurysms and subarachnoid hemorrhage. A cooperative study. Antifibrinolytic therapy in recent onset subarachnoid hemorrhage. Stroke 6:622–629 1975

18.

Nilsson IMAndersson LBjörkman SE: Epsilonaminocaproic acid (EACA) as a therapeutic agent based on 5 years' clinical experience. Acta Med Scand (Suppl 448): 1461966Nilsson IM Andersson L Björkman SE: Epsilonaminocaproic acid (EACA) as a therapeutic agent based on 5 years' clinical experience. Acta Med Scand (Suppl 448):1–46 1966

19.

Norlén GThulin C-A: The use of antifibrinolytic substances in ruptured intracranial aneurysms. Neurochirurgia 12:1001021969Norlén G Thulin C-A: The use of antifibrinolytic substances in ruptured intracranial aneurysms. Neurochirurgia 12:100–102 1969

20.

Park BE: Spontaneous subarachnoid hemorrhage complicated by communicating hydrocephalus: epsilonaminocaproic acid as a possible predisposing factor. Surg Neurol 11:73801979Park BE: Spontaneous subarachnoid hemorrhage complicated by communicating hydrocephalus: epsilonaminocaproic acid as a possible predisposing factor. Surg Neurol 11:73–80 1979

21.

Pechet L: Fibrinolysis. N Engl J Med 273:102410341965Pechet L: Fibrinolysis. N Engl J Med 273:1024–1034 1965

22.

Pochron SPMitchell GAAlbareda Iet al: A fluorescent substrate assay for plasminogen. Thromb Res 13:7337391978Pochron SP Mitchell GA Albareda I et al: A fluorescent substrate assay for plasminogen. Thromb Res 13:733–739 1978

23.

Ransohoff JGoodgold ABenjamin MV: Preoperative management of patients with ruptured intracranial aneurysms. J Neurosurg 36:5255301972Ransohoff J Goodgold A Benjamin MV: Preoperative management of patients with ruptured intracranial aneurysms. J Neurosurg 36:525–530 1972

24.

Raum DMarcus DAlper CAet al: Synthesis of human plasminogen by the liver. Science 208:103610371980Raum D Marcus D Alper CA et al: Synthesis of human plasminogen by the liver. Science 208:1036–1037 1980

25.

Schisano G: Antifibrinolytics in the treatment of subarachnoid hemorrhage due to rupture of arterial aneurysm. J Neurosurg Sci 18:39461974Schisano G: Antifibrinolytics in the treatment of subarachnoid hemorrhage due to rupture of arterial aneurysm. J Neurosurg Sci 18:39–46 1974

26.

Sengupta RPSo SCVillarejo-Ortega FJ: Use of epsilon aminocaproic acid (EACA) in the preoperative management of ruptured intracranial aneurysms. J Neurosurg 44:4794841976Sengupta RP So SC Villarejo-Ortega FJ: Use of epsilon aminocaproic acid (EACA) in the preoperative management of ruptured intracranial aneurysms. J Neurosurg 44:479–484 1976

27.

Smith RRUpchurch JJ: Monitoring antifibrinolytic therapy in subarachnoid hemorrhage. J Neurosurg 38:3393441973Smith RR Upchurch JJ: Monitoring antifibrinolytic therapy in subarachnoid hemorrhage. J Neurosurg 38:339–344 1973

28.

Sonntag VKHStein BM: Arteriopathic complications during treatment of subarachnoid hemorrhage with epsilon-aminocaproic acid. J Neurosurg 40:4804851974Sonntag VKH Stein BM: Arteriopathic complications during treatment of subarachnoid hemorrhage with epsilon-aminocaproic acid. J Neurosurg 40:480–485 1974

29.

Stamm HCaflisch AMall M: Diagnose und therapie der afibrinoganie postpartum. Gynaecologia (Basel) 156:12171963Stamm H Caflisch A Mall M: Diagnose und therapie der afibrinoganie postpartum. Gynaecologia (Basel) 156:12–17 1963

30.

Tovi D: The use of antifibrinolytic drugs to prevent early recurrent aneurysmal subarachnoid haemorrhage. Acta Neurol Scand 49:1631751973Tovi D: The use of antifibrinolytic drugs to prevent early recurrent aneurysmal subarachnoid haemorrhage. Acta Neurol Scand 49:163–175 1973

31.

Tovi DNilsson IM: Increased fibrinolytic activity and fibrin degradation products after experimental intracerebral haemorrhage. Acta Neurol Scand 48:4034151972Tovi D Nilsson IM: Increased fibrinolytic activity and fibrin degradation products after experimental intracerebral haemorrhage. Acta Neurol Scand 48:403–415 1972

32.

Tovi DThulin CA: Ability of tranexamic acid to cross the blood-brain barrier and its use in patients with ruptured intracranial aneurysms. Acta Neurol Scand 48:2571972 (Summary)Tovi D Thulin CA: Ability of tranexamic acid to cross the blood-brain barrier and its use in patients with ruptured intracranial aneurysms. Acta Neurol Scand 48:257 1972 (Summary)

TrendMD

Metrics

Metrics

All Time Past Year Past 30 Days
Abstract Views 57 57 24
Full Text Views 190 190 5
PDF Downloads 48 48 4
EPUB Downloads 0 0 0

PubMed

Google Scholar