Determination of tranexamic acid (AMCA) and fibrin/fibrinogen degradation products in cerebrospinal fluid after aneurysmal subarachnoid haemorrhage

Fodstad, Harald; Pilbrant, A; Schannong, M; Strömberg, Signhild

doi:10.1007/bf01401679

Cited by 31 publications

(12 citation statements)

References 30 publications

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“…Unfortunately, while antifibrinolytic drugs reduced the risk of rebleeding, the overall management outcome was not significantly different, primarily because of a high incidence of cerebral infarction due to vasospasm. Similar results were recorded by Fodstad 14 in a randomized study of tranexamic acid. This group found that the mortality rate was higher in patients who received antifibrinolytic therapy, despite a lower rebleeding rate.…”

Section: Discussionsupporting

confidence: 88%

“…The severity of vasospasm appears to be related to the amount and duration of blood in the basal cisterns. 14 The overall management outcome in patients with aneurysmal SAH for whom delayed surgery is planned may be improved if the reduced risk of rebleeding brought about by antifibrinolytic drug administration could be combined with an agent that would prevent ischemic complications. Recent work on vasospasm has centered on the use of drugs that increase intracellular binding of calcium or that decrease calcium entry into vascular smooth muscle.…”

Section: Discussionmentioning

confidence: 99%

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Combination of aminocaproic acid and nicardipine in treatment of aneurysmal subarachnoid hemorrhage.

Beck

Adams

Flamm

et al. 1988

Stroke

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Antifibrinolytic drags reduce the risk of rebleeding during the first 2 weeks after aneurysmal subarachnoid hemorrhage. However, they do not lower overall mortality, largely because of an increased incidence of cerebral ischemia. The usefulness of antifibrinolytic drugs might be increased if a method to prevent or control vasospasm in patients were to be developed. We recently completed late Phase I and Phase II studies of the calcium ion blocking drug nicardipine in 67 patients treated within 1 week of subarachnoid hemorrhage. Of these 67 patients, 42 had delayed operations and were treated concomitantly with the antifibrinolytic drug aminocaproic add (1.5 g/hr) for an average of 6 days before surgery. The outcome of these 42 patients is the subject of this report. T he use of antifibrinolytic drugs in the management of aneurysmal subarachnoid hemorrhage (SAH) is controversial. 1 " 3 Recently two large multicenter trials showed that the risk of rebleeding was substantially reduced in patients receiving antifibrinolytic drugs compared with a comparable group of patients not receiving antifibrinolytic drugs. 45 However, the overall mortality rate at 3 months between the groups was similar. The reduction of mortality due to rebleeding was negated by increased mortality due to cerebral ischemia among the patients given antifibrinolytic drugs.4 " 6 Antifibrinolytic drugs could become a useful preoperative therapy in patients with recent SAH if the risks of vasospasm and cerebral ischemia could be reduced.We recently performed a prospective dosage escala- Received June 3, 1987; accepted July 14, 1987. tion study of nicardipine, a dihydropyridine calcium ion entry blocking agent that preferentially binds to cerebrovascular smooth muscle, in 67 patients with recent SAH. Forty-two patients had delayed operations planned for the treatment of the aneurysm and were given aminocaproic acid before surgery. These 42 patients were studied for any effect on the incidence and severity of symptomatic vasospasm by the concomitant administration of nicardipine and aminocaproic acid. Subjects and MethodsPatients between the ages of 18 and 75 admitted to University of Iowa Hospitals or to New York University Medical Center within 7 calendar days of SAH from a documented cerebral aneurysm were included in the study. The details of this study are described elsewhere. 7 In all cases, blood in the subarachnoid space was evident on either computed tomography (CT) or nontraumatic lumbar puncture. Cerebral angiography to demonstrate the presence of a saccular aneurysm and the absence of vasospasm was performed before patients were entered into the study. Patients were excluded if they were deeply comatose, if they had a large intracerebral hemorrhage, or if arterial narrowing was found on the initial arteriogram. Patients were also excluded if they were taking a calcium ion blocking

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Combination of aminocaproic acid and nicardipine in treatment of aneurysmal subarachnoid hemorrhage.

Beck

Adams

Flamm

et al. 1988

Stroke

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“…- 23 Focal parenchymal damage may also increase fibrinolysis within the CSF and plasma. The perianeurysmal clot may be dissolved by this increased fibrinolytic activity.…”

mentioning

confidence: 99%

“…31 - 32 The drugs have a short half-life, ranging from 1 to 3 hours. 23 - 3334 The daily dose of EACA, which is the most commonly used drug in the United States, is 24-36 g; that of tranexamic acid, which is most popular in Europe, is around 6 g (4-12 g).…”

mentioning

confidence: 99%

Management of aneurysmal subarachnoid hemorrhage.

Biller

Godersky

Adams

1988

Stroke

146

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“…The variable reported results of antifibrinolytic treatment may be attributable to differences in the dosage, duration, route of administra tion and in the selection of drug. The daily dose of epsilon aminocaproic acid, which is the most commonly used drug in the United States, varies between 24 and 36 g, that of tranexamic acid (TA), the more popular choice in Europe, between 4 and 12 g. Suffi cient dosing of anlifibrinolytic drugs can be surveyed by measuring the concentration of the fibrin degradation products (FDP) in the cerebrospinal fluid [7,14,17,19], whereby an increase of FDP indicates enhanced fibri nolytic activity and, hence, the risk of disso lution of the occluding perianeurysmal fibrin plug.…”

Section: Introductionmentioning

confidence: 99%

Monitoring of Antifibrinolytic Treatment in Subarachnoid Hemorrhage

Hossmann¹,

Bewermeyer²,

Auel³

et al. 1985

Eur Neurol

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21 patients (aged 28–81 years) with recent subarachnoid hemorrhage (10 saccular aneurysms, 3 arteriovenous angiomas, 8 normal angiograms) were continuously infused with tranexamic acid at a dosage of 5 g daily for up to 14 days. Therapy was surveyed by daily measurement of the available plasminogen activity (aPl) with the chromogenic substrate S-2251 and by a modified bioassay, whereby the concentration of tranexamic acid was determined thrombelastographically and expressed as antifibrinolytic equivalent. In addition, a battery of blood coagulation tests was performed daily. 5 patients died, 1 after postoperative stroke, 3 as a result of general complications during intensive care treatment, but only 1 due to rebleeding. 4 patients were successfully operated during the first week, 1 patient after 2 weeks. aPl fell from 99.2% (SEM 3.0%, n = 21) before treatment to 72.9% (SEM 3.5%, n = 21) after 24 h and to the therapeutic level between 50 and 60% from day 2 on. The mean steady state of the antifibrinolytic equivalent corresponded to about 150 µg/ml of tranexamic acid during infusion. Intra- and interindividual changes were relatively small for aPl, when compared with the antifibrinolytic equivalent measured by the bioassay. In 2 elderly patients tranexamic acid infusion had to be terminated because of clinical and laboratory signs of disseminated intravascular coagulation, whereby aPl fell below the therapeutic range, elucidating that this method is a sensitive indicator for a hypercoagulable state and useful for the surveillance of therapy with antifibrinolytic agents.

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Determination of tranexamic acid (AMCA) and fibrin/fibrinogen degradation products in cerebrospinal fluid after aneurysmal subarachnoid haemorrhage

Cited by 31 publications

References 30 publications

Combination of aminocaproic acid and nicardipine in treatment of aneurysmal subarachnoid hemorrhage.

Combination of aminocaproic acid and nicardipine in treatment of aneurysmal subarachnoid hemorrhage.

Management of aneurysmal subarachnoid hemorrhage.

Monitoring of Antifibrinolytic Treatment in Subarachnoid Hemorrhage

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