Fibrinolytic Activity In Cerebrospinal Fluid Research Articles

Fibrinolytic Activity in Cerebrospinal Fluid of Dogs with Different Neurological Disorders

Fibrinolytic activity in cerebrospinal fluid (CSF) is activated in humans by different pathologic processes. To investigate fibrinolytic activity in the CSF of dogs with neurological disorders by measuring CSF D-dimer concentrations. One hundred and sixty-nine dogs with neurological disorders, 7 dogs with systemic inflammatory diseases without central nervous system involvement (SID), and 7 healthy Beagles were included in the study. Dogs with neurological disorders included 11 with steroid-responsive meningitis-arteritis (SRMA), 37 with other inflammatory neurological diseases (INF), 38 with neoplasia affecting the central nervous system (NEO), 28 with spinal compressive disorders (SCC), 15 with idiopathic epilepsy (IE), and 40 with noninflammatory neurological disorders (NON-INF). Prospective observational study. D-dimers and C-reactive protein (CRP) were simultaneously measured in paired CSF and blood samples. D-dimers and CRP were detected in 79/183 (43%) and in 182/183 (99.5%) CSF samples, respectively. All dogs with IE, SID, and controls had undetectable concentrations of D-dimers in the CSF. CSF D-dimer concentrations were significantly (P < .001) higher in dogs with SRMA than in dogs with other diseases and controls. CSF CRP concentration in dogs with SRMA was significantly (P < .001) higher than in dogs of other groups and controls, except for the SID group. No correlation was found between blood and CSF D-dimer concentrations. Intrathecal fibrinolytic activity seems to be activated in some canine neurological disorders, and it is high in severe meningeal inflammatory diseases. CSF D-dimer concentrations may be considered a diagnostic marker for SRMA.

Fibrinolytic activity of the cerebrospinal fluid after subarachnoid haemorrhage.

The fibrinolytic activity of peripheral blood and cerebrospinal fluid was estimated by the fibrin plate method and by assays for fibrin degradation products in 11 patients with proven aneurysmal subarach-noid haemorrhage. Five of the patients were treated conservatively; the remaining 6, surgically. An increase in the fibrinolytic activity of the cerebrospinal fluid, as judged from the appearance of fibrin degradation products, occurred in all the patients on the third day after the initial haemorrhage. This fibrinolytic activity tended to decrease the first three weeks after the onset of the haemorrhage in 7 patients. In the remaining 4 it was still elevated at the end of the third week. In one of these patients haemorrhage recurred. Demonstration of high concentrations of fibrin degradation products in cerebrospinal fluid after surgery on the brain suggests the release of tissue activators from the damaged brain during the operation. Premature dissolution of the haemostatic plug at the site of the ruptured intra-cranial aneurysm might therefore be responsible for the rebleeding. Hence the use of anti-fibrinolytic drugs may be useful in the management of patients with subarachnoid haemorrhage.

On stimulation of fibrinolytic activity by pneumoencephalography.

The fibrinolytic activity of blood and cerebrospinal fluid (CSF) after pneumoencephalography (PE) has been investigated in ten patients. Samples of blood and CSF were collected and assayed before and 10, 20, 30, and 60 minutes after PE. It was noted that the rise in fibrinolytic activity in CSF preceded the increased fibrinolytic activity which occurred in blood and was of shorter duration. It is suggested that two different mechanisms are involved in the enhancement of fibrinolytic activity in blood and CSF. Injection of air may produce the release of fibrinolytic agents into the CSF from meninges and choroidal plexus which are very rich in plasminogen activator. The stimulation of systemic fibrinolytic activity seems instead mediated by the action of the neurovegetative system.

Procoagulant and fibrinolytic activity in cerebrospinal fluid from adults with bacterial meningitis

This study investigated levels of coagulation and fibrinolysis factors in cerebrospinal fluid (CSF) from adults with bacterial meningitis in relation to development of brain infarction. CSF was collected from 92 adults with community-acquired bacterial meningitis, who participated in the prospective Dutch Meningitis Cohort Study; 8 patients with viral meningitis and 9 healthy control subjects. Levels of proteins involved in the coagulation cascade were determined by means of immunoassays. Bacterial meningitis was accompanied by local activation of coagulation, as shown by significantly higher CSF soluble tissue factor (P<0.001) and prothrombin fragment F1+2 concentrations (P<0.001) as compared to viral meningitis patients and controls. This was accompanied by a significantly higher D-dimer formation (P<0.001). In addition, in bacterial meningitis fibrinolysis was attenuated, since CSF plasminogen activator inhibitor (PAI)-1 levels were significantly higher as compared to the controls (P=0.02). In patients with bacterial meningitis who developed brain infarction, CSF PAI-1 levels were higher than in those without infarction (P=0.04). Activation of coagulation and attenuation of fibrinolysis in the CSF are important features of bacterial meningitis; the net effect on fibrin turnover may contribute to the development of brain infarction.

The fibrinolytic activity of cerebrospinal fluid after subarachnoid hemorrhage.

Fibrinolytic activity of cerebrospinal fluid and peripheral blood was studied in 14 patients with subarachnoid hemorrhage during the high-risk period of subarachnoid rebleeding. Fibrinolytic activity of cerebrospinal fluid or peripheral blood could not be demonstrated. Determination of fibrin degradation products showed high levels in cerebrospinal fluid, being a result of meningeal irritation. The findings in this study--as well as other observations--suggest, that antifibrinolytic therapy should not be administered in patients with subarachnoid hemorrhage.

Fibrinolytic activity in CSF of patients with SAH in the acute phase measured by a rapid method (correlation with t-AMCA concentration in CSF.

To decide the minimum dose of antifibrinolytic agent for the conservative treatment of subarachnoid hemorrhage (SAH) in the acute phase, we developed a method to measure reduction in fibrinolytic activity of the cerebrospinal fluid (CSF) within a short period of time. It was reproducible and the result was expressed by the t-AMCA score. CSF was collected every 30 minutes or six hours in nine cases of SAH who were treated with an antifibrinolytic agent (t-AMCA) at a daily dose of 4-6 grams and the t-AMCA score obtained was compared with the dosage, t-AMCA concentration in CSF and daily excretion volume of CSF through drainage. The results showed that the concentration of antifibrinolytic agent in CSF was negatively correlated with the daily excretion volume of CSF, and correlated with the dosage when the excretion volume was under 150 ml/day. The t-AMCA score usually changed in a constant pattern which was not related to the concentration of antifibrinolytic agent in CSF. In cases in which treatment was initiated within 48 hours after the hemorrhage, rapid reduction of the fibrinolytic activity in CSF was obtainted within 24 hours after administration, while in one case in which treatment was performed on the 6th day after hemorrhage, a favorable reduction in the fibrinolytic activity could not be obtained until the third day after administration. In a case in which repeated assays were performed in a short period, rebound fibrinolysis was observed two hours after administration and three days after withdrawal.

Monitoring fibrinolytic activity in the cerebrospinal fluid after aneurysmal subarachnoid haemorrhage: a guide to the risk of rebleeding?

Serial assay of fibrin degradation products (FDPs) was used to monitor fibrinolytic activity in blood and cerebrospinal fluid (CSF) after subarachnoid haemorrhage (SAH) in 64 patients, 43 of whom had aneurysms. CSF levels fell rapidly from high initial values over a few days, thereafter more slowly to reach normal levels after one to six weeks. Probably only the later slow decline is a measure of fibrinolysis, which is obscured in the first few days by the cross antigenicity with FDP's of fibrinogen released by the bleed. After this phase of fibrinogen clearance, early attainment of normal FDP levels appears to be associated with a lower risk of rebleeding in cases of aneurysm. This phenomenon could be useful in deciding whether marginal cases should be treated surgically or conservatively.

Coagulation and fibrinolytic activity of cerebrospinal fluid.

Fibrin/fibrinogen degradation products (fragments D and E) were detected in cerebrospinal fluid in 23.4% of 252 patients admitted to a neurological/neurosurgical unit. Other coagulation proteins of low molecular weight (plasminogen and factor IX) were also present but larger proteins (fibrinogen and factor V) were not. These findings are consistent with protein leakage across a blood-CSF barrier damaged by inflammatory, vascular, or neoplastic disease. Fibrin/fibrinogen degradation products in cerebrospinal fluid after subarachnoid haemorrhage may not, therefore, be a reliable index of increased fibrinolytic activity in the subarachnoid space and may be misleading when selecting patients for fibrinolytic blockade.

Role of local fibrinolytic activity on rebleeding of ruptured aneurysm (author's transl)

The fibrinolytic activity of cerebrospinal fluid has been studied in 60 cases with subarachnoid hemorrhage by Astrup's biochemical method. In 26 cases of them the fibrinolytic activity of CSF has been measured repeatedly during early stage of subarachnoid hemorrhage. It increased especially in the first one week after subarachnoid hemorrhage in all cases, and decreased gradually when the rebleeding of reptured aneurysm did not take place. On the other hand, increased fibrinolytic activity of CSF was detected repeatedly or gradually when rebleeding occured afterward. These results suggested the relationship between rebleeding of ruptured aneurysm and increased fibrinolytic activity of CSF. The authers forcasted the rebleeding of subarachnoid hemorrhage and determined the best time of operation by monitoring of fibrinolytic activity in CSF. Compared with alteration of fibrinolytic activity of CSF, the fibrinolytic activity of serum was normal continuously after subarachnoid hemorrhage. It has been suggested that local fibrinolysis would cause rebleeding of ruptured aneurysm. Fibrin-fibrinogen degradation products (FDP) was increased in CSF with subarachnoid hemorrhage. FDP, D fraction was detected in bloody CSF, but FDP, X, Y, and E fractions were not detected in CSF with subarachnoid hemorrhage immunologically. This result also suggested increased local fibrinolysis. Localization of fibrinolytic activity in tissue has been studied in 9 aneurysms and 5 arterio-venous malformation by Todd's fibrin slide technique and immunofluorence study. Increased activity was seen in adventitia and endothelium of ruptured aneurysm, arachnoid menbrane, area of brain softening and wall of vessels of arterio-venous malformation. Increased fibrinolytic activity in CSF with subarachnoid hemorrhage must be released from these structures. The authors emphasized the important role of local fibrinolytic activity on rebleeding of ruptured aneurysm.

Fibrinolytic Activity of Cerebro-Spinal Fluid and the Development of Artificial Cerebral Haematomas in Dogs

SummaryBlood was injected into the brains of dogs to produce artificial haematomas, and paraffin injected to produce intracerebral paraffin masses. Cerebrospinal fluid (CSF) and peripheral blood samples were withdrawn at regular intervals and their fibrinolytic activities estimated by the fibrin plate method. Trans-form aminomethylcyclohexane-carboxylic acid (t-AMCHA) was administered to some individuals. Genera] relationships were found between changes in CSF fibrinolytic activity, area of tissue damage and survival time. t-AMCHA was clearly beneficial to those animals given a programme of administration. Tissue activator was extracted from the brain tissue after death or sacrifice for haematoma examination. The possible role of tissue activator in relation to haematoma development, and clinical implications of the results, are discussed.

B-2. Intracerebral Paraffin Injection and Changes in Fibrinolytic Activity of Cerebro-Spinal Fluid in Dogs

b-2. Intracerebral Paraffin Injection and Changes in Fibrinolytic Activity of Cerebro-Spinal Fluid in Dogs