fibrinopeptide-a and Subarachnoid-Hemorrhage

Cerebral vasospasm (CVS) is a major contributor to the high morbidity and mortality of aneurysmal subarachnoid hemorrhage (aSAH) patients. We measured histidine-rich glycoprotein (HRG), a new biomarker of aSAH, in cerebrospinal fluid (CSF) to investigate whether HRG might be an early predictor of CVS. A total of seven controls and 14 aSAH patients (8 males, 6 females aged 53.4±15.4 years) were enrolled, and serial CSF and serum samples were taken. We allocated these samples to three phases (T1-T3) and measured HRG, interleukin (IL)-6, fibrinopeptide A (FpA), and 8-hydroxy-2'-deoxyguanosine (8OHdG) in the CSF, and the HRG in serum. We also examined the release of HRG in rat blood incubated in artificial CSF. In contrast to the other biomarkers examined, the change in the CSF HRG concentration was significantly different between the nonspasm and spasm groups (p<0.01). The rat blood/CSF model revealed a time course similar to that of the human CSF samples in the non-spasm group. HRG thus appears to have the potential to become an early predictor of CVS. In addition, the interaction of HRG with IL-6, FpA, and 8OHdG may form the pathology of CVS.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Aged, 80 and over; Animals; Biomarkers; Case-Control Studies; Deoxyguanosine; Female; Fibrinopeptide A; Humans; Interleukin-6; Intracranial Aneurysm; Male; Middle Aged; Proteins; Rats; Rats, Sprague-Dawley; Retrospective Studies; Subarachnoid Hemorrhage; Vasospasm, Intracranial

We previously reported that the coagulation system in cerebrospinal fluid (CSF) is strongly activated in the early stage of a subarachnoid haemorrhage (SAH). We evaluated the relationship among thrombin activity, degree of SAH, amount of clearance of SAH, and vasospasm. The CSF levels of fibrinopeptide A (FPA) were measured by radio-immunoassay in 36 SAH patients, who were diagnosed by computerized tomography (CT) within 12 hours and on whom surgery was performed within 48 hours. Clearance of SAH (%) was evaluated as the size of the clot in the basal cistern visualized between the initial and postoperative CT. The mean level of FPA in the patients of Group 3 (Fisher's CT classification) (182.2 ng/ml) was significantly higher than those in the patients of Group 2 (36.2 ng/ml). There was a significant difference in the mean level of FPA between patients with (47.6 ng/ml) and without infarction (408.3 ng/ml). In 18 of the 27 patients of Group 3 for whom the clearance of the SAH was determined, the patients showing a lower clearance rate (< 50%) of SAH demonstrated a significantly higher rate of infarction and a significantly higher level of FPA (466.6 ng/ml) than did the patients with a higher clearance rate (> 50%) of SAH (79.2 ng/ml). These results suggest that, the thrombin activity in CSF is correlated with the degree of SAH, the persistence of subarachnoid clot and the development of vasospasm.

Topics: Cerebral Infarction; Female; Fibrinopeptide A; Humans; Intracranial Embolism and Thrombosis; Ischemic Attack, Transient; Male; Postoperative Period; Subarachnoid Hemorrhage; Thrombin; Tomography, X-Ray Computed

Fibrinopeptide A (FPA) levels which have been shown to be a quantitative index of thrombin generation, were measured in blood and cerebrospinal fluid (CSF) samples from patients following subarachnoid haemorrhage (SAH) and from a control population. The levels found in samples obtained in patients following SAH are compared with those found in controls and also correlated with clinical grade on admission as assessed by the Glasgow Coma Score and the World Federation of Neurological Surgeons' grading system, and with the amount of subarachnoid blood seen on CT, the occurrence of ischaemic deterioration, the occurrence of low-density change on CT, the presence of vasospasm on angiography, clinical outcome as assessed by the Glasgow Outcome Score 3 months following the ictus, and the incidence of ischaemia as a cause of death or disability as assessed 3 months following the ictus. The levels of FPA found in blood and CSF from patients following SAH were significantly raised when compared with those found in controls. There was significant correlation between blood FPA levels and the amount of subarachnoid blood seen on initial CT. CSF FPA levels had a statistically significant correlation with outcome as assessed at 3 months post-ictus. No statistically significant correlation was found between blood or CSF FPA levels and any of the other variables studied.

Topics: Fibrinopeptide A; Follow-Up Studies; Glasgow Coma Scale; Humans; Intracranial Aneurysm; Ischemic Attack, Transient; Subarachnoid Hemorrhage; Thrombin

Topics: Bradykinin; Female; Fibrinogen; Fibrinopeptide A; Humans; Male; Middle Aged; Subarachnoid Hemorrhage; Time Factors

The cerebrospinal fluid (CSF) and plasma levels of the complement components C3a and C4a in 40 patients suffering from subarachnoid hemorrhage (SAH) were quantitated by radioimmunoassay. Serial measurements of the lumbar CSF levels revealed that the C3a and C4a levels were significantly elevated in the initial stage of SAH, but decreased rapidly. Within 48 hours after SAH, the mean C3a and C4a levels in the cisternal, lumbar, and ventricular CSF were significantly higher in patients with delayed ischemic neurological deficits (DIND) than in those without DIND. The serially measured plasma levels of C3a and C4a in patients with DIND were elevated more than in those without DIND, but they did not show a significant change over time. Simultaneous levels of fibrinopeptide A (FPA), an indicator of thrombin activity in CSF, were also measured by radioimmunoassay. There was a significant correlation between CSF-activated complement components and CSF FPA. These results suggest that complement activation occurred in the subarachnoid space soon after SAH, chiefly due to activation of the coagulation system. The higher CSF levels of C3a and C4a in patients with DIND may indicate a relationship between these components and the pathogenesis of cerebral vasospasms.

Topics: Adult; Aged; Blood Coagulation; Complement Activation; Complement C3a; Complement C4a; Female; Fibrinopeptide A; Humans; Ischemic Attack, Transient; Male; Middle Aged; Subarachnoid Hemorrhage

Topics: Adult; Aged; Aged, 80 and over; Blood Coagulation; Bradykinin; Connective Tissue; Factor XII; Female; Fibrinogen; Fibrinopeptide A; Humans; Male; Middle Aged; Subarachnoid Hemorrhage; Thromboxane B2

Fibrinopeptide A (FPA) levels as an indicator of thrombin activity in the cerebrospinal fluid (CSF) and plasma of 25 patients with subarachnoid haemorrhage (SAH) were measured serially by radioimmunoassay (RIA). FPA levels in CSF were extremely high on days 0-1 (1253 +/- 269 ng/ml, mean +/- standard error) but decreased rapidly (11.3 +/- 3.9 ng/ml on days 2-4, 10.7 +/- 5.9 ng/ml on days 5-7, and 6.3 +/- 1.5 ng/ml on days 8-14). In the controls the FPA concentration in CSF was 1.2 +/- 0.9 ng/ml (mean +/- standard deviation). Plasma FPA levels in patients with SAH showed no statistically significant changes with time. The bradykinin (BK) concentration in CSF and plasma in 27 patients with SAH was measured serially by RIA. The concentrations in CSF were 122.7 +/- 22.7 pg/ml (mean +/- standard error) on day 0, 38.6 +/- 6.1 pg/ml on day 1, 22.7 +/- 6.3 pg/ml on day 2, and 17.1 +/- 3.0 pg/ml or less thereafter. Plasma BK levels in patients with SAH were higher than those in the control group, but there was no statistically significant change over time. From the measurement of FPA it was apparent that the coagulation system in the subarachnoid space is strongly activated in the early stage of SAH. The formation of BK in CSF after SAH is thought to be due to the contact activation of Hageman factor (intrinsic factor) in the subarachnoid space. Trabeculae as collagen bundles in the subarachnoid space were considered to have a possible role in activating the Hageman factor of the coagulation system in SAH.

Topics: Adult; Aged; Blood Coagulation; Bradykinin; Female; Fibrinogen; Fibrinopeptide A; Humans; Male; Middle Aged; Subarachnoid Hemorrhage; Subarachnoid Space; Time Factors

Fibrinopeptide A (FPA), platelet-secreted protein, platelet factor 4 and beta-thromboglobulin were determined in the cerebrospinal fluid of patients who had suffered from subarachnoid hemorrhage and were treated with 6 g tranexamic acid or 4 million KIU aprotinin to prevent rebleeding. Platelet-secreted proteins and FPA were cleared from the cerebrospinal fluid within 3 days after bleeding. Their vasoactive and thrombotic capability is limited to the initiation period of vasospasm that usually comes to clinical observation 3-8 days after bleeding. Increased thrombotic activity of the cerebrospinal fluid, as reflected by high levels of FPA and platelet-secreted protein, seemed to promote the occurrence of neurological deficits.

Topics: beta-Thromboglobulin; Fibrinogen; Fibrinopeptide A; Humans; Ischemic Attack, Transient; Platelet Factor 4; Subarachnoid Hemorrhage; Tranexamic Acid

It is well known that abnormalities of coagulation and fibrinolysis frequently take place during the course of cerebrovascular diseases. In this paper, coagulation and fibrinolytic studies were performed during the course of acute stage through chronic stage of subarachnoid hemorrhage. Tested items were partial thromboplastin time, prothrombin time, FDP, alpha 2-plasmin inhibitor, antithrombin III, fibrinogen, besides, fibrinopeptide A (FPA), and fibrinopeptide B beta (FPB beta) which were being worthy of note. Blood were sampled from peripheral vein (V) and internal jugular vein at jugular bulb (J). And, moreover, cerebrospinal fluid (L) were collected as possible as we could for measuring FPA and FPB beta. The obtained results were summarized as follows; Within forty-eight hours from the onset of subarachnoid hemorrhage, FPA-V, J,L and FPB beta-V, J,L were statistically higher than those of control. FPA-J and FPB beta-V, J, within forty-eight hours from the onset were statistically higher in the cases with brain death than in the survived cases. On the third to fifth day from the onset when so called cerebral vasospasm became apparent to begin, FPA and FPB beta had a tendency to be higher than other periods. Increase of fibrinogen delayed from the peaks of FPA and FPB beta showing the peaks at the seventh to the fourteenth day from the onset of subarachnoid hemorrhage. In three cases with symptomatic vasospasm, FPA and FPB beta showed maximal values two to four days prior to the appearance of symptomatic cerebral vasospasm. Other tests were all within normal limits.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Blood Coagulation Tests; Female; Fibrinogen; Fibrinolysis; Fibrinopeptide A; Fibrinopeptide B; Humans; Intracranial Aneurysm; Ischemic Attack, Transient; Male; Middle Aged; Prognosis; Subarachnoid Hemorrhage