fibrinopeptide-a and Intracranial-Aneurysm

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

The aim of the study was to improve the detection of small hemorrhages with minimal symptoms and of unruptured aneurysms after a subdural and subarachnoid bleeding by the control of the intravascular hemostatic system.. Prospective, open study.. Neurosurgical intensive care unit of a university hospital.. 44 patients undergoing a cranial trepanation. Patients of group 1 (control n = 11) had an intrasellar hypophysoma, patients of group 2 (n = 12) a chronic subdural hematoma without a previous traumatic incident and patients of group 3 (n = 15) a subarachnoid hemorrhage caused by an intracranial aneurysm.. After cranial trepanation changes of plasmatic hemostasis have been assessed by means of immunologically determined parameters of coagulation. The investigation included blood parameters (hemoglobin, hematocrit, thrombocytes), clotting status (prothrombin time, partial thromboplastin time, thrombin time, fibrinogen, plasminogen, antithrombin III [AT III] activity and proteinase inhibitors), as well as immunological methods such as fibrinopeptide A (FPA), thrombin-antithrombin III (TAT), protein C and factor XIII activity (F XIII activity).. In comparison to group 1 (control) a significant difference (p < 0.001) was seen in groups 2 and 3 for thrombin-antithrombin III (TAT), fibrinopeptide A (FPA), protein C, and the antithrombin III activity. Intra- and postoperatively increased TAT levels in groups 2 (16.9 ng/ml) and 3 (21.1 ng/ml) and decreased protein C levels (group 2: 61% and group 3: 58%) demonstrated an intravascular thrombin generation. On account of the elevated FPA levels in groups 2 (6.5 ng/ml) and 3 (5.7 ng/ml) and decreased AT III activity in groups 2 (58%) and 3 (62%), this thrombin generation was only incompletely compensated. Caused by proteolytic thrombin effects, another sign for a thrombin-induced turnover of clotting factors is the significant reduction (p < 0.001) of F XIII activity in groups 2 (40%) and 3 (44%). In comparison to group 1 this significantly reduced F XIII activity in groups 2 and 3 was correlated (r = 0.99) to changes in FPA and TAT plasma levels, an indication of latent chronic clotting activity. No significant difference was found concerning total amount of infusion, intra- and postoperative blood loss and blood parameters. Eight patients (group 2: 5 patients, group 3: 3 patients) showed a rebleeding episode without operative interventions. In these patients increased clotting activity (TAT, FPA, protein C) caused by proteolytic thrombin effects was combined with a factor XIII activity smaller than 40%.. The results of the recent study indicated that immunologically determined TAT, FPA, protein C, factor XIII and AT III activities might serve to improve management in patients with intracranial bleeding events. In view of these parameters the evaluation of risks for a rebleeding is improved. A decrease of the plasma factor XIII activity under 40% associated with a latent clotting activity induced by a thrombin generation caused a higher risk of rebleeding after an initial intracranial bleeding event. The necessity of substituting factor XIII in such cases should be elucidated to minimize risks of rebleeding.

Topics: Aneurysm, Ruptured; Antithrombin III; Blood Coagulation Factors; Blood Coagulation Tests; Cerebral Hemorrhage; Factor XIII; Fibrin; Fibrinogen; Fibrinopeptide A; Hematoma, Subdural; Hemostasis, Surgical; Humans; Intracranial Aneurysm; Peptide Hydrolases; Plasminogen; Postoperative Complications; Protein C; Recurrence; Reference Values; Trephining

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

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