fibrinopeptide-a and Ischemic-Attack--Transient

Increased levels of markers of hemostasis may assist in the determination of the extent of carotid occlusive disease and the identification of neurologically intact individuals at increased risk of ischemic events.. We conducted a prospective study of 304 subjects, including 82 with a recent (< or =7 days) transient ischemic attack (TIA), 157 asymptomatic individuals with a cervical bruit, and 65 control subjects. Baseline evaluation included a neurological assessment, ECG, cervical ultrasonography, and cerebral CT and/or MRI. Levels of markers of coagulation and fibrinolytic activity were also determined. Results were analyzed in relation to the degree of carotid disease and the subsequent occurrence of cerebral and cardiac ischemic events.. Over a mean follow-up period of 2.8 years (SD, 1.3 years), 114 ischemic events occurred. Survival analyses showed that prothrombin fragment 1.2 (F(1.2)) was a predictor of time to cerebral and cardiac ischemic events in the combined TIA and asymptomatic bruit group (relative risk [RR], 1.46; 95% CI, 1.18 to 1.81) as well as in the asymptomatic bruit group separately (RR, 1.70; 95% CI, 1.14 to 2.53). In the TIA group, both F(1.2) (RR, 2.36; 95% CI, 1.19 to 4.68) and severe (> or =80%) carotid stenosis (RR, 3.53; 95% CI, 1.19 to 10.51) were predictive of time to ischemic stroke, myocardial infarction, or vascular death.. In patients with TIAs and in asymptomatic individuals with cervical bruits, F(1.2) levels were found to be independent predictors of subsequent cerebral and cardiac ischemic events. Our results are consistent with an active role of the coagulation system through upregulation of thrombin in carotid disease progression and in the pathogenesis of ischemic events in patients at risk.

Topics: Aged; alpha-2-Antiplasmin; Antifibrinolytic Agents; Antithrombin III; Biomarkers; Carotid Stenosis; Enzyme-Linked Immunosorbent Assay; Female; Fibrinolysin; Fibrinopeptide A; Hemostasis; Humans; Incidence; Ischemic Attack, Transient; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Peptide Hydrolases; Plasminogen Activator Inhibitor 1; Prognosis; Proportional Hazards Models; Prospective Studies; Prothrombin; Quebec; Risk Factors; Survival Rate

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

To determine whether patients with nonvalvular atrial fibrillation (NVAF) have prothrombotic changes compared with patients in sinus rhythm.. Cross-sectional study. Hemostatic function compared in NVAF patients without prior embolic event (transient ischemic attack or embolic stroke) and control subjects without prior thrombotic stroke, and in NVAF patients with prior embolic event and control subjects with prior thrombotic stroke.. Internal medicine outpatient group practice and anticoagulation clinic in 2 teaching hospitals.. A total of 75 NVAF patients (50 without and 25 with prior embolic event) and 42 control patients (31 without and 11 with prior thrombotic stroke) recruited concurrently over 18 months during 1990-91.. Platelet count, prothrombin time (PT), partial thromboplastin time (PTT), and plasma levels of hemoglobin, fibrinogen, von Willebrand factor antigen, factor VIII, fibrin D-dimer, antithrombin III, protein C, protein S, fibrinopeptide A and prothrombin fragment F1+2. All statistical analyses were performed after adjustments for age and sex.. The NVAF patients without a prior embolic event had significantly higher mean hemoglobin and fibrinogen levels (p < 0.001 and p = 0.05, respectively) than the control subjects without prior thrombotic stroke. The 29 NVAF patients not taking warfarin (none had had an embolic event) had significantly lower mean protein C and protein S levels (p = 0.012 and p < 0.001, respectively) and a significantly higher fibrinopeptide A level (p = 0.03, after exclusion of outliers) than the control subjects without prior stroke. The NVAF patients with a prior embolic event had alterations in the hemostatic variables similar to those seen in the control patients with a prior thrombotic stroke. The latter had significantly higher fibrinogen, von Willebrand factor antigen and factor VIII levels (p = 0.04, 0.002 and 0.002, respectively) and significantly lower protein S levels (p = 0.02) than the control subjects without prior stroke.. NVAF patients without a history of an embolic event show evidence of a prothrombotic state compared with patients in sinus rhythm who have not had a thrombotic stroke. NVAF patients with a history of an embolic event show evidence of a prothrombotic state similar to that of patients in sinus rhythm who have had a thrombotic stroke. Prospective studies are needed to determine whether these abnormalities predict higher risk of stroke in individual NVAF patients.

Topics: Aged; Anticoagulants; Antithrombin III; Atrial Fibrillation; Cross-Sectional Studies; Factor VIII; Female; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinopeptide A; Hemoglobins; Hemostasis; Humans; Intracranial Embolism and Thrombosis; Ischemic Attack, Transient; Male; Partial Thromboplastin Time; Peptide Fragments; Platelet Count; Protein C; Protein S; Prothrombin; Prothrombin Time; von Willebrand Factor; Warfarin

Hemostatic abnormalities have been shown previously in stroke patients. The purpose of this study was to assess the activity of selected parameters of the coagulation system in acute reversible cerebral ischemia.. We measured fibrinopeptide A, thrombin-antithrombin III, and D-dimer in 36 patients in both the acute (< 7 days) and postacute stage (1 and 3 months) after a transient ischemic attack (TIA). The results were compared with those of 20 asymptomatic patients with a history of remote TIA and 65 age- and sex-matched controls.. Mean fibrinopeptide A and thrombin-antithrombin III values were elevated in the acute stage after a TIA (P < .02) compared with levels at 1 month. In contrast, D-dimer was significantly increased at all three times points after the event when compared with remote TIA (P < .05) or control subjects (P < .001). No association could be found between marker levels and clinical outcome or the degree of cervical atherosclerosis as assessed by duplex ultrasonography.. These findings suggest that after acute reversible cerebral ischemia, there is early transient activation of thrombogenesis and ongoing fibrinolysis.

Topics: Aged; Aged, 80 and over; Antithrombin III; Biomarkers; Female; Fibrinopeptide A; Follow-Up Studies; Humans; Ischemic Attack, Transient; Male; Middle Aged; Peptide Hydrolases; Reference Values; Thrombin; Time Factors

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

Treatment with warfarin using a target International Normalized Ratio (INR) range of 1.7 to 2.5 is efficacious for many clinical indications, but the minimal intensity of anticoagulation required for antithrombotic protection has yet to be determined. To evaluate whether patients could be reliably monitored with a less intense regimen, we anticoagulated patients with warfarin for several months using a target INR range of 1.3 to 1.6 as determined by prothrombin time (PT) using a sensitive thromboplastin (Dade IS, International Sensitivity Index [ISI] = 1.3). Plasma measurements of F1+2, a marker of factor Xa action on prothrombin in vivo, were also obtained to determine the suppressive effect of warfarin on hemostatic system activity. Overall, 20 of 21 patients with a history of cerebrovascular events (mean age, 61 years) could be reliably regulated with warfarin in the target INR range. F1+2 levels were significantly suppressed from baseline in all patients, with a mean reduction of 49% (range, 28% to 78%). We found a significant relationship between the extent of suppression of prothrombin activation levels and the baseline measurements. A mean reduction of 65% was observed for those patients with baseline F1+2 greater than or equal to 1.5 nmol/L, but only 38% for baseline F1+2 less than or equal to 0.5 nmol/L. Overall, 68% of plasma samples obtained during stable anticoagulation were within the target INR range. PTs were also determined on all plasma samples with two thromboplastins of lower sensitivity (C+, ISI = 2.09; and automated simplastin, ISI = 2.10). Only 47% and 35% of PT determinations, respectively, were within the target range with these reagents. We conclude that prothrombin activation can be significantly suppressed in vivo with use of warfarin in an INR range of 1.3 to 1.6. This level of anticoagulation can be reliably achieved by monitoring PTs with a thromboplastin of high sensitivity.

Topics: Blood Coagulation; Cerebrovascular Disorders; Female; Fibrinopeptide A; Humans; Intracranial Embolism and Thrombosis; Ischemic Attack, Transient; Male; Middle Aged; Monitoring, Physiologic; Peptide Fragments; Prothrombin; Prothrombin Time; Radioimmunoassay; Thromboplastin; Warfarin

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

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

Plasma levels of beta-thromboglobulin (BTG) and fibrinopeptide A (FPA), markers of platelet alpha-granule release and thrombin generation respectively, were measured in 27 subjects with transient cerebral ischaemic attacks (TIA), 43 age-matched controls, and 32 young controls. BTG and FPA were both higher in elderly controls than in young controls. BTG was higher in TIA subjects than in age-matched controls and higher in the 12 TIA subjects who had further vascular events in the next year than in those who had no further events. FPA was not significantly associated with TIA or with further events. These results support a relationship between platelet activation and TIA and suggest that BTG levels indicate a group at higher risk of further vascular events.

Topics: Adult; Age Factors; Aged; Aspirin; Beta-Globulins; beta-Thromboglobulin; Blood Platelets; Cerebrovascular Disorders; Dipyridamole; Female; Fibrinopeptide A; Humans; Ischemic Attack, Transient; Male; Middle Aged; Prognosis; Risk; Time Factors