fibrinopeptide-a and Cerebral-Infarction

We found a heterozygous dysfibrinogenemia caused by a substitution of AαArg16Cys. The proband suffered multiple cerebral infarctions. Routine coagulation tests revealed a prolonged thrombin time. The fibrinogen levels in the functional assays were considerably lower than the levels in the immunological assays. The polymerization of the purified fibrinogen was strongly impaired in the presence of calcium. As previously observed in other heterozygous Aα R16C variants, the release rate and amount of fibrinopeptide A (FPA) were lower in the proband than those in normal controls. Additionally, the release of fibrinopeptide B (FpB) was delayed. The immunoblotting analysis using antibodies against human serum albumin indicated that albumin is bound to Aα R16C. The mass spectrometry analysis showed that the Aα R16C fibrinogen chains appeared in the patient's circulation. The clot structure analysis using scanning electron microscopy (SEM) revealed that the fibrin network was dense and consisted of thin and highly branched fibres. Using overlaid fibrinolytic enzymes in a clot lysis experiment, clot degradation was observed to be delayed. These results indicated that the thrombotic tendency may be ascribed to a fibrinolytic resistance caused by an abnormal clot structure with thin fibres and fibrinogen-albumin complexes.

Topics: Afibrinogenemia; Albumins; Blood Coagulation Tests; Cerebral Infarction; Fibrinogen; Fibrinolysis; Fibrinopeptide A; Heterozygote; Humans; Mutation, Missense; Protein Binding

Topics: Biomarkers; Blood Coagulation Tests; Cerebral Infarction; Disseminated Intravascular Coagulation; Fibrin Fibrinogen Degradation Products; Fibrinopeptide A; Fibrinopeptide B; Humans; Immunoenzyme Techniques; Myocardial Infarction; Peptide Fragments; Pulmonary Embolism; Radioimmunoassay; Thrombophilia; Venous Thrombosis

In order to find out the difference between single brain lacunar infarctions with transient signs and those with long-lasting signs, cerebral blood flow studies and blood tests were performed.. Ten cases of single lacunar infarction with transient signs and 10 of single lacunar infarction with long-lasting signs were studied. Subcortical cystic infarctions with a diameter of less than 1.5 cm were defined as lacunar infarction. Episodes lasting less than 24 hours were classified as transient signs and those lasting 24 hours or more as long-lasting signs.. cerebral blood flows were measured using the stable xenon computed tomography method. The regional cerebral blood flows were measured before and 20 minutes after the intravenous injection of 17 mg/kg acetazolamide. Plasma fibrinopeptide A, platelet factor 4 and beta-thromboglobulin concentrations were determined at the Special Reference Laboratories.. Blood flows in the cerebral cortex and cerebral white matter contralateral to the lacunar infarction were lower in the group with long-lasting signs than in that with transient signs. Cerebrovascular acetazolamide reactivity in the cerebral cortex and white matter contralateral to the lacunar infarction were lower in the group with long-lasting signs than in that with transient signs. Plasma fibrinopeptide A, platelet factor 4 and beta-thromboglobulin concentrations were higher in the long-lasting signs group than in that with transient signs.. There may be some differences in pathogenesis between single lacunar infarction with transient signs and those with long-lasting signs.

Topics: Acetazolamide; Aged; beta-Thromboglobulin; Biomarkers; Carbonic Anhydrase Inhibitors; Cerebral Infarction; Cerebrovascular Circulation; Female; Fibrinopeptide A; Humans; Male; Middle Aged; Platelet Activation; Platelet Factor 4; Tomography, X-Ray Computed

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

The present study was designed to examine the effects of sodium ozagrel on hemostatic markers and cerebral blood flow in lacunar infarction. Ten cases of lacunar infarction in which sodium ozagrel was given (administered group), 10 cases of lacunar infarction in which sodium ozagrel was not given (nonadministered group), and 10 age-matched controls in which cerebrovascular diseases were absent but risk factors were similar to those of the patients (control group) were studied. Intravenous infusion of 80 mg of sodium ozagrel was done twice a day for 2 weeks. Platelet factor 4, beta-thromboglobulin, and fibrinopeptide A were significantly higher in the administered and nonadministered groups than in the control group at the time of admission. Platelet factor 4, beta-thromboglobulin, fibrinopeptide A, and thromboxane B2 were decreased significantly by the administration of sodium ozagrel. The blood flow in the cerebral cortex was significantly lower in the administered and nonadministered groups than in the control group. The blood flows around the infarcted area, in the cerebral cortex, and in the cerebral white matter were significantly increased by the administration of sodium ozagrel. Sodium ozagrel is considered to decrease platelet aggregation and increase cerebral blood flow by decreasing thromboxane A2, which has a platelet-aggregating and a vasoconstricting action. Sodium ozagrel is considered to be effective in the acute phase of lacunar infarction.

Topics: Aged; beta-Thromboglobulin; Cerebral Infarction; Cerebrovascular Circulation; Enzyme Inhibitors; Fibrinopeptide A; Hemostasis; Humans; Magnetic Resonance Angiography; Methacrylates; Middle Aged; Platelet Factor 4; Thromboxane-A Synthase

The purpose of this study was to clarify differences in coagulation and fibrinolytic activation between the various subtypes and phases of ischaemic stroke. Haemostatic activation markers were measured in 52 patients with cardioembolic stroke, 32 with atherothrombotic stroke and 54 with lacunar stroke and compared with 23 age-matched controls. Data were obtained in the acute (< or = 7 days after onset), subacute (8-28 days) and chronic (> or = 29 days) phases of stroke. In patients with cardioembolic stroke, D-dimer and alpha 2-antiplasmin-plasmin complex levels were higher during the acute and subacute phases, while thrombin-antithrombin III complex levels were higher during the acute phase than in patients with lacunar stroke and controls. In cardioembolic stroke, fibrinopeptide A was increased during the acute and subacute phases, thrombin-antithrombin III complexes were higher during the subacute phase and D-dimer levels were higher during the chronic phase. Protein C activity was lower during the acute phase than in atherothrombotic stroke, lacunar stroke and controls. Protein C antigen was lower during the acute phase than in lacunar stroke and controls and during the chronic phase than in lacunar stroke. In contrast, only D-dimer levels were higher in atherothrombotic stroke patients than controls during the acute and chronic phases and no significant alterations in these markers were observed in the patients with lacunar stroke. These findings suggest that measurement of molecular markers of coagulation and fibrinolysis may be useful for detecting intracardiac thrombin and plasmin generation in patients with cardioembolic stroke.

Topics: Aged; alpha-2-Antiplasmin; Antifibrinolytic Agents; Antithrombin III; Arteriosclerosis; Cerebral Infarction; Cerebrovascular Disorders; Female; Fibrin Fibrinogen Degradation Products; Fibrinolysin; Fibrinopeptide A; Hemostasis; Humans; Intracranial Embolism and Thrombosis; Male; Middle Aged; Peptide Hydrolases

We measured levels of fibrinopeptide A, beta-thromboglobulin, and fibrinogen in the plasma of 27 patients 2 months after their first stroke. Concentrations of fibrinopeptide A, a sensitive index of in vivo hypercoagulability, were significantly higher in the 18 ischemic stroke patients than in 40 age- and sex-matched controls and in the six patients who experienced recurrence within 5 years than in the 12 who remained asymptomatic. On the contrary, fibrinopeptide A levels had no prognostic significance among the nine patients with hemorrhagic stroke. Concentrations of beta-thromboglobulin, an index of platelet activation, were higher in the 27 stroke patients than in the 40 controls, but this index was not associated with stroke recurrence. Fibrinogen levels were not significantly higher in stroke patients than in controls. In a multivariate regression analysis of hemostatic and clinical variables, only fibrinopeptide A levels of greater than 4 ng/ml were significantly related to cerebral infarction. Our results support the role of hypercoagulability in the recurrence of ischemic stroke and may allow identification of subjects at high risk for it. If confirmed in more patients, our results could provide a rationale for clinical trials of anticoagulant therapy in such patients.

Topics: beta-Thromboglobulin; Cerebral Infarction; Fibrinogen; Fibrinopeptide A; Humans; Osmolar Concentration; Prognosis; Recurrence; Survival

The mean levels of fibrinopeptide A (FPA), thrombin-antithrombin complex (TAT), and soluble fibrin (tPA method) in cancer patients (n = 32) were intermediate between those of patients with cerebral infarction and pancreatitis who had the most abnormal results and patients with myocardial infarction and pneumonia who had the least abnormal results. Patients with disseminated malignancies (n = 16) had significantly higher mean levels of FPA (10.6 vs. 5.3 nmol/l) and TAT (11.0 vs. 4.4 pmol/l) than patients with limited malignancies (n = 16). The difference in soluble fibrin (fibrin monomer, FM; 22.1 vs. 18.0 nmol/l) was not significant. The values of FPA, FM, and TAT in the patient population correlated significantly. There was a negative correlation between the level of antithrombin and test results for FPA (-0.69), FM (-0.48), and TAT (-0.38) in the cancer patients. Even cancer patients with locally limited disease may have elevated FPA, FM, and TAT test results, indicating a state of definite hypercoagulation.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Antithrombin III; Blood Coagulation Disorders; Blood Coagulation Tests; Cerebral Infarction; Female; Fibrin; Fibrinopeptide A; Humans; Male; Middle Aged; Myocardial Infarction; Neoplasms; Pancreatitis; Peptide Hydrolases; Pneumonia; Predictive Value of Tests; Reference Values

The well-known coagulation inhibitors antithrombin and protein C, and the more recently described inhibitors, heparin cofactor II and extrinsic pathway inhibitor, were measured in plasma during a 7-day observation period, from patients with pneumonia (n = 13), and in stroke patients with infarction (n = 9) and haemorrhage (n = 9). In patients with pneumonia, elevated fibrinopeptide A levels and subnormal antithrombin and protein C levels suggested some degree of consumption of the inhibitors. Later, an increase was observed for all the inhibitors, but was most conspicuous for heparin cofactor II which reached high normal values. C-reactive protein, initially markedly elevated, decreased rapidly. This finding suggests that heparin cofactor II might act as a delayed acute phase reactant. In stroke patients only small, not statistically significant, changes occurred during the observation period, except for heparin cofactor II which increased in patients with haemorrhagic stroke.

Topics: Acute-Phase Proteins; Adult; Aged; Anticoagulants; Antithrombins; C-Reactive Protein; Cerebral Hemorrhage; Cerebral Infarction; Cerebrovascular Disorders; Female; Fibrinopeptide A; Glycoproteins; Heparin Cofactor II; Humans; Male; Middle Aged; Pneumonia

Serial determinations of beta-thromboglobulin (BTG), platelet factor 4 (PF4), fibrinopeptide A (FPA), antithrombin III (ATIII), protein C (PC), fibrin (ogen) degradation product (FDP), FDP D-dimer, activated partial thromboplastin time (APTT), prothrombin time (PT), and euglobulin lysis time (ELT) were performed in 18 patients with non-progressing stroke and 14 patients with progressing stroke in order to predict the development of progressing stroke. Increasing levels of BTG, PF4 and FDP with frequent fluctuation were noted in both kinds of stroke. Fluctuation of FPA levels was also noted but was less pronounced. PC levels were found to be slightly decreased with fluctuation but the mean was still in the lower normal limit. BTG, PF4 and PC all elevated at the time of deterioration of physical condition in patients with progressing stroke, whereas FPA had no definite change at that time. From our study, we conclude that both platelet activation and coagulation process do occur in both kinds of stroke. But the latter plays a minor role in the formation of thrombosis. The hemostasis change, especially concerning the thrombosis formation, probably plays a role in the development of progressing stroke, but we cannot predict their development even by the detections of the newly known molecular substances appearing in various steps of the hemostatic mechanism. Development of new tests for understanding the whole dynamic change of the thrombosis process is necessary for accurate prediction of the progressing stroke in the future.

Topics: Aged; Antithrombin III; beta-Thromboglobulin; Cerebral Infarction; Female; Fibrin Fibrinogen Degradation Products; Fibrinopeptide A; Hemostasis; Humans; Male; Middle Aged; Partial Thromboplastin Time; Platelet Factor 4; Protein C; Prothrombin Time

Topics: Aged; Blood Coagulation; Cerebral Infarction; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinopeptide A; Fibrinopeptide B; Humans; Middle Aged; Myocardial Infarction; Neoplasms; Peptide Fragments