المؤلفون: R. M. Loreth, M. Meyer, F. W. Albert

المصدر: Pathophysiology of Haemostasis and Thrombosis. 31:12-17

مصطلحات موضوعية: Male, medicine.medical_specialty, Fibrinopeptide B, Hemorrhage, Biology, Fibrinogen, Thrombin, Physiology (medical), Internal medicine, medicine, Coagulation testing, Coagulopathy, Humans, Point Mutation, Dysfibrinogenemia, Fibrinopeptide A, Blood coagulation test, Family Health, Genetics, Fibrinogens, Abnormal, Point mutation, Sequence Analysis, DNA, Hematology, Blood Coagulation Disorders, Middle Aged, medicine.disease, Endocrinology, Blood Coagulation Tests, circulatory and respiratory physiology, medicine.drug

الوصف: An abnormal fibrinogen was identified in a man with suspicious prolonged prothrombin time and a mild bleeding tendency. Coagulation studies showed marked prolonged thrombin and reptilase clotting times and a discrepancy between functional fibrinogen test and fibrinogen antigen. The rate of fibrinopeptide B release by thrombin was slightly delayed while the release of fibrinopeptide A was only half the normal amount. DNA sequencing revealed a heterozygous C to T point mutation in position 1202 of exon 2 of the Aα chain, resulting in the substitution of Arg → Cys at position 16, the thrombin cleavage site. This mutation was found also in his 2 children. Both had a mild bleeding tendency too.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1b8cf5fe529f60ba137a4cdc51f386c3Test
https://doi.org/10.1159/000048039Test

المؤلفون: Vicenta Martínez-Sales, Virtudes Vila, M.A. Palencia, Edelmiro Reganon, M.A. Goberna, Justo Aznar, F. Ferrando

المصدر: Pathophysiology of Haemostasis and Thrombosis. 28:301-306

مصطلحات موضوعية: Male, medicine.medical_specialty, Lipoproteins, Myocardial Infarction, Fibrinogen, Thromboplastin, Tissue factor pathway inhibitor, Fibrinolytic Agents, Von Willebrand factor, Physiology (medical), Internal medicine, von Willebrand Factor, Humans, Medicine, Fibrinopeptide, Myocardial infarction, Blood Coagulation, Aged, Fibrinopeptide A, Aspirin, biology, business.industry, Follow up studies, Hematology, Middle Aged, beta-Thromboglobulin, medicine.disease, Thrombosis, Peptide Fragments, Surgery, Cardiology, biology.protein, Female, Prothrombin, business, Follow-Up Studies, medicine.drug

الوصف: This study examines the evolution of the thrombotic activity in patients with myocardial infarction (MI) treated with aspirin (200 mg/day) for 2 years after MI. Plasma samples of 10 patients were collected at 7, 30, 60, 90, 120, 150, 180, 360 and 720 days. In all the samples we measured fibrinogen (Fg), high molecular weight Fg (HMW-Fg), fibrinopeptide A (FPA), prothrombin fragment 1+2 (F1+2), β-thromboglobulin (β-TG), von Willebrand factor (vWF), tissue factor (TF) and TF pathway inhibitor (TFPI). The plasma Fg, HMW-Fg, FPA, F1+2, β-TG and vWF levels were significantly elevated in the patients at the beginning of the study as compared to the normal group. The 95% confidence intervals were Fg 277–333 mg/dl, HMW-Fg 200–244 mg/dl, FPA 5.3–16.5 ng/ml, F1+2 1.4–1.8 nmol/l, β-TG 110–118 IU/ml and vWF 139–195%. At thirty days Fg and HMW-Fg returned to normal levels, whereas the increase in FPA and F1+2 levels persisted throughout the study. At 120 and 150 days, respectively, β-TG and vWF returned to normal levels. The increase in thrombin generation and activity pointed to a persistent hypercoagulable state 2 years after MI. Plasma levels of TF and TFPI showed no statistically significant variations with respect to the normal values over the 2-year period studied. In conclusion, these results suggest a persistent generation and activity of thrombin and cellular activation in these patients after MI.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::41825d92d0fe468e517917a90c3dad9eTest
https://doi.org/10.1159/000022446Test

المؤلفون: G.G. Sorano, P. Paoletti, Francesco Marongiu, G. Casciu, G. Mameli

المصدر: Scopus-Elsevier

مصطلحات موضوعية: Adult, medicine.medical_specialty, Iohexol, medicine.medical_treatment, Antithrombin III, Contrast Media, Fibrin, Fibrin Fibrinogen Degradation Products, Thrombin, Physiology (medical), Internal medicine, D-dimer, Fibrinolysis, medicine, Humans, Fibrinopeptide, Protein Precursors, Aged, Fibrinopeptide A, biology, Chemistry, PROTHROMBIN FRAGMENT 1.2, Osmolar Concentration, Hematology, Middle Aged, Peptide Fragments, Contrast medium, Endocrinology, Biochemistry, biology.protein, Prothrombin, Peptide Hydrolases, medicine.drug

الوصف: The principal aim of this study was to evaluate, on biochemical grounds, whether injection of a low-osmolar nonionic contrast medium (iohexol) can induce a prothrombotic state and/ or a change in fibrinolysis. Fifteen patients were submitted to urographic examination and the assays listed below were performed: before the injection (To), 1 h after (Ti), and 24 h after (T24) the injection of the contrast medium. The following assays were performed: fibrinopeptide A (FPA), prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT), and D dimer (D-D). The assays were carried out on 6 of the patients to whom a saline infusion was administered. Only a mild statistically significant increase was found in FPA levels at 1 h after injection of the contrast medium (mean and CI 95%: T0 4.4, 3.7-5.5; T, 6.0, 4.9-9.1; p = 0.003). F1+2, TAT and D-D did not show any significant change after the injection. These findings show that after injection of iohexol, only a mild, though statistically significant, increase in FPA levels was observed as an expression of increased thrombin activity. In the absence of any significant increases in TAT, F1+2 and D-D, we have no evidence of a prethrombotic state.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::090a9c95172c5a59d5eb43db05e26c37Test
https://doi.org/10.1159/000217444Test

المؤلفون: S. Pukrittayakammee, M. Vlizou, R. Clemens, R. Lorenz, N. Tornieporth

المصدر: Pathophysiology of Haemostasis and Thrombosis. 22:153-159

مصطلحات موضوعية: Hemostasis, Dose-Response Relationship, Drug, Heparin, business.industry, Antivenom, Metalloendopeptidases, Venom, Viper Venoms, Hematology, Pharmacology, Platelet Factor 4, Physiology (medical), Consumptive Coagulopathy, Endopeptidases, Immunology, Humans, Medicine, Fibrinopeptide, business, Platelet factor 4, Fibrinopeptide A, Whole blood

الوصف: Russell’s viper venom (RW) leads to a strong activation of the coagulation system with consumptive coagulopathy and thrombopenia. For better comprehension of the pathophysiologic process, the effect of RW was examined in an in vitro model of hemostasis. The stimulation of the coagulation system and of platelet activity can be discriminated by sequential measuring of fibrinopeptide A (FPA) generation and platelet factor 4 (PF 4) release, respectively. In coagulating whole blood both parameters show a parallel response curve in the control series (n = 6) with an initial slow phase followed by a rapid phase after 4.7 ± 0.8 min (FPA) and 6.0 ± 0.9 min (PF 4) of the incubation period. Varying concentrations of RW (15,50, 100 and 1,000 ng/ml; n = 6 each) cause a dose-dependent stimulation of FPA generation as well as of PF 4 secretion. Clot formation time shows a decrease from 9 min (controls) to 6.3 ± 2.0 min (100 ng/ml RW) and 2.7 ± 0.5 min (1,000 ng/ml), respectively. The concomitant addition of antithrombin III (AT III, 20 U/ml) and RW (100 ng/ml) leads to a nearly complete normalization of hemostasis in vitro. The beginning of the rapid activation phase is comparable to that of the control group, clot formation does not occur during the 10-min incubation period. Heparin (1 IU/ml) acts as an antagonist not only of the venom-induced FPA generation, but also of the PF 4 release. Prostaglandin E1 (PGE1 (150 ng/ml) does not inhibit the RW-stimulated FPA generation, but causes a moderate inhibition of PF 4 secretion, especially during the rapid phase. Clot formation time is prolonged to 7.3 ± 0.5 min, compared to 6.7 ± 2.0 min after RW alone. In conclusion, RW leads to a dose-dependent activation of hemostasis. PGE1 acts as an inhibitor of platelet activity without alteration of FPA generation, while heparin leads to the inhibition of both agents. At high concentrations AT III normalizes hemostasis and thus may become of therapeutic interest.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6121d3fc0d8b82f054d6a66c0281e344Test
https://doi.org/10.1159/000216312Test

المؤلفون: R.C. Maroun

المصدر: Pathophysiology of Haemostasis and Thrombosis. 31:247-256

مصطلحات موضوعية: Sequence analysis, Fibrinopeptide B, Sequence alignment, Context (language use), Hematology, Biology, complex mixtures, Serine, Thrombin, Biochemistry, Snake venom, Physiology (medical), medicine, Peptide sequence, medicine.drug

الوصف: Thrombin is a mammalian serine proteinase that plays a prominent role in the maintenance and regulation of hemostasis through its interaction with various substrates and/or ligands. The venoms of several snakes contain glycosylated serine proteinases that have been recognized to possess one or more of the essential activities of thrombin on fibrinogen (Fg) and/or platelets. These proteinases share about 60% sequence identity. One class of snake venom serine proteinases are those known as thrombin-like (TLE), named after their ability to directly clot Fg in order to preferentially produce fibrinopeptide A, fibrinopeptide B or both. To understand the molecular basis of this phenomenon, the corresponding amino acid sequences and molecular structures need to be analyzed. Given the absence of experimentally determined tertiary structures of snake venom, TLEs, three-dimensional molecular models should prove useful in this context. Towards this goal, we obtained models of snake venom TLEs that used TSV-PA as template, TSV-PA being the only snake venom serine proteinase whose crystal structure is known to date. Along with a comparative sequence analysis the models contribute to the identification and description of thrombin-homologous or alternative binding sites, helping thus to understand differences in specificity.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::92c738145566a81dfbd89fb611107940Test
https://doi.org/10.1159/000048070Test

المؤلفون: L. Vila, Montserrat Borrell, I. Coll, J. Solá, J. Fontcuberta

المصدر: Pathophysiology of Haemostasis and Thrombosis. 20:1-7

مصطلحات موضوعية: Male, medicine.medical_specialty, Alpha (ethology), Fibrinogen, Thrombin, Physiology (medical), Internal medicine, Fibrinogen Barcelona II, medicine, Coagulopathy, Humans, Fibrinopeptide, Amino Acid Sequence, Dysfibrinogenemia, Chromatography, High Pressure Liquid, Fibrinopeptide A, Chemistry, Fibrinogens, Abnormal, Hematology, Blood Coagulation Disorders, Middle Aged, medicine.disease, Pedigree, Kinetics, Endocrinology, Biochemistry, Blood Coagulation Tests, Major bleeding, medicine.drug

الوصف: We describe a new congenital dysfibrinogenemia: fibrinogen Barcelona II in 8 members of a family with no major bleeding or thrombotic tendency. Incubation of this fibrinogen with thrombin at low concentration releases half of the expected normal fibrinopeptide A (FPA) and with some delay it releases an abnormal FPA. Abnormal FPA was purified and sequenced and showed a change in the normal amino acid sequence: arginine in position 16 has been substituted by a histidine. This is another case of dysfibrinogenemia in which Aα 16 Arg → His has been identified as the cause of abnormal behavior of the fibrinogen molecule.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9526b369b05e1de00dc5428c858072dcTest
https://doi.org/10.1159/000216098Test

المؤلفون: Ulrich Abildgaard, Anne Karin Lindahl, Per Morten Sandset

المصدر: Pathophysiology of Haemostasis and Thrombosis. 21:254-257

مصطلحات موضوعية: medicine.drug_class, Lipoproteins, Antithrombin III, Pharmacology, Thromboplastin, Thrombin, In vivo, Physiology (medical), medicine, Humans, Blood Coagulation, Fibrinopeptide A, biology, Heparin, Chemistry, Antithrombin, Anticoagulant, Antibodies, Monoclonal, Biological activity, Hematology, Factor VII, Immunoglobulin G, Immunology, biology.protein, Antibody, medicine.drug

الوصف: Heparinization of blood inhibited the generation of fibrinopeptide A (FPA) after addition of thromboplastin (TP). Heparinization was more effective when performed in vivo than in vitro; the amounts of FPA at 60 s incubation were 8% and 32%, respectively, of control values in nonheparinized blood. When monospecific, neutralizing IgG against extrinsic pathway inhibitor (anti-EPI) were added to heparinized blood prior to TP, the amount of FPA increased to 65%. When monospecific IgG blocking antithrombin (anti-AT) was used, the amount of FPA increased to values similar to those in nonheparinized blood. When anti-AT and anti-EPI were both added to heparinized blood, FPA was generated about 25% faster than in normal blood. These results show that EPI contributes significantly to the anticoagulant effect of heparin in human blood.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8d38b49a616d8d310e57bc3fe19da49eTest
https://doi.org/10.1159/000216234Test

المؤلفون: W. Nieuwenhuizen, P. Mcculloch, W. D. George, Gordon D.O. Lowe, J.T. Douglas

المصدر: Pathophysiology of Haemostasis and Thrombosis. 20:73-80

مصطلحات موضوعية: Male, medicine.medical_specialty, Breast Neoplasms, Fibrinogen, Fibrin, Fibrin Fibrinogen Degradation Products, Immunoenzyme Techniques, Breast Diseases, Breast cancer, Physiology (medical), Internal medicine, medicine, Humans, Fibrinopeptide, medicine.diagnostic_test, biology, business.industry, Antibodies, Monoclonal, Cancer, Hematology, Blood Coagulation Disorders, Middle Aged, medicine.disease, Endocrinology, Coagulation, Immunoassay, Colonic Neoplasms, biology.protein, Cancer research, Female, Breast disease, business, Follow-Up Studies, medicine.drug

الوصف: Disturbances of coagulation were measured in breast cancer, colon cancer and benign breast disease using an enzyme immunoassay against total plasma fibrinogen and fibrin degradation products (TDP). Results were compared with measurements of fibrinopeptide A (FPA) and of serum fibrinogen-related antigen (FRA). Plasma TDP before surgery was significantly higher in colon cancer than in breast cancer patients (p = 0.0009) or in benign breast disease (p = 0.0292). A post-operative rise in TDP at 4 months (colon cancer) or 9 months (breast cancer) was associated with early recurrent disease (p < 0.0173 for colon cancer, p < 0.1835 for breast cancer). No such association was noted with FPA or FRA measurements. TDP may prove to be of value in detecting activation of coagulation by malignant disease.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::da28fadaa6d5f0cc767840976de3e596Test
https://doi.org/10.1159/000216111Test

المؤلفون: T. Mukaida, S. Okuno, K. Okada, T. Matsuo, O. Matsuo, S. Ueshima

المصدر: Pathophysiology of Haemostasis and Thrombosis. 17:89-97

مصطلحات موضوعية: Adult, medicine.medical_specialty, Polymers, Thrombin Time, Immunoelectrophoresis, Fibrinogen, Fibrin Fibrinogen Degradation Products, Physiology (medical), Internal medicine, medicine, Humans, Fibrinopeptide, Dysfibrinogenemia, Polyacrylamide gel electrophoresis, Fibrinopeptide A, Fibrin, medicine.diagnostic_test, business.industry, Fibrinogens, Abnormal, Osmolar Concentration, Thrombin, Hematology, Afibrinogenemia, medicine.disease, Factor XIII, Fibrin Monomer, Molecular biology, Pedigree, Blood, Endocrinology, Hereditary dysfibrinogenemia, Electrophoresis, Polyacrylamide Gel, Female, business, medicine.drug

الوصف: Abnormal function of fibrinogen was observed in a 2 5-year-old woman with no symptoms attributable to dysfibrinogenemia. Disturbed polymerization of fibrin monomer was identified, but the release of fibrinopeptide from the purified fibrinogen and the cross-linking by factor XIII were normal. Other abnormal findings included a high value of fibrinogen degradation products, rapid mobility on immunoelectrophoresis and abnormal spot of γ-chain on two-dimensional polyacrylamide gel electrophoresis. Similar abnormalities were also observed among the patient’s family members.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::85f8d0fe0d4568fd45b5e798968755f0Test
https://doi.org/10.1159/000215563Test

المؤلفون: G. Mulas, A. Medda, Antonella Balestrieri, G. Mameli, M.B. Tronci, A.M. Mamusa, Francesco Marongiu, M R Acca

المصدر: Scopus-Elsevier

مصطلحات موضوعية: Adult, Liver Cirrhosis, Male, medicine.medical_specialty, Cirrhosis, Plasmin, medicine.medical_treatment, Fibrin Fibrinogen Degradation Products, Liver Cirrhosis, Alcoholic, In vivo, Physiology (medical), Internal medicine, Blood plasma, Fibrinolysis, medicine, Humans, Fibrinopeptide, Fibrinopeptide B, Fibrinopeptide A, Disseminated intravascular coagulation, alpha-2-Antiplasmin, business.industry, Fibrinogen, Hematology, Middle Aged, medicine.disease, Peptide Fragments, Endocrinology, Immunology, Female, Chronic disseminated intravascular coagulation, business, medicine.drug

الوصف: In order to detect even minimal fibrinolysis activation in liver cirrhosis, we measured fibrinopeptide Bβ 15–42 (Bβ 15–42), an indicator of plasmin activity in vivo and α2-antiplasmin (α2-AP) in a group of cirrhotic patients. The second goal of this study was to investigate whether an increased fibrinolytic activity is related to a chronic disseminated intravascular coagulation. For this purpose we concomitantly measured fibrinopeptide A (FPA), marker of thrombin activity in vivo. Results show significantly higher levels of Bβ 15–42 in cirrhotic patients than in control (p < 0.01). In patients with high FPA levels we found significantly higher values than in patients with normal FPA (p < 0.01). α2-AP was lower in patients with high FPA levels than in patients with normal FPA (p < 0.05). A significant negative correlation was found between FPA and α2-AP only in patients with high FPA (p < 0.05). There was no relationship between Bβ 15–42 and FPA nor between Bβ 15–42 and α2-AP when all patients were considered. These findings confirm that in liver cirrhosis fibrinolysis activation may occur. The primary pathogenetic role of DIC may be important in this respect. However the lack of correlation between FPA and Bβ 15–42 suggests that other pathogenetic factors may be involved in determining fibrinolysis activation.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6542ed1043ce0ce98124f0862de96fd5Test
https://doi.org/10.1159/000215793Test