摘要:

Pulmonary hypertension is characterized by increased pressure in the pulmonary circulation and, in some cases, inflammation. Significant vascular remodeling occurs in response to these stresses and histopathology demonstrates in-situ thrombosis in a significant number of cases. Elevated shear stresses and inflammation, based on in-vitro data, would be expected to enhance platelet activation and aggregation/adhesion, increase release of von Willebrand factor, increase tissue factor expression, downregulate surface thrombomodulin with diminished thrombin inactivation and decreased protein C activation, and alter fibrinolytic factors with a net loss of fibrinolysis. Data from animal and human studies of pulmonary hypertension provide evidence for increased platelet activation, decreased platelet survival, increased release of von Willebrand factor antigen without an increase in activity, decreased soluble thrombomodulin and a net loss of fibrinolytic activity with excessive release of plasminogen activator inhibitor-1. These changes may result in in-situ thrombosis, which may occur as an inciting event of pulmonary hypertension, or as a consequence of other initiating factors. Chronic anticoagulation has been used in pulmonary hypertension based on observations of increased survival. However, the direct link between altered coagulation and the development or persistence of pulmonary hypertension awaits confirmation. Blood Coag Fibrinol 9:107–117 × 1998 Lippincott-Raven Publishers.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Recombinant factor VIIa (rFVIIa) represents a major therapeutic advance in the treatment of haemophilia patients with inhibitors. The efficacy and safety of rFVIIa has been extensively studied in over 1900 surgical and non-surgical bleeding episodes in over 400 patients with haemophilia A or B (with or without inhibitors) or acquired haemophilia. Of 103 evaluable surgical bleeding episodes, the response to treatment with rFVIIa was considered to be either excellent or effective in 81%, 86% and 92% of major, minor and dental bleeding episodes, respectively. Treatment has been evaluated in 518 serious bleeding episodes and the response was considered either excellent or effective in 62% of muscle, 80% of ear, nose and throat, 88% of central nervous system, 76% of joint, and 75% of internal or retroperitoneal bleeding episodes. An excellent safety profile has also been demonstrated: of 1957 treatments with rFVIIa, only 16 serious adverse events have been reported that were considered to be possibly, but not necessarily, related to treatment. Blood Coag Fibrinol 9:119–128 × 1998 Lippincott-Raven Publishers.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

This study reports on the predictive value of some haemostatic factors [fibrinogen, factor VII and plasminogen activator inhibitor (PAI)], a marker of endothelial damage (soluble thrombomodulin) and several markers of haemostatic system activation (factor VIIa, prothrombin fragment 1+2, thrombin-antithrombin complexes and D-dimers) on the incidence of vascular events in male, non-diabetic patients with chronic ischaemia of the lower limbs. The patients (n = 324) were recruited consecutively in the thermal resort of Royat, France. The low incidence of death from vascular causes during the 2-year survey period (two patients) and the high percentage of former smokers (71%) indicated that this population of patients was affected by an arteriopathy of moderate intensity. After 2 years' follow-up, vascular events had occurred in 51 patients. The clinical and biological profiles did not differ significantly between patients with and without vascular events. However, the risk of vascular events during the 2 years of follow-up was significantly higher in those with high levels of PAI antigen and thrombin-antithrombin complexes. Thus, even in a population of patients with only moderately severe arteriopathy, high levels of thrombin-antithrombin complexes and PAI are predictive of vascular complications. Blood Coag Fibrinol 9:129–135 × 1998 Lippincott-Raven Publishers.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Low-molecular-mass heparins (LMMHs) exert an anti-FXa effect through antithrombin III (ATIII) and tissue factor pathway inhibitor (TFPI) displaced from endothelium and lipoproteins. This global anti-FXa potency is specific for different compounds. Whether these effects have a similar kinetic and duration is a matter of interest. We compared the kinetic profile of the TFPI effect (total and free) to the anti-FXa amidolytic activity induced by therapeutic subcutaneous doses of a new LMMH, Bemiparin. The overall kinetics of the anti-FXa amidolytic activity and the TFPI effect were different, TFPI achieving a maximal effect earlier than the anti-FXa activity and completely disappearing before it. The anti-FXa amidolytic activity of Bemiparin followed a linear dose-response pattern. Neither total nor free TFPI was directly proportional to the dose. At therapeutic subcutaneous doses, Bemiparin exerted an anti-FXa effect through TFPI during the first 2 h, through both ATIII and TFPI during the following 8 h (range 2–10 h) and through ATIII during the last 8 h (range 10–18 h). Blood Coag Fibrinol 9:137–141 × 1998 Lippincott-Raven Publishers.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

A family with hereditary factor X deficiency is presented. One member, a 25-year-old man, showed a mild bleeding tendency. His factor X activity (extrinsic: 56%; intrinsic: 55%; Russell's viper venom: 57%) and his level of circulating factor X antigen (55% of normal) were markedly reduced. Analysis of his factor X gene revealed a single point mutation within exon II resulting in the substitution of +25 Gla (GAA) by Lys (AAA). The mutation was determined by gene analysis to be heterozygous in this patient, his mother and one of his brothers. Clotting assays of factor X purified from the plasma of the index patient revealed an activity of 89% of normal upon activation with Russell's viper venom, 77% of normal in the intrinsic and 81% of normal in the extrinsic coagulation pathway. The mutation responsible for the substitution of Lys for Gla+25 was introduced into an expression plasmid containing a wild type factor X cDNA and expressed in a mammalian cell line. Factor X antigen levels in the cell lysates and in the supernatant were identical in the mutant and wild type constructs. The specific activity of the factor X expressed from the mutant construct was 3% compared with the wild type construct. These data demonstrate that the substitution of Lys for Gla+25 results not only in a reduced level of factor X in the affected family members, but also in a substantial loss of specific factor X activity. Blood Coag Fibrinol 9:143–152 × 1998 Lippincott-Raven Publishers.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

A stable immortalized venous endothelial cell (IVEC) line, obtained by transfection of human umbilical vein endothelial cells (HUVEC), retains many normal differentiated endothelial characteristics. We compared the fibrinolytic activities of IVEC and HUVEC, and observed that IVEC express a more profibrinolytic phenotype than HUVEC, since they bind and activate plasminogen more efficiently, produce more tissue plasminogen activator and urokinase-type plasminogen activator antigens, and secrete less plasminogen activator inhibitor-1 antigen both under basal conditions and after stimulation with lipopolysaccharide, phorbol ester and tumor necrosis factor. Moreover, immunostaining and Western blotting of IVEC for the plasminogen/tissue plasminogen activator receptor annexin II, as well as Northern blotting of annexin II mRNA, revealed similar patterns of surface expression in IVEC and HUVEC. Plasminogen activator inhibitor-2 is expressed similarly in both cell types. IVEC may be a useful human model for functional and pharmacological explorations and modulations of fibrinolytic system components. Blood Coag Fibrinol 9:153–165 × 1998 Lippincott-Raven Publishers.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The pathogenic mechanisms of thrombosis during inflammatory syndromes are unknown. The aim of our study was to evaluate coagulation activation and fibrinolysis and to study an acquired protein S deficiency in 58 patients with an inflammatory syndrome of neoplastic (16), infectious (24) or systemic (18) origin and in 54 control subjects. The results indicated that coagulation activation, demonstrated by an increase in the prothrombin fragment 1+2, was present in patients with an inflammatory syndrome regardless of its origin. Free protein S, the only functionally active protein, was not reduced even though C4b-binding protein was increased in inflammatory syndromes. Thus, a prothrombotic state was found in inflammatory syndromes but is not explained by an acquired protein S deficiency. All except five patients had normal plasminogen activator inhibitor-1 levels. Blood Coag Fibrinol 9:167–171 × 1998 Lippincott-Raven Publishers.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

We report a thrombotic family with combined type I antithrombin deficiency and factor V Leiden (factor V-R506Q) in which the proposita, affected by recurrent venous and arterial thrombosis, was also characterized by mild hyperhomocysteinemia (28 $mUmol/l; normal < 18.5 $mUmol/1). Her two thrombotic sisters, with normal antithrombin levels and factor V molecules, showed hyperhomocysteinemia (51 and 30 $mUol/1, respectively). Four other members of the family had the combined antithrombin/factor V Leiden defect and two of them had thrombosis. The common A223V mutation in the methylenetetrahydrofolate reductase gene, responsible for the thermolabile variant of the enzyme, was found to be heterozygous in the proposita; the two sisters were homozygous and heterozygous, respectively. The heterozygous sister also had a high titre of antiphospholipid antibodies (85 units of immunoglobulin G antiphospholipid antibody/ml). Furthermore, low plasma folate levels were found in the three hyper-homocysteinemic subjects of the family. This family with several prothrombotic defects is a clear example of the polyfactorial nature of thrombophilia. Blood Coag Fibrinol 9:173–176 × 1998 Lippincott-Raven Publishers.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The binding of tissue factor to factors VII and VIIa (VII/VIIa) is the primary step for coagulation activation. Variants of human tissue factor leading to alterations in the binding to factor VII/VIIa have not been reported. We hypothesize that increased or decreased binding of tissue factor to factor VIIa might result in thrombosis and bleeding, respectively. The aim of this study was to establish an enzyme-linked immunosorbent assay to detect abnormalities in the binding of human tissue factor to recombinant factor VIIa (rVIIa). Tissue factor obtained from human monocytes was bound to rVIIa on microtiter wells in the presence of calcium. A murine antibody against human tissue factor and a biotinylated goat anti-mouse immunoglobuline were added. After incubation with streptavidin-horseradish peroxidase, colour development was measured using a chromogenic indicator system. Optimal assay conditions were obtained at tissue factor concentrations of 50–1500 pg/ml and rVIIa concentrations of 2.5 $mUg/ml. The binding of tissue factor to rVIIa was calcium-dependent and was inhibited by a monoclonal tissue factor antibody directed against the binding sites of tissue factor to rVIIa. The assay was evaluated in 23 healthy volunteers. Intra- and interassay variabilities were 3.9% and 10.2%, respectively. Among 22 subjects with unexplained bleeding and 47 patients with unexplained thrombosis, an individual with a decreased or increased binding of tissue factor to rVIIa could not yet be identified. In conclusion, this novel enzyme-linked immunosorbent assay can be used to detect and quantify an increased or a decreased binding of human tissue factor to rVIIa. Studies in patients indicate that, if such a defect exists, it is not a common cause of thrombosis or bleeding. Blood Coag Fibrinol 9:177–182 × 1998 Lippincott-Raven Publishers.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

We have developed an automated chromogenic peptide substrate assay for factor XII (FXIIcs) on a Cobas Mira S Plus clinical chemistry analyser using a new commercially available kit. This was used to determine factor XII (FXII) levels in plasma samples from 320 blood donors, 206 patients with a history of venous thrombosis and 74 lupus anticoagulant positive (LA+) patients. Results were compared with those obtained in a clotting assay for FXII (FXIIct) and an immunochemical assay (FXIIag). A satisfactory correlation coefficient of 0.92 and a regression line equation of y = 7.898 + 0.871x was obtained between FXIIcs and FXIIct in the 320 blood donors. Levels of FXII below the calculated normal range were found in nine blood donors (2.8%) and 16 venous thrombosis patients (7.8%). The blood donors and patients with venous thrombosis with low FXIIcs values had FXII levels below our lower limits of normal for both FXIIct and FXIIag; all were lupus anticoagulant negative. When FXII levels were determined in the 74 LA+ patients, 27 (36.5%) gave markedly lower FXII values in the FXIIct when compared with the FXIIcs. FXIIag levels corresponded with FXIIcs. The automated FXIIcs assay is therefore lupus anticoagulant insensitive and allows us to measure FXII levels accurately and routinely in large numbers of patient samples. Blood Coag Fibrinol 9:183–187 × 1998 Lippincott-Raven Publishers.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID