scholarly journals Altered factor VII activity in hemophilia

Blood ◽  
1985 ◽  
Vol 65 (4) ◽  
pp. 845-849 ◽  
Author(s):  
BC Miller ◽  
MB Hultin ◽  
J Jesty
Keyword(s):  
Factor Viia ◽  
Ex Vivo ◽  
Factor Vii ◽  
Control Group ◽  
Increased Sensitivity ◽  
Assay Methods ◽  
Activity State ◽  
State Factor ◽  
Normal Controls

Abstract Factor VII levels have been studied in hemophilia A and B plasmas and normal controls in a controlled, prospective study. Three assay methods were used: a standard clotting assay (FVIIc-A); a modified clotting assay (FVIIc-B) (Seligsohn et al, Blood 52:978–988, 1978); and a coupled amidolytic assay. By the FVIIc-B assay, the hemophilic plasmas were significantly lower than in the normal group (68.2 +/- 3.3% [SE] and 83.5 +/- 3.8%, respectively; P less than .01). The amidolytic assay, however, which measures total factor VII regardless of its activity state (factor VII or VIIa), was higher in the patient group than in the control group (126.9 +/- 9.6% and 99.4 +/- 5.7%, respectively; P less than .01). Control experiments showed that the differences in FVIIc-B activity were not caused by artifactual activation of factor VII ex vivo in the control group. The mean FVIIc-A assay of hemophilic plasmas (126.3 +/- 6.5%) agreed closely with the amidolytic assay, suggesting that the FVIIc-A method is also insensitive to the factor VII activity state. These data support the hypothesis that the FVIIc-B assay is more sensitive to the presence of factor VIIa. The increased sensitivity of the FVIIc-B assay to factor VII activation was confirmed by comparison of the two clotting assays on plasma subjected to activation in glass at 4 degrees C. The results of this study indicate that factor VII in hemophilic plasma is less activated than in normal plasma. Whether this contributes to the bleeding diathesis of hemophilia is unknown. However, it does provide evidence for the idea that factor VII in vivo is normally subject to some degree of activation by an enzyme (or enzymes) generated by a turnover of the intrinsic pathway.

scholarly journals Altered factor VII activity in hemophilia

Blood ◽  
1985 ◽  
Vol 65 (4) ◽  
pp. 845-849 ◽  
Author(s):  
BC Miller ◽  
MB Hultin ◽  
J Jesty
Keyword(s):  
Factor Viia ◽  
Ex Vivo ◽  
Factor Vii ◽  
Control Group ◽  
Increased Sensitivity ◽  
Assay Methods ◽  
Activity State ◽  
State Factor ◽  
Normal Controls

Factor VII levels have been studied in hemophilia A and B plasmas and normal controls in a controlled, prospective study. Three assay methods were used: a standard clotting assay (FVIIc-A); a modified clotting assay (FVIIc-B) (Seligsohn et al, Blood 52:978–988, 1978); and a coupled amidolytic assay. By the FVIIc-B assay, the hemophilic plasmas were significantly lower than in the normal group (68.2 +/- 3.3% [SE] and 83.5 +/- 3.8%, respectively; P less than .01). The amidolytic assay, however, which measures total factor VII regardless of its activity state (factor VII or VIIa), was higher in the patient group than in the control group (126.9 +/- 9.6% and 99.4 +/- 5.7%, respectively; P less than .01). Control experiments showed that the differences in FVIIc-B activity were not caused by artifactual activation of factor VII ex vivo in the control group. The mean FVIIc-A assay of hemophilic plasmas (126.3 +/- 6.5%) agreed closely with the amidolytic assay, suggesting that the FVIIc-A method is also insensitive to the factor VII activity state. These data support the hypothesis that the FVIIc-B assay is more sensitive to the presence of factor VIIa. The increased sensitivity of the FVIIc-B assay to factor VII activation was confirmed by comparison of the two clotting assays on plasma subjected to activation in glass at 4 degrees C. The results of this study indicate that factor VII in hemophilic plasma is less activated than in normal plasma. Whether this contributes to the bleeding diathesis of hemophilia is unknown. However, it does provide evidence for the idea that factor VII in vivo is normally subject to some degree of activation by an enzyme (or enzymes) generated by a turnover of the intrinsic pathway.

A Longitudinal Study of the Factor VII Rise during Pregnancy

1998 ◽  
Vol 79 (02) ◽  
pp. 328-330 ◽  
Author(s):  
D. Wright ◽  
J. M. Thomson ◽  
A. Sidebotham ◽  
C. F. Hirst ◽  
P. Hirsch ◽  
...  
Keyword(s):  
Weight Gain ◽  
Longitudinal Study ◽  
Factor Viia ◽  
Factor Vii ◽  
Maternal Weight Gain ◽  
Maternal Weight ◽  
Foetal Growth ◽  
Indirect Measures ◽  
Activity State ◽  
State Factor

SummaryA longitudinal study of 21 pregnant women has been undertaken using a variety of factor VII assays, including factor VIIa, to investigate the increase of factor VIIc. All assays demonstrated significant rises (p <0.001), most marked for factor VIIa (82%) and factor VIIc rabbit (81%). Smaller rises were seen for factor VIIc bovine (50%) and VII antigen (40%). Three indirect measures of activity state, factor VIIc rabbit:antigen, bovine:antigen and bovine:rabbit, provided conflicting data. Factor VIIa:antigen showed a significant increase of 36% (p <0.001). Within individual pregnancies the change in factor VIIc rabbit and antigen correlated with maternal weight gain (p <0.05). Two activity state measures, bovine:rabbit and bovine:antigen, showed negative correlation with birthweight. The increases in both zymogen and in activity state appear to contribute to the factor VIIc rise. The extent of this rise appears to be influenced by maternal weight gain. Increased factor VII activation is associated with reduced foetal growth.

A Comparison of Methods for the Measurement of Activated Factor VII

1992 ◽  
Vol 68 (03) ◽  
pp. 301-305 ◽  
Author(s):  
S Kitchen ◽  
R G Malia ◽  
F E Preston
Keyword(s):  
Factor Viia ◽  
Epidemiological Studies ◽  
Factor Vii ◽  
Haemophilia A ◽  
Reference Ranges ◽  
Activated Factor Vii ◽  
Normal Individuals ◽  
Antigen Assay ◽  
Activity State ◽  
Almost All

SummaryA number of different methods are available for the measurement of factor VIIa. Almost all of these employ ratios of two different measurements of factor VII. In order to determine which is the most sensitive to activated factor VII we have compared currently available methods in the following groups: two patients with haemophilia A following treatment with activated recombinant factor VII (rVII a); 6 normal plasmas during cold promoted activation of factor VII; normal individuals (n = 23); and patients with unequivocal disseminated intravascular coagulation (DIC, n = 19). Factor VII was measured in an amidolytic assay (VII: Amid) and an antigen assay (VII:Ag). Clotting activity was measured using rabbit (VII:C Rab), human (VII:C Hum) and bovine (VII:C Bov) thromboplastin.Of the clotting assays the most sensitive to the presence of factor VIIa was that which utilised bovine thromboplastin. Amidolytic and immunological measurements were unaffected by the activity state of factor VII. The ratios VII:C Rab/VII: Ag and VII:C Rab/VII:Amid were insensitive to activated factor VII. The ratios most sensitive to the presence of factor VII a were VII:C Bov/VII: Amid and VII: C Bov/VII:Ag. The ratios VII:C Bov/VII:C Rab and VII:C Bov/VII:C Hum are less sensitive but have the advantage for epidemiological studies of narrower reference ranges.

Ethanol Extract of Achillea fragrantissima Enhances Angiogenesis through Stimulation of VEGF Production

2020 ◽  
Vol 21 ◽  
Author(s):  
Hana M. Hammad ◽  
Amer Imraish ◽  
Maysa Al-Hussaini ◽  
Malek Zihlif ◽  
Amani A. Harb ◽  
...  
Keyword(s):  
Wound Healing ◽  
Rural Communities ◽  
Ex Vivo ◽  
Ethanol Extract ◽  
Aortic Ring ◽  
Treated Group ◽  
Control Group ◽  
Dependent Manner ◽  
Achillea Fragrantissima

Objective: Achillea fragrantissima L. (Asteraceae) is a traditionally used medicinal herb in the rural communities of Jordan. Methods: The present study evaluated the efficacy of the ethanol extract of this species on angiogenesis in both, ex vivo using rat aortic ring assay and in vivo using rat excision wound model. Results: In concentrations of 50 and 100 µg/ml, the ethanol extract showed angiogenic stimulatory effect and significantly increased length of capillary protrusions around aorta rings of about 60% in comparison to those of untreated aorta rings. In MCF-7 cells, the ethanol extract of A. fragrantissima stimulates the production of VEGF in a dose-dependent manner. 1% and 5% of ethanol extract of A. fragrantissima containing vaseline based ointment was applied on rat excision wounds for six days and was found to be effective in wound healing and maturation of the scar. Both preparations resulted in better wound healing when compared to the untreated control group and vaseline-treated group. This effect was comparable to that induced by MEBO, the positive control. Conclusion: The results indicate that A. fragrantissima has a pro-angiogenic effect, which may act through the VEGF signaling pathway.

scholarly journals Improved Detection of Molecular Markers of Atherosclerotic Plaques Using Sub-Millimeter PET Imaging

Molecules ◽  
2020 ◽  
Vol 25 (8) ◽  
pp. 1838 ◽  
Author(s):  
Jessica Bridoux ◽  
Sara Neyt ◽  
Pieterjan Debie ◽  
Benedicte Descamps ◽  
Nick Devoogdt ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Ex Vivo ◽  
High Sensitivity ◽  
Radiochemical Yield ◽  
Control Group ◽  
Complexing Agent ◽  
Atherosclerotic Plaques ◽  
Atherosclerotic Lesions ◽  
Pet Ct

Since atherosclerotic plaques are small and sparse, their non-invasive detection via PET imaging requires both highly specific radiotracers as well as imaging systems with high sensitivity and resolution. This study aimed to assess the targeting and biodistribution of a novel fluorine-18 anti-VCAM-1 Nanobody (Nb), and to investigate whether sub-millimetre resolution PET imaging could improve detectability of plaques in mice. The anti-VCAM-1 Nb functionalised with the novel restrained complexing agent (RESCA) chelator was labelled with [18F]AlF with a high radiochemical yield (>75%) and radiochemical purity (>99%). Subsequently, [18F]AlF(RESCA)-cAbVCAM1-5 was injected in ApoE−/− mice, or co-injected with excess of unlabelled Nb (control group). Mice were imaged sequentially using a cross-over design on two different commercially available PET/CT systems and finally sacrificed for ex vivo analysis. Both the PET/CT images and ex vivo data showed specific uptake of [18F]AlF(RESCA)-cAbVCAM1-5 in atherosclerotic lesions. Non-specific bone uptake was also noticeable, most probably due to in vivo defluorination. Image analysis yielded higher target-to-heart and target-to-brain ratios with the β-CUBE (MOLECUBES) PET scanner, demonstrating that preclinical detection of atherosclerotic lesions could be improved using the latest PET technology.

scholarly journals The Diverse Potential of Gluten from Different Durum Wheat Varieties in Triggering Celiac Disease: A Multilevel In Vitro, Ex Vivo and In Vivo Approach

Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3566
Author(s):  
Federica Gaiani ◽  
Sara Graziano ◽  
Fatma Boukid ◽  
Barbara Prandi ◽  
Lorena Bottarelli ◽  
...  
Keyword(s):  
Immune Response ◽  
Celiac Disease ◽  
Durum Wheat ◽  
Ex Vivo ◽  
Diet Group ◽  
Control Group ◽  
Wheat Varieties ◽  
Before And After

The reasons behind the increasing prevalence of celiac disease (CD) worldwide are still not fully understood. This study adopted a multilevel approach (in vitro, ex vivo, in vivo) to assess the potential of gluten from different wheat varieties in triggering CD. Peptides triggering CD were identified and quantified in mixtures generated from simulated gastrointestinal digestion of wheat varieties (n = 82). Multivariate statistics enabled the discrimination of varieties generating low impact on CD (e.g., Saragolla) and high impact (e.g., Cappelli). Enrolled subjects (n = 46) were: 19 healthy subjects included in the control group; 27 celiac patients enrolled for the in vivo phase. Celiacs were divided into a gluten-free diet group (CD-GFD), and a GFD with Saragolla-based pasta group (CD-Sar). The diet was followed for 3 months. Data were compared between CD-Sar and CD-GFD before and after the experimental diet, demonstrating a limited ability of Saragolla to trigger immunity, although not comparable to a GFD. Ex vivo studies showed that Saragolla and Cappelli activated immune responses, although with great variability among patients. The diverse potential of durum wheat varieties in triggering CD immune response was demonstrated. Saragolla is not indicated for celiacs, yet it has a limited potential to trigger adverse immune response.

Plasma elimination kinetics for factor VII are independent of its activation to factor VIIa and complex formation with plasma inhibitors

2009 ◽  
Vol 101 (05) ◽  
pp. 818-826 ◽  
Author(s):  
Torben Elm ◽  
Mirella Ezban ◽  
Thomas Krogh ◽  
Ditte Karpf ◽  
Anne Steinø ◽  
...  
Keyword(s):  
Complex Formation ◽  
Antithrombin Iii ◽  
Factor Viia ◽  
Factor Vii ◽  
Elimination Kinetics ◽  
Inhibitor Complex ◽  
Α2 Macroglobulin ◽  
Clearance Mechanism ◽  
Deficient Mice

SummaryThe mechanism for the elimination of factor VII (FVII) from the circulation is unknown, just as it is unclear how activation of FVII to FVIIa and subsequent complex formation with antithrombin III (AT) or α2-macroglobulin (α2M) affects clearance. The possibility that the clearance mechanism involves activation and inhibitor complex formation as obligatory intermediate reactions is examined in this study. Human and murine sera were spiked with human FVIIa in the absence and presence of heparin and analysed for complex formation. Complex formation in vivo was studied after intravenous injection of 125I-VIIa in mice; and the pharmacokinetics (PK) of human and murine FVIIa was studied in normal mice. Furthermore, comparative PK studies were performed with FVII, FVIIa, active site blocked FVIIa and a preformed FVIIa-AT complex in normal and α2M-deficient mice. The data demonstrated that FVIIa-AT complexes and to a much lesser extent FVIIa-α2M-complexes accumulated in vivo after FVIIa administration. FVIIa-AT accounted for about 50% of total FVIIa antigen left in the circulation after 3 hours. All FVII derivatives studied including FVII, FVIIa and FVIIa-AT were cleared with similar rates suggesting an elimination kinetics which is unaffected by FVII activation and subsequent inactivation by plasma inhibitors.

Prothrombin Activation Is Increased among Asymptomatic Carriers of the Prothrombin G20210A and Factor V Arg506Gln Mutations

2000 ◽  
Vol 84 (09) ◽  
pp. 396-400 ◽  
Author(s):  
Steve Humphries ◽  
Belinda Smillie ◽  
Lily Li ◽  
Jacqueline Cooper ◽  
Samad Barzegar ◽  
...  
Keyword(s):  
Factor Viia ◽  
Conclusive Evidence ◽  
Factor Ix ◽  
Factor Vii ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Factor X ◽  
Coagulation Proteins ◽  
Prothrombin Activation

SummaryThe risk of venous thrombosis is increased in individuals who carry specific genetic abnormalities in blood coagulation proteins. Among Caucasians, the prothrombin G20210A and factor V Arg506Gln (FV R506Q) mutations are the most prevalent defects identified to date. We evaluated their influence on markers of coagulation activation among participants in the Second Northwick Park Heart Study, which recruited healthy men (aged 50–61 years) from nine general medical practices in England and Wales. They were free of clinical vascular disease and malignancy at the time of recruitment. Genotypes for the two mutations were analyzed using microplate array diagonal gel electrophoresis, and coagulation markers (factor XIIa; activation peptides of factor IX, factor X, and prothrombin; fibrinopeptide A) were measured by immunoassay. Factor VII coagulant activity and factor VIIa levels were determined by a functional clotting assay. Among 1548 men genotyped for both mutations, 28 (1.8%) and 52 (3.4%) were heterozygous for prothrombin G20210A and FV R506Q, respectively. The only coagulation marker that was significantly associated with the two mutations was prothrombin activation fragment F1+2 [mean ± SD, 0.88 ± 0.32 nmol/L in men with prothrombin G20210A (p = 0.002) and 0.89 ± 0.30 in men with FV R506Q (p = 0.0001) versus 0.72 ± 0.24 among non-carriers for either mutation]. This data provides conclusive evidence that heterozygosity for the prothrombin G20210A as well as the FV R506Q mutations in the general population leads to an increased rate of prothrombin activation in vivo.

scholarly journals Characterization of the Cellular Reaction to a Collagen-Based Matrix: An In Vivo Histological and Histomorphometrical Analysis

Materials ◽  
2020 ◽  
Vol 13 (12) ◽  
pp. 2730 ◽  
Author(s):  
Samuel Ebele Udeabor ◽  
Carlos Herrera-Vizcaíno ◽  
Robert Sader ◽  
C. James Kirkpatrick ◽  
Sarah Al-Maawi ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Ex Vivo ◽  
Test Group ◽  
Tissue Reaction ◽  
Implantation Site ◽  
Control Group ◽  
The Matrix ◽  
Tissue Reactions ◽  
Post Implantation

The permeability and inflammatory tissue reaction to Mucomaix® matrix (MM), a non- cross-linked collagen-based matrix was evaluated in both ex vivo and in vivo settings. Liquid platelet rich fibrin (PRF), a blood concentrate system, was used to assess its capacity to absorb human proteins and interact with blood cells ex vivo. In the in vivo aspect, 12 Wister rats had MM implanted subcutaneously, whereas another 12 rats (control) were sham-operated without biomaterial implantation. On days 3, 15 and 30, explantation was completed (four rats per time-point) to evaluate the tissue reactions to the matrix. Data collected were statistically analyzed using analysis of variance (ANOVA) and Tukey multiple comparisons tests (GraphPad Prism 8). The matrix absorbed the liquid PRF in the ex vivo study. Day 3 post-implantation revealed mild tissue inflammatory reaction with presence of mononuclear cells in the implantation site and on the biomaterial surface (mostly CD68-positive macrophages). The control group at this stage had more mononuclear cells than the test group. From day 15, multinucleated giant cells (MNGCs) were seen in the implantation site and the outer third of the matrix with marked increase on day 30 and spread to the matrix core. The presence of these CD68-positive MNGCs was associated with significant matrix vascularization. The matrix degraded significantly over the study period, but its core was still visible as of day 30 post-implantation. The high permeability and fast degradation properties of MM were highlighted.

The Risk of Thrombotic Events in Neonates Treated with Recombinant Factor VIIa.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3193-3193
Author(s):  
John Puetz ◽  
Ginger Darling ◽  
Petr Brabec ◽  
Jan Blatny ◽  
Prasad Mathew
Keyword(s):  
Recombinant Factor Viia ◽  
Factor Viia ◽  
Accurate Determination ◽  
Thrombotic Event ◽  
Fresh Frozen Plasma ◽  
Factor Vii ◽  
Control Group ◽  
Fresh Frozen ◽  
Surgical Bleeding ◽  
A Prospective Study

Abstract Background: In recent years, recombinant factor VIIa (rFVIIa) has been used in non-hemophilia bleeding situations (factor VII deficiency, trauma, liver disease, uremia, surgical bleeding, platelet disorders, and intracranial hemorrhage) for achievement of hemostasis. Although, the risk of thrombosis in hemophilia patients with inhibitors receiving rFVIIa is quite low, its use in other clinical situations has been complicated by some reports of thrombotic events. Recently, rFVIIa has been used to treat coagulopathic and/or bleeding neonates with good success. However, the prevalence of thrombotic events in these neonates is completely unknown. This study was initiated to determine the risk of thrombotic events associated with rFVIIa use in neonates. Methods: We reviewed all published literature in neonates receiving rFVIIa. In addition, we reviewed all data submitted to the SeveN Bleep Registry, a database developed by the scientific standardization subcommittee on pediatric and neonatal hemostasis of the International Society on Thrombosis and Haemostasis (ISTH) to record all uses of rFVIIa in pediatric non-hemophilic patients. As the baseline prevalence of thrombosis for bleeding and/or coagulopathic neonates is also unknown, we also reviewed the records of 100 consecutive neonates from a single institution who received fresh frozen plasma (FFP) alone to treat their coagulopathy and/or bleeding. Results: A total of 98 non-hemophilic neonates received rFVIIa. The majority of these neonates received rFVIIa only after failing to achieve hemostasis with standard care (FFP, cryoprecipitate, platelet transfusions). Of those receiving rFVIIa, 7 had a thrombotic event reported. In the control group that received FFP alone, 7 neonates also suffered a thrombotic event. Although the risk of thrombosis in these two groups is similar, neonates receiving rFVIIa tended to have indwelling line related thrombosis, while those receiving FFP tended to have strokes or myocardial insults. Overall the prevalence of thrombotic events in bleeding and/or coagulopathic neonates appears to be 7%, whether or not they received rFVIIa. Conclusions: In this study, the overall prevalence of thrombotic events was similar in the rFVIIa and FFP group. As data for this study was collected in a retrospective manor, and thereby subject to publication and submission bias, a more accurate determination of the prevalence of thrombosis in neonates will require a prospective study.

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