The Strong Positive Correlation between Factor VII Clotting Activity Using Bovine Thromboplastin and the Activated Factor VII Level

1995 ◽  
Vol 73 (03) ◽  
pp. 429-434 ◽  
Author(s):  
Kazuomi Kario ◽  
Takefumi Matsuo ◽  
Reiko Asada ◽  
Toshiyuki Sakata ◽  
Hisao Kato ◽  
...  
Keyword(s):  
Risk Factor ◽  
Bovine Brain ◽  
Factor Vii ◽  
Rabbit Brain ◽  
Strong Positive Correlation ◽  
Chromogenic Substrate ◽  
Moderate Correlation ◽  
Positive Correlation ◽  
Activated Factor Vii

SummaryWe compared factor VII clotting activity (FVIIc) assays using different thromboplastins to determine which is the most sensitive for activated FVII (FVIIa) or for FVII antigen (FVIIag). FVIIc levels were measured using thromboplastins derived from bovine brain (FVIIc Bov), human placenta (FVIIc Hum), and rabbit brain (FVIIc Rab). FVIIa levels were measured by fluorogenic assays using human soluble tissue factor (rsTF) or bovine rsTF. We also measured FVII activity by an amidolytic assay (FVIIc:am Hum) using human thromboplastin and a chromogenic substrate for thrombin. FVIIag levels were determined by ELISA. In the FVIIa assay, the reaction time obtained from using bovine rsTF was shorter than that with human rsTF, suggesting that the interaction of plasma FVIIa with bovine rsTF was stronger than with human rsTF. The plasma FVIIa levels measured using human rsTF and bovine rsTF were almost the same (r=0.947, p<0.0001). Among the three FVIIc assays, FVIIc Bov had the strongest positive correlation with the plasma FVIIa level (r=0.886, p<0.000l), but had no correlation with FVIIag. An increase of 1 ng/ml in the plasma FVIIa level yielded a 27.9% increase of FVIIc Bov. Plasma FVIIc Hum and FVIIc:am Hum showed moderate correlations with both FVIIa (r=0.520, p<0.02 and r=0.569, p<0.01, respectively) and FVIIag (r=0.438, p<0.05 and r=0.468, p<0.05, respectively). FVIIc Rab had the lowest correlation with FVIIa (r=0.367, p<0.1), but had a moderate correlation with FVIIag (r=0.436, p<0.05). After in vitro cold activation, FVIIc Bov levels increased the most and FVIIc:am levels showed the least change. These findings indicate that consideration of the thromboplastin used for assay is necessary when assessing the clinical significance of FVII activity as a cardiovascular risk factor.

scholarly journals Disseminated intravascular coagulation in rabbits induced by administration of endotoxin or tissue factor: effect of anti-tissue factor antibodies and measurement of plasma extrinsic pathway inhibitor activity

Blood ◽  
1990 ◽  
Vol 75 (7) ◽  
pp. 1481-1489 ◽  
Author(s):  
TA Warr ◽  
LV Rao ◽  
SI Rapaport
Keyword(s):  
Tissue Factor ◽  
Disseminated Intravascular Coagulation ◽  
Factor Viia ◽  
Factor Vii ◽  
Rabbit Brain ◽  
Extrinsic Pathway ◽  
Intravascular Coagulation ◽  
Activated Factor Vii ◽  
Factor Effect

Abstract Rabbits were given polyclonal anti-tissue factor (TF) immunoglobulin G (IgG) before an injection of endotoxin to test the hypothesis that TF triggers disseminated intravascular coagulation (DIC) after endotoxin. The rabbits had been prepared with cortisone to develop DIC after one injection of endotoxin. Anti-TF IgG substantially reduced the falls in fibrinogen, factors V and VIII, and platelets noted in control rabbits given preimmune IgG before endotoxin. At autopsy 24 hours later, fibrin was present in glomerular capillaries of 4 of 5 control rabbits, but in none of 11 rabbits given anti-TF IgG. DIC was also induced in a second group of rabbits by the infusion, over 4 hours, of 1 microgram/kg of purified, reconstituted rabbit brain TF. This resulted in striking falls in plasma fibrinogen, factors V, and VIII that were diminished, but not prevented by prior treatment with anti-TF IgG. Circulating activated factor VII, induced by either TF infusion or endotoxin, could not be detected after DIC. Mean plasma extrinsic pathway inhibitor (EPI) activity did not fall significantly after endotoxin, and only to about 65% of the preinfusion after infusion of TF. Thus, DIC induced by both agents proceeded despite nearly normal plasma EPI levels. Because EPI neutralizes factor VIIa/TF in vitro only after a short lag period, the DIC that persisted for up to 6 hours after injection of endotoxin suggests that TF activity continued to be generated during this period on cells to which the circulating blood was exposed. All animals given endotoxin became ill with cyanosis, tachypnea, cold ears, and diarrhea, regardless of whether they had received anti-TF IgG to attenuate DIC. Infusion of TF caused some animals to die acutely with pulmonary arterial thromboses, but surviving animals did not appear ill. The findings support the hypothesis that exposure of blood to TF triggers DIC after endotoxin, but is not important for the pathogenesis of endotoxin-induced shock.

scholarly journals Disseminated intravascular coagulation in rabbits induced by administration of endotoxin or tissue factor: effect of anti-tissue factor antibodies and measurement of plasma extrinsic pathway inhibitor activity

Blood ◽  
1990 ◽  
Vol 75 (7) ◽  
pp. 1481-1489
Author(s):  
TA Warr ◽  
LV Rao ◽  
SI Rapaport
Keyword(s):  
Tissue Factor ◽  
Disseminated Intravascular Coagulation ◽  
Factor Viia ◽  
Factor Vii ◽  
Rabbit Brain ◽  
Extrinsic Pathway ◽  
Intravascular Coagulation ◽  
Activated Factor Vii ◽  
Factor Effect

Rabbits were given polyclonal anti-tissue factor (TF) immunoglobulin G (IgG) before an injection of endotoxin to test the hypothesis that TF triggers disseminated intravascular coagulation (DIC) after endotoxin. The rabbits had been prepared with cortisone to develop DIC after one injection of endotoxin. Anti-TF IgG substantially reduced the falls in fibrinogen, factors V and VIII, and platelets noted in control rabbits given preimmune IgG before endotoxin. At autopsy 24 hours later, fibrin was present in glomerular capillaries of 4 of 5 control rabbits, but in none of 11 rabbits given anti-TF IgG. DIC was also induced in a second group of rabbits by the infusion, over 4 hours, of 1 microgram/kg of purified, reconstituted rabbit brain TF. This resulted in striking falls in plasma fibrinogen, factors V, and VIII that were diminished, but not prevented by prior treatment with anti-TF IgG. Circulating activated factor VII, induced by either TF infusion or endotoxin, could not be detected after DIC. Mean plasma extrinsic pathway inhibitor (EPI) activity did not fall significantly after endotoxin, and only to about 65% of the preinfusion after infusion of TF. Thus, DIC induced by both agents proceeded despite nearly normal plasma EPI levels. Because EPI neutralizes factor VIIa/TF in vitro only after a short lag period, the DIC that persisted for up to 6 hours after injection of endotoxin suggests that TF activity continued to be generated during this period on cells to which the circulating blood was exposed. All animals given endotoxin became ill with cyanosis, tachypnea, cold ears, and diarrhea, regardless of whether they had received anti-TF IgG to attenuate DIC. Infusion of TF caused some animals to die acutely with pulmonary arterial thromboses, but surviving animals did not appear ill. The findings support the hypothesis that exposure of blood to TF triggers DIC after endotoxin, but is not important for the pathogenesis of endotoxin-induced shock.

Injection of recombinant activated factor VII can induce transient increase in circulating procoagulant microparticles

2004 ◽  
Vol 91 (05) ◽  
pp. 873-878 ◽  
Author(s):  
Bénédicte Hugel ◽  
Benoit Guillet ◽  
Catherine Trichet ◽  
Anne Rafowicz ◽  
Thierry Lambert ◽  
...  
Keyword(s):  
Short Duration ◽  
Platelet Activation ◽  
Thrombin Generation ◽  
Transient Increase ◽  
Factor Vii ◽  
Recombinant Activated Factor Vii ◽  
Activated Factor Vii ◽  
Therapeutic Doses

SummaryRecombinant activated factor VII (rFVIIa) is an effective haemostatic treatment in haemophiliacs with inhibitors. In vitro, FVIIa concentrations corresponding to those obtained with therapeutic doses of rFVIIa have been shown to induce normal thrombin generation and platelet activation in the absence of factors VIII or IX. To further study the in vivo haemostatic changes induced by rFVIIa, circulating procoagulant microparticles (MP) were measured in patients treated with discontinuous injections of Novoseven®. In 6 out of 15 patients, a transient peak of procoagulant MP was observed after injection, occurring 15 min to 2 h after infusion. It was composed primarily of platelet-derived MP and was of very short duration. This peak was not observed in haemophiliacs without inhibitor, who were treated with conventional replacement therapies. Our results provide further in vivo evidence that rFVIIa specifically activates platelets, either directly or as a consequence of a burst of thrombin generation that could account for its haemostatic efficacy.

scholarly journals Study of the Effect of Fibrinogen, Factor XIII and Recombinant Activated Factor VII in a Model of Trauma-Induced Coagulopathy

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 6-7
Author(s):  
Manuel Quintana ◽  
Kapil Nanwani ◽  
Charbel Maroun ◽  
Elena Elena Muñoz ◽  
Ana María Martínez ◽  
...  
Keyword(s):  
Research Funding ◽  
Factor Xiii ◽  
Clot Formation ◽  
Factor Vii ◽  
Recombinant Activated Factor Vii ◽  
Clot Strength ◽  
Activated Factor Vii ◽  
Trauma Induced Coagulopathy ◽  
Procoagulant Effect

Introduction: Trauma-induced coagulopathy (TIC) is a multifactorial condition secondary to severe trauma. In TIC, early fibrinogen (FI) replacement and low dose of recombinant activated factor VII (rFVIIa) may positively impact outcome. Factor XIII (FXIII), on the other hand, may stimulate in vitro clot formation and clot stability. We hypothesized that combination of FI, rFVIIa and FXIII might normalize clot formation more effectively than the isolated use of each concentrate in a model of TIC. Aim: Evaluation of the procoagulant effect of isolated or combined use of FI, rFVIIa and FXIII in a model of TIC. Methods: TIC in vitro model was obtained by dilution of whole blood from seven healthy controls with isotonic saline (NaCl 0.9%) (2:3 whole blood:saline ratio). FI, rFVIIa and FXIII were spiked in combination or alone until obtaining final levels of 2 g/L, 1 μg/mL and 100 IU/dL respectively. Procoagulant effects of the different concentrates or their mixtures were evaluated by Rotational Thromboelastometry (ROTEM®, Werfen) triggered using starTEM® (calcium chloride 0,2 M) and exTEM® reagent (source of tissue factor) diluted with saline up to 1:100.000 (final dilution) for a better evaluation of both the extrinsic and intrinsic pathways of coagulation. The values of clotting time (CT: time until 2 mm of amplitude, in seconds), amplitude (parameter proportional to the clot strength) at 5 minutes (A5, in mm) and clot formation time (CFT: time from CT to 20 mm of amplitude, in seconds) were evaluated. Statistical analysis of differences was performed by One-Way ANOVA test assuming no paring of data and using the Holm-Sidak's correction for multiple comparisons with a family-wise significance and confidence level of 0.01. Statistical significance was set at p&lt; 0.05. Results/Discussion: Data are summarized in Table I and Figure 1. CT needed the combination of two of more concentrates to reach the normal range suggesting that the administration of FI alone in TIC may not be enough to restore the patients' hemostatic potential. In regard to the clot strength evaluated by A5, the addition of FXIII or rFVIIa alone or in combination did not improve the value of A5 that was only normalized by the addition of FI. This effect of FI was increased in the presence of FXIII or rFVIIa which indicated that normal levels of FI might be required for rFVIIa or FXIII to be effective emphasising the possible benefit of the combinatory therapy. Like observed in A5, the velocity of clot formation evaluated by the CFT was normalised only by the addition of FI. However, the combination of FI plus FXIII + rFVIIa had a stronger effect on CFT compared with the combination of FI + FXIII or FI + rFVIIa, indicating that the improvement of thrombin generation due to rFVIIa plus an increment of fibrin formation and net stabilization through the contribution of higher levels of FI and FXIII respectively, might provide a beneficial synergistic procoagulant effect in TIC. Conclusion: The use of FI in TIC may contribute to increase the patient's hemostatic potential but might not be enough. Combinatory therapies based on the administration of FI, rFVIIa and FXIII might be of better benefit in this setting. Ex-vivo studies using blood of patients with stablished TIC might bring new insights on the possible advantages of this combinatory therapy to design more effective protocols to treat this frequent and life-threatening acquired condition. Disclosures Canales: Sandoz: Honoraria; iQone: Honoraria; Janssen: Speakers Bureau; Janssen: Honoraria; Roche: Speakers Bureau; Karyopharm: Honoraria; Sandoz: Speakers Bureau; Novartis: Honoraria; Takeda: Speakers Bureau; Roche: Honoraria; Sandoz: Honoraria; Janssen: Speakers Bureau; Roche: Speakers Bureau; Sandoz: Speakers Bureau; Takeda: Speakers Bureau; Janssen: Honoraria; Karyopharm: Honoraria; Novartis: Honoraria; Celgene: Honoraria; Roche: Honoraria; Gilead: Honoraria. Butta:NovoNordisk: Speakers Bureau; Takeda: Research Funding, Speakers Bureau; SOBI: Speakers Bureau; Pfizer: Speakers Bureau; ROCHE: Research Funding, Speakers Bureau; Novartis: Speakers Bureau; Grifols: Research Funding. Alvarez Román:NovoNordisk,: Research Funding, Speakers Bureau; Takeda: Research Funding, Speakers Bureau; SOBI,: Consultancy, Research Funding, Speakers Bureau; Pfizer,: Research Funding, Speakers Bureau; Roche: Speakers Bureau; Novartis: Speakers Bureau; Bayer: Consultancy; Grifols: Research Funding. Jiménez-Yuste:F. Hoffman-La Roche Ltd, Novo Nordisk, Takeda, Sobi, Pfizer: Consultancy; Grifols, Novo Nordisk, Takeda, Sobi, Pfizer: Research Funding; F. Hoffman-La Roche Ltd, Novo Nordisk, Takeda, Sobi, Pfizer, Grifols, Octapharma, CSL Behring, Bayer: Honoraria.

scholarly journals THE THE EFFECT OF ALMOND OIL ON THE PERMEABILITY OF KETOPROFEN HYDROGEL

2019 ◽  
pp. 65-69
Author(s):  
ZAHRAA ALAA HASAN ◽  
JINAN MUHAMMED MUHSIN AL-MOUSAWY ◽  
HAMID SADEQ KHALEEL ALGHURABI
Keyword(s):  
Kinetic Study ◽  
Gradual Increase ◽  
Penetration Enhancer ◽  
Release Kinetic ◽  
Strong Positive Correlation ◽  
Almond Oil ◽  
Positive Correlation ◽  
Carbopol 940 ◽  
Hydrogel Formulation

Objective: The object of this study is to formulate ketoprofen hydrogels and to evaluate their permeability following the incorporation of almond oil as a penetration enhancer. Methods: Five formulas (F2-F6) of ketoprofen hydrogels were formulated with the employment of carbopol 940 and triethanolamine. A gradual increase in the amount of almond oil was used in each formula. In vitro penetration and release kinetic study was conducted for all the formulations and compared with the control formula (F1) which was prepared without the incorporation of almond oil. Results: There was a strong positive correlation between % of incorporated almond oil and the % of drug released when the samples were compared with F1 that was formulated without almond oil. After 24 h, 90% of medication was penetrated from ketoprofen hydrogel formulation (F6), which had 5% almond oil. Conclusion: Almond oil has successfully worked as a natural penetration enhancer when five ketoprofen hydrogel formulations were prepared and evaluated.

Intra-patient variability of thromboelastographic parameters following in vivo and ex vivo administration of recombinant activated factor VII in haemophilia patients. A multi-centre, randomised trial

2010 ◽  
Vol 103 (02) ◽  
pp. 351-359 ◽  
Author(s):  
Gili Kenet ◽  
Camilla Stenmo ◽  
Allan Blemings ◽  
Wolfgang Wegert ◽  
Jenny Goudemand ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Randomised Trial ◽  
Factor Vii ◽  
Haemophilia A ◽  
Strong Positive Correlation ◽  
Post Dose ◽  
Recombinant Activated Factor Vii ◽  
Activated Factor Vii ◽  
Rfviia Administration

SummaryThromboelastography methods have been used to predict or monitor treatment of haemophilia patients with recombinant activated factor VII (rFVIIa). However, neither of the two thromboelastographic methods (ROTEM and TEG) has as yet been validated. This multi-centre, randomised trial compared both methods in terms of intra- and inter-patient variability following in vivo and ex vivo rFVIIa administration to haemophilia A and B patients with and without inhibitors. Patients (≥16 years old) received the same intravenous rFVIIa dose (45, 90 or 180 μg/kg) twice, 1–12 weeks apart. Blood samples were collected pre-dose and 15, 60, 120 and 240 minutes post-dose for ROTEM and TEG analysis. Pre-dose samples were also spiked ex vivo with rFVIIa (0.6, 1.2 or 2.4 μg/ml), to correspond to the three in vivo doses. Twenty-six haemophilia A and four haemophilia B patients were enrolled. A significant treatment effect was observed with in vivo rFVIIa (p<0.05) with more pronounced effects in inhibitor (n=14) versus non-inhibitor (n=16) patients. There was a strong positive correlation between ROTEM and TEG parameters. Intra- and inter-patient variation was large for all thromboelastography parameters at all time points and rFVIIa doses. Intra-patient variation was generally lower for non-inhibitor than inhibitor patients, and lower following ex vivo spiking versus in vivo rFVIIa administration. In conclusion, there was a clear effect of rFVIIa on all thromboelastography parameters, but the large intra- and inter-patient variability following in vivo rFVIIa administration renders the use of our method unsuitable for dose-response prediction for haemophilia patients in the clinical setting.

In vitro stability of lyophilized and reconstituted recombinant activated factor VII formulated for storage at room temperature

2008 ◽  
Vol 30 (7) ◽  
pp. 1309-1315 ◽  
Author(s):  
Hanne Nedergaard ◽  
Susanne Vestergaard ◽  
Pernille Theil Jensen ◽  
Morten Wagner Kristiansen ◽  
Michael Bech Jensen ◽  
...  
Keyword(s):  
Room Temperature ◽  
Factor Vii ◽  
Recombinant Activated Factor Vii ◽  
Activated Factor Vii ◽  
In Vitro Stability

scholarly journals (252) Correlation of Pungency, Thiosulfinates, Antiplatelet Activity, and Total Soluble Solids in Two Garlic Families

HortScience ◽  
2005 ◽  
Vol 40 (4) ◽  
pp. 1019E-1019 ◽  
Author(s):  
Pablo Cavagnaro ◽  
Douglas Senalik ◽  
Claudio Galmarini ◽  
Philipp Simon
Keyword(s):  
Genetic Correlations ◽  
Soluble Solids ◽  
Organosulfur Compounds ◽  
Strong Positive Correlation ◽  
Soluble Solids Content ◽  
Antiplatelet Activity ◽  
Total Soluble Solids ◽  
Positive Correlation ◽  
Solids Content

Allium plants possess organosulfur compounds and carbohydrates that provide unique flavor and health-enhancing properties. In previous studies of onion F3 families, significant phenotypic and genetic correlations have been reported between pungency, in vitro antiplatelet activity (IVAA), and soluble solids content (SSC); although in other studies SSC and pungency have not always been correlated. In this study we analyzed SSC, pungency, garlic-induced in vitro antiplatelet activity and the content of three predominant thiosulfinates in bulbs from two garlic families obtained from unrelated self-pollinated plants. A strong positive correlation was observed between pungency and IVAA for both sample sets, indicating that it will be difficult to develop garlic populations with low pungency and high IVAA. Allicin was the most abundant thiosulfinate and its content was positively correlated with pungency and IVAA (r= 0.70 and 0.74, respectively). The thiosulfinates AllS(O)SPropenyl and AllS(O)SMe were also positively correlated with pungency and IVAA. When compared with IVAA, AllS(O)SMe had higher r values than AllS(O)SPropenyl (0.88 and 0.50, respectively). These differences could reflect differential platelet anti-aggregatory properties of different thiosulfinates. SSC was not correlated with IVAA, pungency, or thiosulfinates content, suggesting that soluble solids in garlic can be independently selected.

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