bluuebunny/crossref_metadata_2025_split huggingface dataset:
Préparation d’une fraction anti-hémophilique A à partir de plasma A.C.D. standard
Authors: Janiak Alina , Soulier J.-P 
Published: July 2018

RésuméUne méthode d’adsorption préférentielle du facteur VIII à partir du plasma ACD par le phosphate tricalcique à pH 6 est décrite. Le facteur VIII est élue et concentré par fractionnement alcoolique. Afin de stabiliser le facteur VIII, au cours de la préparation, on ajoute 5 mg/cm3 d’acide epsilon-amino-caproïque.Le produit final contient 3 à 10 fois l’activité d’un même volume de plasma ACD (la concentration par mg de protéines est en moyenne de 30 à 50 fois). Le rendement moyen est de l’ordre de 60 p. 100. A côté du facteur VIII, la fraction contient environ la moitié du facteur IX et 20 à 30% de complexe VII; par contre, il est à peu près totalement dépourvu de fibrinogène.Des recherches demeurent nécessaires afin d’apprécier si cette technique peut être appliquée à un fractionnement semi-industriel.
Is there a Hemostatic Effect of Peanuts in Hemophilioid Disorders?
Authors: Brakman Pieter , Sjølin Knud-Erik , Astrup Tage 
Published: July 2018

Summary1. Data on the effect of defatted peanuts in hemophilioid patients (deficient in Factor VIII or Factor IX) are presented.2. Oral administration of peanuts is regularly followed by a decrease in spontaneous fibrinolytic activity of the blood.3. A clinical effect of peanuts is limited and seems to be present only in mild disorders and in periods of mild relapse.4. The data supports the concept that the peanut effect is indirect and is caused by an antiprotease delaying fibrinolysis.
The Nature of the Thromboplastic Activity Appearing during the Clotting of Pig’s Plasma
Authors: Cross M. J 
Published: July 2018

Summary1 During clotting, pigs’ plasma developed thromboplastic activity. This activity was compared with that of thrombin in accelerating the clotting of platelet-deficient plasma and of fibrinogen in the presence and absence of calcium.2. The thromboplastic activity of the plasma could be mimicked by a solution of thrombin of the right strength.3. The thromboplastic activity could be stabilised by freezing but disappeared rapidly at 37° C. Thrombin added to the serum was inactivated at almost exactly the same rate; and the rates of loss of both activities were considerably reduced by cooling, by decalcification with sodium ethylene-diaminetetraacetate, and by acidification.4. It is concluded that the thromboplastic activity of undiluted recalcified pigs’ plasma can be accounted for by its thrombin content alone. It also seems likely that the activity measured in the screening test for disorders of thromboplastin generation described by Hicks and Pitney (1957) can be attributed wholly to thrombin.
Essential Athrombia
Authors: Inceman Seref , Ünügür Asuman , Aran Metin 
Published: July 2018

SummaryA severe hemorrhagic disease was observed in a 15 month old infant. The laboratory studies revealed only one anomaly in the hemostatic mechanism of the patient: an impairment of the functions of agglomeration and adhesivity of his platelets. The authors believe that this is the second case in literature. The agglomeration and adhesive faculty of blood platelets and the relation of these platelet functions with blood coagulation, clot retraction and viscous metamorphosis are discussed.
Tissue Factor Expression during Monocyte-Macrophage Differentiation
Authors: van den Eijnden Mark M E D , Steenhauer Sari-lrina , Reitsma Pieter H , Bertina Rogier M 
Published: July 2018

SummaryTissue factor (TF), the high affinity receptor and cofactor of factor VII, is considered as the main procoagulant in stimulated monocytes and macrophages. We studied the effect of longterm culture (differentiation) on “spontaneous” and induced (LPS) expression of TF (mRNA, antigen, cell surface associated Vlla-cofactor activity) in isolated human monocytes.TF was expressed transiently in monocytes cultured on Teflon membranes (suspension monocytes, Mo-S) and on plastic dishes (adherent monocytes, Mo-A), reaching maximal levels between days 3 and 5. Increased expression of TF was accompanied by increased stable expression of macrophage specific markers (CD71, the mannose receptor, the scavenger receptor).Bacterial lipopolysaccharide (LPS) induced (additional) TF mRNA, antigen, and activity in both Mo-S and Mo-A. In Mo-S and Mo-A of days 3 to 5, the period in which there was “spontaneous” expression of TF, TF response to LPS was considerably lower.It is concluded that during monocyte-macrophage transition, TF is “spontaneously” and transiently expressed and that with respect to TF induction the responsiveness of the cells to LPS is maintained.
Transient Interruption of Arterial Thrombosis by Inhibition of Factor Xa Results in Long-term Antithrombotic Effects in Baboons
Authors: Kotzé H F , Lamprecht S , Badenhorst P N , Roodt J P , van Wyk V 
Published: July 2018

SummaryRecombinant tick anticoagulant peptide (r-TAP) is a potent and specific inhibitor of activated coagulation factor X which effectively interrupts in vivo arterial thrombosis during treatment. It is, however, uncertain if it also affects thrombosis after treatment is stopped. This was tested in a baboon model of arterial thrombosis where platelet deposition onto Dacron vascular graft segments, inserted as extensions into permanent femoral arteriovenous shunts, was measured. The baboons were intravenously treated with 10 μg/kg/min (low dose, aPTT = 39 ± 1 s) and 25 μg/kg/min (high dose, aPTT = 58 ± 2 s) r-TAP for two hours. During treatment the r-TAP inhibited thrombin formation and dose-dependently interrupted platelet deposition onto the graft segment. This effect lasted for up to two hours after treatment with the low dose. Following treatment with the high dose, the graft segments were kept in place for 53 h. After treatment was stopped, platelets again deposited, but at a much lower rate than in control studies. Maximum deposition was approximately 38% lower than in the control studies. Total platelet deposition over 55 h, calculated as the area under the deposition curve, was approximately 40% (p <0.05) less than in the control studies. A significant shortening in the mean platelet life span and an approximately 15-fold increase in thrombin-antithrombin III complexes during the first 31 h indicated that the thrombus surface remained thrombogenic and that the effect of r-TAP was transient. We have shown that 2 h of treatment with a full antithrombotic dose of r-TAP markedly reduced both the rate of platelet deposition after treatment was stopped and the total number of platelets deposited over 55 h. This was in spite of the finding that the antithrombotic effect of r-TAP was transient.
Relative Efficacy of Active Site-Blocked Factors IXa, Xa in Models of Rabbit Venous and Arterio-Venous Thrombosis
Authors: Wong Arnold G , Gunn Alice C , Ku Paul , Hollenbach Stanley J , Sinha Uma 
Published: July 2018

SummaryIn order to investigate the respective roles of prothrombinase and intrinsic tenase (IXa/VIIIa) in venous thrombosis, we compared the antithrombotic efficacy of inhibitors of these two coagulation complexes. The agents tested were dansyl-Glu-Gly-Arg chloromethyl ketone-inactivated bovine factor IXa (IXai) and Glu-Gly-Arg chloromethyl ketone- inactivated human factor Xa (Xai). In vitro formation of active complexes (prothrombinase or tenase) was inhibited by Xai and IXai resulting in IC50 values of 3 nM and 5 nM, respectively. Antithrombotic activity was measured by inhibition of clot accretion on cotton threads placed in the abdominal vena cava of anesthetized rabbits. Intravenous bolus dosing followed by infusion of Xai during the experimental protocol resulted in a dose dependent reduction of clot weight, a dosage of 16.0 μg/kg + 0.28 μg/kg/min being sufficient to produce a 96% inhibition of thrombosis. A much higher dose of IXai (1.0 mg/kg + 17.3 |ig/kg/min) resulted in a 39% reduction of clot weight. In a rabbit arterio-venous shunt model mimicking arterial thrombosis, the relative efficacy of the two agents was found to be more comparable. The doses required for optimum antithrombotic activity were 128.0 μg/kg + 2.2 μg/kg/min for Xai and 1.0 mg/kg+ 17.3 μg/kg/min for IXai. We conclude that, in this study, prothrombinase rather than tenase inhibition was more effective in reducing venous thrombosis and that these effects can be achieved without disruption of extravascular hemostasis.
Angiotensin II Increases Plasminogen Activator Inhibitor-1 and Tissue Factor mRNA Expression without Changing that of Tissue Type Plasminogen Activator or Tissue Factor Pathway Inhibitor in Cultured Rat Aortic Endothelial Cells
Authors: Nishimura Hiromi , Tsuji Hajime , Masuda Haruchika , Nakagawa Katsumi , Nakahara Yoshihumi , Kitamura Hidetsugu , Kasahara Teruhisa , Sugano Tatsuya , Yoshizumi Masami , Sawada Shohei , Nakagawa Masao 
Published: July 2018

SummaryAngiotensin converting enzyme inhibitors (ACE-I) have been reported to prevent the recurrence of cardiovascular events. The mechanism of this decrease, however, can not be completely explained by anti-hypertensive and anti-hypertrophic effects of ACE-I. To investigate the mechanism of this decrease, we studied the regulation of plasminogen activator inhibitor-1 (PAI-1), tissue type plasminogen activator (TPA), tissue factor (TF), and tissue factor pathway inhibitor (TFPI) by angiotensin II (Ang II) in cultured rat aortic endothelial cells. Ang II increased PAI-1 and TF mRNA expression without affecting that of TPA or TFPI. These inductions were accompanied by increases in PAI-1 and TF activities and were inhibited by a type 1 Ang II receptor antagonist. The results suggest that Ang II decreases the antithrombotic properties of endothelial cells which increases the chance of thrombosis. Thus, inhibition of the renin-angiotensin system may be beneficial to prevent thrombus formation in treatment of ischemic heart disease.
A Comparison of Thromboelastography with Heparinase or Protamine Sulfate Added In Vitro during Heparinized Cardiopulmonary Bypass
Authors: Spiess Bruce D , Wall Michael H , Gillies Bruce S , Fitch Jane C K , Soltow Louise O , Chandler Wayne L 
Published: July 2018

SummaryThromboelastography (TEG) has been used after cardiopulmonary bypass (CPB) to diagnose excessive postoperative hemorrhage. Conventional TEG during CPB is not possible due to the sensitivity of the TEG to even small amounts of heparin, which produces a nondiagnostic tracing. The purpose of this study was to compare heparin neutralization using heparinase or protamine in TEG blood samples obtained during CPB. TEG testing was performed on 48 patients before, during and after CPB. Tissue plasminogen activator activity and antigen were measured on a subset of 32 patients. We found: 1) heparinase neutralized at least 10 IU/ml heparin while 1.6 ug/ml protamine neutralized up to 7 IU/ml heparin, 2) in samples with complete heparin neutralization by both methods, there was no significant difference in the R values, 3) while there was good correlation for other TEG parameters between heparinase and protamine treated samples, heparinase treatment produced shorter K values and higher angle, MA and A60, 4) while fibrinolysis was detected using both methods, heparinase treatment suppressed fibrinolysis in the TEG in both samples from patients and after in vitro addition of tissue plasminogen activator, 5) TEG was not a sensitive indicator of t-PA activity, detecting only 21% of samples with increased t-PA activity during bypass, and 5) heparinase was at least 100 times more expensive than protamine. We conclude that while both heparinase and protamine can be used to neutralize heparin in TEG samples obtained during CPB, protamine neutralization is more sensitive to fibrinolysis and less expensive, but the protamine dose must be carefully selected to match the heparin level used at individual institutions.
Effect of Strenuous Exercise on Fibrinogen and Fibrinolysis in Healthy Elderly Men and Women
Authors: Schuit Albertine J , Schouten Evert G , Kluft Cornelis , de Maat Moniek , Menheere Paul P C A , Kok Frans J 
Published: July 2018

SummaryThe elevated incidence of thrombotic disease in elderly people may be associated with an increase in PAI-1 and fibrinogen with ageing. Cross-sectional studies report an inverse relation of PAI-1 and fibrinogen with physical activity, but training studies show inconsistent results. In a controlled intervention study among elderly subjects (aged 60-80 years) we observed a moderate decrease in PAI-1 antigen (4%, -2.1 ± 2.4 ng/ml), a significant increase in t-PA activity (11%, 0.07 ± 0.04 IU/ml) and an unexpected significant increase in fibrinogen (6%, 0.18 ± 0.07 g/1) in subjects following a 6-month intensive training program as compared to controls. Reduction in PAI-1 antigen was significantly associated with a decrease in triglycerides (β = 10.3 ng/ml per 1 mM, p <0.01) and insulin (β = 2.37 ng/ml per 1 mU/1, p = 0.07). Increase in fibrinogen coincided with a rise in C-reactive protein (p <0.001). These data suggest that regular intensive activity may increase fibrinolytic activity in a moderate way, but also may cause chronically elevated plasma levels of acute phase proteins in elderly persons.
Determination of the International Sensitivity Index of a New Near-Patient Testing Device to Monitor Oral Anticoagulant Therapy
Authors: Tripodi Armando , Chantarangkul Veena , Clerici Marigrazia , Negri Barbara , Mannucci Pier Mannuccio 
Published: July 2018

SummaryA key issue for the reliable use of new devices for the laboratory control of oral anticoagulant therapy with the INR is their conformity to the calibration model. In the past, their adequacy has mostly been assessed empirically without reference to the calibration model and the use of International Reference Preparations (IRP) for thromboplastin. In this study we reviewed the requirements to be fulfilled and applied them to the calibration of a new near-patient testing device (TAS, Cardiovascular Diagnostics) which uses thromboplastin-containing test cards for determination of the INR. On each of 10 working days citrat- ed whole blood and plasma samples were obtained from 2 healthy subjects and 6 patients on oral anticoagulants. PT testing on whole blood and plasma was done with the TAS and parallel testing for plasma by the manual technique with the IRP CRM 149S. Conformity to the calibration model was judged satisfactory if the following requirements were met: (i) there was a linear relationship between paired log-PTs (TAS vs CRM 149S); (ii) the regression line drawn through patients data points, passed through those of normals; (iii) the precision of the calibration expressed as the CV of the slope was <3%. A good linear relationship was observed for calibration plots for plasma and whole blood (r = 0.98). Regression lines drawn through patients data points, passed through those of normals. The CVs of the slope were in both cases 2.2% and the ISIs were 0.965 and 1.000 for whole blood and plasma. In conclusion, our study shows that near-patient testing devices can be considered reliable tools to measure INR in patients on oral anticoagulants and provides guidelines for their evaluation.
The 20210 A Allele of the Prothrombin Gene Is a Common Risk Factor among Swedish Outpatients with Verified Deep Venous Thrombosis
Authors: Hillarp Andreas , Zӧller Bengt , Svensson Peter J , Dahlbäck Bjӧrn 
Published: July 2018

SummaryA dimorphism in the 3’-untranslated region of the prothrombin gene (G to A transition at position 20210) has recently been reported to be associated with increases in plasma prothrombin levels and in the risk of venous thrombosis (1). We have examined the prothrombin dimorphism among 99 unselected outpatients with phlebography verified deep venous thrombosis, and in 282 healthy controls. The prevalence of the 20210 A allele was 7.1% (7/99) in the patient group, and 1.8% (5/282) in the healthy control group (p = 0.0095). The relative risk of venous thrombosis was calculated to be 4.2 (95% Cl, 1.3 to 13.6), and was still significant when adjustment was made for age, sex and the factor V:R506Q mutation causing APC resistance [odds ratio 3.8 (95% Cl, 1.1 13.2)]. As previously reported, 28% of the patients were carriers of the factor V:R506Q mutation. Thus, 34% (one patient carried both traits) of unselected patients with deep venous thrombosis were carriers of an inherited prothrombotic disorder. To sum up, our results confirm the 20210 A allele of the prothrombin gene to be an important risk factor for venous thrombosis.
An Exploratory Trial of Two Dosages of a Novel Synthetic Thrombin Inhibitor (Napsagatran, Ro 46-6240) Compared with Unfractionated Heparin for Treatment of Proximal Deep-vein Thrombosis
Authors: Bounameaux Henri , Ehringer Herbert , Hulting Johan , Rasche Herbert , Rapold Hans J , Zultak Maurice ,   ADVENT Investigators
Published: July 2018

SummaryOne hundred and ten patients with acute proximal deep-vein thrombosis were randomized in a sequential dose-finding design, to receive continuous intravenous infusion of napsagatran, a novel synthetic thrombin-inhibitor, at a fixed dose of 5 mg/h (n = 37) or 9 mg/h (n = 26), or APTT-adjusted unfractionated heparin (n = 47). Oral anticoagulants were started on the 2nd day and the study drug was discontinued from the 5th treatment day, as soon as the International Normalized Ratio was above 2.Control venogram (97 venogram pairs evaluable) after 5-8 days of treatment showed improvement in 3 napsagatran-treated patients (versus none in heparin-treated patients) and worsening in 4 napsagatran- treated patients (versus 2 in heparin-treated patients). The venographic Marder’s score did not change among the treatment groups. New lung scan perfusion defects (99 scintigram pairs evaluable) occurred in 4 (11%), 4 (21%), and 4 (10%) patients in the napsagatran (5 mg/h) group, in the napsagatran (9 mg/h) group, and in the heparin control group, respectively. There was no statistically significant difference in any of these endpoints between the 3 groups. No major bleeding was observed and the rare minor bleedings occurred at a similar rate in the three treatment groups.In conclusion, the ADVENT trial has shown data that suggest comparable efficacy and safety of a synthetic, direct thrombin inhibitor (napsagatran) and conventional heparin therapy for treatment of proximal DVT. These results suggest that synthetic direct thrombin inhibitors are a promising class of antithrombotic agents which deserves further development in this field.
New Coagulation Factor V Gene Polymorphisms Define a Single and Infrequent Haplotype Underlying the Factor V Leiden Mutation in Mediterranean Populations and Indians
Authors: Castoldi E , Lunghi B , Mingozzi F , Loannou P , Marchetti G , Bernardi F 
Published: July 2018

SummaryTwo novel polymorphisms were identified in the factor V gene by direct sequencing of intronic areas. One of them, located in intron 9, is the marker closest to the Leiden mutation ever described, whereas the other, in intron 16, displays a rare allele invariantly associated to the mutation. Allele-specific amplification protocols were designed to perform extensive screenings for both polymorphic sites. The new markers were used in combination with six previously described polymorphisms to define specific factor V gene haplotypes. Haplotype investigations in 506Q homozygous thrombotic patients and normal controls showed the presence of a single haplotype underlying the factor V Leiden mutation in Mediterranean populations (among which Greek Cypriots, where the R506Q mutation is particularly frequent) and Indians. When traced in the absence of the Leiden mutation, the background haplotype was found to be present and roughly as frequent as the mutation itself in these populations. These findings indicate a single mutational event, that probably occurred outside Europe, as the cause of the Leiden mutation and provide a powerful tool to investigate its evolutionary history.
An Experimental Multiple-Organ Model for the Study of Regional Net Release/Uptake Rates of Tissue-type Plasminogen Activator in the Intact Pig
Authors: Jern Christina , Seeman-Lodding Heléne , Biber Bjӧrn , Winsӧ Ola , Jern Sverker 
Published: July 2018

SummaryExperimental data indicate large between-organs variations in rates of synthesis of tissue-type plasminogen activator (t-PA), which may reflect important differences in the capacity for constitutive and stimulated t-PA release from the vascular endothelium. In this report we describe a new multiple-organ experimental in vivo model for simultaneous determinations of net release/uptake rates of t-PA across the coronary, splanchnic, pulmonary, and hepatic vascular beds. In eleven intact anesthetized pigs, blood samples were obtained simultaneously from the proximal aorta, coronary sinus, pulmonary artery, and portal and hepatic veins. Plasma flows were monitored separately for each vascular region. Total plasma t-PA was determined by ELISA with a porcine t-PA standard. Regional net release/uptake rates were defined as the product of arteriovenous concentration gradients and local plasma flows. The net release of t-PA across the splanchnic vascular bed was very high, with a mean output of 1,919 ng total t-PA X min-1 (corresponding to 90 ng per min and 100 g tissue). The net coronary t-PA release was 68 ng X min-1 (30 ng X min-1 X 100 g"1)- Pulmonary net fluxes of t-PA were variable without any significant net t-PA release. The net hepatic uptake rate was 4,855 ng X min-1 (436 ng X min-1 X 100 g-1). Net trans-organ changes of active t-PA mirrored those of total t-PA. The results demonstrate marked regional differences in net release rates of t-PA in vivo. The experimental model we present offers new possibilities for evaluation of regional secretion patterns in the intact animal.
The Effect of Active Site-inhibited Factor VIIa on Tissue Factor-initiated Coagulation Using Platelets before and after Aspirin Administration
Authors: Kjalke Marianne , Oliver Julie A , Monroe Dougald M , Hoffman Maureane , Ezban Mirella , Hedner Ulla , Roberts Harold R 
Published: July 2018

SummaryActive site-inactivated factor VIIa has potential as an antithrombotic agent. The effects of D-Phe-L-Phe-L-Arg-chloromethyl ketone-treated factor VIla (FFR-FVIIa) were evaluated in a cell-based system mimicking in vivo initiation of coagulation. FFR-FVIIa inhibited platelet activation (as measured by expression of P-selectin) and subsequent large-scale thrombin generation in a dose-dependent manner with IC50 values of 1.4 ± 0.8 nM (n = 8) and 0.9 ± 0.7 nM (n = 7), respectively. Kd for factor VIIa binding to monocytes ki for FFR-FVIIa competing with factor VIIa were similar (11.4 ± 0.8 pM and 10.6 ± 1.1 pM, respectively), showing that FFR-FVIIa binds to tissue factor in the tenase complex with the same affinity as factor VIIa. Using platelets from volunteers before and after ingestion of aspirin (1.3 g), there were no significant differences in the IC50 values of FFR-FVIIa [after aspirin ingestion, the IC50 values were 1.7 ± 0.9 nM (n = 8) for P-selectin expression, p = 0.37, and 1.4 ± 1.3 nM (n = 7) for thrombin generation, p = 0.38]. This shows that aspirin treatment of platelets does not influence the inhibition of tissue factor-initiated coagulation by FFR-FVIIa, probably because thrombin activation of platelets is not entirely dependent upon expression of thromboxane A2.