bluuebunny/crossref_metadata_2025_split huggingface dataset:
PREVENTION OF DEEP VEIN THROMBOSIS (DVT) BY ENOXAPARINE (LOVENOXR) AFTER SURGERY FOR FRACTURE OF FEMORAL NECK. ONE DAILY INJECTION OF 40 MG VERSUS TWO DAILY INJECTIONS OF 20 MG
Authors: BARSOTTI J , DABO B , ANDREU J , ALISON D , LEROY J , DELAHOUSSE B 
Published: August 2018

In a previous open study, a low-molecular-weight-heparinEnoxa-parine in a dose of 40 mg/24 hrs by subcutaneous (SC) injection, had been shown to be efficient and safe in preventing DVT after total hip replacement (THR), for a non traumatic hip disease. 103 patients (mean age : 82 years ± 10, mean weight : 52 kg ± 10) undergoing an orthopedic operation for fracture of femoral neck were included ina randomized, double blind study. These patients receivedSC Enoxaparine according to two different regimens : 54 patients received the treatment A (2 daily injections of 20 mg), 49 patients received the treatment B (1 daily injection of 40 mg).In both groups, administration of 40 mg of Enoxaparine was begun 12 hours before operation.Patients weretreated for 10-15 days, until bilateral ascending phlebography (BAP) had been completed.Lower limbs BAP were performed in 97 patients. The incidence of DVT is low and not significantly different betweenthe two regimens :a proximal DVT was detected in 6 patients of the group A and in 2 patients of the group B. This differenceis not significant(p = 0.28).3 patients of each group hada distal DVT. No clinical pulmonary embolism occurred.There was no serious bleeding complication, and the two groups are not significantly different on this point; 2 patients in each group had an important hematoma of the thigh.One hematoma, in a patient who received the treatment B, required a surgical treatment.Red cell transfusion requirementswere 2.6U+1.8 in the group A and 2.5 U ±1.4 in the group B (p = 0.84)There was no significant difference in the daily hemoglobinlevels between the two groups.This study shows that one daily SC injection of 40 mg of Enoxaparine is as efficient as two daily SC injections of20 mg of Enoxaparine in preventing DVT, in very elderly patients undergoing orthopedic operation for fracture of the femoral neck. The frequencies of bleeding complications in each group were not significantly different.Enoxaparine (LOVENOXR) - PHARMUKA S.F.
TOTAL HIP REPLACEMENT AND DEEP VEIN THROMBOSIS - RELATIONSHIP TO THE FIBRINOLYTIC SYSTEM
Authors: Eriksson B , Eriksson E , Gyzander E , Teger-Nilsson A C , Riseberg B 
Published: August 2018

Reduced fibrinolytic activity increases the risk of recurrent thromboembolism and it has been suggested thatit also plays a role in postoperative thrombosis.Material and methods. Fibrinolytic parameters were analysed in 29 patients submitted to total hip replacement. Dextran 70 was given as thrombosis prophylaxis. Blood samples weretaken pre operatively, one day and oneweek postoperatively. Venous occlusion test was done in all patients.125 I-fibrinogen test was used for deep vein thrombosis (DVT) screening.Positive test was confirmed with phlebography. Fibrinolytic activity was measured on fibrin plates. Tissueplasminogen activator (t-PA) and itsspecific inhibitor (PAI) were analysed with photometric and immunologicalmethods.Results. The first postoperative dayt-PA activity decreased and PAI increased significantly. One week after operation only PAI showed significatdifference from preoperative values.10 of the patients developed DVT.The PAI level significantly higher in DVT patients preoperatively. Thisdifference in PAI level was significant compared with non-DVT patients also one day and one week postoperatively.Conclusion. The recently discovered t-PA inhibitor (PAI) seems to be correlated to postoperative thrombosis in total hip surgery.
LIPOPROTEIN BINDING TOHUMAN PLATELETS IS LOCATED AT GPIIb/IIIa COMPLEX
Authors: Koller E , Koller F 
Published: August 2018

Human Platelets possess specific binding sites for low density lipoproteins (LDL) and high density lipoproteins(HDL)(1). Binding of both classes of plasma lipoproteins, though competitive, has been shown by several groups to facilitate platelet activation.Isolated washed platelets occasionally aggregate upon addition of high concentrations of LDL even in the absence of known platelet activators. The proteins responsible for this binding have been visualized by ligand blotting (2). Both types of ligand specifically bind to two glycoproteins with molecular weights of 135 and 115 kD, respectively. The conditions of binding to these two proteins, however, markedly differ from those known for other lipoprotein receptors.Following extensive purification, these two species are still present at concentrations relative to each other that depend markedly on the conditions of purification. The purified, solubilized receptor was tested under various conditions, including in the absence and presence of calcium, after disulfide-reduction, and following chymotrypsin digestion. In parallel experiments, the same preparations were tested with respect to binding of fibrinogen, different lectins, and thealloantibody anti-PlAI . The results strongly support the assumption, that the two protein bands associated with lipoprotein binding are constituents of the GP-IIb/IIIa complex.These first results may have greatimplications for our understanding ofthe mechanism by which lipoproteins facilitate platelet stimulation.
INHIBITION OF FACTOR Xa AND THROMBIN BY ANTITHROMBIN III AND HEPARIN DURING HUMAN PROTHROMBIN ACTIVATION
Authors: Schoen P , Hemker H C , Lindhoubt T 
Published: August 2018

Prothrombin-catalyzed human prothrombin activation results in the generation of thrombin and meizothrombin- des FI (MDF1) as was demonstrated by an immunoblot technique. Theheparin-independent second order rate -.onstants of inhibition of both thrombin and MDF1were 3.7 x 105 M-1min-1, whereas the rate constant of inhibition of purified thrombin was 6.5 x 105 M-1min-1 . In the presence of heparin the decay of amidolytic thrombin activity appeared to be bi-exponential and could be modelled by a 4-parameter equation. Fitting the experimental data to this equation gave the pseudo-first-order rate constants of inhibition, as well asthe composition of the reaction with respectto the levels of thrombin and MDF1. The occurence of MDF1 rather than meizothrombin (MT)suggests that MT is very rapidly converted into prothrombin fragment 1 (FI) and MDF1, a "dead-end" product of prothrombin activation. At high prothrombin concentrations (1.0 μM) predominantly MDF1 and not thrombin is formed, indicating that MT itself and/or MDF1 cleaves at Argl56 - Serl57 to produce FI and MDF1. Interestingly, heparin is unable to stimulate the inhibition of MT and MDF1 by AT III. We could demonstrate that MT and MDF1 have a low affinity, if any, for heparin.The kinetics of the heparin-dependent inhibition of prothrom-binase formed thrombin differ from those of purified thrombin added to the prothrombin activation reaction. A lower rate of inactivation of endogenous formed thrombin was observed and,moreover, could not be modelled as a simple random order bi-reactant enzyme-catalyzed reaction. Theseeffects might be caused by the presence of prothrombin activation fragments.Taking the factor Xa inactivation also into account, it appeared that the major effect of heparin onthe thrombin generation was to enhance the inhibition of thrombin rather thanthat of factor Xa. When unfractionated heparin (UFH; mean Mr = 14000, 168 USP units/mg) was compared with a synthetic pentasaccharide (PS; Mr = 1714, 4000 anti-Xa U/mg) on basis of equal anti-Xa U/ml, UFH shortened the half-life time of factor Xa 190-fold, whereas PS shortened the half-life time 17-fold.
A MODIFIED METHOD FOR PURIFICATION OF BOVINE FACTOR VII AND ITS PRIMARY STRUCTURE
Authors: Takeya H , Kawabata S , Miyata T , Morita T , Iwanaga S 
Published: August 2018

A modified method for purification of factor VII from bovine plasma was developed. The isolation procedures consisted of four steps with the ordinary barium citrate adsorption (1), DEAE-Sepharose chromatography (2), twice chromatographies on a benzamidine-Sepharose column (3) and affinity chromatography on Affigel-10 coupled with staphylocoagulase produced by Staphylococcus aureus, strain 213 (4). This final step was very effective for the removal of prothrombin contained in the pooled fraction of factor VII. Thus, these procedures allowed higher recovery of factor VII than the earlier methods and about 7 mg of the material was obtained from 15 liters of plasma. The purified preparation gave a single band on SDS-PAGE in the absence and presence of 2-mercaptoethanol and the apparent Mr was estimated as 53,000.To establish the whole primary structure at protein level, the isolated single chain factor VII was incubated with bovine factor Xlla and the resulting two chains-factor VII was reduced and S-pyridylethylated. The S-alkylated heavy and light chains were then separated on a TSK gel G3000SW followed by reversed phase HPLC on a Phenyl-5PWRP column. The amino acid sequence of the isolated light chain was determined by sequencing the peptides obtained from lysyl endopeptidase and α-chymotrypsin digests and from trypsin digest of the succinylated light chain. The light chain consisted of the total of 152 residues with 10 r-carboxyglutamic acids and contained one oligosaccharide chain at Asn-145. The light chain sequence was compared with that predicted from the cDNA sequence for human factor VII. It had 76 % sequence identity with the human's. The sequence of the factor Vll-heavy chain is being studied
THE ANTITHROMBOTIC EFFECT OF PALM OIL IS CORRELATED WITH ITS CONTENTS OF VITAMIN E
Authors: Hornstra E G , Hennissen A H , Kalafusz R , Tan D T S 
Published: August 2018

Dietary saturated fatty acids are known to increase platelet aggregation and arterial thrombogenesis.We recently demonstrated, however, that palm oil, rich in saturated palmitic acid, has a distinct antithrombotic affect, which is associated with a decrease of the thromboxane-prostacyclin ratio in activated whole blood. To identify the antithrombotic component(s) of palm oil, seven palm oil fractions were prepared with comparable fatty acid compositions of the triglycerides but containing Various amounts of non-triglyceride material with different compositions.These fractions were fed to rats in amounts of 50 energy% for a period of 8 weeks, after which arterial thrombosis tendency was measured upon insertion of an aortic prosthesis, the aorta-loop. During loop insertion, 1 ml blood was collected in citrate for measuring platelet aggregation and ATP release in response to collagen, using the Chronolog whole blood lumi-aggregometer. Arterial thrombosis tendency was found to be negatively related to the total amount of non-triglyceride material in the various fractions (r = 0.78; p <0.05).No significant relationship was observed between arterial thrombus formation and the various sterols present in the non-triglyceride material.A significant negative correlation was found, however, with a-tocopherol (r = 0.86; p <.02). Collagen-induced platelet aggregation and ATP release in whole blood were not correlated to total amounts or α-tocopherol content of the non-triglyceride material.However, significant positive relationships were found between these platelet functions and the amountsof the various sterols (Campesterol: r = 0.70; P < 0.10 β-sitostero1 : r = 0.69; P <0.10. Cholesterol : r = 0.81; P < 0.05).These findings demonstrate that effects of edible oils on platelet function and arterial thrombogenesisare not only mediated by the fatty acid compostion of the triglycerides, but can also be determined by 'minor components', present in the non-triglyceride part of the oils.
DETECTION OF ACTIVATED PLATELETS WITH MONOCLONAL ANTIBODIES
Authors: Metzelaar M J , Nieuwenhuis H K , Sixma J J 
Published: August 2018

Blood tests reflecting in-vivo activation of platelets are potentially useful in evaluating patients with thrombotic diseases. Recently monoclonal antibodies have been described that react preferentially with activated platelets. We prepared an IgG2b antibody, designated RUU-AP 2.28, that reacted with a 53.000 MW protein that is located in a special subclass of platelet granules in unstimulated platelets and that is exposed on the surface of activated platelets. Increased numbers of platelets that expressed the 2.28 antigen on their surface were observed in patients undergoing cardiopulmonary bypass and in patients with acute deep venous thrombosis. The percentage of RUU-AP 2.28 positive platelets in the circulation was 3,9 ± 2.7 (SD)% in the controls, (n = 20), 24.6 ± 13.5% in patients after cardiopulmonary surgery (n = 10) and 8.5% in patients with acute deep venous thrombosis (n = 2).In order to detect also earlier stages of platelet activation, such as secretion-independent phenomena, we produced new monoclonal antibodies by fusing spleen cells from Balb/c mice, immunized with thrombin stimulated, paraformaldehyde fixed platelets, with Ag 8653 myeloma cells. As a screening assay we used an ELISA with freshly fixed platelets or fixed thrombin-activated platelets. We detected six monoclonal antibodies (RUU-AP 1-6) specific for thrombin-activated platelets. The results of the ELISA were confirmed by flow cytofluorometry.None of the antibodies inhibited platelet aggregation induced by ADP, collagen or ristocetin. Ascites of IgGl antibody RUU-AP 3 reacted with normal thrombin-activated platelets but did not react with thrombin-activated platelets from a patient with Glanzmann’s disease. In addition antibody RUU-AP 3 reacted with normal platelets stimulated with 1 pM of ADP. These data suggest that antibody RUU-AP 3 detects a secretion-independent conformational change in the platelet membrane glycoprotein IIb-IIIa complex.
BINDING OF CALCIUM TO HUMAN AND BOVINE FACTOR X
Authors: Monroe D M , Deerfield D W , Olson D L , Stewart T N , Roberts H R , Hiskey R G , Pedersen L G 
Published: August 2018

Human and bovine factor X contain 11 and 12 glutamyl residues respectively within the first forty amino terminal residues that are posttranslationally modified to y-carboxyglutamyl (Gla) residues. Calcium binding to these Gla residues and at other sites is critical for activity in factor X. We have measured calcium binding to human factor X by equilibrium dialysis for the first time. We have also re-examined calcium binding to bovine factor X in order to compare the two species. Factor X (10 μM) was incubated with 45Ca in 20 mM Tris (pH 7.5), 100 mM NaCl in a half cell separated by a 12-14000 molecular weight fast-equilib-rium disk membrane at 25°C for 24 hours. Four aliquots (100 μL each) were removed from each side of the cell and counted. Data were analyzed with a variety of models that allow for more than one class of binding site and for cooperativity among binding sites. Calcium binding to bovine factor X was best simulated by a model that assumes 1 very tight site, 3 cooperative tight sites, and 18 equivalent, non-interacting sites. Based on data from des(Gla)factor X, the first site is probably a high affinity non-Gla binding site. Our results differ from two previously published reports that indicated either 1 tight and 39 loose noncooperative sites (R.H. Yue & M.M. Gertler (1978) Thrombos. Haemostas. (Stuttg.) 40, 350) or 20 calcium binding sites with the first 4 being cooperative (M.J. Lindhout & H.C. Hemker (1978) Biochimica Biophysica Acta 533, 318). Our data on human factor X fit the same model as used for bovine factor X; however, coop-erativity is less in the 3 cooperative sites. Shown below are the first six thermodynamic equilibrium constants derived from a Scatchard analysis of binding data (values are M−1).Both proteins demonstrate the same total number of binding sites and essentially the same value for the first, tight binding site. Bovine factor X exhibits cooperativity, whereas human factor X has reduced cooperativity.
POLYMORPHIC SITES IN FACTOR X GENE
Authors: Chelucci C , Hassan H J , Guerriero R , Leonardi A , Mattia G , Peschle C 
Published: August 2018

The structure of factor X gene has been analyzed by Southern blot in 5 subjects with factor X deficiency.Genomic DNA was digested with 8 different endonucleases and hybridized with a cDNA probe. The congenital deficiency observed in these patients is not apparently due to a major deletion or rearrangement. Since the gene locus is grossly intact, the disease presumably results from point mutation(s) not identified by the utilized endonucleases.Our study was also focused on the presence of polymorphic site(s) in the factor X gene locus. Analysis of 50 normal subjects allowed to identify several polymorphic restriction sites after digestion with EcoRI, Hind III and Pvu II.The restriction pattern obtained after Hind III digestion showed two bands of 7.3 and 6.0 Kb, while in two families an additional 7.6 Kb band was observed. Genomic DNA digested with EcoRI showed a 7.1 and 5.1 Kb fragments, and also a 6.6 Kb band with a 10% f requency.After DNA digestion with Pvu II 5.6, 2.7 and ∼1.0 Kb bands were observed. In three unrelated subjects we observed an additional 3.0 Kb fragment, in two other subjects a 3.5 kb band. Interestingly hybridization with a 178 bp cDNA subclone allowed to map the polymorphic sites in a the 3’ region of the gene locus.
EFFECTS OF HEPARIN AND COUMARIN ON DEPOSITION OF FIBRIN, PLATELETS AND PLATELET THROMBI ON RABBIT AORTA SUBENDOTHELIUM EXPOSED TO FLOWING HUMAN BLOOD
Authors: Inauen W , Bombeli T , Baumgartner H R , Haeberli A , Straub P W 
Published: August 2018

The effect of heparin and phenprocoumon on thrombogenesis induced by rabbit aorta subendothelium (SE) was investigated in 20 volunteers using an ex vivo perfusion system. Blood was drawn directly from an antecubital vein through an annular chamber with exposed SE at lOml/min flow rate (650sec−1 shear rate) for 5min. Following buffer perfusion for 15sec, the middle portion of SE was removed for plasmin digestion and adjacent segments were fixed and embedded for morphometric analysis. Perfusions were performed 20 min after i.v. injection of heparin 1000, 2500 and 5000 IU, respectively; and during the decline and steady-state of prothrombin activity during a 2 weeks treatment with phenprocoumon to target INR of 5.0.The amount of fibrin attached to SE, as measured by fragment E RIA in plasmin digests, correlated negatively with the dose of heparin (r=−0.83, P<0.001, n=48) and with INR during coumarin intake (r=−0.58, P<0.01, n=40). After high doses of either heparin or coumarin fibrin deposition on SE was virtually abolished (table). Platelet adhesion was increased. Platelet thrombus volumes and heights were reduced by heparin and coumarin.We conclude that both heparin and coumarin dose-dependently inhibit fibrin formation induced by SE. In addition, both drugs impair platelet thrombus growth and/or stability indicating that these processes may also depend on the coagulation mechanism.
RESPONSE OF PROTEIN C AND PROTEIN S INHIBITORS IN LONG-TERM ORAL ANTICOAGULANT THERAPY
Authors: Mukhlova Montiel M , Bussey H 
Published: August 2018

Protein C (PC) and its coenzyme Protein S (PS) are physiologic inhibitors of activated factors Va and Villa. Deficiency of either one of these inhibitors has been associated with venous thrombosis. Their activity is dependent on vitamin K for hepatic gamma carboxylation and it is depressed during oral anticoagulant therapy. Because rebound thrombosis complicates cessation of anticoagulant therapy, we investigated the response of PC and PS during long term oral anti coagulation. The study encompassed 30 patients ranging between 26 and 76 years of age, who have received therapeutic doses of coumadin from 15 days to more than 8 years. The conditions for which treatment was initiated were deep vein thrombosis, cerebral vascular accidents and cardiac valve replacements.Factor VII and X activity was assayed by one step routine clotting assays. PC antigen (ag), total PSag and free PSag were assayed by Laurel 1 Rocket electroimmunodiffusion method. The measurement of the free PS was carried out after precipitation of C4b-binding protein with polyethylene glycol. PC activity was measured by clotting assay using PC deficient plasma to which was added patient plasma as a source of PC. Control group of 30 individuals in similar age group were assayed parallel with the patient samples. Compared with the control group the coumadin-treated patients showed substantial decrease of all factors studied. Statistical regression analysis of the coumadin group showed a significant increase in PS free (p = 0.014)during long term anti coagulation, while all of the other variables did not change significantly.PCag and total PSag were decreased and their activities, as expected, were more severely affected. The ratio of PC activity to PCag averages 0.39 (normal >0.80) and free PS represented only 27% of the total PSag (normal about 40%). The inhibitors' persistent activity parallels that of the depression of Factors VII and X and there appears to be a balanced coagulation-inhibi-tion system. If PC and PS play a role in rebound thrombosis after a prolonged anticoagulation therapy, the changes may occur after discontinuation of medication.
CALIBRATED PLASMA PROCEDURE AND INR FOR PT STANDARDIZATION. DATA FROM THE FRENCH ETAL0N0RME QUALITY CONTROL SURVEYS
Authors: GOGUEL A , HOUBOUYAN A , ROUSSI J 
Published: August 2018

One of the aim of the survey conducted in last december 1986 was to assess the efficacy of 2 procedures of standardization :1) the INR system, derived from thromboplastin calibration and adopted in 1983 by the WHO.2) the Reference Calibrated Plasmas (RCP) procedure, evaluated on large scale, through French interlaboratory trials (1977-85), exhibiting net improvement of the dispersion of overall data.Labs were asked to perform with their local thromboplastin and method, the PT of a human lyophilized plasma 86 H/I, originated from long term antivitarnines-K (AVK) treated patients. Results were expressed *in time ; *in % activity, according to the traditional procedure based on saline dilutions of normal plasma ; *in INR using the ISI of the local reagent calibrated by the manufacturer. Calibrated plasmas procedure allow the determination of corrected activity ; *in % activity and INR, according to the linear calibration curve obtained from the PT of 2 reference calibrated plasmas with determinated activities in INR and % activity. These RCP were provided with and tested under the same conditions as plasma 86 H/I6 (2 systems of RCP : AVK and artificially depleted).Statistical analysis shows that the "RCP" procedure leads to the best improvement of the interlaboratory variation for the overall data, and the best uniformization of mean results, whatever the way of expression (%, INR), the thromboplastin brand, and the method of PT testing. Results play also in favour of a system of AVK reference plasmas, giving a better grouping than the artificial calibrated plasmas. The INR system nevertheless provides a common scale of data reporting, but might hold profit from an efficient procedure of standardization, such as the calibrated AVK plasmas procedure.Coefficient of variation (CV) expressed in %. Overall data PT of 86 H/I. French Etalonorme Survey.