bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Prospective Controlled Trial Comparing Weekly Self-testing and Self-dosing with the Standard Management of Patients on Stable Oral Anticoagulation
Authors: Forberg E. , Svolba G. , Jimenez-Boj E. , Krinninger B. , Watzke H. H. 
Published: March 2018

SummaryOral anticoagulant therapy requires frequent laboratory controls of its intensity to assure therapeutic efficacy and to prevent potentially life threatening adverse events. It is generally assumed, that increasing the frequency of testing would lead to a better control of anticoagulation. We tested this hypothesis in a prospective controlled trial comparing weekly self-testing and self-dosing (self management) with the standard-management of these patients in an anticoagulation clinic. Only patients with stable anticoagulation were included into the study. We recorded 2733 weekly determinations of the intensity of anticoagulation (INR) in 49 patients on self-testing and self-dosing and 539 determinations of the INR in 53 patients on standard-management. Two intensities of anticoagulation were used in each group: a target INR of 3.5 for patients with artificial heart valves (target range: 2.5–4.5) and a target INR 2.5 (target range: 2.0–3.0) for patients with atrial fibrillation or venous thromboembolism. The deviation from the target INR, the fraction of INR determinations within the preset therapeutic range and the difference between the target INR and the actually achieved mean INR were the three major endpoints of the study. The mean deviation from the target INR was smaller in the groups of patients on self–management compared to the patients on standard-management. Individual deviations were significantly (p <0.0001) dependent on the type of management in interaction with the treatment intensity in a general linear model. Patients on weekly self-testing and self-dosing had more INR values within the therapeutic range than patients on standard-management (86.2% vs. 80.1% at INR range 2.5–4.5; 82.2 vs. 68.9 at INR range 2.0–3.0). The achieved mean INR was almost identical with the target INR in the patients on self-management but was significantly (p <0.005) below the target INR in the high intensity anticoagulation group on standard-management (target INR:3.5; achieved mean INR: 3.19; CI 0.95: 3.05–3.34).Our data show, that weekly self-testing and self-dosing leads to a better control of anticoagulation than standard treatment in an anticoagulation clinic.The technical equipment used for self testing in this study was provided by Roche Diagnostics, Austria
Gestational Outcome in Thrombophilic Women with Recurrent Pregnancy Loss Treated by Enoxaparin
Authors: Hoffman R. , Blumenfeld Z. , Weiner Z. , Younis J. S. , Brenner B. 
Published: March 2018

SummaryInherited and acquired thrombophilia are associated with recurrent pregnancy loss (RPL). We have evaluated the efficacy and safety of the low molecular weight heparin enoxaparin in 50 women, (mean age 26 ± 3 years) with RPL (>3 losses in 1st, >2 losses in 2nd and >1 loss in 3rd trimester) who were found to harbor thrombophilia. Twentyseven had a solitary thrombophilic defect, and twenty-three women had combined thrombophilic defects: 17 – two defects and 6 – three defects. Following diagnosis of thrombophilia, sixty-one subsequent pregnancies were treated with the low molecular weight heparin enoxaparin throughout gestation until 4 weeks after delivery. Dosage was 40 mg/day in women with solitary defect and 80 mg/day in combined defects. Aspirin, 75 mg daily was given in addition to enoxaparin to women with antiphospholipid syndrome. Forty-six out of 61 (75%) gestations treated by enoxaparin resulted in live birth compared to only 38/193 (20%) of the untreated pregnancies in these 50 women prior to diagnosis of thrombophilia (p <0.00001). In 23 women without a single living child following 82 untreated gestations, antithrombotic therapy resulted in 26/31 (84%) successful deliveries (p <0.0001). In 20 women with a prior living child, antithrombotic therapy improved successful delivery from 33/86 (38%) to 20/21 (95%) (p <0.0001). Enoxaparin dose of 40 mg/day resulted in live birth in 24/35 (69%) of gestations, compared to 19/23 (83%) gestations in women treated with 80 mg/day (p = 0.37). Only one thrombotic episode and one mildbleeding episode were noticed during enoxaparin therapy. Enoxaparin is safe and effective in prevention of pregnancy loss in women with inherited and acquired thrombophilia.
High Molecular Weight Kininogen Is Cleaved by FXIa at Three Sites: Arg409-Arg410, Lys502-Thr503 and Lys325-Lys326
Authors: Mauron T. , Lämmle B. , Wuillemin W. A. 
Published: March 2018

SummaryWe investigated the cleavage of high molecular weight kininogen (HK) by activated coagulation factor XI (FXIa) in vitro. Incubation of HK with FXIa resulted in the generation of cleavage products which were subjected to SDS-Page and analyzed by silverstaining, ligandblotting and immunoblotting, respectively. Upon incubation with FXIa, bands were generated at 111, 100, 88 kDa on nonreduced and at 76, 62 and 51 kDa on reduced gels. Amino acid sequence analysis of the reaction mixtures revealed three cleavage sites at Arg409-Arg410, at Lys502-Thr503 and at Lys325-Lys326. Analysis of HK-samples incubated with FXIa for 3 min, 10 min and 120 min indicated HK to be cleaved first at Arg409-Arg410, followed by cleavage at Lys502-Thr503 and then at Lys325-Lys326.In conclusion, HK is cleaved by FXIa at three sites. Cleavage of HK by FXIa results in the loss of the surface binding site of HK, which may constitute a mechanism of inactivation of HK and of control of contact system activation.
Detection of Complement-fixing Antiphospholipid Antibodies in Association with Thrombosis
Authors: Saito Takako , Matsuda Kumiko , Seino Jin , Shibata Shinobu , Sasaki Takeshi , Munakata Yasuhiko 
Published: March 2018

SummaryAntiphospholipid antibody (aPL) is a hallmark of antiphospholipid syndrome (APS), characterized by thrombosis and recurrent fetal loss. We developed a novel ELISA system to detect complement-fixing ability of anticardiolipin antibody (aCL), and evaluated its clinical usefulness through studying the prevalence of the antibodies in rheumatic diseases, especially in association with thrombosis and recurrent abortion. Among 189 patients with rheumatic diseases, the complement-fixing aCL was positive in 26 (83.9%) of 31 patients with APS and 2 (1.3%) of 158 with other disease categories, whereas it was not positive among 52 normal subjects. Twenty-seven of 28 patients (96.4%), who were positive for complement-fixing aCL, had the episodes or history of thrombosis and/or recurrent abortion, at the time we studied. The remaining one in this group developed APS manifesting pulmonary infarction and occlusion of mesenteric artery 6 months after the evaluation. The sensitivity and specificity of this assay system were 75.0% and 99.3%, respectively, in relation with thrombotic episodes. On the other hand, the IgG aCL were positive in 28 (77.8%) of 36 cases with recent thrombotic episodes and 24 (15.7%) of 153 cases with no recent thrombotic episodes. The sensitivity and specificity of IgG aCL assay system were 77.8% and 84.3%, respectively, in relation with thrombotic episodes. These results indicate that complement-fixing aCL may specifically occur in association with the episodes of thrombosis and/or recurrent abortion in patients with APS compared to IgG-aCL. The method for detecting the complement-fixing aCL is simple, and it provides the useful diagnostic marker for thrombotic manifestations associated with APS.
Elderly Patients Treated with Tinzaparin (Innohep®) Administered once Daily (175 Anti-Xa IU/kg): Anti-Xa and Anti-IIa Activities over 10 Days
Authors: Pautas E. , Février M. , Wipff C. , Durand-Gasselin B. , Laurent M. , Andreux J.-P. , d’Urso M. , Gaussem P. , Siguret V. 
Published: March 2018

SummarySince low molecular weight heparins (LMWH) are partly eliminated by renal excretion, their pharmacodynamic profile may be modified in very elderly patients with age-related renal impairment. The aim of this prospective study was to determine whether tinzaparin (Innohep®) 175 anti-Xa IU/kg administered subcutaneously once daily over 10 days does accumulate in hospital patients greater than 70 years of age. Plasma anti-Xa and anti-IIa amidolytic levels and APTT were determined prior to the first injection (day 0), and then, at peak level i.e. 5 h after the second injection (day 2) and subsequently on days 5, 7 and 10.Thirty consecutive inpatients (6 men, 24 women) requiring LMWHs at a curative dose for acute thromboembolic disease were included. Patients’ characteristics (mean ± SD) were: age 87.0 ± 5.9 years (range 71–96), body weight 62.7 ± 14.6 kg (range 38-90) and creatinine clearance 40.6 ± 15.3 mL/min (range 20–72). The mean actual dose of tinzaparin delivered was 174.8 anti-Xa IU/kg. Since no patient had an anti-Xa activity above 1.5 IU/mL, the dose of tinzaparin remained fixed over 10 days.Anti-Xa and anti-IIa peak levels measured on day 2 were 0.66 ± 0.20 IU/mL (range 0.26–1.04) and 0.33 ± 0.10 IU/mL (range 0.18–0.55), respectively. Ex vivo anti-Xa/anti-IIa ratios were close to 2.1. APTT ratios (patient/control) were strongly correlated with anti-IIa activity (p <0.01). There was no progressive increase of the anti-Xa and anti-IIa activities after repeated administration of tinzaparin over the 10 day treatment period. No correlation was found between anti-Xa and anti-IIa activities and age, weight, or creatinine clearance. No major bleeding occurred during the study and only one minor haematoma at the injection site was reported. No thromboembolic complication or death occurred.Tinzaparin may thus be administered safely at a treatment dose (175 anti-Xa IU/kg) in older patients with age-related renal impairment. Neither dose adjustment, nor serial anti-Xa activity monitoring seems to be required in patients with creatinine clearance above 20 mL/min during the first ten day treatment.
Some Factor VIII (FVIII) Inhibitors Recognise a FVIII Epitope(s) that Is Present only on FVIII-vWF Complexes
Authors: Lavend’homme Renaud , Peerlinck Kathelijne , Jacquemin Marc , Hoylaerts Marc , Jorieux Sylvie , Mazurier Claudine , Vermylen Jos , Saint-Remy Jean-Marie , Gilles Jean Guy 
Published: March 2018

SummaryA mild haemophilia A patient (LE) with an Arg2150His mutation in the C1 domain of the factor VIII (FVIII) light chain was shown to have anti-FVIII antibodies inhibiting wild type but not self FVIII. Polyclonal anti-FVIII antibodies of this patient were purified by affinity adsorption using recombinant FVIII (rFVIII) and/or plasma-derived FVIII-von Willebrand factor (vWF) complexes. A distinct population of antibodies was obtained that bound to FVIII-vWF complexes but not to rFVIII, indicating that an epitope was created by the association of FVIII to vWF. Such antibodies belonged to the IgG2 isotype, but the FVIII epitopes to which they bind could not be mapped with precision due to vWF dependency. Depletion experiments showed that anti-FVIII antibodies recognising FVIII-vWF complex also distinguished wild-type from mutated self FVIII, indicating that the Arg2150His mutation alters the B cell epitope formed by the association of FVIII to vWF. To determine whether the Arg2150His substitution also alters the formation of the FVIII-vWF complex, the interaction between mutated or normal FVIII with vWF was evaluated in plasma. The dissociation rate of mutated FVIII from vWF was found to be significantly increased. The presence of an Arg2150His mutation therefore results in the disappearance of a FVIII B cell epitope generated by the association of FVIII with vWF. Patients carrying such an Arg2150His mutation and receiving infusion of wild-type FVIII may therefore be at risk of developing inhibitors to allogeneic FVIII only.
A Collaborative Study to Establish the 2nd International Standard for Antithrombin Concentrate
Authors: Walker A. Dawn , Heath Alan B. , Gray Elaine 
Published: March 2018

SummaryEighteen laboratories participated in a collaborative study to calibrate a replacement for the 1st International Standard for Antithrombin, Concentrate (88/548). Excellent agreement between laboratories, as indicated by mean % gcv of 3.3 and 5.9 for functional and antigenic assays, was observed when the candidate concentrate (96/520) was assayed against the 1st International Standard for Antithrombin, Concentrate (88/548). The functional potency was found to be 7.9% (p <0.05) lower than the antigenic potency. Based on the results and with the agreement of the participants of this study and the authorisation of the Expert Committee on Biological Standardisation of the World Health Organisation, the antithrombin concentrate, coded 96/520, has been established as the 2nd International Standard for Antithrombin, Concentrate, with labelled potencies for both functional (4.7 IU/ampoule) and antigenic (5.1 IU/ampoule) activities.
A Bispecific Antifibrin-antiplatelet Urokinase Conjugate (BAAUC) Induces Enhanced Clot Lysis and Inhibits Platelet Aggregation
Authors: Ruef Johannes , Nordt Thomas , Peter Karlheinz , Runge Marschall , Kübler Wolfgang , Bode Christoph 
Published: March 2018

SummaryThrombolysis is well established in the treatment of acute myocardial infarction. However, clinical application of thrombolytic agents has limitations with respect to efficacy and specificity. To achieve highly effective and at the same time clot-selective plasminogen activation urokinase was coupled to a bispecific antibody consisting of the mono-valent Fab’ from the antifibrin monoclonal antibody 59D8 and the monovalent Fab’ from the anti-glycoprotein GPIIb/IIIa monoclonal antibody 7E3. The bispecific antifibrin-antiplatelet urokinase conjugate (BAAUC) was synthesized and characterized. Assays with either immobilized platelets, GPIIb/IIIa or fibrin showed an increase in plasminogen activation compared to uncoupled urokinase by 10-fold, 58-fold and 13-fold, respectivley (p < 0.0001 each). In vitro clot lysis was performed on platelet-rich and fibrin-rich clots and revealed an up to 5-fold higher potency of BAAUC compared to uncoupled urokinase (p < 0.0001). In vitro platelet aggregation was effectively inhibited by the hybrid molecule, whereas urokinase had no effect. BAAUC and two monospecific urokinase-conjugates, UK-59D8-IgG and UK-7E3-(Fab’)2 were compared with each other with regard to similar tests. In vitro clot assays with platelet-rich and platelet-poor clots were performed. BAAUC achieved a significantly higher plasminogen activation compared to each of the monospecific conjugates (p < 0.05, respectively). We conclude that BAAUC, a bispecific plasminogen activator with antifibrin and antiplatelet properties has the potency to lyse both fibrin-rich and platelet-rich thrombi with high efficacy and to effectively inhibit platelet aggregation.
Persistent Impairment of Platelet Aggregation following Cessation of a Short-course Dietary Supplementation of Moderate Amounts of N-3 Fatty Acid Ethyl Esters
Authors: Maria Cerbone Anna , Cirillo Ferdinando , Coppola Antonio , Risè Patrizia , Stragliotto Eduardo , Galli Claudio , Giordano Mauro , Tremoli Elena , Di Minno Giovanni 
Published: March 2018

SummaryThe duration of the effect of a short-course (1-mo twice-daily) supplementation of moderate amounts (2.28 g) of n-3 fatty acid ethyl esters (FA) on platelet lipid composition and aggregation was compared with that of olive oil (3 g/d) supplementation in 14 healthy volunteers. The FA preparation employed contained eicosapentaenoic acid (EPA) and docosahexaenoic acids (DHA) in a ratio of 1:1.4. A marked rise (p <0.05) in the plasma and platelet content of EPA and DHA, and minimal changes in the content of arachidonic acid (AA) were documented at withdrawal of the n-3 FA supplementation. EPA/AA and DHA/AA ratios in platelet phospholipids showed that the FA accumulation persisted 8-12 wks after stopping the supplementation (p <0.05). The aggregation of platelets in response to collagen or ADP, and thromboxane B2 (TXB2) formation were impaired at withdrawal. The impaired aggregation lasted 8-12 weeks (p always <0.05), whereas TXB2 formation returned to basal values 4 weeks after stopping the n-3 supplementation. No correlation was found between impaired aggregation and TXB2 formation. In contrast, the impaired sensitivity to ADP (p = 0.036) and, to a lesser extent, to collagen (p = 0.068) were related to changes in the intracellular pH (pHi) of the Na+/H+ reverse transport. No changes in platelet composition or function were observed either during or following olive oil supplementation. These results document a long-lasting impairment of platelet sensitivity to ADP and collagen; changes in the pHi values of the Na+/H+ reverse transport, and a simultaneous persistent accumulation of EPA and DHA in platelet phospholipids, after stopping a short-course dietary supplementation of moderate amounts of n-3 fatty acid ethyl esters.
Changes in the Levels of Soluble Adhesion Molecules and Coagulation Factors in Patients with Deep Vein Thrombosis
Authors: Quarmby J. W. , Collins M. , Lockhart S. M. , Burnand K. G. , Smith A. 
Published: March 2018

SummaryCurrent biochemical markers of thrombosis, such as d-dimer, are of little value in demonstrating the presence of thrombus postoperatively, as their levels are elevated by surgery. Thrombosis involves adhesive interactions between the endothelium, platelets and leukocytes. The aim of the study was to determine which of a panel of haemostatic and adhesion factors are altered by the presence of thrombus, but not by surgery. These factors were measured in 20 patients with established spontaneous DVTs, 13 patients having hip replacement surgery and 28 control patients. Circulating levels of P-selectin, VCAM-1 and tissue factor were found to be increased when thrombus was present (p <0.018, p <0.0001, p <0.0028 respectively), but were not altered by surgery. The significance of these circulating factors in venous thrombosis remains to be established, but it is conceivable that they are the product of increased leukocyte trafficking and activity. Assay of VCAM-1, in particular, may be of use in the early detection of venous thrombi in postoperative patients.
Differences in Levels of Soluble E-selectin and VCAM-1 in Malignant versus non Malignant Mediterranean Spotted Fever
Authors: Tissot-Dupont Hervé , Grau Georges-Emile , Camoin-Jau Laurence , Raoult Didier , Sampol José , Dignat-George Françoise 
Published: March 2018

SummaryIn the present study, we investigated the plasma levels of soluble adhesion molecules E-selectin, P-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in 24 patients with Mediterranean spotted fever (MSF), 6 of whom with a malignant form. Measurements were performed on blood samples collected before treatment (T1), then twice during treatment (T2 and T3). Before treatment, MSF patients taken as a whole presented elevated levels of sICAM-1 and sVCAM-1 and normal levels of sE-selectin and sP-selectin compared to healthy controls. We found that sICAM-1 was elevated both in mild and malignant MSF. sE-selectin and sVCAM-1 were elevated only in patients with the malignant form and allowed to discriminate the two clinical subgroups. Their levels decreased after treatment with sE-selectin reaching control values at T2 whereas sVCAM-1 remained higher over the course of the malignant form. In patients with mild MSF, sP-selectin steadily increased after treatment, whereas it did not present any modification at any of the two sampling times in patients with the malignant form. Raised plasma levels of sE-selectin and sVCAM-1 reflect endothelial activation in malignant rickettsial disease and may be sufficiently early markers to influence the therapeutic decision.
Calibration of Local Systems with Lyophilized Calibrant Plasmas Improves the Interlaboratory Variability of the INR in the Italian External Quality Assessment Scheme
Authors: Chantarangkul Veena , Cesana Bruno , Mannucci Pier Mannuccio , Tripodi Armando 
Published: March 2018

SummaryCalibration with lyophilized calibrant plasmas certified in terms of PT with International Reference Preparations for thromboplastin has been proposed to minimize the effect of coagulometers on the INR. Aim of this study was to test the ability of local calibration with lyophilized calibrant plasmas, combined with a modified statistical approach, to improve the interlaboratory variability of the INR measured on two test plasmas (one coumarin and one artificially-depleted) by participants in the External Quality Assessment Scheme (EQAS). Sets of lyophilized calibrant and test plasmas were sent to the participants in the EQAS, who were asked to determine PT with their own reagent/ instrument combination (local system). Results were returned as PT together with information on the type of local system, the stated International Sensitivity Index (ISI) and the geometric mean of PTs determined by testing with the local system fresh plasmas from 20 healthy subjects. Ninety-two participants using 9 and 11 brands of reagents and instruments returned results. The CV of the INR determined with the stated ISI for the coumarin (Mean INR = 4.39) and artificially-depleted (Mean INR = 4.23) test plasmas were 11.2% and 10.3% and were reduced on the average by 34% and 54%, respectively, when the INR was calculated with the local ISI.In conclusions, results from this field study involving laboratories and testing systems representative of the real situation in oral anticoagulant monitoring in our country, indicate that local calibration by artificially-depleted plasmas, combined with the proposed statistical approach, is suitable to improve the interlaboratory agreement on the INR.
Monocyte Procoagulant Activity Induced by Adherence to an Artificial Surface Is Reduced by End-point Immobilized Heparin-coating of the Surface
Authors: Hamers Maria , Møller Anne-Sophie , Sakariassen Kjell , Barstad Marius 
Published: March 2018

SummaryHeparin-coating improves the biocompatibility of blood contacting artificial surfaces. This led us to investigate the impact of heparin-coating (Carmeda AB, Stockholm) of polymetylmetacrylate on the expression of monocyte tissue factor procoagulant activity (TF-PCA) by surface adhesion. Also, the anticoagulant effect of heparin-coating in the presence or absence of adherent procoagulant monocytes was assessed. This is of particular interest, since activation of extrinsic coagulation by adherent monocyte TF-PCA may play a significant role in thrombin generation during extracorporeal circulation.Monocytes exposed to heparin-coated or non-coated polymetylmetacrylate expressed TF-PCA. The heparin coat did not affect the rate of monocyte adhesion. However, heparin-coating reduced the induction of TF-PCA of non-adherent and adherent monocytes by 17 and 33% (p 0.001 and p 0.0003), respectively. Heparin-coating in the absence of monocytes, totally inhibited the clotting of recalcified plasma (p 0.003). In contrast, in the presence of adherent monocytes expressing TF-PCA, surface-bound heparin did not inhibit clotting. However, inclusion of heparin in a plasma concentration of 8.9 IU/ml totally inhibited the activation of coagulation.It is apparent that heparin-coating of an artificial surface is an efficient means to inhibit coagulation of recalcified plasma, but much less so when procoagulant monocytes are adherent to the coated surface. The present findings are of clinical relevance, since monocytes will adhere to blood contacting surfaces of extracorporeal circuits or to implanted vascular prostheses and subsequently express TF-PCA, and this may promote thromboembolism.