bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blood Coagulation and Fibrinolysis Activation during Sudden Arterial Occlusion of Lower Extremities – an Association with Ischemia and Patient Outcome
Authors: Peltonen Seija , Lassila Riitta , Rossi Perttu , Salenius Juha-Pekka , Lepäntalo Mauri 
Published: July 2018

SummaryWe compared hemostatic and fibrinolytic plasma markers in 41 patients having acute or subacute occlusion of lower limb arteries with 20 patients suffering stable peripheral arterial occlusive disease (PAOD). During occlusion, the amount of thrombin-antithrombin III (TAT) complex was five-fold higher compared with stable PAOD, being 16 μg/l [95% confidence interval (CI) 11-21 μg/1] vs 3 μg/l (95% CI 2-4 μg/l), p <0.003. Similarly, D-dimer was over four-fold (p = 0.0001), while tissue plasminogen activator and plasminogen activator inhibitor-1 (PAI-1) antigens were about two-fold (p = 0.02 and p <0.003, respectively) higher than in PAOD. Coagulation and fibrinolysis markers were increased most in patients with recent symptom onset, which mainly represented embolus rather than thrombosis. The marker levels assessing coagulation and fibrinolysis were related with myoglobin and CK, indicators of skeletal muscle damage. Finally, increased TAT, PAI-1 antigen, and myoglobin concentrations associated with poor outcome.
Role of FCγRIIA Gene Polymorphism in Human Platelet Activation by Monoclonal Antibodies
Authors: Bachelot Christilla , Saffroy Raphaël , Gandrille Sophie , Aiach Martine , Rendu Francine 
Published: July 2018

SummaryThe aim of this study was to determine if there is a correlation between the activity of a MoAb as an agonist and its ability to bind to the Fc platelet receptor, FcγRIIa. A polymorphism at amino acid 131 [arginine (Arg) or histidine (His)] of FcγRIIa was first shown to be determinant for MoAb-IgG1 binding on monocytes. To clarify the role of this polymorphism in platelet activation by MoAb-IgG1 we (i) established the FCγRIIA polymorphism at the gene level by adapting the denaturating gradient gel electrophoresis method, (ii) analyzed the binding affinity of the MoAbs to FrγRIIa on platelets from homozygous Arg, homozygous His, and heterozygous Arg/His donors, and (iii) characterized the different reactivities of platelets according to the FCγRIIA polymorphism. Among 167 Caucasian donors we found 46% heterozygous Arg/His, 36% homozygous His and 18% homozygous Arg. ALB6, an anti CD9, P256 an anti GPIIb-IIIa, and AP3 an anti-GPIIIa were chosen according to their ability (ALB6, P256) or not (AP3) to activate platelets. These 3 MoAbs-IgG1 bind to FcγRIIa with a stronger affinity for the Arg-form of FcγRIIa, a result which was confirmed with the use of diverse MoAbs directed against various antigens. The different abilities of MoAbs to bind to the two FcγRIIa forms were well correlated to the different platelet responses induced by ALB6 and P256. However, low concentrations of ALB6, which allow full activation of platelets from homozygous Arg donors, as did P256, did not induce any activation of platelets from homozygous His donors, whereas P256 is able to induce a low aggregation. The results further define the respective roles of the antigen and the Fc receptor, depending on the MoAb, and the role of the FcγRIIa polymorphism in platelet activation induced by MoAbs. In addition, the results obtained with MoAbs unable to induce platelet activation provide evidence that the binding of a MoAb on FcγRIIa does not predict its ability to activate platelets.
Smoking, Haemostatic Factors and the Severity of Aorto-lliac and Femoro-Popliteal Disease
Authors: Smith F B , Lee A J , Fowkes F G R , Rumley A , Lowe G D O 
Published: July 2018

SummaryTo determine relationships between haemostatic and rheological factors and severity of peripheral atherosclerosis and differences by site, an angiographic cross-sectional survey was carried out on 192 men and women with intermittent claudication or rest pain. 34 patients were classified as having aorto-iliac disease, 85 femoro-popliteal disease and 73 dual-site disease. Mean levels of haemostatic or rheological factors did not differ significantly between the three site groups. In all 192 patients, disease severity in the femoro-popliteal segments was correlated with plasma nephelometric fibrinogen (r = 0.20, p ≤0.01), von Willebrand factor (r = 0.14, p ≤0.05) and fibrin D-dimer (r = 0.22, p ≤0.001). On multiple regression analyses, fibrinogen was independently associated with disease severity in the femoro-popliteal segments (p ≤0.05), but not in the aorto-iliac segments. Adjustment for packyears or serum thiocyanate had little effect on the association of fibrinogen with severity of disease. An inverse relationship between plasminogen activator inhibitor and disease severity in the femoro-popliteal segments was found only in men (r = -0.24, p ≤0.01). We conclude that elevated fibrinogen and disturbed fibrinolytic activity may be related to the extent of disease within the femoro-popliteal arteries, more so than in the aorto-iliac arteries.
Platelet Adhesion following the Administration of Tissue-type Plasminogen Activator and Its Reversal by Vitamin E in Rats
Authors: Jen Chauying J , Dong Huei-Ping , Chen Hsiun-ing , Wing Lih-Yuh C , Tang Ming-Jer , Chang Wen-Chang , Lin Ming T , Shi Guey-Yueh 
Published: July 2018

SummaryThrombolytic therapy is known to induce platelet-related side effects. We used a parallel-plate flow chamber, which was connected to the femoral artery of the rat, to measure platelet adhesion ex vivo. A collagen-coated arterioarterial shunt between two carotid arteries was used to measure shunt patency duration as an index of antithrombotic efficacy. Tissue-type plasminogen activator (t-PA), vitamin E, and the combination of these two were intravenously administered for 60 min. Measurements were performed before drug administration, and at 30, 60, 120 min after the initiation of drug infusion. Our results indicated that (1) treatments with t-PA or t-PA/vitamin E prolonged the time to shunt occlusion at 30 and 60 min; (2) t-PA enhanced platelet adhesion at 60 and 120 min; (3) vitamin E tended to reduce platelet adhesion; (4) t-PA/vitamin E reduced the t-PA-enhanced platelet adhesion; (5) at the high-density area of platelet adhesion under t-PA treatment, the adherent platelets demonstrated severe morphological changes which could be blocked by vitamin E. These data suggest that t-PA may enhance platelet adhesion in rats and that this adverse effect can be suppressed by co-administration of vitamin E.
Inhibition by Argatroban, a Specific Thrombin Inhibitor, of Platelet Activation by Fibrin Clot-associated Thrombin
Authors: Lunven Catherine , Gauffeny Christiane , Lecoffre Catherine , O’Brien Donogh P , Roome Nigel O , Berry Christopher N 
Published: July 2018

SummaryClot-associated thrombin retains amidolytic activity, and is resistant to inhibition by heparin, but not to low molecular weight thrombin inhibitors. We show that clot-associated thrombin induces platelet aggregation, is resistant to heparin:antithrombin III, less so to recombinant hirudin (rHV2Lys47) but not to argatroban, an active-site directed thrombin inhibitor. Fibrin clots prepared with human fibrinogen and thrombin were used to aggregate rabbit washed platelets assessed by single platelet counting, thromboxane B2 (TXB2) immunoassay and scanning electron microscopy. Fibrin clots decreased platelet counts, and released TXB2. Electron microscopy showed platelet aggregates on the clot surface. Argatroban concentration-dependently inhibited such aggregation with IC50s of 21 nM and 13 nM versus aggregation and TXB2 release respectively. The IC50s of Argatroban against fluid-phase thrombin producing similar aggregation were 12 nM (aggregation) and 33 nM (TXB2). rHV2Lys47 was less active against clot-induced aggregation (IC50 = 1.8 nM) than against fluid-phase thrombin (IC50 = 0.06 nM). Heparin had an IC50 of 0.02 mU/ml against aggregation induced by fluid-phase thrombin, but much greater concentrations are required to inhibit clot-induced aggregation (IC50 = 48 mU/ml). These data provide a basis for the superiority of direct-acting thrombin inhibitors over heparin in platelet rich thrombi.
Fibrinogen Binding to ICAM-1 on EA.hy 926 Endothelial Cells Is Dependent on an Intact Cytoskeleton
Authors: van de Stolpe Anja , Jacobs Nancy , Hage Willem J , Tertoolen Leon , van Kooyk Yvette , Nováková Irena RO , de Witte Theo 
Published: July 2018

SummaryFibrinogen is a ligand for Intercellular Adhesion Molecule-1 (ICAM-1), and enhances monocyte-endothelial cell interaction by coupling Mac-1 on monocytes to ICAM-1 on endothelial cells. We investigated the role of the cytoskeleton in fibrinogen binding to the human endothelial cell line EA.hy 926 using immunofluorescence techniques. In this cell line TNFα induced the simultaneous appearance of stress fibers and of ICAM-1, which was clustered predominantly on endothelial cell projections. Incubation of TNFα-stimulated endothelial cells with fibrinogen resulted in binding of fibrinogen to ICAM-1 on these cell projections. Disruption of the cytoskeleton by cytocholasin B abolished fibrinogen binding. Activation of protein kinase C with 12-O-tetradecanoyl phorbol- 13-acetate resulted in simultaneous loss of both stress fibers and fibrinogen binding. These results suggest that a connection between ICAM-1 and the cytoskeleton results in clustering of ICAM-1 on cell projections, which is required for fibrinogen binding.
Inhibition of Protein S by Autoantibodies in Patients with Acquired Protein S Deficiency
Authors: Sorice M , Arcieri P , Griggi T , Circella A , Misasi R , Lenti L , Di Nucci G D , Mariani G 
Published: July 2018

SummaryThis study was undertaken to analyze antibodies to protein S (PS) in patients with an acquired PS deficiency. Plasma from symptomatic patients with acquired (n = 14) or congenital (n = 10) PS deficiency and 10 healthy donors was screened for PS antibodies by immunoblotting and for anti-phospholipid antibodies. PS antibodies (IgG) were detected in five of the patients with acquired PS deficiency. These antibodies belonged to the G1 and G4 immunoglobulin subclasses. IgG fractions from the same 5 patients were shown to inhibit PS activity. The inhibition of PS activity by the 5 IgG fractions was shown to be time-and dose-dependent and was abolished following incubation with purified PS, while no effect was found after absorption with cardiolipin micelles. In addition, anticardiolipin monoclonal or human purified antibodies, failed to exert significant PS inhibition. These findings demonstrate that anti-PS antibodies are able to inhibit PS activity and that this is independent of anti-phospholipid antibodies. Given the clinical features of the patients, these antibodies should be regarded as an expression of the broad autoimmune syndrome involving the phospholipid-binding plasma proteins.
Increased Expression of Plasminogen Activator Inhibitor-1 in R.rickettssi-infected Endothelial Cells
Authors: Shi Rui-Jin , Simpson-Haidaris Patricia J , Marder Victor J , Silverman David J , Sporn Lee Ann 
Published: July 2018

SummaryChanges in PAI-1 expression in human umbilical vein endothelial cells (HUVEC) were studied following in vitro infection with Rickettsia rickettsii. A 1.8-fold increase in secreted PAI-1 activity occurred in infected versus control cultures (p = 0.03) at 24 h but not at earlier timepoints. A similar increase (1.4-fold) in secreted PAI-1 antigen (p <0.005) was measured by ELISA. To determine whether this increase was due to increased synthesis of PAI-1, HUVEC were metabolically labeled with 35S-methionine concurrent with R. rickettsii infection. Such infection resulted in a 1.9-fold increase in labeled PAI-1 in the medium at 24 h (p = 0.036). Increase in steady-state levels of PAI-1 mRNA were detected as early as 18 h by Northern blot analysis, peaking (5.5-fold) at approximately 24 h. These results indicate that PAI-1 production is increased in RR-infected endothelial cells, an effect that may contribute to the vascular occlusions noted in Rocky Mountain spotted fever.
Influence of Maximal Ergometric Exercise on Endothelin Concentrations in Relation to Molecular Markers of the Hemostatic System
Authors: Röcker Lothar , Möckel Martin , Westpfahl-W Klaus-Peter , Gunga Hanns-Christian 
Published: July 2018

SummaryThe effects of moderate 30 min cycle ergometer exercise (aerobic metabolism; 0.85-3.71 mmol · 1−1 lactate) followed by short-term exercise at maximal capacity (anaerobic metabolism; 5.09 to 17.75 mmol · 1−1 lactate) on endothelin (ET) and hemostatic variables (tissue plasminogen activator [t-PA] antigen, prothrombin fragments [F1,2], thrombin-antithrombin III complex [TAT], prothrombin time and partial thromboplastin time) were investigated in 15 male healthy subjects of varying fitness levels. Endothelin was measured twice, before and immediately after maximal cycle exercise. The results show an increase in endothelin concentration [10.0 pg · m1−1 (baseline) + 6.1 pg · m1−1 (increase post exercise)]. ET did not increase under control conditions. Moderate 30 min exercise caused an increase in t-PA antigen concentration (3.66 + 3.15 ng · m1−1) and short-term maximal exercise produced a markedly higher elevation in this variable (+10.6 ng · m1−1). F1,2 increased (810 + 40 pmol · 1−1) under moderate and by 150 pmol · 1−1 under anaerobic exercise. TAT increased only at maximal exercise levels (1.01 + 0.32 ng · 1−1). No changes were found in any of these variables under control conditions. No correlation of endothelin and the hemostatic variables was found.It is concluded that endothelin and hemostatic markers increase independently during moderate and maximal exercise.
Factor V (Arg506⟶ Gln) Mutation in Young Survivors of Myocardial Infarction
Authors: Ardissino Diego , Peyvandi Flora , Merlini Piera Angelica , Colombi Elisabetta , Mannucci Pier Mannuccio 
Published: July 2018

SummaryMany young patients with venous thromboembolic disease are partially resistant to the anticoagulant action of activated protein C as a result of factor V (Arg506 ⟶ Gln) mutation. The frequency of this mutation in young patients with arterial thrombotic diseases, such as myocardial infarction, is less well established. We studied 100 young patients with myocardial infarction and 100 age- and sex-matched controls. One patient (1%; 95% CL 0.05-6.2) and two controls (2%; 95% CL 0.3-7.7) were heterozygotes for the mutation; there was no homozygote in either group. Hence, premature myocardial infarction is not associated with heterozygosity for factor V (Arg506 ⟶ Gln) mutation.
The Therapeutic Range for Heparin Therapy: Relationship between Six Activated Partial Thromboplastin Time Reagents and Two Heparin Assays
Authors: Kitchen S , Preston F E 
Published: July 2018

SummaryThe activated partial thromboplastin time (APTT) is the most commonly used test for laboratory monitoring of unfractionated heparin therapy. Since there are differences between APTT reagents in respect of responsiveness to heparin the widely used therapeutic range of 1.5-2.5 (APTT ratios) may not be appropriate for all reagents.The aim of this study was to assess the relationship between 6 different APTT reagents using a manual technique, 2 of these reagents used in combination with a coagulometer, a heparin assay by protamine titration and a chromogenic anti-Xa assay. Samples from 42 patients treated with unfractionated heparin for thromboembolic disease were studied, 12 of whom were receiving warfarin therapy with International Normalised Ratios (INR) of >1.3.For normal subjects, APTT results were highly dependent on the method used and statistically significant differences were noted. The ratio of patient to mean normal APTT was calculated for each APTT method. When 30 samples from heparinised patients (with INRs of <1.3) were analysed manually, the APTT ranges equivalent to 0.2-0.4 u/ml heparin by protamine titration (by regression analysis) were 1.6-1.9 for Boehringer reagent (the least responsive) up to 2.2-2.9 for Instrumentation Laboratory reagent (the most responsive). The concentration of heparin associated on average with APTT ratios of 1.5-2.5 varied approximately twofold to threefold between reagents.
Hereditary Macrothrombocytopenia and Pregnancy
Authors: Altès Albert , Pujol-Moix Nuria , Muñiz-Diaz Eduardo , Madoz Pedro , Parra Juan , Fontcuberta Jordi 
Published: July 2018

SummaryIntroduction. Hereditary macrothrombocytopenias (HM) are a group of infrequent disorders characterized by hereditary giant platelets. Little has been published about the course of these diseases during pregnancy and delivery. Subjects and methods. Forty consecutive thrombocytopenic pregnant women were studied. Platelet count, mean platelet volume and blood smear examination were performed. Platelet antibodies were studied by immunofluorescence. Familial study, bleeding time, ultrastructural platelet examination, a von Willebrand disease screening and aggregation tests were carried out when HM was suspected. Results. Four cases of HM were diagnosed. Giant platelets were observed in all cases, with the typical ultrastructural pattern. Dohle-like cytoplasmic inclusions in granulocytes were observed in one case. Platelet antibodies were detected in only one case. No prophylactic measures to prevent haemorrhage were adopted, and all patients underwent vaginal deliveries. Haemorrhagic events were absent in both mothers and children. Conclusions. The prevalence of HM in pregnant trombocytopenic women is higher than assumed. Prophylactic treatment should be avoided in the absence of a history of haemorrhagic complications and obstetrical risk factors.
The Antiaggregating and Antithrombotic Activity of Ticlopidine Is Potentiated by Aspirin in the Rat
Authors: Herbert J M , Bernat A , Samama M , Maffrand J P 
Published: July 2018

SummarySince ticlopidine specifically inhibits ADP-induced platelet aggregation without affecting prostaglandin metabolism, it seemed interesting to evaluate the effect of aspirin with regard to the antithrombotic efficacy of ticlopidine. Ticlopidine was administered orally to rats alone or in combination with aspirin and the efficacy of the association was determined in several experimental models. A synergistic effect of the ticlopidine/aspirin association was demonstrated with regard to ADP- and collagen-induced platelet aggregation measured ex vivo but also in several experimental thrombosis models including silk thread-induced thrombosis in an arteriovenous shunt, wire coil-induced thrombosis and 111In-labelled platelet deposition on the subendothelium following air drying injury of the rat carotid artery. Similar results were obtained with regard to myointimal proliferation following air-induced injury of the rat carotid artery which occurred as a consequence of vascular injury. The ticlopidine/aspirin combination showed only additive-type effects on bleeding time prolongation induced by tail transection in the rat.
Genetic Diagnosis of Dysplasminogenemia: Detection of an Ala601 -Thr Mutation in 118 out of 125 Families and Identification of a New Asp676-Asn Mutation
Authors: Tsutsumi Seiji , Saito Tetsuo , Sakata Toshiyuki , Miyata Toshiyuki , Ichinose Akitada 
Published: July 2018

SummaryDysplasminogenemia (plasminogen abnormality) is frequently found in association with thrombosis. Two types of mutation, Ala601-Thr and Val355-Phe, have already been identified; the precise genetic defects of most of these patients, however, remain unknown. In this study, we examined the genetic DNAs of two unrelated cases by single-strand conformational polymorphism and nucleotide sequencing analysis. A new mutation, designated as Asp676-Asn, has been identified in these cases. This mutation leads to the loss of a negatively-charged residue and the creation of a potential carbohydrate attachment site, which may impair the enzymatic properties of plasminogen. As many as 158 individuals with dysplasminogenemia were analyzed by a combination of in vitro amplification and restriction digestion. Among 125 unrelated families, the Ala601-Thr mutation accounted for about 94% of cases. The Val355-Phe mutation was found in four unrelated families, indicating that it is a recurring mutation and is not very rare.
Association of Factor VII:C Levels with Environmental and Genetic Factors in Patients with Ischaemic Heart Disease and Coronary Atheroma Characterised by Angiography
Authors: Heywood Daniella M , Ossei-Gerning Nicholas , Grant Peter J 
Published: July 2018

SummaryElevated Factor VII:C (FVII:C) levels are an independent risk factor for acute myocardial infarction. To examine the association between FVII:C levels, genetic and environmental factors in patients with a history suggestive of ischaemic heart disease, 270 patients were studied. FVII:C levels were significantly associated with the Msp I and promoter insertion polymorphisms. FVII:C correlated with environmental factors, and these correlations remained when analysed by genotype. In a multiple regression model, genotype, body mass index, cholesterol, triglycerides and gender remained as independent and significant predictors of FVII:C levels. There was no significant difference in FVII:C concentrations with severity of atheroma, or in patients with a history of myocardial infarction. These findings provide further evidence linking FVII:C with Msp I and promoter insertion genotypes and with environmental factors in established IHD, but suggest there is not a genotype-environment interaction or a relationship between FVII:C levels and severity of ischaemic heart disease.
The Largest Isoform of Platelet Membrane Glycoprotein Iba Is Commonly Distributed in Eastern Asian Populations
Authors: Ishida Fumihiro , Furihata Kenichi , Ishida Kimitaka , Kodaira Hiroshi , Sup Han Kyou , Da-Zhuang Liu , Kitano Kiyoshi , Kiyosawa Kendo 
Published: July 2018

SummaryPlatelet membrane glycoprotein Iba has at least two polymorphisms which affect phenotype. One is the dimorphism at codon 145, and the other is a molecular weight polymorphism due to variable numbers of tandem repeats (TR) in the macroglycopeptide region. These two polymorphisms are in linkage disequilibrium. The frequencies of these polymorphisms differ considerably depending on race, and the largest variant with four TR is almost exclusively present in the Japanese population. We examined the genotypes of HPA-2 and TR polymorphism in three different races from Eastern Asia; the Japanese (n = 103), Korean (n = 101) and Chinese population (n = 177). The gene frequency of HPA-2 differed significantly among these three populations. Among HPA-2b-positive individuals, the A isoform with four TR and B with three TR were present in all three populations and A dominated over B. Individuals homozygous for the A isoform were found in both Japanese and Korean populations. These findings indicate that the largest haplotype is common in the Eastern Asian region.