bluuebunny/crossref_metadata_2025_split huggingface dataset:
Platelet Unresponsiveness to Collagen: Involvement of Glycoprotein Ia-IIa (α2β1 Integrin) Deficiency Associated with a Myeloproliferative Disorder
Authors: Handa Makoto , Kawai Yohko , Kamata Tetuji , Koyama Takushi , Nagai Hirofumi , Ikeda Yasuo , Watanabe Kiyoaki 
Published: July 2018

SummaryWe studied a 66-year-old man with a myeloproliferative disorder who presented with a prolonged bleeding time and marked thrombocytosis (platelet count, 3,890 × 109/1). There was no past history of a bleeding disorder. The patient had normal coagulation data. His platelets completely lacked collagen-induced platelet aggregation and adhesion, but showed normal responses to other agonists. All family members tested showed normal platelet aggregation with collagen.Analysis of 125I surface-labeled platelets by two-dimensional SDS gel electrophoresis disclosed absence of the spot corresponding to platelet membrane GPIa (α2) but no other significant deficiencies of major platelet glycoproteins i.e., GPIb, IIb-IIIa, and IV. Immunoisolation studies of the patient’s platelets indicated that neither anti-GPIa nor anti-GPIIa (β1) monoclonal antibody (mAb) isolated any surface membrane proteins corresponding to GPIa. GPVI, a putative collagen receptor, was immunoisolated from the platelets. Indirect immunofluorescence study using flow cytometry confirmed that the patient’s platelets were totally deficient in surface expression of the GPIa-IIa complex (α2β1, integrin). In contrast, phytohemoagglutinin-activated T-lymphocytes from the patient expressed normal concentrations of this complex.The data suggest that our patient had an acquired deficiency of the platelet GPIa-IIa complex, due to a myeloproliferative disorder, which might account for the absence of responsiveness of his platelet to collagen.
Haemostasis Factors in Angina Pectoris; Relation to Gender, Age and Acute-phase Reaction
Authors: Haverkate F , Thompson S G , Duckert F 
Published: July 2018

SummaryThe ECAT Angina Pectoris Study is a European multicentre study with the aim of investigating the pathogenetic and predictive role of haemostatic factors in the progression of coronary heart disease. It is the largest study performed up to now with regard to both the number of patients with angina pectoris (n = 3043) and the number of haemostasis assays (n = 23) included.The present paper presents baseline cross-sectional data with particular reference to the relationship of haemostatic factors with each other and with the coronary risk factors age, gender and acute-phase reaction (1). Two clusters of haemostatic factors could be distinguished in which each variable was correlated (P < 0.001) to every other variable: (a) Eight fibrinolysis assays including t-PA, PAI-1 and euglo- bulin clot lysis time (ECLT), for which PAI-1 appeared to be the dominating factor; (b) antithrombin III, protein C, α2-antiplasmin and plasminogen, the interdependence of which has no obvious explanation. (2). Twelve out of the 23 haemostasis assays were associated (P < 0.01) with age. Except for α2-antiplasmin, these relationships indicated an increased tendency to thrombosis with increasing age. (3). Gender differences found in 14 haemostasis parameters do not indicate a consistent difference in the tendency to thrombosis between men and women. Eight haemostasis parameters were on average higher in female than in male patients in the age group over 50 years. (4). C-reactive protein, an acute-phase reactant, was positively correlated (P < 0.001) with fibrinogen, factor VIIIc, von Willebrand factor, the fibrinolysis assays t-PA, PAI-1, ECLT and plasminogen. These parameters are therefore potential markers of an ongoing, low-grade inflammatory response in patients with atherosclerosis and, as most of them have been reported as cardiovascular risk markers, they may be involved in the pathogenesis of the disease as a link in the relation between inflammation and arterial thrombosis.
Relationships of Insulin and Intact and Split Proinsulin to Haemostatic Function in Young Men with and without Coronary Artery Disease
Authors: Båvenholm Peter , Proudler Anthony , Silveira Angela , Crook David , Blombäck Margareta , de Faire Ulf , Hamsten Anders 
Published: July 2018

SummaryGlucose intolerance, hyperinsulinaemia, dyslipoproteinaemia and multiple disturbances of haemostatic function are characteristics of young men with premature coronary artery disease. The relations between glucose, insulin and insulin propeptides, in the fasting state, and after an oral glucose load, and haemostatic function were examined in 62 consecutive non-diabetic men with myocardial infarction before the age of 45 and in 41 age-matched healthy men. “True” hyperinsulinaemia, raised plasma concentrations of insulin propeptides, dyslipoproteinaemia, elevated plasma levels of fibrinogen, factor VII antigen (VIIag) and plasminogen activator inhibitor-1 (PAI-1) activity, and lower antithrombin activity (p <0.05-0.001) characterized the patients. PAI-1 activity was more closely associated with insulin, intact proinsulin and des 31,32proinsulin in patients than in controls, whereas the plasma levels of fibrinogen, activated factor VII (VIIa) and VIIag were stronger correlated with insulin and insulin propeptides in subjects without coronary artery disease. Very low density lipoprotein (VLDL) triglyceride was a strong determinant of VIIag and PAI-1 activity levels in both cases and controls, whereas VLDL triglyceride in controls and LDL cholesterol in patients related significantly to the plasma fibrinogen concentration. Thus, our data suggests that plasma insulin and insulin propeptides might be involved in the regulation of plasma fibrinogen concentration, factor VII level and plasma PAI-1 activity. However, apolipoprotein B-containing lipoproteins appear to influence the relationships between insulin, insulin propeptides and haemostatic factors in individuals with premature coronary artery disease.
Varicose Vein Stripping - A Prospective Study of the Thrombotic Risk and the Diagnostic Significance of Preoperative Color Coded Duplex Sonography
Authors: Böhler Kornelia , Baldt Manfred , Schuller-Petrovic Sanja , Grünwald Christian , Sellner Wolfgang , Watzke Herbert , Wolff Klaus 
Published: July 2018

SummaryInsufficiency of epifascial veins promotes venous ulceration and increases thromboembolic risk in general surgery patients. Epifascial varicose vein stripping is therefore considered the most effective prophylactic procedure. Thromboembolic risk of patients undergoing this surgical procedure has not yet been prospectively evaluated but appears to be lower than in general surgery patients. The gold standard of preoperative assessment of varicose surgery patients is ascending pressure phlebography, but this technique is invasive, time consuming and costly.We prospectively investigated 100 consecutive varicose vein surgery patients for postoperative thrombosis. Ascending pressure phlebography (APP) and colour coded duplex sonography (CCDS) were performed before and 10 to 21 days after the stripping operation in 100 and 70 patients, respectively.APP revealed no postoperative deep vein thrombosis in all 100 limbs investigated (0 percent; 95 percent confidence interval: 0 to 2.95). With regard to epifascial vein reflux there was good agreement between APP and CCDS (quadratic weighted kappa: 0.76). In 67 out of 73 superficial veins investigated excellent agreement of diagnostic accuracy was found for both diagnostic procedures (91.78 percent; 95 percent confidence interval: 82.96 to 96.92).We conclude that thrombotic risk of varicose vein surgery is low in properly selected patients. CCDS provides a high degree of accuracy in diagnosis of reflux and regular vein morphology and should therefore replace APP; however, APP does remain essential in the preoperative workup of a typical anatomical variants.
Comparison of Antithrombotic Effects of GPIIb-IIIa Receptor Antagonist and TXA2 Receptor Antagonist in the Guinea-pig Thrombosis Model: Possible Role of TXA2 in Reocclusion after Thrombolysis
Authors: Takiguchi Yoshiharu , Asai Fumitoshi , Wada Kouichirou , Nakashima Mitsuyoshi 
Published: July 2018

SummaryThe effects of Ro 44-9883, a new specific antagonist of platelet glycoprotein IIb-IIIa receptor, on thrombus formation and reocclusion after thrombolysis induced by tissue-type plasminogen activator (t-PA) were compared with those of vapiprost, a thromboxane (TX) A2 receptor antagonist, using a photochemically-induced thrombosis model in the guinea-pig femoral artery. Pretreatment with Ro 44-9883 (5,10 and 20 μg/kg/min, i. v.) prolonged the time required to occlude the artery in a dose-dependent manner. Ro 44-9883 at 10 and 20 μg/kg/min significantly inhibited ex vivo platelet aggregation in whole blood induced by collagen, ADP or U46619. Vapiprost 0.3 mg/kg inhibited thrombus formation and platelet aggregation induced by collagen or U46619, to the same extent as Ro 44-9883 at the higher doses. In the thrombolysis study, Ro 44-9883 at the higher doses given as comedication with t-PA reduced the time to achieve reperfusion and increased the vascular patency after successful reperfusion. Vapiprost also significantly reduced the time to reperfusion and prevented reocclusion. However, the vascular patency after thrombolysis by t-PA with vapiprost was significantly increased compared with Ro 44-9883. Ro 44-9883 inhibited platelet aggregation, but did not prevent TXA2 formation in platelets. Thus, vascular contraction mediated by platelet-derived TXA2 may be responsible for lower efficacy of Ro 44-9883 against reocclusion compared with vapiprost. These results indicate that not only platelet aggregation but also vasoconstriction may contribute to reocclusion after t-PA-induced thrombolysis in the guinea-pig.
Ristocetin-induced Platelet Agglutination Stimulates GPIIb/IIIa-dependent Calcium Influx
Authors: Bertolino Giampiera , Noris Patrizia , Spedini Pierangelo , Balduini Carlo L 
Published: July 2018

SummaryWe found that intracellular Ca2+ concentration i[Ca2+]i) increased during ristocetin-induced agglutination of aequorin loaded platelets resuspended in plasma. Chelation of extracellular Ca2+ had no effect on platelet clumping, but delayed and greatly reduced Ca2+ increase, indicating that it derived for the most part from Ca2+ influx. Nine monoclonal antibodies (MA) against glycoprotein (GP) Ib largely prevented ristocetin-induced platelet clumping and [Ca2+]i increase, while three anti-GPIb MA with no effect on platelet clumping did not interfere with Ca2+ movement. In unstirred samples platelet agglutination was greatly reduced and [Ca2+]i increase was abolished, suggesting that close plate- let-to-platelet contact, in addition to von Willebrand factor (vWF) binding to GPIb, is necessary for Ca2+ transient. Nine MA against GPIIb/IIIa, the gly-arg-gly-asp-ser (GRGDS) peptide and GPIIb/IIIa complex dissociation had no effect on platelet agglutination, but significantly reduced Ca2+ increase. Our results suggest that platelet clumping induced by vWF binding to GPIb is responsible for GPIIb-IIIa dependent Ca2+ influx.
Cultured Endothelial Cells Regulate Platelet Adhesion to their Extracellular Matrix by Regulating its von Willebrand Factor Content
Authors: Wu Ya-Ping , Sixma Jan J , de Groot Philip G 
Published: July 2018

SummaryEndothelial cells and their extracellular matrix formed in vitro are often used as a model for subendothelium in studies on platelet-vessel wall interaction. We have characterized the influence of culture conditions of endothelial cells on the formation of extracellular matrix and on the interaction of the matrix with platelets. Passage number, time of confluence, serum concentration and the addition of heparin, growth factors and antibiotics to the culture medium were varied and the extracellular matrices were isolated. The amount of fibronectin and von Willebrand factor present in the matrix were measured and the number of platelets adhering to these matrices after perfusion with citrated whole blood at a shear rate of 1000 s-l was determined. A three times increase of the amount of von Willebrand factor in the matrix was found when the serum concentration was increased from 2.5% to 30%. When the passage number of the cells was increased or the period during which the cells were at confluence was extended, the amount of von Willebrand factor in the matrix was decreased up to 50%. Addition of heparin or ECGS (endothelial cell growth supplement) decreased the von Willebrand factor content in the matrix. Addition of penicillin or streptomycin to the culture medium had no influence on the amount of von Willebrand factor deposited in the matrix or secreted into the medium, however, other antibiotics such as gentamycin and neomycin decrease the amount of von Willebrand factor in the matrix. No influence on the amount of fibronectin in the matrix was found under all conditions tested.There was a strong correlation between the amount of von Willebrand factor in the matrix and the number of platelets adhering to the matrix. A decrease or increase of the amount of von Willebrand factor was always correlated with a decrease or increase of the number of platelets adhering to the matrix. These results indicate that the synthesis and deposition of von Willebrand factor in the extracellular matrix by cultured endothelial cells is very sensitive to variations in culture conditions and that the amount of von Willebrand factor in the matrix predominantly determines the reactivity of the matrix for platelets.
The Suppression of the Coagulation of Nonanticoagulated Whole Blood in vitro by Human Umbilical Endothelial Cells Cultivated on Microcarriers is not Dependent on Protein C Activation
Authors: Kohler Hans-Peter , Müller Michele , Bombeli Thomas , Straub P Werner , Haeberli André 
Published: July 2018

SummaryHuman umbilical vein endothelial cells (HUVEC) were cultivated on globular microcarriers in order to improve the endothelial cell surface to blood-volume ratio over the conventional flat bed cultures. HUVEC-beads were tested for their modulation of blood coagulation using a combination of two steps: HUVEC-beads were added into the syringe used for the venipuncture, in order to achieve immediate contact between cells and blood, and no anticoagulant was used during the incubation time of HUVEC-beads with whole blood. The coagulation initiation produced by venipuncture was almost completely suppressed as judged by thrombin measurements over a period of 60 min. The activated partial thromboplastin time showed a prolongation by a factor >3. Direct measurements of activated protein C (APC) were negative. Moreover, inhibition of APC-generation with a monoclonal anti-human protein C antibody did not affect the anticoagulant properties of endothelial cells. Therefore the anticoagulant properties exerted by HUVEC-beads are not dependent on APC.
Abnormal Processing of the Glycoprotein IIb Transcript due to a Nonsense Mutation in Exon 17 Associated with Glanzmann’s Thrombasthenia
Authors: Tomiyama Yoshiaki , Kashiwagi Hirokazu , Kosugi Satoru , Shiraga Masamichi , Kanayama Yoshio , Kurata Yoshiyuki , Matsuzawa Yuji 
Published: July 2018

SummaryWe analyzed the molecular genetic defect responsible for type I Glanzmann’s thrombasthenia in a Japanese patient. In an immunoblot assay using polyclonal anti-GPIIb-IIIa antibodies, some GPIIIa (15% of normal amount) could be detected in the patient’s platelets, whereas GPIIb could not (<2% of normal amount). Nucleotide sequence analysis of platelet GPIIb mRNA-derived polymerase chain reaction (PCR) products revealed that patient’s GPIIb cDNA had a 75-bp deletion in the 3’ boundary of exon 17 resulting in an in-frame deletion of 25 amino acids. DNA analysis and family study revealed that the patient was a compound heterozygote of two GPIIb gene defects. One allele derived from her father was not expressed in platelets, and the other allele derived from her mother had a 9644C → T mutation which was located at the position -3 of the splice donor junction of exon 17 and resulted in a termination codon (TGA). Moreover, quantitative analysis demonstrated that the amount of the abnormal GPIIb transcript in the patient’s platelets was markedly reduced. Thus, the C → T mutation resulting in the abnormal splicing of GPIIb transcript and the reduction in its amount is responsible for Glanzmann’s thrombasthenia.
Antiphospholipid Antibodies, Haemostatic Variables and Thrombosis – A Survey of 144 Patients
Authors: Ames Paul R J , Pyke Stephen , Iannaccone Luigi , Brancaccio Vincenzo 
Published: July 2018

SummarySeveral clotting abnormalities have been put forth to explain the thrombotic tendency of the antiphospholipid syndrome, but a possible role for fibrinogen and von Willebrand factor has been poorly investigated. The present cross-sectional retrospective study evaluated the relationship of IgG anticardiolipin antibodies, lupus anticoagulants, fibrinogen and von Willebrand factor with the occurrence of arterial and venous thromboses in patients with antiphospholipid antibodies. Among the clotting assays for the detection of lupus anticoagulant, dilute Russell’s viper venom time correlated with a history of venous thrombosis more strongly than activated partial thromboplastin time (p <0.0002 vs p <0.009) and was the only test which correlated with a history of arterial thrombosis (p <0.01), also at low levels of IgG anticardiolipin antibodies (p = 0.003). By regression analysis, and after correction for confounders, serum levels of IgG anticardiolipin antibodies were found to be positively associated with the number of venous events (p <0.001). Plasma levels of fibrinogen and von Willebrand factor were associated with each other (p <0.0001; r: 0.48) and with the occurrence of arterial and venous thromboses (p <0.001). Moreover, plasma levels of fibrinogen and von Willebrand factor in thrombotic patients with antiphospholipid antibodies were significantly higher than those of a control group of thrombotic patients who suffered thrombosis for other reasons (p <0.0001 and p = 0.0008 respectively). Titres of IgG anticardiolipin antibodies correlated with plasma levels of von Willebrand factor (p <0.0001; r: 0.42). These findings support the hypothesis that within the antiphospholipid antibody family, subgroups exist which may preferentially associate with arterial or venous occlusions and raise the possibility that elevated plasma levels of fibrinogen and von Willebrand factor may be implicated in the thrombotic tendency of the antiphospholipid syndrome through an involvement of the vascular endothelium, as the relationship between IgG anticardiolipin and von Willebrand factor suggests. Measurement of fibrinogen and von Willebrand factor in prospective studies, besides anticardiolipin antibodies and lupus anticoagulants, may help assess the risk of developing arterial and venous thrombosis in patients with antiphospholipid antibodies.
Platelet Accumulation on Fibrin-coated Polyethylene: Role of Platelet Activation and Factor XIII
Authors: Rubens F D , Perry D W , Hatton M W C , Bishop P D , Packham M A , Kinlough-Rathbone R L 
Published: July 2018

SummaryPlatelet accumulation on small- and medium-calibre vascular grafts plays a significant role in graft occlusion. We examined platelet accumulation on the surface of fibrin-coated polyethylene tubing (internal diameter 0.17 cm) during 10 min of flow (l0ml/min) at high wall shear rate (764 s-1). Washed platelets labelled with 51Cr were resuspended in Tyrode solution containing albumin, apyrase and red blood cells (hematocrit 40%). When the thrombin that was used to form the fibrin-coated surface was inactivated with FPRCH2C1 before perfusion of the tubes with the platelet:red blood cell suspension, the accumulation of platelets was 59,840 ± 27,960 platelets per mm2, whereas accumulation on fibrin with residual active thrombin was 316,750 ± 32,560 platelets per mm2 (n = 4). When the fibrin on the surface was cross-linked by including recombinant factor XIII (rFXIII) in the fibrinogen solution used to prepare the fibrin-coated surface, platelet accumulation, after thrombin neutralization, was reduced by the cross-linking from 46,974 ± 9702 to 36,818 ± 7964 platelets per mm2 (n = 12, p <0.01). Platelet accumulation on tubes coated with D-dimer was ten times less than on tubes coated with D-domain; this finding also supports the observation that cross-linking of fibrin with the formation of γ-γ dimers reduces platelet accumulation on the fibrin-coated surface. Thrombin-activated platelets themselves were shown to cross-link fibrin when they had adhered to it during perfusion, or in a static system in which thrombin was used to form clots from FXIII-free fibrinogen in the presence of platelets. Thus, cross-linking of fibrin by FXIII in plasma or from platelets probably decreases the reactivity of the fibrin-containing thrombi to platelets by altering the lysine residue at or near the platelet-binding site of each of the γ-chains of the fibrinogen which was converted into the fibrin of these thrombi.
Comparison of Postoperative Pain and Recovery between Single-Port and Two-Port Thoracoscopic Lobectomy for Lung Cancer
Authors: Liu Zhengcheng , Yang Rusong , Shao Feng 
Published: July 2018

Objective To investigate whether the single-port (SP) technique had more favorable postoperative outcomes than had the two-port (TP) technique.
Methods One hundred sixty-six single-port video-assisted thoracoscopic surgery (SP-VATS) lobectomy and 162 two-port video-assisted thoracoscopic surgery (TP-VATS) lobectomy had been successfully completed between August 2015 and September 2016. A single incision of ∼3 cm was made in an intercostal space along the anterior axillary line. Perioperative outcomes and the safety between SP-VATS and TP-VATS lobectomy for NSCLC was compared.
Results In the SP-VATS group, incision size was kept to a minimum, with a median of 3 cm; mediastinal lymph node dissection was performed in all patients with malignancy. Overall, median operative time was 89 minutes, and median chest tube duration was 3.1 days. The VAS on postoperative days 3, 7, and 14 was less in the SP-VATS group than that in the TP-VATS group. The VAS on days 1, 30, 60, 90, 180, and 360 did not differ significantly between the two groups. The number of days of use of analgesic agents after surgery was less in the SP-VATS group. The pathological symptoms of wound pain were significantly less in the SP-VATS group.
Conclusions Compared with the multiport approach, SP VATS lobectomy might reduce postoperative pain and lead to faster recovery.
The Micro-Elimination Approach to Eliminating Hepatitis C: Strategic and Operational Considerations
Authors: Safreed-Harmon Kelly , Thursz Mark , Dillon John , El-Sayed Manal , Elsharkawy Ahmed , Hatzakis Angelos , Jadoul Michel , Prestileo Tullio , Razavi Homie , Rockstroh Jürgen , Wiktor Stefan , Colombo Massimo , Lazarus Jeffrey 
Published: July 2018

AbstractThe introduction of efficacious new hepatitis C virus (HCV) treatments galvanized the World Health Organization to define ambitious targets for eliminating HCV as a public health threat by 2030. Formidable obstacles to reaching this goal can best be overcome through a micro-elimination approach, which entails pursuing elimination goals in discrete populations through multi-stakeholder initiatives that tailor interventions to the needs of these populations. Micro-elimination is less daunting, less complex, and less costly than full-scale, country-level initiatives to eliminate HCV, and it can build momentum by producing small victories that inspire more ambitious efforts. The micro-elimination approach encourages stakeholders who are most knowledgeable about specific populations to engage with each other and also promotes the uptake of new models of care. Examples of micro-elimination target populations include medical patients, people who inject drugs, migrants, and prisoners, although candidate populations can be expected to vary greatly in different countries and subnational areas.