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Introduction: G20210A (c.*97G>A) prothrombin gene variant, found in white population has been associated with an increased risk of venous thromboembolism (VTE). Other rare polymorphisms in F2 gene (C20209T) have been reported, more rare and touching black people, but its potential association with VTE remain uncertain. Methods: About a 69 years‐old Caucasian woman presenting an unprovoked deep venous thrombosis of the leg, we analyzed retrospectively 25.000 thrombophilia tests on a 11‐year period of time (2007–2018), at Nice and Marseille University Hospitals, and performed extensive review of the literature. Results: Genetic determination included a similar PCR protocol and sequencing. Twenty‐one heterozygous cases out of 25.585 determinations (0.08%) was found. The C20209T mutation detected in our Caucasian patient is rare, with a frequency that differed from what was reported in the previous literature, mainly in non‐Caucasian patients (Africans, Africans‐Americans, and Caribbeans). One hundred and thirteen patients with this mutation have been described in the literature, of which only one homozygous. Conclusion: This study is the most important on C20209T mutation performed at present, allowing to precise its frequency and its potential role in venous thromboembolism. [ABSTRACT FROM AUTHOR]

Introduction: Antiphospholipid syndrome (APS) is an autoimmune thrombotic disease with various systemic presentations. This study aimed to identify homogeneous groups of patients based on a non-supervised hierarchical cluster analysis and assess the rate of relapse associated with antinuclear antibodies (ANA). Methods: This retrospective observational study enrolled patients, over a 90-month period, who had APS as defined by the 2006 Sydney classification criteria, and for whom ANA workup was performed. Agglomerative unsupervised hierarchical clustering was conducted to classify patients into subgroups using 24 variables reflecting a range of clinical and biological baseline features associated with APS. Results: Hundred and seventy-four patients were included and were categorized into four phenotypes. Cluster 1 (n=73) associated mostlymiddle-agedmen with risk factors for cardiovascular disease. Obstetrical APS with low-risk thrombosis made up cluster 2 (n=25). Patients with venous thromboembolism (VTE), microvascular findings and double/triple positive APL antibodies (50%) were represented in cluster 3 (n=33). Whereas cluster 4 (n=43) characterized a predominantly female subpopulation with positive ANA and systemic lupus (n=23) that exhibited a high thrombotic risk and more frequent relapses (n=38) (p<0.001). Conclusions: This study identified four homogenous groups of patients with APS listed as: i) cardiovascular and arterial risk, ii) obstetrical, iii) VTE and microvascular, and iv) ANA-positive APS. We found that ANA-positivity was associated with higher rates of relapse. Applying ANA status to classification criteria could constitute a novel approach to tailoring management for APS, based on phenotypic patterns and risk assessment. [ABSTRACT FROM AUTHOR]

Shockingly, the global identification rate for haemophilia patients stands at only 31%, with the lowest rates observed in regions like Africa (8%) and Southeast Asia (17%),[3] and the identification rates for other bleeding disorders, including VWD, are even significantly lower. Dear Editor, Prompt and accurate diagnosis is crucial in effectively managing haemophilia and Von Willebrand Disease (VWD).[[1]] In haemophilia, delayed diagnosis or inadequate management can result in serious consequences such as life-threatening bleeding events leading to joint damage and disability, as well as the consequences of iron deficiency. A foundation to better care: Target product profile for haemophilia and Von Willebrand disease point-of-care diagnostics in low-resource settings In conclusion, the development of a TPP for POC devices designed specifically for haemophilia and VWD diagnosis in low-resource settings is a critical step towards addressing the challenges faced in diagnosing inherited bleeding disorders. [Extracted from the article]

Keywords: haemophilia; low-resource countries; point of care; target product profile EN haemophilia low-resource countries point of care target product profile 671 673 3 03/17/23 20230301 NES 230301 Dear Editor, Haemophilia is a rare X-linked congenital bleeding disorder characterized by a deficiency in coagulation factor VIII (FVIII:C) in the case of haemophilia A (HA), or factor IX (FIX) in the case of haemophilia B (HB), caused by pathogenic variants in the I F8 i or the I F9 i genes, respectively.[[1]] The condition is usually suspected in individuals presenting with a history of haemorrhagic symptoms such as easy bruising, spontaneous bleeding, particularly into the joints, muscles and soft tissues, or excessive bleeding following surgery or trauma.[3] In patients presenting with clinical symptoms, the diagnosis of haemophilia is based on the results of laboratory tests. The TPP will also be useful in monitoring, evaluating and tracking any future haemophilia POC devices to support the increased rate of identification of people with haemophilia in resource-limited settings. Establishing a TPP for haemophilia should aid in the resolution of challenges encountered during the early development of haemophilia POC devices, as well as the prevention of late-stage development and deployment failures. [Extracted from the article]

We hope that the IHTC Fellowship program continues to facilitate the training of healthcare professionals around the globe, enhancing their knowledge and skills to better serve the bleeding disorders community for years to come. Our ability to overcome many challenges over the lifetime of the IHTC Fellowship program is proof that the WFH and its designated IHTCs will continue to evolve to meet the needs of medical and paramedical professionals worldwide. [Extracted from the article]

Replacement therapy with plasma‐derived or recombinant FVIII and FIX (pdFVIII/pdFIX or rFVIII/rFIX) concentrates is the standard of treatment in patients with haemophilia A and B, respectively. Measurement of factor VIII (FVIII:C) or factor IX (FIX:C) levels can be done by one‐stage clotting assay (OSA) or chromogenic substrate assay (CSA). The French study group on the Biology of Hemorrhagic Diseases (a collaborative group of the GFHT and MHEMO network) presents a literature review and proposals for the monitoring of FVIII:C and FIX:C levels in treated haemophilia A and B patients, respectively. The use of CSA is recommended for the monitoring of patients treated with pdFVIII or rFVIII including extended half‐life (EHL) rFVIII. Except for rFVIII‐Fc, great caution is required when measuring FVIII:C levels by OSA in patients substituted by EHL‐rFVIII. The OSA is recommended for the monitoring of patients treated with pdFIX or rFIX. Large discordances in the FIX:C levels measured for extended half‐life rFIX (EHL‐rFIX), depending on the method and reagents used, must lead to great attention when OSA is used for measuring FIX:C levels in patients substituted by EHL‐rFIX. Data of most of recent studies, obtained with spiked plasmas, deserve to be confirmed in plasma samples of treated patients. [ABSTRACT FROM AUTHOR]

Résumé: Une surveillance biologique des hémophiles substitués est nécessaire afin d'ajuster la dose de facteurs administrés qu'ils soient d'origine plasmatique ou recombinante. La méthode de dosage de l'activité du facteur IX (FIX:C) la plus répandue est la méthode chronométrique basée sur la mesure du temps de céphaline avec activateur (TCA). Le nombre important de réactifs de TCA et les différents couples automates/réactifs expliquent les difficultés de standardisation de ces dosages. Le groupe français d'études de la biologie des maladies hémorragiques (groupe collaborateur du GFHT et de la filière MHEMO), présente une revue de la littérature et des propositions pour le suivi biologique des patients hémophiles B substitués. Une méthode chronométrique calibrée avec un standard raccordé à l'étalon international OMS est recommandée pour le suivi des patients traités par FIX plasmatiques ou recombinants. Les méthodes chromogéniques sont acceptables pour le suivi des patients traités par Rixubis® et les données sont à ce jour insuffisantes pour le Benefix®. Concernant les FIX recombinants de demi-vie allongée (rFIX-EHL), il existe de grande discordance dans les taux de FIX:C en fonction des méthodes et des réactifs. Une grande vigilance est nécessaire pour le dosage de l'activité du FIX:C par méthode chronométrique chez les patients substitués par ces nouveaux médicaments. Les méthodes chromogéniques ne sont pas équivalentes et ne sont pas validées pour l'ensemble de ces rFIX-EHL. La majorité des études présente des résultats obtenus avec des plasmas surchargés qui doivent être confirmés avec des plasmas de patients traités. Replacement therapy with plasma-derived or recombinant FIX (pdFIX or rFIX) concentrates is the standard of treatment in patients with hemophilia B. The method predominantly used for measuring factor IX (FIX:C) levels is the one-stage clotting assay (OSA) but this method depends on the activated partial thromboplastin time (APTT) reagent and the coagulation analyzer used, and wide variations in the measurements of FIX recovery have been reported with some factor concentrates. The French study group on the biology of hemorrhagic diseases (a collaborative group of the GFHT and MHEMO network), presents a review of the literature and proposals for the monitoring of FIX:C levels in treated hemophilia B patients. The use of OSA calibrated with a plasma reference tested against the current FIX WHO International Standard is recommended for the monitoring of patients treated with pdFIX or rFIX. Chromogenic substrate assays (CSA) are adequate for the monitoring of patients treated with Rixubis®, but data available for Benefix® are currently too limited. For extended half-life rFIX (EHL-rFIX), large discordances in the FIX:C levels measured were evidenced, depending on the method and reagents used. Great attention is therefore required for measuring FIX:C levels by OSA in patients substituted by EHL-rFIX. Commercial kits for CSA are not equivalent, and although potentially useful, they are not validated for all EHL-rFIX. Most of recent studies reported data obtained with spiked plasmas, which deserve to be confirmed on plasma samples collected in treated patients. [ABSTRACT FROM AUTHOR]

Résumé: Une surveillance biologique des hémophiles substitués est nécessaire pour ajuster la dose de facteurs administrés qu'ils soient d'origine plasmatique ou recombinante. La méthode de référence pour le dosage de l'activité du facteur VIII (FVIII:C) chez les patients hémophiles A substitués est la méthode chromogénique, mais elle est peu répandue dans les laboratoires qui utilisent le plus souvent la méthode chronométrique basée sur la mesure du temps de céphaline avec activateur (TCA). Le nombre important de réactifs de TCA et les différents couples automates/réactifs expliquent les difficultés de standardisation de ces dosages. Le groupe français d'études de la biologie des maladies hémorragiques (groupe collaborateur du GFHT et de la filière MHEMO), présente une revue de la littérature et des propositions pour le suivi biologique des patients hémophiles A substitués. Une méthode chromogénique, calibrée avec un standard raccordé à l'étalon international de l'Organisation mondiale de la santé (OMS), est recommandée pour le suivi des patients traités par FVIII plasmatique (pdFVIII) ou recombinant (rFVIII) y compris pour les nouveaux rFVIII à demi-vie allongée (extended half life : EHL). Une méthode chronométrique est acceptable pour le pdFVIII et la plupart des rFVIII. Pour la surveillance d'un traitement par Refacto AF®, une comparaison préalable avec la méthode chromogénique est requise. Concernant les rFVIII-EHL, la méthode chronométrique n'est acceptable aujourd'hui que pour l'Elocta®. Une grande vigilance doit être apportée lors de l'utilisation d'une méthode chronométrique pour les autres rFVIII-EHL. La majorité des études présente des résultats obtenus avec des plasmas surchargés qui doivent être confirmés avec des plasmas de patients traités. Replacement therapy with plasma-derived or recombinant FVIII (pdFVIII or rFVIII) concentrates is the standard of treatment in patients with hemophilia A. The reference method used for measuring factor VIII (FVIII:C) levels in patients treated by FVIII concentrates is the chromogenic substrate assay (CSA). However, the one-stage clotting assay (OSA) is predominantly used in current clinical practice, but this method depends on the activated partial thromboplastin time (APTT) reagent and the coagulation analyzer used, and wide variations in the measurements of FVIII recovery have been reported with some factor concentrates. The French study group on the biology of hemorrhagic diseases (a collaborative group of the GFHT and MHEMO network) presents a review of the literature and proposals for the monitoring of FVIII:C levels in treated hemophilia A patients. The use of CSA calibrated with a plasma reference tested against the current FVIII WHO (World Health Organization) International Standard is recommended for the monitoring of patients treated with pdFVIII or rFVIII including extended half-life (EHL) rFVIII. OSA are adequate for the monitoring of patients treated with pdFVIII or with most of rFVIII concentrates. However, preliminary comparison with CSA is mandatory before measuring FVIII:C by OSA in patients treated by Refacto AF®. For rFVIII-EHL, OSA are only acceptable for Elocta®. Great caution is therefore required when measuring FVIII:C levels by OSA in patients substituted by other EHL-rFVIII. Indeed, most of recent studies reported data obtained with spiked plasmas, which deserve to be confirmed on plasma samples collected in treated patients. [ABSTRACT FROM AUTHOR]

Abstract: Individualized anticoagulation management and improvement of the safety and effectiveness of oral anticoagulant have always been the focus of clinicians' attention. D‐dimer, a sensitive marker of thrombosis and coagulation activation, is not only traditionally used in the diagnosis of venous thromboembolism, acute aortic dissection, and disseminated intravascular coagulation but can also be used as a helpful marker in the management of oral anticoagulant, including evaluating the anticoagulation quality, predicting clinical outcomes, and determining the optimal duration and intensity of anticoagulation. [ABSTRACT FROM AUTHOR]

Introduction A maximum delay between blood collection and coagulation testing of 4 hours is recommended by most guidelines. As information on optimal storage times is limited, we investigated the potential effect of different storage times of unspun tubes, that is, ≤2, 4, 6, and 8 hours, on routine coagulation test results. Methods Four evacuated polymer tubes containing 0.109 mol/L tri-Na citrate were drawn from 144 patients, including 39 patients on vitamin K-antagonists. Except for storage time, all tubes underwent the same preanalytical process. Prothrombin time ( PT)/international normalized ratio ( INR), activated partial thromboplastin time ( aPTT), fibrinogen, factor V ( FV), FVIII, and D-dimer were evaluated in two centers using the same technical conditions. Results Analytical comparison of aPTT, fibrinogen, FV, and FVIII results evaluated after prolonged storage times vs a <2-hours storage demonstrated significant difference, whereas PT/ INR and D-dimer remained unchanged up to 8 hours. Mean bias between test results obtained after prolonged storage times remained below the desirable values for all studied parameters except for FVIII evaluated after 6- and 8-hours storages, but only in patients with FVIII above 100 IU/ dL. Even though the corresponding bias of −5.2% and −8.5%, respectively, remained within the GEHT recommended limits of variation, its evaluation after an 8-hours storage could lead to significant underestimation of FVIII. Conclusion These results suggest that, in the studied technical conditions, PT/ INR, aPTT, fibrinogen, FV, and D-dimer can be reliably evaluated in tubes stored unspun at room temperature for up to 8 hours after blood collection. That optimal delay should be of 6 hours for FVIII. [ABSTRACT FROM AUTHOR]

Introduction Activated partial thromboplastin time ( aPTT) is a routine clotting assay that is widely used to globally screen for coagulation abnormalities. It is commonly admitted that a prolonged test result, may trigger the need for specific assays to be performed, particularly factor measurement. However, the sensitivity of aPTT reagents to deficiencies of clotting factors varies. Methods We evaluated, according to the recommendation of the CLSI H47-A2 guideline, the responsiveness to single factor levels of five aPTT reagents by using factor-deficient plasmas spiked with a calibration plasma to produce individual factor activities ranging from <1 to ~100 Unit (U)/ dL. Test results were expressed as the sample-to-control ratio, the latter was defined as the clotting time obtained in the calibration plasma containing ~100 U/ dL factor activity. The factor activity producing a prolongation of aPTT above the upper limit of its specific normal range (in ratio) was assigned as the factor responsiveness in U/ dL to that reagent. Results Responsiveness ranged from 34 to 47 U/ dL to FVIII:C, from 18 to 57 U/ dL to FIX, from 38 to 52 U/ dL to FXI, from 29 to 50 U/ dL to FXII, from 40 and 59 U/ dL to FV, from 7.5 to 49 U/ dL to FX, and from 9.1 to 10.5 U/ dL to FII. Conclusions These results suggest that the sensitivity of the tested aPTT reagents to single factor deficiency is highly variable. Moreover, for one given aPTT reagent, its sensitivity was very different depending on the deficient factor. This must be considered when analyzing clinical materials. [ABSTRACT FROM AUTHOR]

The pediatric hemostatic balance, which is different from that in adults, is an evolving process as the hemostatic system changes and matures throughout the time from fetal to adult life, particularly in the first months of life. The concept of developmental hemostasis was confirmed by several studies evaluating different patients' population in various technical conditions. All these studies demonstrated that, at birth, the plasma levels of most coagulation factors were around half that found in adults, the preterm newborns having lower levels than full-term newborns. Adult values were usually reached between a few months of age and up to above 16 years for specific parameters. If the global trends are consistent across the studies, differences in absolute values could be demonstrated that are likely due to differences in the reagents and/or the instruments used. Accordingly, it is recommended by the Perinatal and Pediatric Haemostasis Subcommittee of the Scientific and Standardization Committee of the ISTH for each laboratory to define the age-dependent reference ranges using its own technical condition. The understanding of that concept of developmental hemostasis, which is now universally accepted, is critical to ensure optimal prevention, diagnosis, and treatment of thrombotic and hemorrhagic diseases in children. Actually, developmental hemostasis could affect the interaction between anticoagulant drugs and the coagulation system and so explain in part the discrepancy between anticoagulation in adults and in children. Finally, developmental hemostasis could probably provide a protective mechanism for neonates and children, contributing to the decreased risk of thrombosis and/or bleeding in these age-groups. [ABSTRACT FROM AUTHOR]

Achieving forest conservation together with poverty alleviation and equity is an unending challenge in the tropics. The Makira REDD+ pilot project located in northeastern Madagascar is a well-suited case to explore this challenge in conditions of extreme poverty and climatic vulnerability. We assessed the potential effect of project siting on the livelihoods of the local population and which households would be the most strongly impacted by conservation measures. Farmers living in hilly areas must resort to slash-and-burn agriculture (tavy) since a combination of topographic and climatic constraints, such as cyclones, makes permanent rice cultivation very difficult. These are the people who suffer most from conservation-related restriction measures. For practical reasons the project, unfortunately, did not target these farmers. The main focus was on communities with a lower cyclonic risk that are able to practice permanent rice agriculture in the lowlands. To reduce deforestation without violating the principles of equity, REDD+ projects in Madagascar need to better target populations facing high climatic risks and invest in efforts to improve the farmers' agricultural systems. [ABSTRACT FROM AUTHOR]

Background The notion of individual burden, associated with a disease, has been introduced to determine the 'disability' in the broadest sense (psychological, social, economic and physical). Atopic dermatitis ( AD) is one of the most common chronic inflammatory skin diseases with an estimated prevalence of 5%-30% in children. Objective To develop and validate a specific questionnaire which assess the burden of families of children with AD: the Atopic dermatitis Burden Scale ( ABS). Methods Items for inclusion in ABS were initially generated from a literature review and a verbatim report from parents whose child had AD. ABS was refined via item reduction according to interquestion correlations, consensus among experts and exploratory factor analysis. Internal consistency was determined by calculating the Cronbach's α, concurrent validity by calculating the correlation between ABS and the Short-Form 12 items. Discriminant validity was analysed according to the severity degrees of AD assessed by Patient-Oriented SCORing index of Atopic Dermatitis ( PO- SCORAD). Results From an initial list of 29 items, ABS was reduced to a 14-item questionnaire, grouped into four dimensions based on the exploratory factor analysis. Construct validity was demonstrated and ABS showed good internal coherence (Cronbach's α: 0.78). ABS was significantly correlated to the mental dimension of Short-Form 12 ( r = −0.49), but it was not correlated to the physical dimension ( r = 0.04). ABS scores were significantly different according to the severity degrees of AD, with higher ABS score in parents whose child had severe AD. Conclusion The ABS questionnaire is a validated tool for assessing the burden of families of children with AD. An implementation of a prospective study is planned to estimate sensitivity to change and to confirm its domain structure in larger samples. [ABSTRACT FROM AUTHOR]

In high current, high voltage, high temperature (T>125^\circC) power applications, commercially available conventional silicon thyristors are not suited because they present high leakage current. In this context, this paper presents a high-symmetrical (voltage) thyristor structure that presents a lower leakage current and higher breakover voltage as compared with the conventional thyristor at T>125^\circC. It is shown through 2-D physical simulations that the replacement of the P-emitter of a standard symmetrical thyristor by a judicious association of P diffusions and Schottky contacts at the anode side contributes to the reduction of the leakage current in the forward blocking state at high temperature. A fine tune of the anode side configuration will improve the forward OFF-state behavior with only a negligible ON-state voltage drop degradation. Moreover, the comparison with the conventional anode short thyristor shows that the insertion of Schottky contacts leads to the same improvements in terms of OFF-state forward breakover voltage and leakage current and also presents a high reverse blocking voltage. [ABSTRACT FROM PUBLISHER]

The article discusses a study to determine the association between GAS6 rs8191974 polymorphism and patients suffering from acute myocardial infarction (AMI). A definition of the AMI is presented. The authors conclude that rs8191974 polymorphism was not found associated with carotid atherosclerosis, but rather MERTK and TYRO3 receptor gene polymorphism.

Two-dimensional numerical simulations have been performed to define the sensitive volume and triggering criteria of single-event burnouts (SEBs) for standard and superjunction MOSFETs and planar and trench IGBTs for different configurations of ionizing tracks and for different conditions of polarization and temperature. The analysis of the results gives a better understanding of the SEB mechanism in each structure and a comparison of behavior and robustness of these technologies under heavy-ion irradiation. [ABSTRACT FROM AUTHOR]

Coagulation factor VIII (FVIII) is usually evaluated using activated partial thromboplastin time-based one-stage clotting assays. Guidelines for clotting factor assays indicate that a calibration curve should be included each time the assay is performed. Therefore, FVIII measurement is expensive, reagent- and time-consuming. The aim of this study was to compare FVIII activities obtained using the same fully automated assay that was calibrated once (stored calibration curve) or each time the assay was performed. Unique lots of reagents were used throughout the study. We analysed 255 frozen plasma samples from patients who were prescribed FVIII measurement including treated and untreated haemophilia A patients. Twenty-six runs were performed on a 28-week period, each including four lyophilized control and at most 10 patient plasma samples. In control samples, FVIII activities were not significantly different when the assay was performed using the stored calibration curve or was daily calibrated. The same applied to FVIII activities in patient plasma samples that were not significantly different throughout the measuring range of activities [68.3% (<1-179) vs. 67.6% (<1-177), P = 0.48] and no relevant bias could be demonstrated when data were compared according to Bland and Altman. These results suggest that in the studied technical conditions, performing the FVIII assay using a stored calibration curve is reliable, for at least 6 months. Therefore, as far as the same lots of reagents are used, it is not mandatory to include a calibration curve each time the FVIII assay was performed. However, this strategy has to be validated if the assay is performed in different technical conditions. [ABSTRACT FROM AUTHOR]

This column describes Washington State's historic statewide initiative to implement ten high-fidelity assertive community treatment teams. Legislative support and administrative leadership facilitated the implementation of this evidence-based practice as part of a comprehensive transformation initiative within public mental health services for people with serious mental illness. Stakeholder feedback and initial fidelity reviews suggest that the first year has been successful. Crucial strategies that were important to the teams' successful implementation, such as training and consultation, are examined. Challenges, such as staff turnover, are described along with targeted approaches that have been integral to overcoming them. Next steps to promote sustainability and implications for state mental health authorities are discussed. [ABSTRACT FROM AUTHOR]

The measurement of D-dimer, a specific fibrin degradation product, was recently introduced in the diagnosis strategy of pulmonary embolism (PE).New rapid and automated assays based on various principles are now available.The aim of our study was to assess the reliability of 2 rapid quantitative assays [VIDAS D-DIMER (BioMerieux) and STA-Liatest D-DI (Diagnostica Stago)] in the diagnosis of PE and to compare the results with those obtained with an ELISA (Asserachrom D-Di).All 3 D-dimer assays demonstrated high sensitivity and negative predictive value (100%), which enabled physicians to validly exclude the diagnosis of PE when D-dimer levels were below the defined cut-off levels. [ABSTRACT FROM AUTHOR]

We have investigated the molecular bases of familial antithrombin deficiency in eight French families. Eight mutations in the antithrombin coding exons were identified, seven of which were novel mutations. In all cases, individuals were heterozygous for the mutation. We found two small frameshift deletions in exon 3a, leading to type I deficiency. Five missense mutations in exons 3b or 5 also caused type I deficiency and their potential consequences on the antithrombin three-dimensional structure were analysed. The last mutation in exon 4 was associated with a type II ‘reactive site’ deficiency: a dysfunctional antithrombin that is affected in its interaction with thrombin was present in circulation. [ABSTRACT FROM AUTHOR]

The effects of aprotinin, a broad-based proteinase inhibitor, in the management of hemorrhagic complications during prolonged venovenous extracorporeal CO2 removal in patients with adult respiratory distress syndrome are not evaluated. In two patients, aprotinin infusion was added to heparin to treat bleeding, occurring after few days of bypass and responsible for respiratory and hemodynamic deterioration. After aprotinin infusion (loading dose of 2 x 10(6) kIU followed by a continuous infusion of 5 x 10(5) kIU/h) combined with heparin, bleeding vanished until the end of bypass. [ABSTRACT FROM AUTHOR]

This study was designed to evaluate platelet activation, enhancement of coagulation and fibrinolysis in patients with chronic renal failure on long-term haemodialysis. Beta thromboglobulin (BTG), platelet factor 4 (PF4), fibrinopeptide A, tissue plasminogen activator (t-PA) activity and antigen, tissue plasminogen activator inhibitor (PAI), fibrin, and fibrinogen degradation products were studied during dialysis. The influence of two types of membrane on these parameters was also evaluated. The patients comprised 24 individuals on long-term haemodialysis on either cuprophan membrane (CUP) (12 patients) or polyacrylonitrile membrane (AN 69) (12 patients). Blood samples were collected before, at 15 min, and at the end of dialysis. The results demonstrated that platelet activation was permanent and increased during haemodialysis. However, no difference could be demonstrated between patients treated on CUP and patients treated on AN 69. Coagulation was also enhanced permanently but did not show modification during haemodialysis. Fibrinolysis was activated at the end of haemodialysis in half the patients, but again no difference could be demonstrated between patients treated on AN 69 and CUP membranes. It was concluded that the process of haemodialysis itself enhanced platelet activation, coagulation, and fibrinolysis but that both membranes were of equal effect [ABSTRACT FROM PUBLISHER]

We have studied the mechanism of the response to iron deficiency in rape ( Brassica napus L.), taking into account our previous results: net H extrusion maintains a pH shift between the root apoplast and the solution, and the magnitude of the pH shift decreases as the buffering power in the solution increases. The ferric stress increased the ability of roots to reduce Fe[III]EDTA. Buffering the bulk solution (without change in pH) inhibited Fe[III]EDTA reduction. At constant bulk pH, the inhibition (ratio of the Fe[III]EDTA-reduction rates measured in the presence and in the absence of buffer) increased with the rate of H extrusion (modulated by the length of a pretreatment in 0.2 mM CaSO). These results support the hypothesis that the apoplastic pH shift caused by H excretion stimulated Fe[III] reduction. The shape of the curves describing the pH-dependency of Fe[III]EDTA reduction in the presence and in the absence of a buffer fitted this hypothesis. When compared to the titration curves of Fe[III]citrate and of Fe[III]EDTA, the curves describing the dependency of the reduction rate of these chelates on pH indicated that the stimulation of Fe[III] reduction by the apoplastic pH shift due to H excretion could result from changes in electrostatic interactions between the chelates and the fixed chargers of the cell wall and-or plasmalemma. Blocking H excretion by vanadate resulted in complete inhibiton of Fe[III] reduction, even in an acidic medium in which there was neither a pH shift nor an inhibitory effect of a buffer. This indicates that the apoplastic pH shift resulting from H pumping is not the only mechanism which is involved in the coupling of Fe[III] reduction to H transport. Our results shed light on the way by which the strong buffering effect of HCOin some soils may be involved in iron deficiency encountered by some of the plants which grow in them. [ABSTRACT FROM AUTHOR]

The effect of HCOon ion absorption by young corn roots was studied in conditions allowing the independent control of both the pH of uptake solution and the CO partial pressure in air bubbled through the solution. The surface pH shift in the vicinity of the outer surface of the plasmalemma induced by active H excretion was estimated using the initial uptake rate of acetic acid as a pH probe (Sentenac and Grignon (1987) Plant Physiol. 84, 1367). Acetic acid and orthophosphate uptake rates and NOaccumulation were slowed down, while Rb uptake and K accumulation rates were increased by HCO. These effects were similar to those induced by 4-(2-hydroxyethyl)-1-piperazineethane sulfonic acid/2-amino-2-(hydroxymethyl)-1,3-propanediol (Hepes-Tris). They were more pronounced when the H excretion was strong, were rapidly reversible and were not additive to those of Hepes-Tris. The hypothesis is advanced that the buffering system CO/HCO/HCOaccelerated the diffusion of equivalent H inside the cell wall towards the medium. This attenuated the surface pH shift in the vicinity the plasma membrane and affected the coupling between the proton pump and cotransport systems. [ABSTRACT FROM AUTHOR]