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Clinical use of recombinant human activated factor VII (rFVIIa) in the prevention and treatment of bleeding episodes in patients with Glanzmann’s thrombasthenia
No full textMan-Chiu PoonDepartments of Medicine, Pediatrics and Oncology and Southern Alberta Bleeding Disorders Clinic, University of Calgary and Calgary Health Region, Calgary, Alberta, CanadaAbstract: Glanzmann’s thrombasthenia (GT) is a congenital qualitative platelet disorders due to the deficiency or defect of platelet membrane GPIIb/IIIa (integrin αIIbβ3). The standard treatment for bleeding is platelet transfusion but repeated transfusion may result in the development of anti-platelet antibodies (to HLA and/or GPIIbIIIa) rendering future platelet transfusion ineffective. Alternative effective agent(s) are needed. There are increasing reports documenting efficacy of high dose rFVIIa in GT patients with adverse events uncommon. The efficacy is supported by evidence that high concentration FVIIa binds to activated platelet surface and improves thrombin generation to enhance deposition (adhesion) and aggregation of platelets lacking GPIIb/IIIa. While there are increasing clinical experiences, evidence-based clinical data are not available. There is a need for more clinical studies, particularly clinical trials, to further assess the efficacy, safety (particularly thrombotic events) and optimal regimen of rFVIIa in GT patients, either singly or in combination with other hemostatic agents such as platelet transfusion. In the absence of this data, for treatment of severe bleeding in GT patients with platelet antibodies and platelet refractoriness, rFVIIa at dose 90 μg/kg every 2 h for 3 or more doses could be considered. This more “optimal regimen” derived from a recent International Survey needs confirmation with larger studies. What the optimal regimen for surgical coverage is remains unresolved.Keywords: Glanzmann’s thrombasthenia, recombinant human activated factor VII (rFVIIa), bleeding, surgery, platelet transfusion, GPIIb/III
Schematic tissue factor-independent, platelet-dependent model of primary hemostatic plug formation in Glanzmann’s thrombasthenia (GT) platelets deficient in membrane glycoprotein (GP) IIb-IIIa (integrin aβ)
No full textFVIIa-tissue factor (TF) complex on TF-bearing cells at the site of vascular injury activates FX to FXa, which in turn complexes with FVa on the TF-bearing cells to initiate generation of a small amount of thrombin (FIIa) from prothrombin (FII). This initially generated thrombin is not sufficient to allow fibrin formation, but is sufficient to activate the GT platelets, causing degranulation and release of FV. FVIIa binds to activated platelets weakly. At high concentration (eg, high dose rFVIIa therapy), the bound FVIIa can directly activate FX to FXa to mediate generation of high concentration of thrombin (thrombin burst). The augmented thrombin generation results in increased number of activated platelets deposited (adhesion) to the wound site, and increased available platelet procoagulant surface to facilitate more thrombin generation and more platelet activation. The augmented thrombin generated also converts fibrinogen to fibrin. Activated GT platelets cannot utilize fibrinogen for aggregation reaction as they lack the fibrinogen receptor integrin aβ. However, binding of fibrin/polymeric fibrin to an as yet unidentified platelet surface receptor can mediate aggregation of the GT platelets at the wound site (even though less potent than fibrinogen mediated aggregation of normal platelets) resulting in primary hemostatic plug formation. Adapted from .<p><b>Copyright information:</b></p><p>Taken from "Clinical use of recombinant human activated factor VII (rFVIIa) in the prevention and treatment of bleeding episodes in patients with Glanzmann’s thrombasthenia"</p><p></p><p> 2007;3(5):655-664.</p><p>Published online Jan 2007</p><p>PMCID:PMC2291310.</p><p></p
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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