| 1. |
- Aberg, Mikael, et al.
(författare)
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Tissue Factor Noncoagulant Signaling : Mechanisms and Implications for Cell Migration and Apoptosis
- 2015
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Ingår i: Seminars in Thrombosis and Hemostasis. - : Georg Thieme Verlag KG. - 0094-6176 .- 1098-9064. ; 41:7, s. 691-699
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Tidskriftsartikel (refereegranskat)abstract
- Tissue factor (TF) is a 47-kDa transmembrane glycoprotein and the main initiator of the blood coagulation cascade. Binding to its ligand factor VIIa (FVIIa) also initiates noncoagulant signaling with broad biological implications. In this review, we discuss how TF interacts with other cell-surface proteins, which affect biological functions such as cell migration and cell survival. A vast number of publications have demonstrated the importance of TF-induced activation of protease-activated receptors, but recently published research has indicated a more complicated picture. As it has been discovered that TF interacts with integrins and receptor tyrosine kinases, novel signaling mechanisms for the TF/FVIIa complex have been presented. The knowledge of these new aspects of TF signaling may, for instance, facilitate the development of new treatment strategies for cancer and acute coronary syndromes, two examples of diseases characterized by aberrant TF expression and signaling.
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| 2. |
- Berntorp, Erik, et al.
(författare)
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Prophylaxis for Hemophilia in the Era of Extended Half-Life Factor VIII/Factor IX Products
- 2016
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Ingår i: Seminars in Thrombosis and Hemostasis. - : Georg Thieme Verlag. - 0094-6176 .- 1098-9064. ; 42:5, s. 518-525
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Tidskriftsartikel (refereegranskat)abstract
- There are two main bioengineering approaches to extending the half-life of factor (F)VIII or FIX products used for hemophilia replacement therapy. These are fusion to Fc-immunoglobulin G (FVIII and FIX) or to albumin (FIX) or pegylation/glycopegylation (FVIII and FIX). Four FVIII and three FIX products are in clinical development or have recently been licensed in regions of the world. The reported half-life extension is approximately 1.5-fold for FVIII and 2.5-fold, or even longer, for FIX. Clinical trials have shown promising results with respect to extension of dose intervals and efficacy in the treatment and prevention of bleeding events. The role of these products in clinical practice has been discussed in terms of either improving convenience and adherence through prolongation of the interval between infusions or maintaining current intervals thereby increasing trough levels and the safety margin against bleeds. This review of extended half-life products addresses the possibilities and problems of their introduction in hemophilia treatment.
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| 3. |
- Dahlbäck, Björn
(författare)
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Vitamin K–Dependent Protein S : Beyond the Protein C Pathway
- 2018
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Ingår i: Seminars in Thrombosis and Hemostasis. - : Georg Thieme Verlag. - 0094-6176 .- 1098-9064. ; 44:2, s. 176-184
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Tidskriftsartikel (refereegranskat)abstract
- Protein S is a vitamin K–dependent plasma glycoprotein circulating in plasma at a concentration of around 350 nM. Approximately 60% of protein S in human plasma is bound to the complement regulatory protein C4b-binding protein (C4BP) in a high-affinity, high-molecular-weight complex. Protein S in plasma has multiple anticoagulant properties and heterozygous protein S deficiency is associated with increased risk of venous thrombosis. Homozygous deficiency in man and mice is associated with severe thrombosis in fetal life, defects in the vascular system development, and not compatible with life. Protein S has additional functions beyond being an anticoagulant. It affects the complement regulatory properties of C4BP, and moreover, protein S interacts with tyrosine kinase receptors of the TAM family, which comprises Tyro3, Axl, and Mer. The TAM receptor interaction is important for the ability of protein S to stimulate phagocytosis of apoptotic cells. This review will discuss the multiple functions of protein S, describing its role as cofactor to activated protein C with a subsequent focus on the other functions of protein S.
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| 4. |
- Fischer, Kathelijn, et al.
(författare)
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Targeting Factor Replacement Therapy in Severe Hemophilia: Which Level Is Important?
- 2015
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Ingår i: Seminars in Thrombosis and Hemostasis. - : Georg Thieme Verlag. - 1098-9064 .- 0094-6176. ; 41:8, s. 860-863
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Tidskriftsartikel (refereegranskat)abstract
- The original aim of prophylactic replacement therapy was to convert the bleeding pattern of severe hemophilia to that of moderate hemophilia through regular infusions of clotting factor concentrates. However, targeting prophylaxis on minimum trough levels does not prevent all bleeding. At the group level, there is a clear association of factor levels with bleeding and outcome. But bleeding phenotype in individual patients shows large variation, independent of trough levels maintained. The association of peak levels with bleeding on prophylaxis is not established. Experience with surgery suggests that certain peak levels need to be achieved during other hemostatic challenges, such as playing sports. Individualization of prophylaxis should include timing of infusion according to special activities. The clinical relevance of factor levels is even more urgent since the recent introduction of long-acting clotting factor concentrates with their different pharmacokinetic profiles and the prospect of gene therapy resulting in constant factor levels. It should be considered that the success of any prophylactic regimen is also dependent on other factors, such as the age at initiation of prophylaxis, adherence, lifestyle, cartilage susceptibility, and the other components of the clotting system. Factor levels are thus an important but quite small piece in the total picture of treating hemophilia and we currently cannot identify a specific trough or peak level to use for monitoring. At the same time, knowledge of a patients' level during the infusion intervals may help to individualize and adjust treatment according to the clinical symptoms.
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| 5. |
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| 6. |
- Hansson, Emma C., 1985, et al.
(författare)
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Antiplatelet Therapy, Platelet Function Testing, and Bleeding Complications in Cardiac Surgery Patients
- 2017
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Ingår i: Seminars in Thrombosis and Hemostasis. - : Georg Thieme Verlag KG. - 0094-6176 .- 1098-9064. ; 43:7, s. 699-705
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Tidskriftsartikel (refereegranskat)abstract
- Antiplatelet therapy with acetylsalicylic acid, alone or in combination with a P2Y(12) inhibitor, reduces thromboembolic events in patients with coronary artery disease but increases the risk for spontaneous and perioperative bleeding complications. Both the antiplatelet effect and the risk for bleeding complications are larger with the new generation P2Y(12) inhibitors prasugrel and ticagrelor than with clopidogrel. In this review, the perioperative handling of acetylsalicylic acid and the P2Y(12) inhibitors clopidogrel, prasugrel, and ticagrelor will be discussed. In addition, the concept of platelet function testing in the surgical setting will be covered.
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| 7. |
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| 8. |
- Karlsson, Ove
(författare)
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Experience of Point-of-Care Devices in Obstetrical Care
- 2017
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Ingår i: Seminars in Thrombosis and Hemostasis. - 0094-6176 .- 1098-9064. ; 43:4, s. 397-406
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Forskningsöversikt (refereegranskat)abstract
- Copyright © 2017 by Thieme Medical Publishers, Inc. During pregnancy and puerperium, there are pronounced hemostatic changes characterized by increased coagulability and decreased fibrinolysis. In addition, hemostasis can change dramatically during obstetric complications. Several reports have described substandard management of hemostatic defects in this setting and state the need for guidelines and better care. Point-of-care devices can assess hemostatic status and are especially suitable in perioperative settings. Using point-of-care devices, no time is required for transportation, allowing faster availability of results and providing potential for better care of the patient. This article will demonstrate the use of a viscoelastic method in six different patients; five with impaired hemostasis, and where the use of viscoelastic method contributes or should have contributed to better care. The cases represent patients with normal delivery; postpartum hemorrhage (PPH); PPH with low fibrinogen; placental abruption; preeclampsia with hemolysis, elevated liver enzymes, low platelet count syndrome; and finally, one patient with sepsis. This article also shows the need for good practices and good supervision to implement the devices in patient care.
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| 9. |
- Naudin, C, et al.
(författare)
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Factor XII Contact Activation
- 2017
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Ingår i: Seminars in thrombosis and hemostasis. - : Georg Thieme Verlag KG. - 1098-9064 .- 0094-6176. ; 43:8, s. 814-826
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Tidskriftsartikel (refereegranskat)abstract
- Contact activation is the surface-induced conversion of factor XII (FXII) zymogen to the serine protease FXIIa. Blood-circulating FXII binds to negatively charged surfaces and this contact to surfaces triggers a conformational change in the zymogen inducing autoactivation. Several surfaces that have the capacity for initiating FXII contact activation have been identified, including misfolded protein aggregates, collagen, nucleic acids, and platelet and microbial polyphosphate. Activated FXII initiates the proinflammatory kallikrein-kinin system and the intrinsic coagulation pathway, leading to formation of bradykinin and thrombin, respectively. FXII contact activation is well characterized in vitro and provides the mechanistic basis for the diagnostic clotting assay, activated partial thromboplastin time. However, only in the past decade has the critical role of FXII contact activation in pathological thrombosis been appreciated. While defective FXII contact activation provides thromboprotection, excess activation underlies the swelling disorder hereditary angioedema type III. This review provides an overview of the molecular basis of FXII contact activation and FXII contact activation–associated disease states.
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| 10. |
- Prandoni, Paolo, et al.
(författare)
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Extensive Computed Tomography versus Limited Screening for Detection of Occult Cancer in Unprovoked Venous Thromboembolism : A Multicenter, Controlled, Randomized Clinical Trial
- 2016
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Ingår i: Seminars in Thrombosis and Hemostasis. - : Georg Thieme Verlag KG. - 0094-6176 .- 1098-9064. ; 42:8, s. 884-890
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Tidskriftsartikel (refereegranskat)abstract
- Patients with unprovoked venous thromboembolism (VTE) may harbor occult cancer. Whether an extensive diagnostic work-up for cancer has additional value over a more limited screening for detection of underlying malignancy in these patients is controversial. We performed a randomized multicenter trial to assess if in patients with unprovoked VTE, a computed tomography (CT)-based diagnostic strategy including thoracic, abdominal, and pelvic CT in combination with fecal occult blood test yields a higher cancer detection rate than a nonstandardized testing approach based on physicians' clinical judgment and patients' preferences. Cancer-free patients were followed up for up to 24 months. Of the 195 consecutive patients with unprovoked VTE who were eligible for this investigation, an occult cancer was identified in 10 of the 98 patients (10.2%) randomized to the CT-based strategy, and in 8 of the 97 (8.2%) allocated to the personalized strategy (absolute difference, 2.0%; 95% confidence interval, -7.2-11.1; p=0.81). During follow-up, cancer was identified in an additional 2 patients in each group. Overall, 7 (7.1%) patients of the CT-based strategy died, as compared with 11 (11.3%) of the personalized strategy, with 2 and 4, respectively, due to cancer. In conclusion, a CT-based strategy in combination with fecal occult blood test does not provide a clinically significant benefit over more limited cancer screening for detecting occult cancer in patients with unprovoked VTE. (ClinicalTrials.gov number, NCT00361647).
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