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- Hillarp, Andreas, et al.
(författare)
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Effects of the oral, direct factor Xa inhibitor rivaroxaban on commonly used coagulation assays
- 2011
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Ingår i: JOURNAL OF THROMBOSIS AND HAEMOSTASIS. - : Blackwell Publishing. - 1538-7933 .- 1538-7836. ; 9:1, s. 133-139
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Rivaroxaban is an oral direct factor Xa inhibitor developed for prophylaxis and treatment of thromboembolic disorders. Laboratory monitoring is not necessary but the dose-dependent effects on common reagents and assay procedures are largely unknown. Objectives: To investigate the effect of rivaroxaban on commonly used coagulation assays. Materials and Methods: Rivaroxaban was added to plasma from healthy subjects in the concentration range 0-1000 mu g L-1 and analyzed using different reagents for activated partial thromboplastin time (APTT), prothrombin time (PT), antithrombin, fibrinogen and activated protein C (APC) resistance assays. Results: At an expected peak concentration of rivaroxaban in clinical use, the APTTs were almost invariably prolonged but at lower concentrations the effect was weak. The concentration needed to double the APTT varied between 389 +/- 106 and 617 +/- 149 mu g L-1 for different reagents. The PT assays showed a marked degree of difference. In general, the Quick PT type assays were more sensitive compared with the Owren type PT assays. The results from antithrombin assays were dependent on the type of reagent, with the Xa-based assay being sensitive for rivaroxaban with an estimated increase of 0.09 IU mL-1 per 100 mu g L-1 rivaroxaban. There were only minor effects on fibrinogen assays based on thrombin reagents. The APTT-based assay for APC resistance is affected in a dose-dependent manner whereas an assay based on the activation of coagulation at the prothrombinase level was unaffected. Conclusions: Different assays, and even different reagents within an assay group, display variable effects by therapeutic concentrations of rivaroxaban.
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| 4. |
- Hanson, Ellen, et al.
(författare)
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Plasma levels of von Willebrand factor in the etiologic subtypes of ischemic stroke
- 2011
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 9:2, s. 275-281
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Tidskriftsartikel (refereegranskat)abstract
- Background: Compared with coronary artery disease, there are few studies on von Willebrand factor (VWF) in ischemic stroke (IS). Moreover, there is little information on VWF in the etiologic subtypes of IS. Objectives: The aim of the present study was to investigate VWF in IS and in the etiologic subtypes of IS. Patients/methods: The Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS) is a case-control study comprising 600 patients and 600 matched controls. Etiologic IS subtype was defined according to the TOAST criteria. Blood sampling was performed in the acute phase and after 3 months. Results: The levels of VWF were increased in overall IS, at both time-points. The 3-month VWF levels were increased in the subtypes of large-vessel disease (LVD), cardioembolic (CE) stroke and cryptogenic stroke, but not in the subtype of small-vessel disease (SVD), as compared with the controls. The acute phase VWF levels were significantly increased in all four subtypes. In the multivariate regression analysis, with vascular risk factors as covariates, the 3-month VWF levels were associated with CE stroke and cryptogenic stroke, and the acute phase VWF levels with all subtypes. There were significant subtype-specific differences in VWF, with the highest levels in LVD and CE stroke. Conclusions: The present results show that VWF levels are increased in patients with IS. Furthermore, the VWF levels differ between etiologic IS subtypes and thus, it is important to consider etiologic subtypes in future studies of VWF in patients with IS.
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| 6. |
- Hanson, Ellen, et al.
(författare)
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Plasma factor VII-activating protease antigen levels and activity are increased in ischemic stroke.
- 2012
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Ingår i: Journal of thrombosis and haemostasis : JTH. - : Elsevier BV. - 1538-7836 .- 1538-7933. ; 10:5, s. 848-56
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Tidskriftsartikel (refereegranskat)abstract
- Factor VII-activating protease (FSAP) is a recently discovered plasma protease with a role in the regulation of hemostasis and vascular remodeling processes. Higher levels and activity of FSAP have been reported in patients with deep vein thrombosis, but there are no data on plasma FSAP in ischemic stroke (IS).
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| 7. |
- Schulman, S., et al.
(författare)
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Definition of major bleeding in clinical investigations of antihemostatic medicinal products in surgical patients
- 2010
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 8:1, s. 202-204
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Tidskriftsartikel (refereegranskat)abstract
- The definition of major bleeding varies between studies on surgical patients, particularly regarding the criteria for surgical wound-related bleeding. This diversity contributes to the difficulties in comparing data between trials. The Scientific and Standardization Committee (SSC), through its subcommittee on Control of Anticoagulation, of the International Society on Thrombosis and Haemostasis has previously published a recommendation for a harmonized definition of major bleeding in non-surgical studies. That definition has been adopted by the European Medicines Agency and is currently used in several non-surgical trials. A preliminary proposal for a parallel definition for surgical studies was presented at the 54(th) Annual Meeting of the SSC in Vienna, July 2008. Based on those discussions and further consultations with European and North American surgeons with experience from clinical trials a definition has been developed that should be applicable to all agents that interfere with hemostasis. The definition and the text that follows have been reviewed and approved by relevant co-chairs of the subcommittee and by the Executive Committee of the SSC. The intention is to seek approval of this definition from the regulatory authorities to enhance its incorporation into future clinical trial protocols.
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| 8. |
- Schulman, S, et al.
(författare)
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Response to rebuttal, definition of major bleeding in surgery: an anaesthesiologist's point of view.
- 2010
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Ingår i: Journal of thrombosis and haemostasis. - : Elsevier BV. - 1538-7836 .- 1538-7933. ; 8:6, s. 1443-1444
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Tidskriftsartikel (refereegranskat)abstract
- See also Schulman S, Angeras U, Bergqvist D, Eriksson B, Lassen MR, Fisher W. Definition of major bleeding in clinical investigations of anti-hemostatic medicinal products in surgical patients. J Thromb Haemost 2010; 8: 202–4; Rosencher N, Zufferey P, Samama C-M. Definition of major bleeding in surgery: an anesthesiologist's point of view: a rebuttal. This issue, pp 1442–3. We read with interest the comments by Rosencher et al. about our definition of major bleeding in surgical patients. The component of our definition that is the focus of this discussion is criterion 5, i.e. the unexpected bleeding with some additional requirements [1]. We are aware that anesthesiologists frequently make use of more detailed calculations of blood loss. Their way of calculating blood loss is certainly more accurate than the criterion of a defined drop in hemoglobin or the need for 2 or more units of blood transfusion. In theory, such calculations are physiologically relevant for the decision to give a blood transfusion and may, therefore, result in more appropriate and hopefully reduced use of blood transfusions as indicated in the OSTHEO study [2]. However, criteria that are based on blood loss calculations have never been used for recognition of major bleeding. One of us (B.E.) evaluated blood loss, transfusion requirement and delta-hemoglobin in phase II studies on desirudin and melagatran. These variables had a lower sensitivity than the surgeon’s subjective view of ’serious bleeding‘ or ’overt bleeding‘ in the dose response of these anticoagulants. There is thus insufficient evidence to propose that calculated blood loss could be superior to differentiate between drug-induced and surgical bleeding. The European Medicines Agency (EMEA) guideline from 2007 (printed 2008) [3] is the one we want to improve and correct with our set of definitions. That guideline primarily uses the criteria defined by ISTH for medical patients. As additional support, calculated blood loss is in the middle of a long list of examples. In our work with the ISTH guidelines, we have tried to consider the important factors for both the surgeon and the patient. At the same time, it was necessary to create a definition that could not only be applied to most types of surgery represented in clinical trials using new anticoagulants, but also to keep it comparatively simple. The fact that both European and North American orthopedic and general surgeons could agree on these criteria was a big step forward. Although we admit that criterion no. 5 remains partly subjective, we find that the criterion suggested by Rosencher et al., ’all abnormal bleeding notified by the local investigator‘ is highly subjective and susceptible to influence by the knowledge that the patient is taking part in a trial with a new hemostatic agent. In trials, the local investigator is frequently not the operating surgeon. Who better than the surgeon present in the operating theatre, can assess what is unexpected (for the circumstances) and what represents prolonged bleeding? Some of us have been members of multiple committees for central event-adjudication for these studies, and we have often found that advice from the surgeon is the most helpful for gauging the seriousness of the wound bleeding and any likely association to study drug rather than to other bleeding risk factors. We, therefore, feel that the ISTH guideline for surgical patients is workable, in line with standard clinical practice and acceptable in any multicenter trial. A completely scientific and evidence-based process to develop ideal guidelines should select different strict criteria and prospectively evaluate their sensitivity for clinically important outcomes, including long-term function.
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| 9. |
- Hillarp, Andreas, et al.
(författare)
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Effects of the oral, direct factor Xa inhibitor apixaban on routine coagulation assays and anti-FXa assays
- 2014
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 12:9, s. 1545-1553
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionApixaban is an oral direct factorXa inhibitor developed for the prophylaxis and treatment of thromboembolic disorders. Laboratory monitoring is not necessary, but the effects on common coagulation reagents and assays constitute clinically valuable information. ObjectivesTo investigate the effects of apixaban on commonly used coagulation methods, and to evaluate anti-FXa assays for specific determination of the drug concentration. Materials and MethodsApixaban was added to plasma from healthy subjects in the concentration range 0-1000gL(-1), and analyses were performed with different reagents for activated partial thromboplastin time (APTT), prothrombin time (PT), antithrombin, proteinC, and proteinS. A lupus anticoagulant assay and an APTT assay with varying phospholipid concentrations were used to study the phospholipid dependence. ResultsIn general, apixaban showed fewer effects invitro than have been shown for rivaroxaban, another direct FXa inhibitor. The concentration needed to double the APTT varied between 2200 and 4700gL(-1), and the concentration needed to double the PT varied between 700 and 3900gL(-1). The effects on antithrombin, proteinC and proteinS assays were dependent on the type of reagent. Apixaban did not cause false-positive lupus anticoagulant results. Chromogenic anti-FXa assays showed linear dose-response curves with apixaban. ConclusionsTherapeutic concentrations of apixaban variably affect different assay groups, and even different reagents within an assay group. The effects were much smaller than with rivaroxaban. The use of APTT and/or PT assays to screen the anticoagulant activity of apixaban cannot be recommended. A chromogenic anti-FXa assay can be used for reliable measurements of apixaban concentration.
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| 10. |
- Josefsson, Emma C., et al.
(författare)
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Consensus report on markers to distinguish procoagulant platelets from apoptotic platelets : communication from the Scientific and Standardization Committee of the ISTH
- 2023
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Ingår i: Journal of Thrombosis and Haemostasis. - : John Wiley & Sons. - 1538-7933 .- 1538-7836. ; 21:8, s. 2291-2299
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Procoagulant platelets are a subpopulation of highly activated platelets that promote coagulation through surface-exposed, negatively charged phospholipids, especially phosphatidylserine (PS). Procoagulant platelets are important for clot stabilization during haemostasis and an increased number of these platelets is associated with thrombotic risk. There is a need for harmonisation in this area since many of the markers and methods used to assess procoagulant platelets are not specific when used in isolation but are also associated with platelet apoptosis.OBJECTIVE: We initiated this project to identify a minimum set of markers and/or methods that can detect and distinguish procoagulant platelets from apoptotic platelets.METHODS AND RESULTS: The study design involved a primary panel with twenty-seven international experts participating in an online survey and moderated virtual focus group meetings. Primary and secondary panel members were then invited to provide input on themes and statements generated from the focus groups. This led to a recommendation to use flow cytometry and a combination of the following three surface markers to differentiate procoagulant from apoptotic platelets: P-selectin (CD62P), PS (recognized by annexin V), and a platelet-specific receptor GPIX (CD42a) or αIIb integrin (CD41, GPIIb).CONCLUSION: Procoagulant platelets are expected to be positive for all three markers, while apoptotic platelets will be positive for annexin V and the platelet specific surface receptor(s) but negative for P-selectin.
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