| 1. |
- Andersson Shams Hakimi, Caroline, et al.
(författare)
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Effects of fibrinogen and platelet supplementation on clot formation and platelet aggregation in blood samples from cardiac surgery patients.
- 2014
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Ingår i: Thrombosis research. - : Elsevier BV. - 1879-2472 .- 0049-3848. ; 134:4, s. 895-900
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Tidskriftsartikel (refereegranskat)abstract
- Bleeding after cardiac surgery may be caused by surgical factors, impaired haemostasis, or a combination of both. Transfusion of blood products is used to improve haemostasis, but little is known about what combination is optimal. We hypothesized that addition of both fibrinogen and platelets to blood samples from cardiac surgery patients would improve clot formation and platelet aggregation to a greater extent than if the components were added separately.
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| 2. |
- 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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| 3. |
- Hillarp, Andreas, et al.
(författare)
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Effects of the oral, direct factor Xa inhibitor edoxaban on routine coagulation assays, lupus anticoagulant and anti-Xa assays
- 2018
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 78:7-8, s. 575-583
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Tidskriftsartikel (refereegranskat)abstract
- Edoxaban is an oral direct factor Xa inhibitor for prophylaxis and treatment of thromboembolic disorders. The effects on common coagulation assays are clinically valuable information and in certain clinical situations a quick assessment of the anticoagulant is wanted. Our aim was to investigate the effect of edoxaban on routine coagulation methods and evaluate anti-Xa assays, commonly used for other direct factor Xa inhibitors, for estimation of the drug concentration. Edoxaban was spiked to plasma samples from healthy subjects in the concentration range 0-742 mu g/L and analyzed using different reagents for activated partial thromboplastin time (APTT) and prothrombin time (PT). Assays for antithrombin, activated protein C resistance, lupus anticoagulant (LA) and chromogenic anti-Xa assays were also included. Edoxaban displayed similar effects in vitro to other oral direct Xa inhibitors. The concentration needed to double the coagulation time varied between assays and reagents; 539-758 mu g/L for the APTT and between 329 and 2505 mu g/L for the PT. Edoxaban gave false high antithrombin activities in assays based on Xa-inhibition. Two integrated assays for LA, both based on activation with dilute Russell's viper venom, displayed different results. Chromogenic anti-Xa assays displayed linear dose-response curves with edoxaban up to approximately 500 mu g/L. In conclusion, therapeutic concentrations of edoxaban variably affect different coagulation assays, and even different reagents within an assay group. In comparison with other oral Xa-inhibitors, the in vitro effects of edoxaban were more similar to rivaroxaban than apixaban. For measurement of edoxaban concentration in plasma, it is possible to use the chromogenic anti-Xa assays.
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| 4. |
- 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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| 5. |
- Lindahl, Tomas, et al.
(författare)
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Effects of the oral, direct thrombin inhibitor dabigatran on five common coagulation assays
- 2011
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Ingår i: Thrombosis and Haemostasis. - : F K Schattauer Verlagsgesellschaft MBH. - 0340-6245 .- 2567-689X. ; 105:2, s. 371-378
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Tidskriftsartikel (refereegranskat)abstract
- Dabigatran is an oral, reversible thrombin inhibitor that has shown promising results in large clinical trials. Laboratory monitoring is not needed but the effects on common coagulation assays are incompletely known. Dabigatran was added to plasma from healthy subjects in the concentration range 0-1,000 μg/l and analysed using several reagents for activated thromboplastin time (APTT), prothrombin time (PT), fibrinogen, antithrombin, and activated protein C resistance. Typical trough concentrations are about 50 μg/l, peak concentrations 100-300 μg/l. At 100 μg/l all APTT-results were prolonged. The concentration required to double APTT ranged between 227 and 286 μg/l, the responses for all five reagents were similar. PT-reagents were much less affected with almost no samples above INR 1.2 at 100 μg/l. The effect was sample dilution dependent with PT Quick type more sensitive than PT Owren type methods. If a patient on dabigatran has prolonged APTT, >90 seconds, and Quick PT INR>2 or Owren PT INR>1.5 over-dosing or accumulation of dabigatran should be considered. Two of four fibrinogen reagents underestimated the fibrinogen concentration considerably at expected peak concentration. Methods based on inhibition of thrombin over-estimated the antithrombin concentration, but not Xa-based. The APC-resistance methods over-estimated the APC-ratio, which may lead to miss-classification of factor V Leiden patients as being normal. Different coagulation assays, and even different reagents within an assay group, display variable effects at therapeutic concentrations of dabigatran. Some of these assay variations are of clinical importance, thus knowledge is needed for a correct interpretation of results.
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| 6. |
- Radulovic, Vladimir, 1969, et al.
(författare)
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Comparable effect of recombinant and plasma-derived human fibrinogen concentrate on ex vivo clot formation after cardiac surgery.
- 2012
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Ingår i: Journal of thrombosis and haemostasis : JTH. - : Elsevier BV. - 1538-7836. ; 10:6
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Tidskriftsartikel (refereegranskat)abstract
- There is a renewed interest in fibrinogen today and its importance for hemostasis [1,2]. The use of fibrinogen concentrate has been associated with improved outcome compared to transfusion of plasma [2] and perioperative supplementation with fibrinogen has reduced bleeding and transfusion requirements [3-5]. All available fibrinogen concentrates are today derived from human plasma but there are development projects aiming to produce recombinant human fibrinogen. The present study compares for the first time the functional properties of recombinant fibrinogen derived from a human cell line with fibrinogen derived from human plasma. © 2012 International Society on Thrombosis and Haemostasis.
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