| 1. |
- Abshire, T, et al.
(författare)
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Prophylaxis Escalation in Severe von Willebrand Disease: A Prospective Study from the von Willebrand Disease Prophylaxis Network.
- 2015
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 13:9, s. 1585-1589
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Tidskriftsartikel (refereegranskat)abstract
- Treatment of mucosal bleeding (epistaxis, gastrointestinal and menorrhagia) and joint bleeding remains problematic in clinically severe von Willebrand Disease (VWD). Patients are often unresponsive to treatment (e.g. desmopressin or antifibrinolytic therapy) and may require von Willebrand (VW) factor replacement therapy. There are little data on the use of prophylaxis in VWD and none applied in a prospective, treatment escalation design.
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| 3. |
- Bowyer, A. E., et al.
(författare)
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Measuring factor IX activity of nonacog beta pegol with commercially available one-stage clotting and chromogenic assay kits : A two-center study
- 2016
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 14:7, s. 1428-1435
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Tidskriftsartikel (refereegranskat)abstract
- Essentials: Validated assays are required to precisely measure factor IX (FIX) activity in FIX products. N9-GP and two other FIX products were assessed in various coagulation assay systems at two sites. Large variations in FIX activity measurements were observed for N9-GP using some assays. One-stage and chromogenic assays accurately measuring FIX activity for N9-GP were identified. Summary: Background: Measurement of factor IX activity (FIX:C) with activated partial thromboplastin time-based one-stage clotting assays is associated with a large degree of interlaboratory variation in samples containing glycoPEGylated recombinant FIX (rFIX), i.e. nonacog beta pegol (N9-GP). Validation and qualification of specific assays and conditions are necessary for the accurate assessment of FIX:C in samples containing N9-GP. Objectives: To assess the accuracy of various one-stage clotting and chromogenic assays for measuring FIX:C in samples containing N9-GP as compared with samples containing rFIX or plasma-derived FIX (pdFIX) across two laboratory sites. Methods: FIX:C, in severe hemophilia B plasma spiked with a range of concentrations (from very low, i.e. 0.03 IU mL-1, to high, i.e. 0.90 IU mL-1) of N9-GP, rFIX (BeneFIX), and pdFIX (Mononine), was determined at two laboratory sites with 10 commercially available one-stage clotting assays and two chromogenic FIX:C assays. Assays were performed with a plasma calibrator and different analyzers. Results: A high degree of variation in FIX:C measurement was observed for one-stage clotting assays for N9-GP as compared with rFIX or pdFIX. Acceptable N9-GP recovery was observed in the low-concentration to high-concentration samples tested with one-stage clotting assays using SynthAFax or DG Synth, or with chromogenic FIX:C assays. Similar patterns of FIX:C measurement were observed at both laboratory sites, with minor differences probably being attributable to the use of different analyzers. Conclusions: These results suggest that, of the reagents tested, FIX:C in N9-GP-containing plasma samples can be most accurately measured with one-stage clotting assays using SynthAFax or DG Synth, or with chromogenic FIX:C assays.
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| 4. |
- Brekkan, Ari, et al.
(författare)
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Population Pharmacokinetics of Plasma-Derived Factor IX : Procedures for Dose Individualization
- 2016
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 14:4, s. 724-732
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Tidskriftsartikel (refereegranskat)abstract
- Background: Population pharmacokinetic (POPPK) models describing factor IX (FIX) activity levels in plasma, in combination with individual FIX measurements, may be used to individualize dosing in the treatment of hemophilia B. Objectives: The aim was to reevaluate a previously developed POPPK model for FIX activity and to explore the number and timing of FIX samples required in pharmacokinetic (PK) dose individualization. Methods: The POPPK model was reevaluated using an extended data set. Several sampling schedules, varying with respect to the timing and number of samples, were evaluated in a simulation study with relative dose errors compared between schedules. The performance of individually calculated doses was compared with commonly prescribed FIX doses with respect to the number of patients with a trough FIX activity > 0.01 U mL(-1). Results and conclusions: A three-compartment PK model best described the FIX activity levels. The number and timing of samples greatly influenced imprecision in dose prediction. Schedules with single samples taken on both day 2 and day 3 were identified as being convenient schedules with an acceptable performance level. Individually calculated doses performed better with respect to patient target attainment than a fixed 40 U kg(-1) dose regardless of how many samples were available to calculate individual doses. The results of this study suggest that PK dose tailoring with limited sampling may be applicable for plasma-derived FIX products.
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| 6. |
- Bruzelius, M., et al.
(författare)
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Predicting venous thrombosis in women using a combination of genetic markers and clinical risk factors
- 2015
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 13:2, s. 219-227
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundFamily history of venous thromboembolism (VTE) has been suggested to be more useful in risk assessment than thrombophilia testing. ObjectivesWe investigated established genetic susceptibility variants for association with VTE and evaluated a genetic risk score in isolation and combined with known trigger factors, including family history of VTE. Patients/MethodA total of 18 single nucleotide polymorphisms (SNPs) selected from the literature were genotyped in 2835 women participating in a Swedish nationwide case-control study (the ThromboEmbolism Hormone Study [TEHS]). Association with VTE was assessed by odds ratios (ORs) with 95% confidence interval (CI) using logistic regression. Clinical and genetic predictors that contributed significantly to the fit of the logistic regression model were included in the prediction models. SNP-SNP interactions were investigated and incorporated into the models if found significant. Risk scores were evaluated by calculating the area under the receiver-operating characteristics curve (AUC). ResultsSeven SNPs (F5 rs6025, F2 rs1799963, ABO rs514659, FGG rs2066865, F11 rs2289252, PROC rs1799810 and KNG1 rs710446) with four SNP-SNP interactions contributed to the genetic risk score for VTE, with an AUC of 0.66 (95% CI, 0.64-0.68). After adding clinical risk factors, which included family history of VTE, the AUC reached 0.84 (95% CI, 0.82-0.85). The goodness of fit of the genetic and combined scores improved when significant SNP-SNP interaction terms were included. ConclusionPrediction of VTE in high-risk individuals was more accurate when a combination of clinical and genetic predictors with SNP-SNP interactions was included in a risk score.
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| 10. |
- Dahlbäck, Björn, et al.
(författare)
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New functional test for the TFPIα cofactor activity of Protein S working in synergy with FV-Short
- 2019
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 17:4, s. 585-595
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Tidskriftsartikel (refereegranskat)abstract
- Essentials Protein S and FV-Short are synergistic cofactors to Tissue Factor Pathway Inhibitor α (TFPIα). An assay for the TFPIα synergistic cofactor activity of protein S with FV-Short was developed. The assay was specific for the synergistic TFPIα-cofactor activity of free protein S. Protein S deficient individuals with known mutations were correctly distinguished from controls. Summary: Background Protein S is an anticoagulant cofactor to both activated protein C and tissue factor pathway inhibitor (TFPIα). The TFPIα-cofactor activity of protein S is stimulated by a short isoform of factor V (FV-Short), the two proteins functioning in synergy. Objective Using the synergistic TFPIα-cofactor activity between protein S and FV-Short to develop a functional test for plasma protein S. Patients/Methods TFPIα-mediated inhibition of FXa in the presence of FV-Short, protein S and negatively charged phospholipid vesicles was monitored in time by synthetic substrate S2765. TFPIα, FXa and FV-Short were purified proteins, whereas diluted plasma from protein S deficient patients or controls were used as source for protein S. Results The assay was specific for free protein S demonstrating good correlation to free protein S plasma levels (r = 0.92) with a Y-axis intercept of −5%. Correlation to concentrations of total protein S (free and C4BPβ+-bound) was lower (r = 0.88) and the Y-axis intercept was +46%, which is consistent with the specificity for free protein S. The test distinguished protein S-deficient individuals from 6 families with known ProS1 mutations from family members having no mutation. Protein S levels of warfarin-treated protein S deficient cases were lower than protein S in cases treated with warfarin for other causes. Conclusions We describe a new assay measuring the TFPIα-cofactor activity of plasma protein S. The test identifies type I/III protein S deficiencies and will be a useful tool to detect type II protein S deficiency having defective TFPIα-cofactor activity.
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