Role of enhanced half-life factor VIII and IX in the treatment of haemophilia

2015 ◽  
Vol 169 (6) ◽  
pp. 768-776 ◽  
Author(s):  
Ali J. Mahdi ◽  
Samya G. Obaji ◽  
Peter W. Collins
Keyword(s):  
Factor Viii ◽  
Half Life ◽  
Viii And Ix ◽  
Life Factor

The Australian experience with switching to extended half‐life factor VIII and IX concentrates: On behalf of the Australian Haemophilia Centre Directors' Organisation

Haemophilia ◽  
2020 ◽  
Vol 26 (3) ◽  
pp. 529-535 ◽  
Author(s):  
Yvonne Brennan ◽  
Sumit Parikh ◽  
Simon McRae ◽  
Huyen Tran
Keyword(s):  
Factor Viii ◽  
Half Life ◽  
Viii And Ix ◽  
Australian Experience ◽  
Life Factor

Prophylaxis for Hemophilia in the Era of Extended Half-Life Factor VIII/Factor IX Products

2016 ◽  
Vol 42 (05) ◽  
pp. 518-525 ◽  
Author(s):  
Erik Berntorp ◽  
Nadine Andersson
Keyword(s):  
Half Life ◽  
Safety Margin ◽  
Clinical Development ◽  
Factor Ix ◽  
Life Extension ◽  
Bleeding Events ◽  
Treatment And Prevention ◽  
Trough Levels ◽  
Life Factor

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.

Continuous infusion of extended half-life factor VIII (efmoroctocog alpha) for surgery in severe haemophilia A

Haemophilia ◽  
2018 ◽  
Vol 24 (4) ◽  
pp. e280-e283
Author(s):  
I. C. L. Kremer Hovinga ◽  
R. E. G. Schutgens ◽  
P. R. van der Valk ◽  
L. F. D. van Vulpen ◽  
E. P. Mauser-Bunschoten ◽  
...  
Keyword(s):  
Factor Viii ◽  
Continuous Infusion ◽  
Half Life ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Life Factor

Benefits and limitations of extended plasma half-life factor VIII products in hemophilia A

2020 ◽  
Vol 29 (3) ◽  
pp. 303-309 ◽  
Author(s):  
Pier Mannuccio Mannucci
Keyword(s):  
Factor Viii ◽  
Half Life ◽  
Hemophilia A ◽  
Extended Plasma ◽  
Plasma Half Life ◽  
Life Factor

scholarly journals Extended Half-Life Factor VIII/Factor IX Products: Assay Discrepancies and Implications for Hemophilia Management

2020 ◽  
Vol 40 (S 01) ◽  
pp. S15-S20
Author(s):  
Jens Müller ◽  
Georg Goldmann ◽  
Natascha Marquardt ◽  
Bernd Pötzsch ◽  
Johannes Oldenburg
Keyword(s):  
Factor Viii ◽  
Half Life ◽  
In Vitro Study ◽  
Factor Ix ◽  
University Hospital ◽  
Spiked Plasma ◽  
Structural Differences ◽  
The University ◽  
Life Factor

AbstractDue to structural differences between extended half-life (EHL) factor VIII (FVIII) or FIX products and equivalent plasma wild-type molecules used for assay calibration, reagent-dependent discrepancies during monitoring of FVIII- and FIX-replacement therapies with EHL products have been described. To assess the performance of available one-stage clotting and chromogenic substrate assays on the Siemens Atellica COAG 360 analyzer, an in vitro study using spiked plasma samples was performed. The described results confirm previously described findings and allowed allocation of each EHL product to an appropriate assay. In addition, corresponding EHL product–specific analytes were defined within the order entry system of the University Hospital Bonn. The requirement of product-specific FVIII and FIX assays complicates patient monitoring and demonstrates the need for both continuous education and communication between treating physicians and the coagulation laboratory.

scholarly journals Monitoring standard and extended half‐life products in hemophilia: Assay discrepancies for factor VIII and IX in pre‐ and postinfusion samples

2020 ◽  
Vol 4 (7) ◽  
pp. 1114-1120
Author(s):  
Cecilia Augustsson ◽  
Eva Norström ◽  
Nadine Gretenkort Andersson ◽  
Eva Zetterberg ◽  
Jan Astermark ◽  
...  
Keyword(s):  
Factor Viii ◽  
Half Life ◽  
Viii And Ix

Extended half-life factor VIII for immune tolerance induction in haemophilia

Haemophilia ◽  
2016 ◽  
Vol 22 (6) ◽  
pp. e552-e554 ◽  
Author(s):  
L. M. Malec ◽  
J. Journeycake ◽  
M. V. Ragni
Keyword(s):  
Factor Viii ◽  
Immune Tolerance ◽  
Half Life ◽  
Tolerance Induction ◽  
Immune Tolerance Induction ◽  
Life Factor

scholarly journals Thrombelastography (TEG) and Thrombin Generation Assay (TGA) in Severe Hemophilia Following Factor Replacement Therapy

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4666-4666 ◽  
Author(s):  
Tania T. Sarker ◽  
Donald Brophy ◽  
Meera B. Chitlur
Keyword(s):  
Factor Viii ◽  
Half Life ◽  
Thrombin Generation ◽  
Factor Activity ◽  
Treatment Frequency ◽  
Thrombin Generation Assay ◽  
Fviii Activity ◽  
The Mean ◽  
Life Factor ◽  
Time Point

Abstract Background: Monitoring therapy in hemophilia is a major challenge. Measurement of factor levels is time consuming and not available in time to make clinical decisions. With the introduction of extended half-life factor products, determination of treatment frequency becomes important. Global hemostatic assays such as Thrombelastography (TEG) and Thrombin Generation Assay (TGA) may improve monitoring. Focused toward individualizing therapy, these assays may help determine treatment frequency based not just on Factor VIII PK (pharmacokinetic), but also on total hemostatic potential. Objective: To determine the correlation between TGA and TEG parameters, and Factor activity and half-life (t1/2). Design/Methods: With IRB approval and participant consent baseline FVIII activity was obtained at enrollment, 15minutes, 1, 4, 8, 24 and 48 hours post factor replacement in patients who had not received replacement factor for a minimum of 72 hours and were not bleeding. FVIII:C, TEG, and TGA at each time point were measured. Non-compartmental PK analysis was performed on each individual patient profile to measure Factor VIII terminal half-life (t 1/2), mean normalized factor clearance rate and volume of distribution at steady-state (Vdss). Pearson correlation statistical analyses on other variables were performed using JMP ¨ Pro version 12.0.1 (SAS Institute, Cary, NC, USA) Results: 27 patients with hemophilia have enrolled, with a median age of 14 years (range: 2-24 years). 9 patients were eliminated from analysis because of a diagnosis of inhibitors (n=1), factor activity >1% (n=4), inadequate sample collection (n=2), patient on episodic factor replacement (n=1), and inaccurate TGA time point (n=1). The mean Factor level prior to factor administration, after elimination of the subjects (n=18) was 0.4%. As expected, our results indicate a rise in ETP and Factor activity following factor replacement, peaking at 15 minutes post infusion. The mean normalized factor clearance rate was 3.3 ± 1.2ml/h/kg. The Vdss was 2.3 ± 1 L and Factor VIII t½ was 11.5 ± 3 hours. There were strong correlations between ETP and FVIII:C (R2=0.65; p<0.0001), Peak and FVIII:C (R2=0.6; p<0.0001), R Time and Factor VIII:C (R2=0.71; p<0.0001), Peak and R Time (R2=0.59; p<0.0001), ETP and R Time (R2=0.51; p<0.0001) as shown in table 1. Table 1. Correlation data on Factor VIII:C with TGA & TEG Parameters; and TGA parameters with TEG R time R2 P-value TGA Parameters (Peak & ETP) ETP and Factor VIII:C 0.65 p<0.0001 Peak and Factor VIII:C 0.60 p<0.0001 TEG Parameter (R Time) R Time and Factor VIII:C 0.71 p<0.0001 TEG and TGA Parameters Peak and R Time 0.59 p<0.0001 ETP and R Time 0.51 p<0.0001 Conclusions: Global hemostatic assays are less expensive than traditional PK testing and are available at the time of care decisions. Results of global coagulation assays (TEG and TGA) correlated closely with FVIII activities. Global assays may predict breakthrough bleeding independent of factor levels, representing an improvement in monitoring over traditional PK. With the emergence of the bioengineered extended half-life factor products, there is a renewed interest in pharmacokinetic analysis and individualization of therapy. Assays like TEG provide the opportunity to receive feed back in real time that corresponds to FVIII activity, and enable us to make treatment decisions rapidly for each individual patient. Since these assays measure more than just the factor activity, the parameters such as ETP on TGA may be more prognostic of bleeding tendency, as has been shown previously. Pharmacokinetic and pharmacodynamics analysis of this data is ongoing. Our small sample size precludes us from making global predictions. Larger multi center trials would assist in confirming these findings. Disclosures No relevant conflicts of interest to declare.

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