Limited sampling strategies for accurate determination of extended half‐life factor VIII pharmacokinetics in severe haemophilia A patients

Haemophilia ◽  
2021 ◽  
Author(s):  
Alanna McEneny‐King ◽  
Pierre Chelle ◽  
Margaret H. Goggans ◽  
Patricia J. Barker ◽  
Timothy W. Jacobs ◽  
...  
Keyword(s):  
Factor Viii ◽  
Half Life ◽  
Accurate Determination ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Sampling Strategies ◽  
Limited Sampling ◽  
Life Factor

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

scholarly journals Safety and efficacy of BAY 94–9027, an extended‐half‐life factor VIII, during minor surgical procedures in patients with severe haemophilia A

Haemophilia ◽  
2021 ◽  
Author(s):  
Elena Santagostino ◽  
Shadan Lalezari ◽  
Mark T. Reding ◽  
Jonathan Ducore ◽  
Heng Joo Ng ◽  
...  
Keyword(s):  
Factor Viii ◽  
Surgical Procedures ◽  
Half Life ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Safety And Efficacy ◽  
Minor Surgical Procedures ◽  
Life Factor

scholarly journals In silico evaluation of limited sampling strategies for individualized dosing of extended half-life factor IX concentrates in hemophilia B patients

2021 ◽  
Author(s):  
T. Preijers ◽  
M. W. F. van Spengler ◽  
K. Meijer ◽  
K. Fijnvandraat ◽  
K. Fischer ◽  
...  
Keyword(s):  
In Silico ◽  
Half Life ◽  
Factor Ix ◽  
Hemophilia B ◽  
Weekly Dose ◽  
Sampling Strategies ◽  
Time Profiles ◽  
Limited Sampling ◽  
Individualized Dosing ◽  
Life Factor

Abstract Purpose Hemophilia B is a bleeding disorder, caused by a factor IX (FIX) deficiency. Recently, FIX concentrates with extended half-life (EHL) have become available. Prophylactic dosing of EHL-FIX concentrates can be optimized by assessment of individual pharmacokinetic (PK) parameters. To determine these parameters, limited sampling strategies (LSSs) may be applied. The study aims to establish adequate LSSs for estimating individual PK parameters of EHL-FIX concentrates using in silico evaluation. Methods Monte Carlo simulations were performed to obtain FIX activity versus time profiles using published population PK models for N9-GP (Refixia), rFIXFc (Alprolix), and rIX-FP (Idelvion). Fourteen LSSs, containing three or four samples taken within 8 days after administration, were formulated. Bayesian analysis was applied to obtain estimates for clearance (CL), half-life (t1/2), time to 1% (Time1%), and calculated weekly dose (Dose1%). Bias and precision of these estimates were assessed to determine which LSS was adequate. Results For all PK parameters of N9-GP, rFIXFc and rIX-FP bias was generally acceptable (range: −5% to 5%). For N9-GP, precision of all parameters for all LSSs was acceptable (< 25%). For rFIXFc, precision was acceptable for CL and Time1%, except for t1/2 (range: 27.1% to 44.7%) and Dose1% (range: 12% to 29.4%). For rIX-FP, all LSSs showed acceptable bias and precision, except for Dose1% using LSS with the last sample taken on day 3 (LSS 6 and 10). Conclusion Best performing LSSs were LSS with samples taken at days 1, 5, 7, and 8 (N9-GP and rFIXFc) and at days 1, 4, 6, and 8 (rIX-FP), respectively.

scholarly journals Case report: successful perioperative management of patients with haemophilia A using an extended half-life factor VIII (Efmoroctocog alfa) during neurosurgical procedures

2021 ◽  
Vol 12 ◽  
pp. 204062072199368
Author(s):  
Florian Kocher ◽  
Andreas Seeber ◽  
Johannes Kerschbaumer ◽  
Stefan Schmidt ◽  
Dominik Wolf ◽  
...  
Keyword(s):  
High Risk ◽  
Factor Viii ◽  
Half Life ◽  
Perioperative Management ◽  
Fatal Outcome ◽  
Bleeding Complications ◽  
Neurosurgical Procedures ◽  
Haemophilia A ◽  
Surgical Interventions ◽  
Life Factor

Patients with haemophilia A (HA) undergoing neurosurgical procedures have a high risk of haemorrhage with potential fatal outcome. Here, we present a successful perioperative haemostatic concept applying an extended half-life factor VIII (EHL FVIII), Efmoroctocog alfa, in two patients with HA undergoing neurosurgery for paramedian right-sided disc herniation (case 1) and astrocytoma (case 2). After adequate EHL FVIII treatment the surgical procedures were performed without any bleeding complications despite the high-risk interventions. Laboratory measurements confirmed stable FVIII levels throughout the hospital stay. We suggest close interdisciplinary collaboration between involved clinicians as mandatory prerequisite for an optimized perioperative management in patients with HA. The presented cases indicate, that the increased stability, safety and fewer injections provide a rationale to use EHL FVIII products in HA patients undergoing surgical interventions with a very high bleeding risk.

scholarly journals Extended half-life pegylated, full-length recombinant factor VIII for prophylaxis in children with severe haemophilia A

Haemophilia ◽  
2016 ◽  
Vol 23 (2) ◽  
pp. 238-246 ◽  
Author(s):  
E. S. Mullins ◽  
O. Stasyshyn ◽  
M. T. Alvarez-Román ◽  
D. Osman ◽  
R. Liesner ◽  
...  
Keyword(s):  
Factor Viii ◽  
Half Life ◽  
Full Length ◽  
Recombinant Factor Viii ◽  
Haemophilia A ◽  
Severe Haemophilia

Management of Haemophilia in Sweden

1976 ◽  
Vol 35 (03) ◽  
pp. 510-521 ◽  
Author(s):  
Inga Marie Nilsson
Keyword(s):  
Factor Viii ◽  
Total Population ◽  
Age Groups ◽  
Factor Ix ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Haemophilia B ◽  
Human Fraction ◽  
Mild Haemophilia

SummaryThe incidence of living haemophiliacs in Sweden (total population 8.1 millions) is about 1:15,000 males and about 1:30,000 of the entire population. The number of haemophiliacs born in Sweden in 5-year periods between 1931-1975 (June) has remained almost unchanged. The total number of haemophilia families in Sweden is 284 (77% haemophilia A, 23% haemophilia B) with altogether 557 (436 with A and 121 with B) living haemophiliacs. Of the haemophilia A patients 40 % have severe, 18 % moderate, and 42 % mild, haemophilia. The distribution of the haemophilia B patients is about the same. Inhibitors have been demonstrated in 8% of the patients with severe haemophilia A and in 10% of those with severe haemophilia B.There are 2 main Haemophilia Centres (Stockholm, Malmo) to which haemophiliacs from the whole of Sweden are admitted for diagnosis, follow-up and treatment for severe bleedings, joint defects and surgery. Minor bleedings are treated at local hospitals in cooperation with the Haemophilia Centres. The concentrates available for treatment in haemophilia A are human fraction 1-0 (AHF-Kabi), cryoprecipitate, Antihaemophilic Factor (Hyland 4) and Kryobulin (Immuno, Wien). AHF-Kabi is the most commonly used preparation. The concentrates available for treatment in haemophilia B are Preconativ (Kabi) and Prothromplex (Immuno). Sufficient amounts of concentrates are available. In Sweden 3.2 million units of factor VIII and 1.0 million units of factor IX are given per year. Treatment is free of charge.Only 5 patients receive domiciliary treatment, but since 1958 we in Sweden have practised prophylactic treatment of boys (4–18 years old) with severe haemophilia A. At about 5-10 days interval they receive AHF in amounts sufficient to raise the AHF level to 40–50%. This regimen has reduced severe haemophilia to moderate. The joint score is identical with that found in moderate haemophilia in the same age groups. For treatment of patients with haemophilia A and haemophilia B complicated by inhibitors we have used a large dose of antigen (factor VIII or factor IX) combined with cyclophosphamide. In most cases this treatment produced satisfactory haemostasis for 5 to 30 days and prevented the secondary antibody rise.

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