Continuous infusion of coagulation factors

Bátorová, Angelika; Martinowitz, Uri

doi:10.1046/j.1365-2516.2002.00635.x

Cited by 53 publications

(55 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…By comparison, FVIII turnover in an adult of 70 kg has been evaluated at about 140 U/h. 24,25 Altogether, these data identify the human lung as a significant source of FVIII. This first identification of extrahepatic cells spontaneously producing FVIII opens the way to the study of the acute and chronic regulation of FVIII production.…”

Section: Resultsmentioning

confidence: 77%

FVIII production by human lung microvascular endothelial cells

Jacquemin

Neyrinck

Hermanns

et al. 2006

Blood

View full text Add to dashboard Cite

show abstract

Section: Resultsmentioning

confidence: 77%

FVIII production by human lung microvascular endothelial cells

Jacquemin

Neyrinck

Hermanns

et al. 2006

Blood

View full text Add to dashboard Cite

show abstract

“…Unfortunately, in all these studies, only the FVIII loading dose was based on an individual PK-profile obtained several days before surgery. [30][31][32][33][34][35] Iterative perioperative FVIII dosing-adjustments after first loading dose could not be performed as there was no population PK model. The perioperative population PK model presented here will now make Bayesian adaptive dosing in this setting possible.…”

Section: Discussionmentioning

confidence: 99%

A population pharmacokinetic model for perioperative dosing of factor VIII in hemophilia A patients

et al. 2016

View full text Add to dashboard Cite

T he role of pharmacokinetic-guided dosing of factor concentrates in hemophilia is currently a subject of debate and focuses on longterm prophylactic treatment. Few data are available on its impact in the perioperative period. In this study, a population pharmacokinetic model for currently registered factor VIII concentrates was developed for severe and moderate adult and pediatric hemophilia A patients (FVIII levels <0.05 IUmL -1 ) undergoing elective, minor or major surgery. Retrospective data were collected on FVIII treatment, including timing and dosing, time point of FVIII sampling and all FVIII plasma concentrations achieved (trough, peak and steady state), brand of concentrate, as well as patients' and surgical characteristics. Population pharmacokinetic modeling was performed using non-linear mixed-effects modeling. Population pharmacokinetic parameters were estimated in 75 adults undergoing 140 surgeries (median age: 48 years; median weight: 80 kg) and 44 children undergoing 58 surgeries (median age: 4.3 years; median weight: 18.5 kg). Pharmacokinetic profiles were best described by a two-compartment model. Typical values for clearance, inter-compartment clearance, central and peripheral volume were 0.15 L/h/68 kg, 0.16 L/h/68 kg, 2.81 L/68 kg and 1.90 L/68 kg. Interpatient variability in clearance and central volume was 37% and 27%. Clearance decreased with increasing age (P<0.01) and increased in cases with blood group O (26%; P<0.01). In addition, a minor decrease in clearance was observed when a major surgical procedure was performed (7%; P<0.01). The developed population model describes the perioperative pharmacokinetics of various FVIII concentrates, allowing individualization of perioperative FVIII therapy for severe and moderate hemophilia A patients by Bayesian adaptive dosing. ABSTRACT

show abstract

“…In this study, the reservoir and tubing were changed every 24 h according to regulatory requirements that are based on theoretical risk of bacterial growth. We therefore performed stability and sterility testing of rFVIII-FS in CADD and WalkMed mini pumps over a duration of at least twice that used in the clinical setting and demonstrated that rFVIII-FS retained ‡75% of its activity [3,14]; thus, we included stability evaluation with these additives. In this extended stability study, rFVIII-FS retained >80% of its initial activity for at least 7 days, with an apparent improvement to rFVIII-FS stability in the presence of UFH or LMWH.…”

Section: Discussionmentioning

confidence: 99%

Stability, efficacy, and safety of continuously infused sucrose‐formulated recombinant factor VIII (rFVIII‐FS) during surgery in patients with severe haemophilia

et al. 2009

Self Cite

View full text Add to dashboard Cite

Bolus injection (BI) of sucrose-formulated recombinant factor VIII (rFVIII-FS) is an approved treatment for haemophilia patients undergoing major surgery. Continuous infusion (CI) during surgery has potential benefits by providing steady administration of replacement factor to the patient, avoiding high peaks and low troughs. We tested the stability of rFVIII-FS under CI conditions and conducted a single-centre, open-label, phase III study to evaluate the efficacy and safety of CI using rFVIII-FS in haemophilia A patients undergoing surgery. Patients received bolus rFVIII-FS to achieve >or=80% FVIII levels 30-60 min presurgery, followed by CI of rFVIII-FS at a rate calculated to maintain haemostatic factor levels until days 8-10 post surgery. The rate of infusion was adjusted according to daily calculations derived from the actual clearance. The stability of rFVIII-FS was found to be appropriate for CI for 7 days under the same conditions as clinical settings. Fourteen patients (mean age 37.8 years) receiving on-demand FVIII treatment without a history of inhibitors underwent 15 surgical procedures including joint replacements, synovectomies, multiple tooth extractions, and cholecystectomy. Bleeding was similar to that observed in non-haemophilia patients undergoing similar operations in the same department. Haemostasis during surgery was considered by the attending surgeons as 'excellent' or 'good' in all cases; study investigators rated all 15 cases as 'excellent' overall. There were no adverse events, including inhibitor formation, related to rFVIII-FS. rFVIII-FS was found to be suitable for use in CI in haemophilia A patients undergoing major surgery.

show abstract

Continuous infusion of coagulation factors

Abstract: continuous infusion, factor VIII, factor IX, haemophilia, recombinant FVIIIa, von willebrand disease.

Cited by 53 publications

References 42 publications

FVIII production by human lung microvascular endothelial cells

FVIII production by human lung microvascular endothelial cells

A population pharmacokinetic model for perioperative dosing of factor VIII in hemophilia A patients

Stability, efficacy, and safety of continuously infused sucrose‐formulated recombinant factor VIII (rFVIII‐FS) during surgery in patients with severe haemophilia

Contact Info

Product

Resources

About