The use of a chromogenic assay for factor VIII in patients with factor VIII inhibitors or von Willebrand's disease

Hutton, R A; Yamaga, Ayaka; Matthews, K.B.; Woodhams, Barry

doi:10.1016/0049-3848(91)90281-z

Cited by 6 publications

(3 citation statements)

References 2 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Actin FSL was the optimum OSA reagent, with the least variability across the range. In contrast, a clinically important overestimation was observed with Actin FS across all three activity levels and some underestimation with SynthASil; similar findings have been reported for other FVIII replacement therapies 10,31 . The observed differences in OSA and CSA performance may be at least partly attributed to variations in assay reagents, incubation times, and thrombin concentration impacting the activation kinetics of efanesoctocog alfa 24 …”

Section: Discussionsupporting

confidence: 71%

A global comparative field study to evaluate the factor VIII activity of efanesoctocog alfa by one‐stage clotting and chromogenic substrate assays at clinical haemostasis laboratories

Pipe,

Sadeghi‐Khomami,

Konkle

et al. 2023

Haemophilia

View full text Add to dashboard Cite

IntroductionStructural and chemical modifications of factor VIII (FVIII) products may influence their behaviour in FVIII activity assays. Hence, it is important to assess the performance of FVIII products in these assays. Efanesoctocog alfa is a new class of FVIII replacement therapy designed to provide both high sustained factor activity levels and prolonged plasma half‐life.AimEvaluate the accuracy of measuring efanesoctocog alfa FVIII activity in one‐stage clotting assays (OSAs) and chromogenic substrate assays (CSAs).MethodsHuman plasma with no detectable FVIII activity was spiked with efanesoctocog alfa or a full‐length recombinant FVIII product comparator, octocog alfa, at nominal concentrations of 0.80 IU/mL, 0.20 IU/mL, or 0.05 IU/mL, based on labelled potency. Clinical haemostasis laboratories (N = 35) tested blinded samples using in‐house assays. Data from 51 OSAs (14 activated partial thromboplastin time [aPTT] reagents) and 42 CSAs (eight kits) were analyzed.ResultsEfanesoctocog alfa activity was reliably (±25% of nominal activity) measured across all concentrations using OSAs with Actin FSL and multiple other aPTT reagents. Under‐ and overestimation of FVIII activity occurred with some reagents. No specific trend was observed for any class of aPTT activators. A two‐ to three‐fold overestimation was consistently observed using CSAs and the OSA with Actin FS as the aPTT reagent across evaluated concentrations.ConclusionUnder‐ or overestimation occurred with some specific OSAs and most CSAs, which has been previously observed with other modified FVIII replacement products. Efanesoctocog alfa FVIII activity was measured with acceptable accuracy and reliability using several OSA methods and commercial plasma standards.

show abstract

Section: Discussionsupporting

confidence: 71%

A global comparative field study to evaluate the factor VIII activity of efanesoctocog alfa by one‐stage clotting and chromogenic substrate assays at clinical haemostasis laboratories

Pipe,

Sadeghi‐Khomami,

Konkle

et al. 2023

Haemophilia

View full text Add to dashboard Cite

show abstract

“…Chromogenic assays are appealing for FVIII inhibitor detection, because they have been shown to be insensitive to heparin, lupus anticoagulants and other non‐specific inhibitors of coagulation . Their use in the Bethesda assay has been reported previously . Chromogenic and clot‐based assays differ in several key characteristics.…”

Section: Discussionmentioning

confidence: 99%

Comparison of clot‐based, chromogenic and fluorescence assays for measurement of factor VIII inhibitors in the US Hemophilia Inhibitor Research Study

Miller

Rice

Boylan

et al. 2013

Journal of Thrombosis and Haemostasis

112

View full text Add to dashboard Cite

Summary Background Detection and validation of inhibitors (antibodies) to hemophilia treatment products are important for clinical care, evaluation of product safety, and assessment of population trends. Methods Centralized monitoring for factor VIII (FVIII) inhibitors was conducted for patients in the Hemophilia Inhibitor Research Study using a previously reported modified Nijmegen-Bethesda clotting assay (NBA), a chromogenic Bethesda assay (CBA), and a novel fluorescence immunoassay (FLI). Results NBA and CBA were performed on 1005 specimens and FLI on 272 specimens. CBA was negative on 880/883 specimens (99.7%) with Nijmegen-Bethesda units (NBU)<0.5 and positive on 42/42 specimens (100%) with NBU≥2.0 and 43/80 specimens (53.8%) with NBU 0.5–1.9. Among specimens with positive NBA and negative CBA, 58.1% were FLI-negative, 12.9% had evidence of lupus anticoagulant, and 35.5% had non-time-dependent inhibition. CBA and FLI were positive on 72.4% and 100% of 1.0–1.9 NBU specimens and 43.1% and 50.0% of 0.5–0.9 NBU specimens. FLI detected antibodies in 98.0% of CBA-positive and 81.6% of NBA-positive specimens (P=0.004). Among 21 new inhibitors detected by NBA, 5 (23.8%) with 0.7–1.3 NBU did not react in CBA or FLI. Among previously positive patients with 0.5–1.9 NBU, 7/25 (28%) were not CBA or FLI positive. FLI was positive on 36/169 NBU-negative specimens (21.3%). Conclusions FVIII specificity could not be demonstrated by CBA or FLI for 26% of inhibitors of 0.5–1.9 NBU; such results must be interpreted with caution. Low titer inhibitors detected in clot-based assays should always be repeated, with consideration given to evaluating their reactivity with FVIII using more specific assays.

show abstract

“…Forh aemophilia Ad iagnosis,t here are severalchromogenic FVIII methods butso fartheyare not commonly used in the coagulation laboratoryeventhough FVIII inhibitors also maybedetermined (30,46). This is in contrast to FVIII potencyassignments of FVIII concentrates, for whichp urpose the chromogenic method is recommended by ISTH (5) anditisasw ellthe European Pharmacopoeian referencemethod.…”

Section: Bleedingmentioning

confidence: 99%

Chromogenic methods in coagulation diagnostics

Rosén¹

2005

Hamostaseologie

View full text Add to dashboard Cite

ZusammenfassungChromogene Peptidsubstrate wurden vor mehr als 30 Jahren entwickelt. Obgleich sich die Anwendung chromogener Substratmethoden bei der Gerinnungs- und Fibrinolyse-Diagnostik nicht so rasch etablierte, wie anfangs angenommen, haben sich diese Methoden inzwischen zur Bestimmung verschiedener Analyte (z. B. Antithrombin, F.VIII, Protein C, Plasminogen, Plasmininhibitor, Heparine und Pentasaccharide) einen festen Platz erobert. Das Aufkommen direkter Thrombin- und Faktor-Xa-Inhibitoren veranlasste zur Entwicklung neuer, spezifischer chromogener Methoden. Diese können Eingang in die Routineanwendung finden, wenn sich die neuen Wirkstoffe als valider Ersatz für Kumarinderivate erweisen. Auch für andere Analyte wurde eine Vielzahl chromogener Untersuchungsmethoden entwickelt. Das aktuelle Interesse an globalen chromogenen Methoden für die Thrombinbildung und den Protein-C-Weg kann sich als klinisch relevant herausstellen und damit Eingang in die Routineanwendung finden.

show abstract

The use of a chromogenic assay for factor VIII in patients with factor VIII inhibitors or von Willebrand's disease

Cited by 6 publications

References 2 publications

A global comparative field study to evaluate the factor VIII activity of efanesoctocog alfa by one‐stage clotting and chromogenic substrate assays at clinical haemostasis laboratories

A global comparative field study to evaluate the factor VIII activity of efanesoctocog alfa by one‐stage clotting and chromogenic substrate assays at clinical haemostasis laboratories

Comparison of clot‐based, chromogenic and fluorescence assays for measurement of factor VIII inhibitors in the US Hemophilia Inhibitor Research Study

Chromogenic methods in coagulation diagnostics

Contact Info

Product

Resources

About