Monitoring of Emicizumab (ACE910): comparison between clotting and chromogenic assay

Türkantoz, Halet; Varnholt, Dirk; Tiede, Andreas

doi:10.1055/s-0039-3400714

Cited by 4 publications

(5 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our data predict that CSA assays would be useful for the exclusion of emicizumab in for example monitoring of anti‐FVIII antibodies in a chromogenic Bethesda assay 11 or in the monitoring of any co‐administered rFVIII or pdFVIII therapy. A recent comparison of mOSA and CSA in plasma spiked with both emicizumab and recombinant human FVIII concluded that falsely elevated emicizumab concentrations were observed due to the additional effect of the rFVIII concentrate 15 . More studies, ideally in patient samples, are required to assess the simultaneous measurement of emicizumab and rFVIII.…”

Section: Discussionmentioning

confidence: 99%

Effects of emicizumab on APTT, one‐stage and chromogenic assays of factor VIII in artificially spiked plasma and in samples from haemophilia A patients with inhibitors

2020

View full text Add to dashboard Cite

Introduction Emicizumab (Hemlibra, Roche‐Chugai) is a recombinant humanized bispecific IgG4 antibody which mimics some of the actions of activated factor VIII (FVIIIa) by binding to factor X (FX) and activated factor IX (FIXa) to activate FX. Aim To evaluate the effect of emicizumab on the APTT, standard one‐stage APTT‐based FVIII activity assay (sOSA) using plasma calibrators, modified OSA (mOSA) using r2 Diagnostics emicizumab specific calibrator and chromogenic FVIII assays. Tests were performed on plasma artificially spiked with emicizumab and from four severe haemophilia A (SHA) patients treated with emicizumab. Method APTT in spiked plasma was performed with 13 APTT reagents and in SHA patients with 5 reagents. OSA in spiked plasma was performed with 9 APTT reagents, 7 APTT reagents were used for OSA in SHA patients and six chromogenic substrate assays (CSA) were performed. Results In SHA, APTTs normalized after the first dose of emicizumab. At weeks 32/36 of treatment, the mean sOSA FVIII:C ranged from 2.47 IU/mL (Synthasil) to greater than 7.00 IU/mL with all other reagents. mOSA ranged from 59.8 µg/mL (Synthasil) to 74.5 µg/mL (APTT SP). Bovine CSA did not recover any FVIII:C activity. Hyphen Biomed human CSA, demonstrated FVIII activity when calibrated against a plasma calibrator. Conclusion The APTT was significantly shortened in the presence of emicizumab. sOSA FVIII:C levels were erroneously high, and it is not recommended that these be performed. Quantification of emicizumab concentration was possible by mOSA. Human CSA was sensitive to emicizumab and surrogate FVIII:C activity could be determined. Bovine CSA were insensitive to emicizumab and could not be used to quantify emicizumab concentration.

show abstract

Section: Discussionmentioning

confidence: 99%

Effects of emicizumab on APTT, one‐stage and chromogenic assays of factor VIII in artificially spiked plasma and in samples from haemophilia A patients with inhibitors

2020

View full text Add to dashboard Cite

show abstract

“…Moreover, an in vitro study based on a modified one‐stage FVIII assay showed increased FVIII activities in plasma spiked with 10 or 50 µg/mL of emicizumab and r‐pFVIII compared with emicizumab alone. This indicates that the modified one‐stage FVIII assay is specific not only for emicizumab 59 . Therefore, the combined use of r‐pFVIII and emicizumab might present the additional advantage of easier and precise monitoring using FVIII assays.…”

Section: Use Of R‐pfviii In Peole With Inherited Hemophilia a And Inhibitors Treated With Emicizumabmentioning

confidence: 99%

“…This indicates that the modified one‐stage FVIII assay is specific not only for emicizumab. 59 Therefore, the combined use of r‐pFVIII and emicizumab might present the additional advantage of easier and precise monitoring using FVIII assays. In addition, it has been shown that FVIII measurement with one‐stage coagulation assays and chromogenic assays show smaller difference with r‐pFVIII compared with pd‐pFVIII.…”

Section: Use Of R‐pfviii In Peole With Inherited Hemophilia a And Inhibitors Treated With Emicizumabmentioning

confidence: 99%

Recombinant porcine factor VIII: Lessons from the past and place in the management of hemophilia A with inhibitors in 2021

Dargaud

Escuriola‐Ettingshausen²

2021

Research and Practice in Thrombosis and Haemostasis

View full text Add to dashboard Cite

The most serious complication of factor VIII (FVIII) replacement therapy is the occurrence of anti‐FVIII alloantibodies that can strongly reduce or abolish the effect of human FVIII products. Bypassing agents to control bleeding episodes are recommended for these patients, but their efficacy is difficult to predict and monitor. FVIII products derived from porcine plasma had an important role in the treatment of hemophilia A for 50 years, from 1954 to 2004. Indeed, porcine FVIII could achieve hemostasis in patients in whom human FVIII products were ineffective. A recombinant porcine FVIII product is now available. This highly purified protein has the same biochemical and hemostatic properties, but much lower risks of infection and toxicity compared with plasma‐derived porcine FVIII. The product is licensed in the United States and Europe for the treatment of acquired hemophilia A. However, this recombinant molecule could also be of clinical interest for people with inherited hemophilia A and inhibitors, particularly for the management of bleeding episodes in people receiving emicizumab as prophylactic treatment in the absence of anti‐porcine FVIII antibodies.

show abstract

“…A second study of plasma artificially spiked with 10 or 50 µg/mL emicizumab reported the use of a modified OS FVIII assay using higher plasma dilution and r 2 emicizumab calibrators to quantify emicizumab concentration. It is important to note that addition of an unidentified recombinant human FVIII or porcine FVIII (Obizur, Takeda) increased the overall result compared to emicizumab alone indicating that the modified OS FVIII assay is not specific for just emicizumab 46 …”

Section: Emicizumabmentioning

confidence: 99%

Laboratory issues in gene therapy and emicizumab

Bowyer¹,

Lowe²,

Tiefenbacher³

2020

Haemophilia

View full text Add to dashboard Cite

The treatment options for the haemostatic disorders, haemophilia A and haemophilia B, have progressed rapidly over the last decade. The introduction of extended half‐life recombinant factor VIII (FVIII) and factor IX (FIX) concentrates to replace these missing clotting factors highlighted discordance between one‐stage activated partial thromboplastin time (APTT)‐based clotting factor assays and chromogenic factor assays with some products. This raised awareness of the importance of investigation of potential reagent or assay differences by pharmaceutical companies. In 2017, the FVIII mimetic, emicizumab, was approved as a prophylactic treatment for haemophilia A patients with anti‐FVIII inhibitors. The mechanism of action of emicizumab causes interference with some commonly used haemostasis tests including the APTT and its associated one‐stage APTT‐based clotting assays. Chromogenic assays may also be affected but this is dependent on the particular constituents of the reagents. Chromogenic assays containing human factor IXa (FIXa) and factor X (FX) are sensitive to the presence of emicizumab but those containing bovine FIXa and FX are unaffected. Many haemostasis laboratories have been required to evaluate new assays to enable accurate monitoring of emicizumab in patient plasma. A number of gene therapy approaches have been trialled in both haemophilia A and haemophilia B but there are scant data published on the measurement of FVIII and FIX in these patients and whether there are discrepancies between reagents or assay methodologies.

show abstract

Monitoring of Emicizumab (ACE910): comparison between clotting and chromogenic assay

Cited by 4 publications

References 0 publications

Effects of emicizumab on APTT, one‐stage and chromogenic assays of factor VIII in artificially spiked plasma and in samples from haemophilia A patients with inhibitors

Effects of emicizumab on APTT, one‐stage and chromogenic assays of factor VIII in artificially spiked plasma and in samples from haemophilia A patients with inhibitors

Recombinant porcine factor VIII: Lessons from the past and place in the management of hemophilia A with inhibitors in 2021

Laboratory issues in gene therapy and emicizumab

Contact Info

Product

Resources

About