Laboratory coagulation tests and recombinant porcine factor VIII: A United Kingdom Haemophilia Centre Doctors’ Organisation guideline

Bowyer, Annette; Gray, Elaine; Lowe, Anna; Murphy, Paul; Platton, Sean; Riddell, Anne; Chowdary, Pratima; Lester, Will; Jenkins, P. Vincent

doi:10.1111/hae.14536

Cited by 9 publications

(13 citation statements)

References 32 publications

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“…As a result, inter-laboratory variability in measurements can occur due to different instruments, methods of detection, assay set-up, reference standard calibration, reagent source and reagent composition. Generally, clinical laboratories use OSA to analyse post-infusion plasma samples collected from patients treated with rpFVIII, but CSAs are also in use and have variability resulting from different methods, instruments and assay kits [ 23 , 24 ]. The source and composition of aPTT reagents used for OSA was identified as a source of variability in results of post-infusion FVIII activity tests as well as potency assignment of rpFVIII [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

“…The correct measurement of FVIII activity in AHA patients treated with Obizur ® is very important for patient safety and even for the correct use of resources. Recently, the “United Kingdom Haemophilia Centre Doctors’ Organisation” (UKHCDO) published recommendations for measuring FVIII in AHA patients in treatment with rpFVIII, excluding the use of the chromogenic assay (CSA) due to its high underestimation of FVIII levels except in the case of patients with AHA who receive emicizumab; however, the latter eventuality is still an off-label treatment [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

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Analytical Performance of Different Laboratory Methods for Measuring Susoctocog-Alfa

et al. 2022

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Recombinant porcine factor VIII (rpFVIII) is indicated for treating bleeding episodes in acquired haemophilia A, but there are few data regarding laboratory methods to adequately monitor treatment. This study involving three Italian laboratories aimed to evaluate the analytical performance of different assays for measuring rpFVIII. Five spiked rpFVIII samples (0.5–1.5 IU/mL) were analysed on three days, in triplicate, with eleven combinations of reagents (Werfen, Boston, MA, USA: SynthasIL and SynthaFax for one-stage assay, Chromogenix Coamatic FVIII for chromogenic assay), FVIII depleted plasmas (with or without von Willebrand factor—VWF) and calibrators (HemosIL human calibrator plasma, porcine calibrator diluted in FVIII deficient plasma with or without VWF). The assays were performed on ACL TOP analysers (Werfen, Boston, MA, USA). Intra- and inter-assay and inter-laboratory Coefficient of Variation (CV%) were calculated together with percentage of recovery (% recovery) on the expected value. The results showed that the reagent combinations reaching satisfactory analytical performance are: SynthasIL/human calibrator/deficient plasma+VWF (total recovery 99.4%, inter-laboratory CV 4.04%), SynthasIL/porcine calibrator/deficient plasma+VWF (total recovery 111%, inter-laboratory CV 2.75%) and Chromogenic/ porcine calibrator/deficient plasma+VWF (total recovery 96.6%, inter-laboratory CV 8.32%). This study highlights that the use of porcine standard (when available) and FVIII deficient plasma with VWF should be recommended.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Analytical Performance of Different Laboratory Methods for Measuring Susoctocog-Alfa

et al. 2022

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“…The bleeding episodes of patients with acquired hemophilia A can be more commonly treated with aPCC or rFVIIa, but rpFVIII may also be an option. They also require a chromogenic FVIII assay 15 using non-human reagents 16 to determine the blood level of FVIII if they are under prophylaxis with emicizumab, because chromogenic FVIII assays underestimate the plasma level of rpFVIII (ref. 15 ).…”

Section: Exploration Of Coagulation In Patients Under Prophylaxis Wit...mentioning

confidence: 99%

“…They also require a chromogenic FVIII assay 15 using non-human reagents 16 to determine the blood level of FVIII if they are under prophylaxis with emicizumab, because chromogenic FVIII assays underestimate the plasma level of rpFVIII (ref. 15 ). Clinicians who use emicizumab must know that it interferes with haemostasis tests, especially those based on activated partial thromboplastin times (APTT) (ref.…”

Section: Exploration Of Coagulation In Patients Under Prophylaxis Wit...mentioning

confidence: 99%

From a bispecific monoclonal antibody to gene therapy: A new era in the treatment of hemophilia A

Mihăilă¹

2023

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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The treatment of hemophilia A has progressed amazingly in recent years. Emicizumab, a bispecific-humanized monoclonal antibody, is able to improve coagulation by bridging activated factor IX and factor X. Emicizumab is administered subcutaneously and much less often compared to factor VIII products. It has low immunogenicity, does not require dose adjustment, and can be administered regardless of the presence of factor VIII inhibitors. Thrombin generation assays but not factor VIII activity are indicated to guide and monitor the treatment. Emicizumab has enabled the conversion of patients with severe forms into patients with milder forms of hemophilia A. It has reduced the number of bleeding episodes compared to both on-demand and prophylactic substitution therapy and has an excellent safety profile. Gene therapy can elevate factor VIII plasma levels for many years after a single treatment course, could offer longterm protection from bleeding episodes, and minimize or eliminate the need for substitutive treatment with factor VIII concentrates. Gene therapy can provoke an immune response, manifested by an increase in common liver enzymes, that require immunotherapy. Long term monitoring is necessary to identify possible adverse effects. Future objectives are: the development of an ideal viral vector, the possibility of its re-administration, the use of gene therapy in hemophiliac children, and determining whether it can be successfully used to induce immune tolerance to factor VIII ceteri paribus. The future will determine the place of each type of treatment and group of patients for which it is indicated.

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“…Porcine-derived products (Obizur, porcine rFVIII, BAX801) are reliably assessed using OSA methods; CSA methods are less reliable. 25 26 27 28…”

Section: Fviii and Fix Factor Assays: General Laboratory Considerationsmentioning

confidence: 99%

Factor VIII and Factor IX Activity Measurements for Hemophilia Diagnosis and Related Treatments

Bowyer

Gosselin

2022

Semin Thromb Hemost

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Accurate measurement of clotting factors VIII (FVIII) or IX (FIX) is vital for comprehensive diagnosis and management of patients with hemophilia A or B. The one-stage activated partial thromboplastin time (aPTT)-based clotting assay is the most commonly used method worldwide for testing FVIII or FIX activities. Alternatively, FVIII and FIX chromogenic substrate assays, which assess the activation of factor X, are available in some specialized laboratories. The choice of reagent or methodology can strongly influence the resulting activity. Variation between one-stage FVIII or FIX activities has been reported in the measurement of some standard and extended half-life factor replacement therapies and gene therapy for hemophilia B using different aPTT reagents. Discrepancy between one-stage and chromogenic reagents has been demonstrated in some patients with mild hemophilia A or B, the measurement of some standard and extended half-life factor replacement therapies, and the transgene expression of hemophilia A and B patients who have received gene therapy. Finally, the measurement of bispecific antibody therapy in patients with hemophilia A has highlighted differences between chromogenic assays. It is imperative that hemostasis laboratories evaluate how suitable their routine assays are for the accurate measurement of the various hemophilia treatment therapies.

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Laboratory coagulation tests and recombinant porcine factor VIII: A United Kingdom Haemophilia Centre Doctors’ Organisation guideline

Cited by 9 publications

References 32 publications

Analytical Performance of Different Laboratory Methods for Measuring Susoctocog-Alfa

Analytical Performance of Different Laboratory Methods for Measuring Susoctocog-Alfa

From a bispecific monoclonal antibody to gene therapy: A new era in the treatment of hemophilia A

Factor VIII and Factor IX Activity Measurements for Hemophilia Diagnosis and Related Treatments

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