Novel assays in the coagulation laboratory: a clinical and laboratory perspective

Teichman, Jennifer; Chaudhry, Harman; Sholzberg, Michelle

doi:10.1016/j.transci.2018.07.008

Cited by 12 publications

(20 citation statements)

References 52 publications

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“…15 However, OSA results are subject to interlaboratory variation, due in part to the wide range of aPTT reagents available and clot detection techniques used. 14 An alternative to the FVIII OSA is the two-stage FVIII clotting assay, which was first developed in 1955 as a modified thromboplastin dilution test. 13,16 As with the FVIII OSA, FVIII concentration is the rate-determining step in the two-stage assay, but despite being less susceptible to reagent variation, this assay is not commonly used in the clinical setting due to its complexity.…”

Section: Current Methods In the Coagulation Laboratorymentioning

confidence: 99%

Laboratory Monitoring in Emicizumab-Treated Persons with Hemophilia A

et al. 2019

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Hemophilia A (HA) is an X-linked hereditary bleeding disorder caused by deficiency of coagulation factor (F) VIII activity. One of the greatest complications in the treatment of HA is the development of neutralizing alloantibodies, known as FVIII inhibitors. HA patients who develop FVIII inhibitors have limited treatment options available to them and experience greater disease- and treatment-related burdens than HA patients without FVIII inhibitors. Emicizumab, a recently approved bispecific monoclonal antibody, mimics the function of FVIIIa by bridging FIXa and FX to restore effective hemostasis. Although emicizumab and FVIII show some functional similarities, several key differences influence the results of standard laboratory assays when conducted in the presence of emicizumab, and can result in a misleading interpretation of coagulation assays in emicizumab-treated patients. Here, we discuss current laboratory monitoring methods, including activated partial thromboplastin time, FVIII one-stage clotting assays, FVIII chromogenic assays, and global coagulations assays; address why these conventional methods may be inappropriate for monitoring of HA patients receiving emicizumab; and suggest alternative methods applicable to monitoring HA treatment in an evolving treatment landscape.

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Section: Current Methods In the Coagulation Laboratorymentioning

confidence: 99%

Laboratory Monitoring in Emicizumab-Treated Persons with Hemophilia A

et al. 2019

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“…Advances in gene therapy also offer hope to PwH, 21,22 but may necessitate long‐term monitoring of factor levels to confirm continued efficacy. Ultimately, while the development of innovative coagulant agents has the potential to reduce treatment burden and increase the quality of life for PwH, methods for precise monitoring of hemostatic parameters with these products/approaches need to evolve in parallel 20,23,24 …”

Section: Introductionmentioning

confidence: 99%

Laboratory testing in hemophilia: Impact of factor and non‐factor replacement therapy on coagulation assays

Peyvandi

Kenet

Pekrul³

et al. 2020

Journal of Thrombosis and Haemostasis

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The advent of extended half‐life (EHL) recombinant clotting factors and innovative non‐factor replacement therapeutics, such as emicizumab, offers several advantages over existing products for the prophylactic treatment of people living with hemophilia (PwH). These include low annual bleeding rates with less frequent dosing, higher trough plasma concentrations, and a more convenient route of administration. However, increasing use of these therapies poses challenges to clinicians and coagulation laboratories due to the lack of standardized assays for monitoring of hemostatic parameters, and the potential for misinterpretation of test results, which may jeopardize patient safety. Definitive diagnosis of hemophilia and treatment monitoring is reliant on demonstrating factor VIII (FVIII; hemophilia A) or factor IX (FIX; hemophilia B) deficiency using a functional coagulation assay. The most frequently used assays are based on activated partial thromboplastin time, using a one‐stage or two‐stage process. While one‐stage and chromogenic assays have performed well with human‐derived FVIII and FIX and full‐length recombinant products, EHL recombinant factors are heterogeneous in structure and mode of action and therefore show wide variation in activity levels between different one‐stage assays, and between one‐stage and chromogenic assays. In the context of the recommended stepwise approach for laboratory diagnosis of hemophilia, we examine the diagnostic challenges associated with the use of EHL factors and novel non‐factor therapeutics and consider the optimal diagnostic approach in PwH who are receiving these treatments. Ultimately, accurate diagnostic solutions are a prerequisite for personalized therapy to minimize treatment burden and improve quality of life in PwH.

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“…The factor-deficient plasma and the patient sample are preincubated with a contact activator and phospholipids while calcium chloride is later added to initiate fibrin clot formation. 80 The FVIII or FIX concentration in the patient plasma is thus presumably the rate-limiting determining factor of the aPTT.…”

Section: Factor Assays and Extended Half-life Productsmentioning

confidence: 99%

The Evolution of Hemophilia Care: Clinical and Laboratory Advances, Opportunities, and Challenges

2020

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Hemophilia A (HA) and B (HB) are X-linked bleeding disorders caused by mutations in the F8 or F9 gene that result in the absence, or reduced activity, of the corresponding clotting factor. The severity of bleeding and related complications is proportional to the amount of residual circulating functional factor. The development of a safe and effective hemophilia treatment lasted several decades and has been mainly based on clotting factor replacement. Advances in the engineering and manufacturing of clotting concentrates have led to the widespread availability of extended half-life products that reduced the number of intravenous infusions needed to achieve adequate trough levels. The recent development of new nonfactor replacement treatments and biotechnology techniques has offered therapeutic alternatives for hemophilia patients with and without inhibitors. These are characterized by an easier route of administration, low immunogenicity, and, regarding gene therapy and cell-based treatments, potential long-term protection from bleeding after a single treatment course. In this review, we analyze recent progresses in the management of hemophilia and discuss opportunities and challenges.

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Novel assays in the coagulation laboratory: a clinical and laboratory perspective

Cited by 12 publications

References 52 publications

Laboratory Monitoring in Emicizumab-Treated Persons with Hemophilia A

Laboratory Monitoring in Emicizumab-Treated Persons with Hemophilia A

Laboratory testing in hemophilia: Impact of factor and non‐factor replacement therapy on coagulation assays

The Evolution of Hemophilia Care: Clinical and Laboratory Advances, Opportunities, and Challenges

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