Distinguishing lupus anticoagulants from factor VIII inhibitors in haemophilic and non‐haemophilic patients

Rampersad, Angeli; Boylan, Brian; Miller, Connie H.; Shapiro, Amy D.

doi:10.1111/hae.13565

Cited by 11 publications

(14 citation statements)

References 20 publications

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“…Immunoassays to detect anti-FVIII antibodies may help to distinguish LA from FVIII inhibitors in such cases. 13,29 The Nijmegen modification has been developed to improve specificity in the detection of low-titer inhibitors. 30 Pre-analytical heat inactivation of test plasma may improve assay accuracy/sensitivity.…”

Section: Bethesda Assay and Modificationsmentioning

confidence: 99%

International recommendations on the diagnosis and treatment of acquired hemophilia A

et al. 2020

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A cquired hemophilia A (AHA), a rare bleeding disorder caused by neutralizing autoantibodies against coagulation factor VIII (FVIII), occurs in both men and women without a previous history of bleeding. Patients typically present with an isolated prolonged activated partial thromboplastin time due to FVIII deficiency. Neutralizing antibodies (inhibitors) are detected using the Nijmegen-modified Bethesda assay. Approximately 10% of patients do not present with bleeding and, therefore, a prolonged activated partial thromboplastin time should never be ignored prior to invasive procedures. Control of acute bleeding and prevention of injuries that may provoke bleeding are top priorities in patients with AHA. We recommend treatment with bypassing agents, including recombinant activated factor VII, activated prothrombin complex concentrate, or recombinant porcine FVIII in bleeding patients. Autoantibody eradication can be achieved with immunosuppressive therapy, including corticosteroids, cyclophosphamide and rituximab, or combinations thereof. The median time to remission is 5 weeks, with considerable interindividual variation. FVIII activity at presentation, inhibitor titer and autoantibody isotype are prognostic markers for remission and survival. Comparative clinical studies to support treatment recommendations for AHA do not exist; therefore, we provide practical consensus guidance based on recent registry findings and the authors' clinical experience in treating patients with AHA.

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Section: Bethesda Assay and Modificationsmentioning

confidence: 99%

International recommendations on the diagnosis and treatment of acquired hemophilia A

et al. 2020

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“…While rare, the presence of LAs in PwHA is significant in that they can interfere with the ability to detect and monitor FVIII inhibitors by Bethesda assays based on aPTT, and in a few instances even with chromogenic Bethesda assays (which are recommended for management of emicizumab patients). 3 Therefore, it is valuable to explore the effect of emicizumab on several functional assays for LA detection based on different assay principles. The intent of this letter is to supplement the findings of our previous study 1 by investigating the effect of emicizumab on the results of LA detection assays.…”

Section: Dear Editorsmentioning

confidence: 99%

Effects and interferences of emicizumab, a humanized bispecific antibody mimicking activated factor VIII cofactor function, on lupus anticoagulant assays

Adamkewicz¹,

Kiialainen

Paz‐Priel³

2019

Int J Lab Hematology

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“…However, the use of CSA formats may generally lower the potential interference of non-target inhibitory substances such as lupus anticoagulants and may therefore increase assay specificity. 21,22 Commonly Used OSC and CS Assay Reagents (A) OSC assays. Due to dilution of the patient sample in FVIII-or FIX-deficient plasma (containing defined amounts of the remaining coagulation factors [grey characters]), either FVIII or FIX stemming from the patient sample (black characters) becomes the only variable that influences the activated partial thromboplastin time (aPTT) of the mixture: in brief, addition of the aPTT reagent activates the intrinsic, non-Ca 2þ -dependent pathway of the mixture (down to FXI[a]) during initial incubation.…”

Section: Detection Of Fviii/fix Inhibitors ([Nijmegen]-bethesda Assay)mentioning

confidence: 99%

An Update on Laboratory Diagnostics in Haemophilia A and B

et al. 2022

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Haemophilia A (HA) and B (HB) are X-linked hereditary bleeding disorders caused by lack of activity of coagulation factors VIII (FVIII) or IX (FIX), respectively. Besides conventional products, modern replacement therapies include FVIII or FIX concentrates with an extended half-life (EHL-FVIII/FIX). Two main strategies for measuring plasma FVIII or FIX activity are applied: the one-stage clotting assay (OSCA) and the chromogenic substrate assay (CSA), both calibrated against plasma (FVIII/FIX) standards. Due to the structural modifications of EHL-FVIII/FIX, reagent-dependent assay discrepancies have been described when measuring the activity of these molecules. Assay discrepancies have also been observed in FVIII/FIX gene therapy approaches. On the other hand, nonfactor replacement by the bispecific antibody emicizumab, a FVIIIa-mimicking molecule, artificially shortens activated partial thromboplastin time–based clotting times, making standard OSCAs inapplicable for analysis of samples from patients treated with this drug. In this review, we aim to give an overview on both, the currently applied and future therapies in HA and HB with or without inhibitors and corresponding test systems suitable for accompanying diagnostics.

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Distinguishing lupus anticoagulants from factor VIII inhibitors in haemophilic and non‐haemophilic patients

Abstract: Assessment of anti-FVIII profiles along with the CBA may be useful to distinguish a clinically relevant low-titre FVIII inhibitor from a transient LA in HA patients.

Cited by 11 publications

References 20 publications

International recommendations on the diagnosis and treatment of acquired hemophilia A

International recommendations on the diagnosis and treatment of acquired hemophilia A

Effects and interferences of emicizumab, a humanized bispecific antibody mimicking activated factor VIII cofactor function, on lupus anticoagulant assays

An Update on Laboratory Diagnostics in Haemophilia A and B

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