Hamostaseologie 2019; 39(S 01): S1-S92
DOI: 10.1055/s-0039-1680132
SY15 Measurements and Haemostasis
Georg Thieme Verlag KG Stuttgart · New York

Monitoring of Emicizumab and Factor VIII Concentrate Interaction

I. Pekrul
1   Department of Anaesthesology, Ludwig-Maximilians University, Munich, Germany
2   Department of Transfusion Medicine, Cell Therapeutics and Hemostaseology, Ludwig-Maximilians University, Munich, Germany
,
N.B. Binder
3   Technoclone Herstellung von Diagnostika und Arzneimitteln GmbH, Wien, Austria
,
M. Spannnagl
1   Department of Anaesthesology, Ludwig-Maximilians University, Munich, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
13 February 2019 (online)

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    Background: Emicizumab offers a new treatment approach for patients with hemophilia A with or without inhibitors. In perioperative and emergency situations additional factor supplementation (on-demand) may be necessary on top of emicizumab prophylactic therapy regime. Individualizing is necessary within respect to maximal efficacy without thromboembolic risk. Factor concentrates and emicizumab have complex mode of interaction but finally lead to thrombin generation.Modelling complex procoagulant therapies is necessary to individualize therapy.

    The aim of our in vitro study was to observe the effect of various factor VIII (FVIII) concentrates on top of emicizumab on thrombin generationusing standardized Ceveron®TG Assay.

    Methods: Plasma from Haemophilia A patients with and without inhibitors was used for spiking with emicizumab and various concentrates. Thrombin generation (TGA) was determined fully automated under standardized conditions on the coagulation analyzer Ceveron® α TGA with Ceveron®TGA RB assay kit. Ceveron®TGA RB trigger composed of tissue factor and negatively charged phospholipids is specially adapted to detect very sensitive changes in the positive feedback loop of intrinsic pathway activation upon activation of the extrinsic pathway, giving the assay high sensitivity to changes in the low range of FVIII and FIX levels. A calibration curve was made once at the beginning of the study using the standard analyzer settings for TGA calibration. nM Peak Thrombin values were used for result evaluation.

    Results: We could show that under standardized conditions, the potency in restoring thrombin generation in identical matrix is similar between the tested compounds (>150nM at 0.1IU/mL FVIII compared with < 25nM in Haemophilia A patient samples), with no need of special calibration or application.

    Haemophilia A samples spiked with increasing concentrations of emicizumab showed a continuous increase in peak thrombin over an extended concentration range, when thrombin generation was measured under standardized conditions.

    Comparison of peak thrombin results of Haemophilia A samples with emicizumab and Haemophilia A samples with emicizumab and FVIII concentrates showed an additional and additive effect on thrombin generation.

    Conclusion: Thrombin generation measurement in samples with emicizumab at clinically relevant plasma levels could therefore serve as a fine-tuned indicator for hemostatic balance (individualized therapy) in patients under prophylactic replacement therapy with emicizumab and/or different FVIII concentrates.


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    No conflict of interest has been declared by the author(s).