Background: Management of breakthrough bleeding events in patients on emicizumab involves episodic treatment with the bypassing agents (BPA), activated prothrombin complex concentrate (aPCC) and recombinant activated FVII (rFVIIa). A concomitant drug reaction between emicizumab and aPCC resulting in thrombotic events was noted in the HAVEN clinical trials.

Aims: We aimed to assess the effect of spiking various concentrations of BPA on plasma taken from patients on emicizumab on thrombin generation.

Methods: Patients with severe hemophilia A (HA) with inhibitors who are currently on emicizumab and who achieved steady state were recruited to participate. Table 1 describes the concentrations of the bypassing agents and descriptive statistics are provided for the different TGA parameters.

Results: Eleven patients with severe HA and inhibitors currently on emicizumab for at least 6 weeks were enrolled in the study. The TGA parameters were assessed. The summary statistics are provided in tables 2a and 2b.

Conclusions: Due to the known thrombotic complications when emicizumab is used in conjunction with aPCC, there has been a large-scale abandonment of the use of aPCC in patients on emicizumab. However, it is possible that aPCC can be used safely with emicizumab albeit with lower doses than may typically be used and below the doses in the prescribing information. This, in turn, could suggest which doses of both rFVIIa and especially aPCC could be studied in a trial (or even used safely) when managing breakthrough bleeding or surgery in patients on emicizumab. In conclusion, we have demonstrated that lower doses of aPCC could potentially be used safely and effectively in inhibitor patients on emicizumab. It would be important to test this hypothesis in a clinical study.

[Table-1 Concentrations for in vitro spiking]

[Table 2a – 2b]

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/comparison-of-bypassing-agents-in-patients-on-emicizumab-using-global-hemostasis-assays/