Thrombin generation and Emicizumab

Additional findings from the determination of thrombin generation potential

Thrombin Generation Assays (TGA) are based on monitoring the formation of thrombin by means of a fluorogenic substrate upon activation of the coagulation cascade by tissue factor. This assay can be used to monitor hemophiliacs during inhibitor bypassing therapy.

In case of breakthrough bleeding while on emicizumab treatment, patients with inhibitors still require treatment with BPA. 

There may be some inherent risks associated when combining emicizumab with APCCs. TGA might be useful in order to individually tailor bypassing therapy.

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Literature

1. Yasim Dargaud, Anne Lienhart, Maissaa Janbain, Sandra Le Quellec, Nathalie Enjolras, Claude Nigrier: "Use of thrombin generation assay to personalize treatment of breakthrough bleeds in a patient with hemophilia and inhibitors receiving prophylaxis with emicizumab". Haemotologica; April 2018: 103
2. Oldenburg J, Mahlangu JN, Kim B, et al. "Emicizumab prophylaxis in hemophilia A with inhibitors". N Eng J Med. 2017; 377(9):809-818
3. Lenting PJ, Denis CV, Christophe OD. "Emicizumab, a bispecific antibody recognizing coagulation factors IX and X: how does it actually compare to factor VIII Blood". 2017; 103(23):2463-2468
4. Turecek PL, Váradi K, Keil B, et al. "Factor VIII inhibitor-bypassing agents act by including thrombin generation and can be monitored by a thrombin generation assay". Pathophysiol Haemost Thromb. 2003; 33(1):16-22
5. Luna-Záizar H, Beltrán-Miranda CP, Esparaza-Flores MA, et al. "Thrombin generation as objective parameter of treatment response in patients with severe haemophilia A and high-titre inhibitors". Haemophilia 2014; 20(1)