The effect of emicizumab and bypassing agents in patients with hemophilia – An in vitro study
Abstract Background Emicizumab is a nonfactor replacement therapy for hemophilia A (HA) and is a bispecific monoclonal antibody mimicking factor VIII by binding both factors IXa and X. Although it reduces the frequency of bleeding episodes, there is still need for bypassing agents in case of breakth...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-07-01
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| Series: | Research and Practice in Thrombosis and Haemostasis |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/rth2.12561 |
| _version_ | 1797721991092895744 |
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| author | Nina Haagenrud Schultz Heidi Glosli Stine Bjørnsen Pål Andre Holme |
| author_facet | Nina Haagenrud Schultz Heidi Glosli Stine Bjørnsen Pål Andre Holme |
| author_sort | Nina Haagenrud Schultz |
| collection | DOAJ |
| description | Abstract Background Emicizumab is a nonfactor replacement therapy for hemophilia A (HA) and is a bispecific monoclonal antibody mimicking factor VIII by binding both factors IXa and X. Although it reduces the frequency of bleeding episodes, there is still need for bypassing agents in case of breakthrough bleeds or need for surgery. The HAVEN‐1 study showed an increased risk of thrombotic events and episodes of thrombotic microangiopathic hemolytic anemia with simultaneous treatment with emicizumab and activated prothrombin complex concentrate (aPCC) in high doses (>100 U/kg daily) for more than 1 day, and it is suspected that these drugs have a synergistic hemostatic effect. Objectives To evaluate and compare the hemostatic effect of bypassing agents in vitro in people with HA before and after starting treatment with emicizumab to investigate if dosing should be adjusted to optimize treatment. Patients/Methods Blood collected before and after start of treatment with emicizumab was spiked with aPCC and recombinant factor VIIa (rFVIIa) at different concentrations. The effect of aPCC and rFVIIa was assessed by thrombin generation assay and thromboelastometry. Results Six people with HA were included. The response to aPCC in thrombin generation after starting emicizumab was significantly stronger than before. This synergistic effect was less pronounced for emicizumab and rFVIIa. Furthermore, aPCC shortened thromboelastometry clotting time more effectively after starting emicizumab than before starting this treatment. Conclusions We demonstrated a strong synergistic effect of emicizumab and aPCC and a similar but less pronounced effect of rFVIIa in people treated with emicizumab. |
| first_indexed | 2024-03-12T09:41:19Z |
| format | Article |
| id | doaj.art-79b73affbc374ae49b6af79c4ec9592d |
| institution | Directory Open Access Journal |
| issn | 2475-0379 |
| language | English |
| last_indexed | 2024-03-12T09:41:19Z |
| publishDate | 2021-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Research and Practice in Thrombosis and Haemostasis |
| spelling | doaj.art-79b73affbc374ae49b6af79c4ec9592d2023-09-02T13:13:46ZengElsevierResearch and Practice in Thrombosis and Haemostasis2475-03792021-07-0155n/an/a10.1002/rth2.12561The effect of emicizumab and bypassing agents in patients with hemophilia – An in vitro studyNina Haagenrud Schultz0Heidi Glosli1Stine Bjørnsen2Pål Andre Holme3Department of Haematology Oslo University Hospital Oslo NorwayDivision of Paediatric and Adolescent Medicine Centre for Rare Disorders Oslo University Hospital Oslo NorwayResearch Institute of Internal Medicine Oslo University Hospital Oslo NorwayDepartment of Haematology Oslo University Hospital Oslo NorwayAbstract Background Emicizumab is a nonfactor replacement therapy for hemophilia A (HA) and is a bispecific monoclonal antibody mimicking factor VIII by binding both factors IXa and X. Although it reduces the frequency of bleeding episodes, there is still need for bypassing agents in case of breakthrough bleeds or need for surgery. The HAVEN‐1 study showed an increased risk of thrombotic events and episodes of thrombotic microangiopathic hemolytic anemia with simultaneous treatment with emicizumab and activated prothrombin complex concentrate (aPCC) in high doses (>100 U/kg daily) for more than 1 day, and it is suspected that these drugs have a synergistic hemostatic effect. Objectives To evaluate and compare the hemostatic effect of bypassing agents in vitro in people with HA before and after starting treatment with emicizumab to investigate if dosing should be adjusted to optimize treatment. Patients/Methods Blood collected before and after start of treatment with emicizumab was spiked with aPCC and recombinant factor VIIa (rFVIIa) at different concentrations. The effect of aPCC and rFVIIa was assessed by thrombin generation assay and thromboelastometry. Results Six people with HA were included. The response to aPCC in thrombin generation after starting emicizumab was significantly stronger than before. This synergistic effect was less pronounced for emicizumab and rFVIIa. Furthermore, aPCC shortened thromboelastometry clotting time more effectively after starting emicizumab than before starting this treatment. Conclusions We demonstrated a strong synergistic effect of emicizumab and aPCC and a similar but less pronounced effect of rFVIIa in people treated with emicizumab.https://doi.org/10.1002/rth2.12561activated prothrombin complex concentrateblood coagulation testsemicizumabhemophilia ArFVIIa |
| spellingShingle | Nina Haagenrud Schultz Heidi Glosli Stine Bjørnsen Pål Andre Holme The effect of emicizumab and bypassing agents in patients with hemophilia – An in vitro study Research and Practice in Thrombosis and Haemostasis activated prothrombin complex concentrate blood coagulation tests emicizumab hemophilia A rFVIIa |
| title | The effect of emicizumab and bypassing agents in patients with hemophilia – An in vitro study |
| title_full | The effect of emicizumab and bypassing agents in patients with hemophilia – An in vitro study |
| title_fullStr | The effect of emicizumab and bypassing agents in patients with hemophilia – An in vitro study |
| title_full_unstemmed | The effect of emicizumab and bypassing agents in patients with hemophilia – An in vitro study |
| title_short | The effect of emicizumab and bypassing agents in patients with hemophilia – An in vitro study |
| title_sort | effect of emicizumab and bypassing agents in patients with hemophilia an in vitro study |
| topic | activated prothrombin complex concentrate blood coagulation tests emicizumab hemophilia A rFVIIa |
| url | https://doi.org/10.1002/rth2.12561 |
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