Successful Perioperative Combination of High-Dose FVIII Therapy Followed by Emicizumab in a Patient with Hemophilia A with Inhibitors
We managed perioperative hemostasis for a 72-year-old man with hemophilia A and low inhibitor titers (3 BU/mL), who underwent osteosynthesis for supracondylar fracture of the left humerus. He was treated perioperatively using the combination of high doses of factor VIII (FVIII) with recombinant huma...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Georg Thieme Verlag KG
2019-10-01
|
| Series: | TH Open |
| Subjects: | |
| Online Access: | http://www.thieme-connect.de/DOI/DOI?10.1055/s-0039-3401001 |
| _version_ | 1818142813506764800 |
|---|---|
| author | Shuichi Okamoto Nobuaki Suzuki Atsuo Suzuki Sachiko Suzuki Shogo Tamura Mochihito Suzuki Nobunori Takahashi Toshihisa Kojima Takeshi Kanematsu Tetsuhito Kojima Hitoshi Kiyoi Naoki Ishiguro Tadashi Matsushita |
| author_facet | Shuichi Okamoto Nobuaki Suzuki Atsuo Suzuki Sachiko Suzuki Shogo Tamura Mochihito Suzuki Nobunori Takahashi Toshihisa Kojima Takeshi Kanematsu Tetsuhito Kojima Hitoshi Kiyoi Naoki Ishiguro Tadashi Matsushita |
| author_sort | Shuichi Okamoto |
| collection | DOAJ |
| description | We managed perioperative hemostasis for a 72-year-old man with hemophilia A and low inhibitor titers (3 BU/mL), who underwent osteosynthesis for supracondylar fracture of the left humerus. He was treated perioperatively using the combination of high doses of factor VIII (FVIII) with recombinant human Factor VIII Fc fusion protein (rFVIIIFc), followed by emicizumab. On the day of surgery (day 0), he was administered bolus infusion of 150 IU/kg rFVIIIFc, followed by continuous infusion at a dose of 4 IU/kg/h. Emicizumab, 3 mg/kg, was injected subcutaneously once a week, on days 5, 12, 19, and 26. Inhibitors were detected on day 6 at a titer of 4 BU/mL and FVIII:C decreased to below assay sensitivity limits on day 10. The rate of increase in inhibitor titers was high, with inhibitors increasing to 343.4 BU/mL on day 14. The transition of thrombin production by thrombin generation assay (TGA) showed temporary decrease in thrombin production on day 7, although it was restored by day 10, i.e., five days after commencement of emicizumab therapy. Rotational thromboelastometry displayed consistent results with TGA, showing that clotting time was prolonged and the alpha angle decreased to less than measurable levels on day 6, although they were improved by day 10. There were no bleeding-related events or other adverse events throughout the perioperative period. In conclusion, emicizumab was effective for the management of perioperative hemostasis after development of an anamnestic response in a patient with hemophilia A with inhibitors. Combination therapy with high doses of FVIII followed by emicizumab could be a workable alternative for patients with hemophilia A with inhibitors. |
| first_indexed | 2024-12-11T11:21:44Z |
| format | Article |
| id | doaj.art-012056557f67465d8e017da3023608cd |
| institution | Directory Open Access Journal |
| issn | 2512-9465 |
| language | English |
| last_indexed | 2024-12-11T11:21:44Z |
| publishDate | 2019-10-01 |
| publisher | Georg Thieme Verlag KG |
| record_format | Article |
| series | TH Open |
| spelling | doaj.art-012056557f67465d8e017da3023608cd2022-12-22T01:09:09ZengGeorg Thieme Verlag KGTH Open2512-94652019-10-010304e364e36610.1055/s-0039-3401001Successful Perioperative Combination of High-Dose FVIII Therapy Followed by Emicizumab in a Patient with Hemophilia A with InhibitorsShuichi Okamoto0Nobuaki Suzuki1Atsuo Suzuki2Sachiko Suzuki3Shogo Tamura4Mochihito Suzuki5Nobunori Takahashi6Toshihisa Kojima7Takeshi Kanematsu8Tetsuhito Kojima9Hitoshi Kiyoi10Naoki Ishiguro11Tadashi Matsushita12Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, JapanDepartment of Transfusion Medicine, Nagoya University Hospital, Nagoya, JapanDepartment of Medical Technique, Nagoya University Hospital, Nagoya, JapanDepartment of Pathophysiological Laboratory Sciences, Nagoya University Graduate School of Medicine, Nagoya, JapanDepartment of Orthopaedics/Rheumatology, Nagoya University Graduate School of Medicine, Nagoya, JapanDepartment of Orthopaedics/Rheumatology, Nagoya University Graduate School of Medicine, Nagoya, JapanDepartment of Orthopaedics/Rheumatology, Nagoya University Graduate School of Medicine, Nagoya, JapanDepartment of Orthopaedics/Rheumatology, Nagoya University Graduate School of Medicine, Nagoya, JapanDepartment of Clinical Laboratory, Nagoya University Hospital, Nagoya, JapanDepartment of Pathophysiological Laboratory Sciences, Nagoya University Graduate School of Medicine, Nagoya, JapanDepartment of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, JapanDepartment of Orthopaedics/Rheumatology, Nagoya University Graduate School of Medicine, Nagoya, JapanDepartment of Transfusion Medicine, Nagoya University Hospital, Nagoya, JapanWe managed perioperative hemostasis for a 72-year-old man with hemophilia A and low inhibitor titers (3 BU/mL), who underwent osteosynthesis for supracondylar fracture of the left humerus. He was treated perioperatively using the combination of high doses of factor VIII (FVIII) with recombinant human Factor VIII Fc fusion protein (rFVIIIFc), followed by emicizumab. On the day of surgery (day 0), he was administered bolus infusion of 150 IU/kg rFVIIIFc, followed by continuous infusion at a dose of 4 IU/kg/h. Emicizumab, 3 mg/kg, was injected subcutaneously once a week, on days 5, 12, 19, and 26. Inhibitors were detected on day 6 at a titer of 4 BU/mL and FVIII:C decreased to below assay sensitivity limits on day 10. The rate of increase in inhibitor titers was high, with inhibitors increasing to 343.4 BU/mL on day 14. The transition of thrombin production by thrombin generation assay (TGA) showed temporary decrease in thrombin production on day 7, although it was restored by day 10, i.e., five days after commencement of emicizumab therapy. Rotational thromboelastometry displayed consistent results with TGA, showing that clotting time was prolonged and the alpha angle decreased to less than measurable levels on day 6, although they were improved by day 10. There were no bleeding-related events or other adverse events throughout the perioperative period. In conclusion, emicizumab was effective for the management of perioperative hemostasis after development of an anamnestic response in a patient with hemophilia A with inhibitors. Combination therapy with high doses of FVIII followed by emicizumab could be a workable alternative for patients with hemophilia A with inhibitors.http://www.thieme-connect.de/DOI/DOI?10.1055/s-0039-3401001factor viii inhibitorssurgeryhemophilia therapy |
| spellingShingle | Shuichi Okamoto Nobuaki Suzuki Atsuo Suzuki Sachiko Suzuki Shogo Tamura Mochihito Suzuki Nobunori Takahashi Toshihisa Kojima Takeshi Kanematsu Tetsuhito Kojima Hitoshi Kiyoi Naoki Ishiguro Tadashi Matsushita Successful Perioperative Combination of High-Dose FVIII Therapy Followed by Emicizumab in a Patient with Hemophilia A with Inhibitors TH Open factor viii inhibitors surgery hemophilia therapy |
| title | Successful Perioperative Combination of High-Dose FVIII Therapy Followed by Emicizumab in a Patient with Hemophilia A with Inhibitors |
| title_full | Successful Perioperative Combination of High-Dose FVIII Therapy Followed by Emicizumab in a Patient with Hemophilia A with Inhibitors |
| title_fullStr | Successful Perioperative Combination of High-Dose FVIII Therapy Followed by Emicizumab in a Patient with Hemophilia A with Inhibitors |
| title_full_unstemmed | Successful Perioperative Combination of High-Dose FVIII Therapy Followed by Emicizumab in a Patient with Hemophilia A with Inhibitors |
| title_short | Successful Perioperative Combination of High-Dose FVIII Therapy Followed by Emicizumab in a Patient with Hemophilia A with Inhibitors |
| title_sort | successful perioperative combination of high dose fviii therapy followed by emicizumab in a patient with hemophilia a with inhibitors |
| topic | factor viii inhibitors surgery hemophilia therapy |
| url | http://www.thieme-connect.de/DOI/DOI?10.1055/s-0039-3401001 |
| work_keys_str_mv | AT shuichiokamoto successfulperioperativecombinationofhighdosefviiitherapyfollowedbyemicizumabinapatientwithhemophiliaawithinhibitors AT nobuakisuzuki successfulperioperativecombinationofhighdosefviiitherapyfollowedbyemicizumabinapatientwithhemophiliaawithinhibitors AT atsuosuzuki successfulperioperativecombinationofhighdosefviiitherapyfollowedbyemicizumabinapatientwithhemophiliaawithinhibitors AT sachikosuzuki successfulperioperativecombinationofhighdosefviiitherapyfollowedbyemicizumabinapatientwithhemophiliaawithinhibitors AT shogotamura successfulperioperativecombinationofhighdosefviiitherapyfollowedbyemicizumabinapatientwithhemophiliaawithinhibitors AT mochihitosuzuki successfulperioperativecombinationofhighdosefviiitherapyfollowedbyemicizumabinapatientwithhemophiliaawithinhibitors AT nobunoritakahashi successfulperioperativecombinationofhighdosefviiitherapyfollowedbyemicizumabinapatientwithhemophiliaawithinhibitors AT toshihisakojima successfulperioperativecombinationofhighdosefviiitherapyfollowedbyemicizumabinapatientwithhemophiliaawithinhibitors AT takeshikanematsu successfulperioperativecombinationofhighdosefviiitherapyfollowedbyemicizumabinapatientwithhemophiliaawithinhibitors AT tetsuhitokojima successfulperioperativecombinationofhighdosefviiitherapyfollowedbyemicizumabinapatientwithhemophiliaawithinhibitors AT hitoshikiyoi successfulperioperativecombinationofhighdosefviiitherapyfollowedbyemicizumabinapatientwithhemophiliaawithinhibitors AT naokiishiguro successfulperioperativecombinationofhighdosefviiitherapyfollowedbyemicizumabinapatientwithhemophiliaawithinhibitors AT tadashimatsushita successfulperioperativecombinationofhighdosefviiitherapyfollowedbyemicizumabinapatientwithhemophiliaawithinhibitors |