An evaluation of circulating activated TAFI in septic DIC: a case series and review of the literature
Abstract Background Administration of recombinant human soluble thrombomodulin (rTM) is often used in Japan to treat septic disseminated intravascular coagulation (DIC). Thrombin-activatable fibrinolysis inhibitor (TAFI) is a fibrinolysis inhibitor activated by the thrombin-thrombomodulin complex, h...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-02-01
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| Series: | Thrombosis Journal |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12959-022-00364-4 |
| _version_ | 1819274942449975296 |
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| author | Takaaki Totoki Takashi Ito Midori Kakuuchi Nozomi Yashima Ikuro Maruyama Yasuyuki Kakihana |
| author_facet | Takaaki Totoki Takashi Ito Midori Kakuuchi Nozomi Yashima Ikuro Maruyama Yasuyuki Kakihana |
| author_sort | Takaaki Totoki |
| collection | DOAJ |
| description | Abstract Background Administration of recombinant human soluble thrombomodulin (rTM) is often used in Japan to treat septic disseminated intravascular coagulation (DIC). Thrombin-activatable fibrinolysis inhibitor (TAFI) is a fibrinolysis inhibitor activated by the thrombin-thrombomodulin complex, however, it is unknown whether circulating activated TAFI is increased after rTM administration in patients with DIC. Furthermore, the relationship between TAFI activation and the prognosis of septic DIC is not defined yet. Case presentation We report a series of 8 patient’s TAFI activation with septic DIC treated by rTM. We sought to investigate the effect of rTM on TAFI activation and the association of plasma activated TAFI (TAFIa/ai) levels with the prognosis of septic DIC. Using plasma samples from clinical studies conducted from May 2016–March 2017 on eight patients with septic DIC at Kagoshima University Hospital, we measured plasma levels of total TAFI, TAFIa/ai, thrombin-antithrombin complex (TAT), prothrombin fragment 1 + 2 (F1 + 2), soluble fibrin (SF), antithrombin (AT), protein C (PC), protein S (PS), and plasminogen activator inhibitor-1 (PAI-1) before and after intravenous rTM administration. Then, we evaluated the relationship of these marker levels to prognosis. The thrombin-rTM complex activated TAFI in vitro in plasma from a healthy volunteer. However, TAFIa/ai levels did not significantly increase over baseline in the septic DIC patients after intravenous rTM administration. Baseline TAFIa/ai levels in non-survivors were significantly higher than those in survivors. Conclusions Plasma TAFIa/ai did not increase with rTM administration. Elevated baseline TAFIa/ai concentration may be a negative prognostic indicator in septic DIC. Larger studies are needed to confirm the in vivo effect of rTM on TAFI activation. |
| first_indexed | 2024-12-23T23:16:27Z |
| format | Article |
| id | doaj.art-bd2206a6bbb041968c43447f08d1634f |
| institution | Directory Open Access Journal |
| issn | 1477-9560 |
| language | English |
| last_indexed | 2024-12-23T23:16:27Z |
| publishDate | 2022-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Thrombosis Journal |
| spelling | doaj.art-bd2206a6bbb041968c43447f08d1634f2022-12-21T17:26:29ZengBMCThrombosis Journal1477-95602022-02-012011510.1186/s12959-022-00364-4An evaluation of circulating activated TAFI in septic DIC: a case series and review of the literatureTakaaki Totoki0Takashi Ito1Midori Kakuuchi2Nozomi Yashima3Ikuro Maruyama4Yasuyuki Kakihana5Department of Anesthesiology & Critical Care Medicine, Kyushu UniversityDepartment of Emergency and Intensive Care Medicine, Kagoshima University Graduate School of Medical and Dental SciencesDepartment of Emergency and Intensive Care Medicine, Kagoshima University Graduate School of Medical and Dental SciencesDepartment of Emergency and Intensive Care Medicine, Kagoshima University Graduate School of Medical and Dental SciencesDepartment of Systems Biology in Thromboregulation, Kagoshima University Graduate School of Medical and Dental SciencesDepartment of Emergency and Intensive Care Medicine, Kagoshima University Graduate School of Medical and Dental SciencesAbstract Background Administration of recombinant human soluble thrombomodulin (rTM) is often used in Japan to treat septic disseminated intravascular coagulation (DIC). Thrombin-activatable fibrinolysis inhibitor (TAFI) is a fibrinolysis inhibitor activated by the thrombin-thrombomodulin complex, however, it is unknown whether circulating activated TAFI is increased after rTM administration in patients with DIC. Furthermore, the relationship between TAFI activation and the prognosis of septic DIC is not defined yet. Case presentation We report a series of 8 patient’s TAFI activation with septic DIC treated by rTM. We sought to investigate the effect of rTM on TAFI activation and the association of plasma activated TAFI (TAFIa/ai) levels with the prognosis of septic DIC. Using plasma samples from clinical studies conducted from May 2016–March 2017 on eight patients with septic DIC at Kagoshima University Hospital, we measured plasma levels of total TAFI, TAFIa/ai, thrombin-antithrombin complex (TAT), prothrombin fragment 1 + 2 (F1 + 2), soluble fibrin (SF), antithrombin (AT), protein C (PC), protein S (PS), and plasminogen activator inhibitor-1 (PAI-1) before and after intravenous rTM administration. Then, we evaluated the relationship of these marker levels to prognosis. The thrombin-rTM complex activated TAFI in vitro in plasma from a healthy volunteer. However, TAFIa/ai levels did not significantly increase over baseline in the septic DIC patients after intravenous rTM administration. Baseline TAFIa/ai levels in non-survivors were significantly higher than those in survivors. Conclusions Plasma TAFIa/ai did not increase with rTM administration. Elevated baseline TAFIa/ai concentration may be a negative prognostic indicator in septic DIC. Larger studies are needed to confirm the in vivo effect of rTM on TAFI activation.https://doi.org/10.1186/s12959-022-00364-4Disseminated intravascular coagulationThrombin-activatable fibrinolysis inhibitorSepsisThrombomodulin |
| spellingShingle | Takaaki Totoki Takashi Ito Midori Kakuuchi Nozomi Yashima Ikuro Maruyama Yasuyuki Kakihana An evaluation of circulating activated TAFI in septic DIC: a case series and review of the literature Thrombosis Journal Disseminated intravascular coagulation Thrombin-activatable fibrinolysis inhibitor Sepsis Thrombomodulin |
| title | An evaluation of circulating activated TAFI in septic DIC: a case series and review of the literature |
| title_full | An evaluation of circulating activated TAFI in septic DIC: a case series and review of the literature |
| title_fullStr | An evaluation of circulating activated TAFI in septic DIC: a case series and review of the literature |
| title_full_unstemmed | An evaluation of circulating activated TAFI in septic DIC: a case series and review of the literature |
| title_short | An evaluation of circulating activated TAFI in septic DIC: a case series and review of the literature |
| title_sort | evaluation of circulating activated tafi in septic dic a case series and review of the literature |
| topic | Disseminated intravascular coagulation Thrombin-activatable fibrinolysis inhibitor Sepsis Thrombomodulin |
| url | https://doi.org/10.1186/s12959-022-00364-4 |
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