Journal of thrombosis and haemostasis : JTH · 2026
Single-domain antibodies to reverse the effects of factor Xa inhibitors on coagulation tests.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Zhao Junxiong, Hoornstra Ischa, Huskens Dana, Swieringa Frauke, Stroobants An K, Rijpma Sanna, Heylen René, de Laat Bas, Roest Mark
Аннотация
BACKGROUND: Direct oral anticoagulants (DOACs) interfere with coagulation assays, complicating the diagnosis of thrombophilia and lupus anticoagulants. Single-domain antibodies (sdAbs) may be used to neutralize anticoagulant effects in vitro, thereby restoring physiological coagulation for accurate diagnostic testing.
OBJECTIVES: To develop and validate sdAbs specific to DOACs that inhibit factor Xa, specifically edoxaban, apixaban, and rivaroxaban.
METHODS: Llama-derived sdAbs specific to DOACs were selected via phage display. To enhance efficacy, bivalent sdAbs were engineered. Both single and bivalent forms were tested in healthy control plasma using various coagulation assays (thrombin generation, prothrombin time [PT], and activated partial thromboplastin time [APTT]), dilute Russell's viper venom time, and international normalized ratio. The ability of these specific sdAbs to reverse the effects of edoxaban, apixaban, and rivaroxaban was also evaluated in plasma samples from patients currently receiving these medications.
RESULTS: Antiedoxaban, antiapixaban, and antirivaroxaban sdAbs achieved reversal of edoxaban, apixaban, and rivaroxaban, respectively, as demonstrated by thrombin generation, PT, APTT, dilute Russell's viper venom time, and international normalized ratio assays for both the single and bivalent variants. Specifically, each anti-DOAC sdAb effectively reversed the effects of its respective DOAC on lag time and peak thrombin levels, without overshooting a prothrombotic response. Furthermore, in plasma from edoxaban-, apixaban-, or rivaroxaban-treated patients, the corresponding sdAbs restored both PT and APTT.
CONCLUSIONS: We selected and validated sdAbs that specifically reverse the inhibitory effects of edoxaban, apixaban, and rivaroxaban, without procoagulant activity. These low-cost reversal agents work directly on plasma or whole blood without incubation or preanalytical steps. They enable rapid, reliable baseline coagulation testing in patients treated with these DOACs.
OBJECTIVES: To develop and validate sdAbs specific to DOACs that inhibit factor Xa, specifically edoxaban, apixaban, and rivaroxaban.
METHODS: Llama-derived sdAbs specific to DOACs were selected via phage display. To enhance efficacy, bivalent sdAbs were engineered. Both single and bivalent forms were tested in healthy control plasma using various coagulation assays (thrombin generation, prothrombin time [PT], and activated partial thromboplastin time [APTT]), dilute Russell's viper venom time, and international normalized ratio. The ability of these specific sdAbs to reverse the effects of edoxaban, apixaban, and rivaroxaban was also evaluated in plasma samples from patients currently receiving these medications.
RESULTS: Antiedoxaban, antiapixaban, and antirivaroxaban sdAbs achieved reversal of edoxaban, apixaban, and rivaroxaban, respectively, as demonstrated by thrombin generation, PT, APTT, dilute Russell's viper venom time, and international normalized ratio assays for both the single and bivalent variants. Specifically, each anti-DOAC sdAb effectively reversed the effects of its respective DOAC on lag time and peak thrombin levels, without overshooting a prothrombotic response. Furthermore, in plasma from edoxaban-, apixaban-, or rivaroxaban-treated patients, the corresponding sdAbs restored both PT and APTT.
CONCLUSIONS: We selected and validated sdAbs that specifically reverse the inhibitory effects of edoxaban, apixaban, and rivaroxaban, without procoagulant activity. These low-cost reversal agents work directly on plasma or whole blood without incubation or preanalytical steps. They enable rapid, reliable baseline coagulation testing in patients treated with these DOACs.