Department of Pediatrics, Nara Medical University, Kashihara, Nara, Japan.
Center of Postgraduate Training Nara Medical University Hospital, Kashihara, Nara, Japan.
Haemophilia. 2024 May;30(3):836-844. doi: 10.1111/hae.14997. Epub 2024 Mar 24.
Emicizumab (Emi) is used as haemostatic prophylaxis for patients with haemophilia A (PwHA). Disseminated intravascular coagulation (DIC) is a condition characterized by persistent systemic activation of coagulation, but there is yet no information on coagulation and fibrinolysis potentials in Emi-treated PwHA with DIC.
To examine the effect of Emi on coagulation and fibrinolysis potentials in HA-model DIC plasmas.
Plasma from a patient with sepsis-DIC (seven patients) was treated with anti-factor (F)VIII monoclonal antibody (HA-model DIC plasma) and incubated with Emi (50 µg/mL). The plasma was then assessed using clot-fibrinolysis waveform analysis (CFWA). Coagulation and fibrinolysis parameters were expressed as ratios relative to normal plasma (|min1|-ratio and |FL-min1|-ratio, respectively).
In case 1, coagulant potential was slightly high and fibrinolytic potential was extremely low, presenting a coagulant-dominant state (|min1|-ratio/|FL-min1|-ratio: 1.1/.38). In cases 2-5, fibrinolytic potential was not suppressed, but there were marked hypercoagulant potentials, indicating relative coagulant-dominant states. In case 6, coagulant and fibrinolytic potentials were increased but well balanced (|min1|-ratio/|FL-min1|-ratio: 1.38/1.28). In case 7, both potentials were severely deteriorated in not only CFWA but also the thrombin/plasmin generation assay. The addition of Emi into the HA-model DIC plasmas increased |min1|-ratio values in all cases, but the coagulant potentials did not exceed the initial ones (DIC plasma before treatment with anti-FVIII antibody).
The presence of Emi in the HA-model DIC plasma improved coagulation potentials, but did not increase coagulation potentials beyond those of DIC plasma in non-HA states.
依美珠单抗（emicizumab，Emi）被用作甲型血友病（haemophilia A，PwHA）患者的止血预防药物。弥散性血管内凝血（disseminated intravascular coagulation，DIC）的特征为持续全身性凝血激活，但目前尚无关于接受 Emi 治疗的 DIC 血友病患者的凝血和纤溶潜能的信息。
研究 Emi 对血友病 A 模型 DIC 血浆中凝血和纤溶潜能的影响。
用抗因子 VIII 单克隆抗体处理脓毒症-DIC 患者的血浆（7 例患者）（血友病 A 模型 DIC 血浆），并与 Emi（50μg/mL）孵育。然后使用凝块-纤溶波分析（clot-fibrinolysis waveform analysis，CFWA）评估血浆。凝血和纤溶参数表示为与正常血浆的比值（|min1|-比值和 |FL-min1|-比值）。
在病例 1 中，凝血潜能稍高，纤溶潜能极低，呈凝血优势状态（|min1|-比值/|FL-min1|-比值：1.1/.38）。在病例 2-5 中，纤溶潜能未受抑制，但存在明显的高凝潜能，表明存在相对凝血优势状态。在病例 6 中，凝血和纤溶潜能增加，但平衡良好（|min1|-比值/|FL-min1|-比值：1.38/1.28）。在病例 7 中，无论是 CFWA 还是凝血酶/纤溶酶生成测定，凝血和纤溶潜能均严重恶化。在血友病 A 模型 DIC 血浆中加入 Emi 后，所有病例的|min1|-比值均增加，但凝血潜能未超过初始值（未用抗 FVIII 抗体治疗前的 DIC 血浆）。
Emi 存在于血友病 A 模型 DIC 血浆中可改善凝血潜能，但不会使非血友病 A 状态下的 DIC 血浆的凝血潜能增加。
