低抗凝血酶活性可增强凝血酶生成能力，且该能力取决于相关凝血因子的活性。
Thrombin generation capacity is enhanced by low antithrombin activity and depends on the activity of the related coagulation factors.
作者信息
Tsuchida Takumi, Hayakawa Mineji, Kawahara Shota, Kumano Osamu
机构信息
Department of Emergency Medicine, Hokkaido University Hospital, N14W5 Kita-ku, Sapporo, 060-8648, Japan.
Sysmex Corporation, 4-4-4 Takatsukadai, Nishi-ku, Kobe, 651-2271, Japan.
出版信息
Thromb J. 2022 May 18;20(1):29. doi: 10.1186/s12959-022-00388-w.
BACKGROUND
Supplementation with antithrombin (AT) concentrates is now common in the treatment of congenital and acquired AT deficiency. However, there is no established consensus on the target and timing of supplementation. We aimed to elucidate the effects of AT deficiency on the balance between coagulation activation and inhibition using a thrombin generation assay as in vitro global assay.
METHODS
Samples were prepared by admixing commercially acquired AT-deficient plasma with < 1% AT activity with pooled normal plasma. The AT activity in each sample was adjusted to 100, 90, 70, 50, 40, 30, 10, 5, and < 1%. A thrombin generation assay was performed in each sample. AT concentrate-spiked samples were also prepared by adjusting the AT activities in four types of the concentrates: one recombinant and three plasma-derived AT concentrates. The final targeted AT activities in the samples were adjusted to 100, 50, 30, and 5% by spiking each concentrate into the AT-deficient plasma. We also prepared samples with five levels of prothrombin time (PT) % in coagulation factors with the AT activity fixed at 30% by dilution by mixing AT-deficient plasma and normal plasma with Owren's veronal buffer to adjust the coagulation factor activities in several proportions. The theoretical target PT% values were 100, 66, 50, 40, and 30%. A thrombin generation assay was performed on all samples.
RESULTS
The ability to generate thrombin depended on the AT activity, and the amount of thrombin generation was increased as AT was decreased. Additionally, the amount of thrombin generation was changed significantly when AT activity was ≤ 50%, indicating that AT suppressed thrombin generation. In particular, thrombin generation was remarkable when AT activity was < 30%, and it can be assumed that the prognosis is poor due to organ failure from thrombotic tendency.
CONCLUSIONS
The results presented in this basic research were found to be consistent with the clinical findings to date. The mechanism by which 30-50% of AT activity is set as the clinical boundary was elucidated by the thrombin generation assay.
背景
补充抗凝血酶（AT）浓缩物目前在先天性和获得性AT缺乏症的治疗中很常见。然而，关于补充的目标和时机尚未达成共识。我们旨在使用凝血酶生成试验作为体外整体试验来阐明AT缺乏对凝血激活与抑制平衡的影响。
方法
通过将商业获得的AT活性低于1%的AT缺乏血浆与混合的正常血浆混合来制备样本。将每个样本中的AT活性调整为100%、90%、70%、50%、40%、30%、10%、5%和低于1%。对每个样本进行凝血酶生成试验。还通过调整四种类型浓缩物中的AT活性来制备添加了AT浓缩物的样本：一种重组AT浓缩物和三种血浆来源的AT浓缩物。通过将每种浓缩物添加到AT缺乏血浆中，将样本中的最终目标AT活性调整为100%、50%、30%和5%。我们还制备了凝血因子中凝血酶原时间（PT）%有五个水平的样本，通过用奥伦氏巴比妥缓冲液稀释将AT活性固定在30%，通过混合AT缺乏血浆和正常血浆以几种比例调整凝血因子活性。理论目标PT%值为100%、66%、50%、40%和30%。对所有样本进行凝血酶生成试验。
结果
凝血酶生成能力取决于AT活性，随着AT降低，凝血酶生成量增加。此外，当AT活性≤50%时，凝血酶生成量有显著变化，表明AT抑制凝血酶生成。特别是，当AT活性<30%时，凝血酶生成显著，并且可以推测由于血栓形成倾向导致器官衰竭，预后较差。
结论
本基础研究的结果与迄今为止的临床发现一致。凝血酶生成试验阐明了将30 - 50%的AT活性设定为临床界限的机制。
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