Department of Medical Science and Public Health, University of Cagliari, Cagliari, Italy.
Atherosclerosis and Thrombosis Unit, IRCCS Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy.
Hamostaseologie. 2019 Nov;39(4):398-403. doi: 10.1055/s-0039-1691752. Epub 2019 Jul 30.
Factor XI (FXI) deficiency is a bleeding disorder which causes a bleeding tendency after trauma or surgery. An inhibitor may be acquired secondary to replacement therapy.
To study on genetical and functional grounds a family admitted to our Haemostasis and Thrombosis Centre for an incidental finding of a prolonged activated partial thromboplastin time (aPTT) in three members.
aPTT mixing test, dosage of FXI activity and antigen, FXI inhibitor titration, DNA analysis and clot waveform analysis (CWA) were performed.
Patients II.1, II.3 and II.4 showed a severe FXI deficiency (0.7, 0.7 and 1.8%, respectively) and low antigen level. Since the proposita was already treated with plasma, the dosage of the inhibitor was determined to be 6.4 Bethesda units. They were homozygous for the p.Glu117Stop mutation. The other family members were heterozygous. The velocity and the maximum acceleration of the clot formation were lower than those of the other family members and the normal subjects but higher than those of patients with acquired haemophilia A.
A mixing test of a prolonged aPTT should be performed because it will be present both in patients with or without the inhibitor. A molecular analysis in severe FXI deficiency is warranted as it may have prognostic significance. CWA may be helpful for better understanding the pathophysiology of this kind of defect.
因子 XI（FXI）缺乏症是一种出血性疾病，在外伤或手术后会导致出血倾向。抑制剂可能是由于替代治疗而获得的。
基于遗传和功能研究，我们的止血和血栓形成中心收治了一个家族，该家族的三名成员的活化部分凝血活酶时间（aPTT）延长，这是偶然发现的。
进行 aPTT 混合试验、FXI 活性和抗原测定、FXI 抑制剂滴度测定、DNA 分析和凝块波形分析（CWA）。
患者 II.1、II.3 和 II.4 表现出严重的 FXI 缺乏症（分别为 0.7%、0.7%和 1.8%）和低抗原水平。由于先证者已经接受了血浆治疗，因此测定抑制剂的剂量为 6.4 个 Bethesda 单位。他们均为 p.Glu117Stop 突变的纯合子。其他家族成员为杂合子。凝块形成的速度和最大加速度均低于其他家族成员和正常对照者，但高于获得性血友病 A 患者。
对于延长的 aPTT，应进行混合试验，因为它存在于有或没有抑制剂的患者中。对于严重的 FXI 缺乏症，应进行分子分析，因为它可能具有预后意义。CWA 可能有助于更好地理解这种缺陷的病理生理学。
