Diagnosis and Management of Congenital and Acquired FXIII Deficiencies
Diagnosis and Management of Congenital and Acquired FXIII Deficiencies
复制标题
DOI：
10.1055/s-0036-1572326
复制
发表时间：
2016-06-01
影响因子：
5.7
通讯作者：
Katona, Eva
中科院分区：
文献类型：
--
作者：
Muszbek, Laszlo;Katona, Eva
遗传性FXIII A亚单位缺陷(FXIII-A)是一种罕见的(1：2,000,000)但非常严重的出血素质。在近亲婚姻和创始人效应突变相结合的社区，这种情况的发生率要高得多。由于颅内出血的高风险，终身预防是强制性的，最好使用FXIII浓缩液。FXIII-B亚单位缺乏症患者的出血素质为轻至中度。FXIII缺乏经常与伤口愈合受损有关。患有FXIII缺乏症的妇女不能足月妊娠；在严重的情况下，自然流产发生在怀孕的前三个月。血浆来源的热灭活FXIII浓缩物和重组FXIII-A可用于预防；建议每周服用35至40U/kg的剂量，并应以高于5%的FXIII活性为目标。在怀孕期间，建议每周进行两次预防，目标谷值大于10%，分娩期间FXIII活性应超过30%。在手术过程中，目标应高于50%的FXIII活性。同种抗体使FXIII缺乏症难以治疗，但幸运的是，这种情况极其罕见。获得性FXIII缺乏症可能涉及这两个亚基。抗FXIII亚单位自身抗体也出现在严重出血并发症中，死亡率相对较高。诊断FXIII缺乏症的一线试验应是基于氨释放或胺掺入的定量功能测定。传统的血栓溶解度测定的灵敏度不足以进行适当的筛查。FXIII缺陷的分类需要抗原分析。在抗FXIII抗体的情况下，诊断库应辅之以胺化试验/Bethesda-type抑制剂分析以及检测/测量抗体与FXIII及其亚单位的结合的分析。
Inherited deficiency of FXIII A subunit (FXIII-A) is a rare (1:2,000,000) but very severe bleeding diathesis. The incidence is much higher in communities where the practice of consanguineous marriage is combined with founder effect mutation. Because of the high risk of intracranial bleeding, life-long prophylaxis, preferably using FXIII concentrate, is mandatory. In FXIII-B subunit deficiency the bleeding diathesis is mild to moderate. FXIII deficiency is frequently associated with impaired wound healing. Women suffering from FXIII deficiency cannot carry pregnancies to term; in severe cases spontaneous abortion occurs in the first trimester. Plasma-derived heat-inactivated FXIII concentrate and recombinant FXIII-A are available for prophylaxis; a 4 weekly dose of 35 to 40 U/kg is recommended and a trough level of greater than 5% FXIII activity should be aimed for. During pregnancy, 2 weekly prophylaxis with a target trough level of greater than 10% is recommended, and during labor FXIII activity should exceed 30%. During surgical procedures, the target should be higher than 50% FXIII activity. Alloantibodies make FXIII deficiency difficult to manage, but fortunately they are extremely rare. Acquired FXIII deficiency may involve both subunits. Autoantibodies against FXIII subunits also manifest in severe bleeding complication with a relatively high mortality rate. The first-line test in the diagnosis of FXIII deficiency should be a quantitative functional assay based on the measurement of ammonia release or amine incorporation. The sensitivity of the traditional clot solubility assay is not sufficiently robust to enable proper screening. Antigen assays are needed for the classification of FXIII deficiencies. In the case of anti-FXIII antibodies, the diagnostic armory should be supplemented by amixing test/Bethesda-type inhibitor assay and by assays that detect/measure the binding of antibodies to FXIII and to its subunits.