Lassila Riitta
Coagulation Disorders Unit, Department of Hematology, Helsinki University Hospital, Comprehensive Cancer Center, University of Helsinki, Helsinki, Finland.
Semin Thromb Hemost. 2016 Jun;42(4):440-4. doi: 10.1055/s-0036-1572324. Epub 2016 Apr 12.
Factor (F) XIII deficiency is a congenital rare bleeding disorder (RBD), with an estimated prevalence of 1 in 1 to 2 million individuals, and more than 1,200 patients have been diagnosed to date. In newborns, umbilical cord bleeding is typical, and later in life during trauma, surgery and even spontaneously prolonged bleeds, reproduction, and delivery complications occur frequently without appropriate replacement therapy. Also, an acquired form of FXIII deficiency may occur via massive bleeds or neutralizing antibodies. In the inherited form of FXIII deficiency, prophylaxis with FXIII concentrate is administered to prevent the very high risk of intracranial bleeds, the incidence being close to 30%. Laboratory diagnosis of FXIII deficiency is based on measuring plasma FXIII antigen and activity, and it is claimed that FXIII activity of around 5 IU/dL would suffice to protect from bleeds. However, at the low levels of detection, most FXIII methods are inaccurate, and quality controls and collaboration with reference laboratories are important to improve the accuracy of low-level FXIII measurements. The trough target for prophylaxis should be set to 10 to 20 IU/dL, which is achievable by administration of 25 to 35 IU/kg every 4 to 6 weeks. However, general risk factors influencing hemostasis should be carefully evaluated, including anemia and hypertension. Fibrin cross-linking by FXIII is of major importance and red cells bind to fibrin partially via platelets and FXIII to promote clot strength. Physiologically, platelets and macrophages contain FXIII providing cellular support; thus, the patients may benefit from platelet transfusion during problematic bleeds. Plasma-derived and recently a recombinant FXIII concentrate are available; however, the latter has mainly anecdotal data regarding management of bleeds and surgery, and its access is limited due to the high cost. The international registry RBD database, (RBDD) continues to gain cumulative knowledge, and registration of all FXIII deficient patients, both inherited and acquired, is highly recommended.
因子（F）XIII缺乏症是一种先天性罕见出血性疾病（RBD），估计患病率为100万至200万人中有1人，迄今为止已诊断出1200多名患者。在新生儿中，脐带出血很典型，在生命后期，在创伤、手术期间，甚至在没有适当替代治疗的情况下，自发的长时间出血、生殖和分娩并发症也经常发生。此外，获得性FXIII缺乏症可能通过大量出血或中和抗体而发生。在遗传性FXIII缺乏症中，给予FXIII浓缩物进行预防以防止颅内出血的极高风险，颅内出血的发生率接近30%。FXIII缺乏症的实验室诊断基于测量血浆FXIII抗原和活性，据称约5 IU/dL的FXIII活性足以预防出血。然而，在低检测水平时，大多数FXIII检测方法不准确，质量控制以及与参考实验室的合作对于提高低水平FXIII测量的准确性很重要。预防的谷值目标应设定为10至20 IU/dL，每4至6周给予25至35 IU/kg即可达到。然而，应仔细评估影响止血的一般危险因素，包括贫血和高血压。FXIII对纤维蛋白的交联至关重要，红细胞部分通过血小板和FXIII与纤维蛋白结合以增强凝块强度。生理上，血小板和巨噬细胞含有FXIII以提供细胞支持；因此，患者在出现问题性出血时可能受益于血小板输注。有血浆来源的以及最近一种重组FXIII浓缩物；然而，后者关于出血和手术管理的主要是轶事性数据，并且由于成本高其可及性有限。国际注册RBD数据库（RBDD）不断积累知识，强烈建议对所有遗传性和获得性FXIII缺乏症患者进行登记。
