Department of Molecular Patho-Biochemistry and Patho-Biology, Yamagata University School of Medicine, Yamagata, Japan.
The Japanese Collaborative Research Group (JCRG) on Autoimmune Acquired Coagulation Factor Deficiencies supported by the Japanese Ministry of Health, Labor and Welfare (MHLW), Yamagata, Japan.
Haemophilia. 2021 May;27(3):454-462. doi: 10.1111/hae.14298. Epub 2021 Apr 12.
Autoimmune factor XIII (FXIII) deficiency (AiF13D) due to anti-FXIII autoantibodies is an extremely rare, life-threatening bleeding disorder that mostly occurs in the elderly. The number of patients diagnosed with AiF13D has been increasing in Japan, probably because of the nationwide survey on AiF13D supported by the Japanese Ministry of Health, Labour and Welfare.
To explore the pathologic characteristics of coagulation parameters in AiF13D.
AiF13D-suspected cases were consulted, and underwent unified/integrated coagulation screening and were definitively diagnosed as AiF13D separately.
AiF13D patients had lower FXIII antigen levels than non-AiF13D patients, but their values overlapped. Among a series of 22-item screening tests and their resulting parameters, the 'FXIII inhibitory potential' yielded by a 1:1 mixing test of the patient's and healthy control's plasma and its 'residual FXIII activity' in 54 AiF13D cases were most distinguishable from 139 non-AiF13D cases, followed by FXIII activity per se and FXIII-specific activity. While the cross-linked α -plasmin inhibitor level reduced, the levels of D-dimer, fibrin/fibrinogen degradation products and plasmin-plasmin inhibitor complex increased, probably because the patients' haematoma nonspecifically induced secondary fibrinolysis in both AiF13D and non-AiF13D patients.
AiF13D appears to induce a hypocoagulopathy combined with a hyper-fibrinolytic state secondary to severe FXIII deficiency caused by anti-FXIII autoantibodies, and the consequent bleeding further modifies its pathological conditions. In addition, the 1:1 mixing test of FXIII activity was confirmed to be a reliable screening method for AiF13D, especially when its derivative parameter, such as the 'FXIII inhibitory potential' or 'FXIII inhibitory potential ratio', is employed.
由于抗 FXIII 自身抗体引起的自身免疫性因子 XIII（FXIII）缺乏症（AiF13D）是一种极其罕见的、危及生命的出血性疾病，主要发生在老年人中。由于日本厚生劳动省支持的全国性 AiF13D 调查，日本被诊断为 AiF13D 的患者人数一直在增加。
探讨 AiF13D 患者凝血参数的病理特征。
咨询 AiF13D 可疑病例，并进行统一/综合凝血筛查，分别明确诊断为 AiF13D。
AiF13D 患者的 FXIII 抗原水平低于非 AiF13D 患者，但两者有重叠。在 22 项筛选测试及其结果参数的系列中，患者和健康对照血浆 1:1 混合测试产生的“FXIII 抑制潜能”及其在 54 例 AiF13D 病例中的“残余 FXIII 活性”与 139 例非 AiF13D 病例最具区分度，其次是 FXIII 活性本身和 FXIII 特异性活性。虽然交联α-纤溶酶抑制剂水平降低，但 D-二聚体、纤维蛋白/纤维蛋白原降解产物和纤溶酶-纤溶酶抑制剂复合物的水平增加，可能是由于患者血肿在 AiF13D 和非 AiF13D 患者中均非特异性地诱导了继发性纤溶。
AiF13D 似乎由于抗 FXIII 自身抗体引起的严重 FXIII 缺乏导致的低凝状态，并伴有继发性高纤溶状态，由此导致的出血进一步改变了其病理状态。此外，FXIII 活性的 1:1 混合测试被证实是一种可靠的 AiF13D 筛选方法，尤其是当使用其衍生参数（如“FXIII 抑制潜能”或“FXIII 抑制潜能比”）时。
