Dempfle C E
University of Heidelberg, Mannheim University Hospital, I. Department of Medicine, Germany.
Semin Thromb Hemost. 2000;26(6):631-41. doi: 10.1055/s-2000-13221.
In the course of fibrin formation, the D-domains of adjacent fibrin molecules within the fibrin polymer are covalently linked by factor XIIIa, leading to the formation of a D-domain dimer. Proteolysis of this cross-linked fibrin generates fibrin fragments D-dimer and E as terminal products. Fragment D-dimer therefore is an indicator for the proteolysis of cross-linked fibrin, whereas the monomeric fragment D can stem from fibrinogen and non-cross-linked fibrin. Various monoclonal antibodies have been prepared that distinguish between fragments D-dimer and D and allow the detection of fibrin derivatives in the presence of fibrinogen. These anti-D-dimer-antibodies have been shown to react with fragment D-dimer, but also detect dimeric D-domains within larger fibrin compounds, including cross-linked fibrin complexes generated in an early phase of coagulation activation. Assay systems for D-dimer antigen therefore may uncover intravascular clot formation early, by detection of fibrin complexes, and after completion of clot formation, by the detection of proteolytic fragments released from the particulate clot. Various trials have shown that low concentrations of D-dimer antigen in the blood exclude recent venous thrombosis or pulmonary embolism. Elevated levels may be caused by venous thrombotic disease, but also by a variety of other conditions, leading to intra- or extravascular fibrin formation. Assay systems include manual immunoagglutination assays, immunofiltration assays, microtiter plate enzyme-linked immunosorbent assay (ELISA) systems, automated ELISA systems, and latex-enhanced photometric immunoassays. According to clinical studies, D-dimer assays may be the "first line" of technical screening in symptomatic outpatients with suspected venous thrombosis or pulmonary embolism, but further prospective management trials, and improved standardization of assay systems, are needed for the validation of this approach.
在纤维蛋白形成过程中，纤维蛋白聚合物内相邻纤维蛋白分子的D结构域通过因子XIIIa共价连接，导致形成D结构域二聚体。这种交联纤维蛋白的蛋白水解产生纤维蛋白片段D-二聚体和E作为终产物。因此，片段D-二聚体是交联纤维蛋白蛋白水解的指标，而单体片段D可源自纤维蛋白原和非交联纤维蛋白。已经制备了多种单克隆抗体，可区分片段D-二聚体和D，并能在存在纤维蛋白原的情况下检测纤维蛋白衍生物。这些抗D-二聚体抗体已被证明可与片段D-二聚体反应，但也能检测较大纤维蛋白化合物中的二聚体D结构域，包括凝血激活早期产生的交联纤维蛋白复合物。因此，D-二聚体抗原检测系统可通过检测纤维蛋白复合物在血管内血栓形成早期发现，以及在血栓形成完成后通过检测从颗粒状血栓释放的蛋白水解片段发现。各种试验表明，血液中低浓度的D-二聚体抗原可排除近期静脉血栓形成或肺栓塞。水平升高可能由静脉血栓性疾病引起，但也可能由多种其他情况导致，从而导致血管内或血管外纤维蛋白形成。检测系统包括手动免疫凝集试验、免疫过滤试验、微量滴定板酶联免疫吸附测定（ELISA）系统、自动化ELISA系统和乳胶增强光度免疫测定。根据临床研究，D-二聚体检测可能是疑似静脉血栓形成或肺栓塞的有症状门诊患者技术筛查的“一线”方法，但需要进一步的前瞻性管理试验以及改进检测系统的标准化来验证这种方法。
