Asakura Hidesaku, Sano Yoko, Omote Mika, Yoshida Tomotaka, Ontachi Yasuo, Mizutani Tomoe, Kaneda Minori, Yamazaki Masahide, Morishita Eriko, Takami Akiyoshi, Miyamoto Ken-ichi, Nakao Shinji
Department of Internal Medicine (III), Kanazawa University School of Medicine, Kanazawa, Ishikawa, Japan.
Int J Hematol. 2004 May;79(4):394-9. doi: 10.1532/ijh97.03168.
Plasma D-dimer (DD) is considered to be one of the most useful markers in the diagnosis and assessment of disseminated intravascular coagulation (DIC). The present study was performed to clarify the role of DD in a rat model of lipopolysaccharide (LPS)-induced DIC in which low-molecular-weight heparin (LMWH) and tranexamic acid (TA) were used. We investigated whether a relationship exists between plasma DD levels and severity of DIC. Experimental DIC was induced in rats by a sustained 4-hour infusion of 30 mg/kg LPS administered via the tail vein (LPS group). Rats received either LPS alone (LPS group) or LPS combined with 200 U/kg LMWH (LPS+LMWH group) or 50 mg/kg TA (LPS+TA group) from -30 minutes to 4 hours. Blood was drawn from each rat at 4, 8, and 12 hours. Plasma levels of thrombin-antithrombin complex (TAT) and creatinine were suppressed in the LPS+LMWH group, and less glomerular fibrin deposition was observed compared with the LPS group. On the other hand, an increased level of creatinine and increased glomerular fibrin deposition were observed in the LPS+TA group compared with the LPS group. LMWH demonstrated a protective effect against LPS-induced DIC, resulting in increased survival at 12 hours, whereas TA had the opposite effect. From these results, it appears that LMWH protects against LPS-induced DIC, but TA exacerbates LPS-induced DIC. It was interesting that plasma levels of DD were almost completely suppressed by concurrent administration of either TA or LMWH in this LPS-induced DIC model. This finding suggested that plasma levels of DD were suppressed by inhibition of coagulation (reduced deposition of fibrin) in the LPS+LMWH group and that DD levels were also suppressed by inhibition of fibrinolysis (reduced degradation of fibrin by plasmin) in the LPS+TA group. Thus care should be taken when evaluating the significance of plasma DD levels, because suppressed levels can occur with progressive fibrin deposition and worsening organ dysfunction or improvement in the course of DIC.
血浆D-二聚体（DD）被认为是弥散性血管内凝血（DIC）诊断和评估中最有用的标志物之一。本研究旨在阐明DD在脂多糖（LPS）诱导的DIC大鼠模型中的作用，该模型使用了低分子量肝素（LMWH）和氨甲环酸（TA）。我们研究了血浆DD水平与DIC严重程度之间是否存在关联。通过经尾静脉持续4小时输注30mg/kg LPS诱导大鼠实验性DIC（LPS组）。大鼠在-30分钟至4小时期间接受单独的LPS（LPS组）或LPS联合200U/kg LMWH（LPS+LMWH组）或50mg/kg TA（LPS+TA组）。在4、8和12小时从每只大鼠采集血液。LPS+LMWH组血浆凝血酶-抗凝血酶复合物（TAT）水平和肌酐水平受到抑制，与LPS组相比，肾小球纤维蛋白沉积较少。另一方面，与LPS组相比，LPS+TA组肌酐水平升高，肾小球纤维蛋白沉积增加。LMWH对LPS诱导的DIC具有保护作用，导致12小时时存活率增加，而TA则具有相反的作用。从这些结果来看，似乎LMWH可预防LPS诱导的DIC，但TA会加重LPS诱导的DIC。有趣的是，在这个LPS诱导的DIC模型中，同时给予TA或LMWH几乎完全抑制了血浆DD水平。这一发现表明，LPS+LMWH组中血浆DD水平因凝血抑制（纤维蛋白沉积减少）而受到抑制，而LPS+TA组中DD水平也因纤维蛋白溶解抑制（纤溶酶对纤维蛋白降解减少）而受到抑制。因此，在评估血浆DD水平的意义时应谨慎，因为在DIC病程中，随着纤维蛋白沉积进展、器官功能障碍加重或病情改善，血浆DD水平可能会受到抑制。
