妊娠期血浆D-二聚体、纤维蛋白原参考区间的初步建立

Initial establishment of plasma D-dimer and fibrinogen refence range in pregnant women

目的探讨妊娠期血浆D-二聚体、纤维蛋白原水平的变化，初步建立妊娠各期血浆D-二聚体、纤维蛋白原参考区间。方法选择2014年1一12月就诊于首都医科大学附属北京同仁医院（以下简称“我院”）西区的1065名健康单胎孕妇、2例孕期静脉血栓，3例弥散性血管内凝血（DIC）患者以及健康非孕妇对照者120名（健康对照组）。将孕妇按孕龄分为三组：早孕组（〈14周，351名），中孕组（14～27周，348名），晚孕组（〉27～40周，366名），使用SYSMEX CS-5100全自动血凝分析仪，对各组孕妇血浆D-二聚体、纤维蛋白原进行检测及统计学分析，初步建立妊娠期血浆D-二聚体、纤维蛋白原参考区间。妊娠期组妇女血浆D-二聚体、纤维蛋白原浓度呈偏态分布，D-二聚体浓度采用百分位数（％）表示参考区间的单侧上限，纤维蛋白原浓度采用双侧百分位数法表示（P2.5～P97.5）。采用本研究建立的D-二聚体参考区间评估2例孕期静脉血栓，3例DIC患者血浆D-二聚体水平，验证研究中建立的参考区间的有效性。结果随孕龄的增加血浆D一二聚体及纤维蛋白原水平逐渐升高，不同孕龄组间D-二聚体及纤维蛋白原水平比较，差异均有统计学意义（P〈0．05）。相关性分析显示，妊娠期妇女血浆D-二聚体水平与孕龄呈正相关（r=O．735，P〈0．05），尤其在孕32周后增加明显。早孕组、中孕组、晚孕组及健康对照组血浆D-二聚体水平分别为0．41（O．22，o．59）、1．46（1．03，2．05）、1．70（1．20，2．43）、0．23（0．12，0．37）mg／LFEU。妊娠期间血浆D-二聚体浓度在不同孕龄组间差异有统计学意义（P〈0．05），应建立不同参考区间。早孕组、中孕组、晚孕组血浆D-二聚体参考区间分别为0～0．73、0～3．09、0～4．14mg／LFEU；采用D一二聚体参考区间评估的2例静脉血栓和3例DIC孕妇的D-二聚体水平，结果均为阳性。血浆纤维蛋白原水平在早孕期未见明显升高，孕中、晚期血浆纤维蛋白原浓度与孕龄呈正相关（r=O．706，P〈0．05）。血浆纤维蛋白原水平分别为2．59（2．32，2．94）、4．16（3．67，4．42）、4．46（4．07，4．78）、2．53（2．27，2．86）g／L，除早孕组外，其他组均明显高于健康对照组（P〈0．05），中、晚孕期血浆纤维蛋白原参考区间分别为2．69～5．64、3．02～6．05g／L。结论初步建立我院检验科的健康孕妇妊娠各期血浆D-二聚体、纤维蛋白原参考区间，提高D-二聚体、纤维蛋白原在妊娠期的使用价值。

Objective To explore the levels of plasma D-dimer and fibrinogen in pregnant women, and establish the reference range in different period of pregancy. Methods 1065 healthy pregnant women, 2 cases of venous thrombosis and 3 cases of DIC patients, and 120 healthy women without pregnancy （healthy group） were selected from January to December 2014 in West District of Beijing Tongren Hospital, Capital Medical University （＂our hospital＂ for short）. Ac- cording to different gestation week, the health pregnant women were divided into 3 groups： early-pregnant group （〈14 weeks, n -- 351）, middle-pregnant group （14-27 weeks, n = 348）, late-pregnant group （〉27-40 weeks, n = 366）. The reference range of plasma D-dimer and fibrinogen concentration were determined by SYSMEX CS-5100 automatic co- agulation analyzer. D-dimer and fibrinogen concentration showed non-normal distribution, the normal values of D- dimer were established by using percentile （P95）. The normal values of fibrinogen were established by using bilateral percentile （P2.5-P97.5）- Results of 2 cases of venous thrombosis and 3 cases of DIC patients were used to validate the es- tablished normal value. Results Levels of plasma D-dimer and fibrinogen reference increased with the increase of ges- tational age, the differences of D-dimer and fibrinogen level between different gestational age group were statistically significant （P 〈 0.05）. Correlation analysis showed that, the levels of plasma D-dimer was positively correlated with gestati0nal age （r = 0.735, P 〈 0.05）, it increased after 32 weeks gestation. The D-dimer concentration in early-preg- nant group, middle-pregnant group, late-pregnant group, and healthy group were 0.41 （0.22, 0.59）, 1.46 （1.03, 2.05）, 1.70 （1.20, 2.43）, 0.23 （0.12, 0.37） mg/L FEU, which showed statistical difference （P 〈 0.01）.The reference ranges were 0-0.73, 0-3.09, 0-4.14 mg/L FEU for early-pregnant, middle-pregnant and late-pregnant. The reference range of DD was 0-4.14 mg/L FEU. 2 cases of venous thrombosis and 3 cases of DIC patients showed positive results with above normal values. In addition to the early-pregnancy group, the levels of plasma fibrinogen was positively correlated with gesta- tional age （r = 0.706, P 〈 0.05）. The fibrinogen concentration in different group were 3.20 （2.69, 3.56）, 4.16 （3.67, 4.42）, 4.46 （4.07, 4.78）, 3.16 （2.67, 3.42） g/L. In addition to the early-pregnancy group, other groups were significantly higher than that of healthy group （P 〈 0.01）. The reference ranges of middle-pregnant group, late-pregnant group were 2.69-5.64, 3.02-6.05 g/L. Conclusion D-dimer and fibrinogen reference ranges in healthy pregnant women are estab- lished in the laboratory of our hospital, improve use value of D-dimmer and fibrinogen in pregnancy.