【作者】 袁素娥；

【导师】 李映兰；

【作者基本信息】 中南大学 ， 护理学， 2010， 硕士

【摘要】 目的观察MAR S人工肝治疗肝衰竭时无肝素循环和肝素化循环技术对患者疗效、血细胞数量、出血和凝血的影响；尝试初步建立MARS治疗肝衰竭中抗凝剂应用的安全模式和个体化处理标准。方法采用前瞻性实验性研究法。以2009年8月至2010年8月在中南大学湘雅医院人工肝治疗中心行MARS治疗的肝衰竭患者为研究对象,根据不同抗凝方式将其随机分为两组：无肝素组和肝素组,无肝素组采用定时生理盐水冲洗管路、保证血流速度、加强监测等手段干预,如出现凝血,临床需要使用抗凝药物者根据医嘱加用抗凝,提前终止试验。肝素组采用首剂注射半量(2050U)至全量低分子肝素(4100U)、术中间断抗凝。将两组术前、术后肝功能(Tbil、DbiLA)、肾功能(BUN、SCR)、血细胞计数(RBC、Hb、BPC)进行比较,选择治疗Oh(即治疗前)、30Min、1h、2h、3h、4h、5h、6h(即治疗结束时)共8个时点动态观察PT、PTA、TT、APTT、INR等凝血指标的变化,观察管路／滤器凝血、破膜、出血等不良事件发生频率及严重程度。采用SPSS18.0统计软件包对资料进行统计学分析。统计方法包括描述性统计分析、独立样本t检验和方差分析、协方差分析。结果1.2009年8月至2010年8月中南大学湘雅医院人工肝治疗中心完成MARS治疗45例,符合入选标准病例32例,治疗32例次。单次治疗持续时间6小时,肝素组18例次均顺利完成治疗,无肝素组14例次中1例因严重凝血治疗中断,3例因凝血需加用抗凝药物提前终止试验。2.两组患者接受MARS治疗前均为深度黄疸,血清蛋白明显低于正常低值,RBC、Hb、BPC计数低于正常低值,PTA<40%, PT、TT、APTT显著延长,两组治疗前基本情况比较无差异。3.两组均表现为Tbil、DbiL、BUN、SCR等蛋白结合毒素和水溶性毒素显著下降,两组比较下降差值无差异。4.肝素组治疗前RBC.Hb分别为3.21±0.78×1012/l、102.52±21.586g/L,治疗后为3.02±0.81×1012/l、97.08±22.73 g/L,无肝素组治疗前RBC、Hb分别为3.49±0.66×1012/l、102.50±35.24 g/L,治疗后为3.28±0.64×1012/l、107.10±15.45g/L,两组均下降不明显,无统计学差异。5.肝素组治疗前BPC为107.86±104.54×109/L,治疗后为94.86±108.26×109/L(t=1.826,P=0.083),无肝素组治疗前BPC为86.70±52.37×109/L,治疗后为60.60±32.78×109/L,(t=2.782,P=0.021)。无肝素组BPC下降有统计学意义。6两组对PT、PTA、INR的影响方差分析无差异,对APTT、TT. Fbg的影响有显著性差异。APTT:肝素组使用首剂抗凝药物后APTT迅速升高,30min即达峰值,无肝素组也有上升,但速度相对缓慢,两组治疗中各时点APTT的中位数比较有统计学意义(t=2.201,P=0.036)。TT：肝素组使用首剂抗凝药物后TT也表现为迅速升高,30min达峰值,4h再次出现第二次高峰,但低于第一次,治疗结束时仍高十治疗前水平。无肝素组维持平稳状态,两组治疗中各时点TT的中位数比较有显著性差异(t=3.287、P=0.003)。Fbg：两组MARS治疗中Fbg变化曲线有交互(F=3.630,P=0.001),比较有显著性差异。肝素组Fbg趋于平稳,治疗结束时略有上升,无肝素组Fbg逐步下降,治疗6小时降低显著,两者在治疗2.5h出现交叉。7.肝素组6例Ⅰ度凝血,1例Ⅱ度凝血,术中未发生出血,术后2例出血；无肝素组6例Ⅰ度凝血,1例Ⅲ度凝血,术中术后均未发生出血。两组均无过敏病例。两组比较无统计学差异(P=0.845)。结论1.MARS治疗肝衰竭时,肝素化循环和无肝素循环均可引起BPC下降,无肝素循环下降程度高于肝素化循环。2.PTA是判断肝衰竭患者凝血功能的重要指标,但不是唯一标准。MARS治疗前需要结合BPC、FDP、D-二聚体等实验室检测以及临床症状等综合分析,判断凝血状态,选择抗凝方式。3.高凝期选择肝素循环实施MARS,有助于体外循环顺利完成的同时改善高凝状态,防治DIC。4.低凝期选择无肝素循环能有效预防出血的发生,并通过降低血液中类肝素样物质等改善患者凝血机制。更多还原

【Abstract】 Objective:To investigate the impacts of curative effect, blood cell amounts, bleeding and clotting on which different anticoagulation systems (no heparin or low-dose heparin loop recycling technology) have in molecular adsorbent recirculating system (MARS) in subjects with liver failure. Attempting to establish a safe and individualized anticoagulant model in MARS.Methods:A prospective experimental observation was designed. Patients with liver failure from artificial liver treatment center of Xiangya Hospital, Central South University were randomly divided into two groups according to different anticoagulation meanings. One was no heparin group, in which normal saline was used to irrigate pipes regularly to ensure flow velocity. In case of coagulation, anticoagulants were added immediately, cuing test termination. The other was low-dose heparin group given with half (2050U) or full (4100U) amount of low molecular weight heparin for first dose. And during the whole therapy, anticoagulants were empirically given. Index of liver function (Tbil, DbiL A), renal function (BUN, SCR) and blood cell counts (RBC, Hb, BPC) were compared preoperatively and postoperatively between the two groups. Time points of Omin,30min, 1h,2h,3h,4h 5h and 6h were elected to observe coagulation changes of PT, PTA, TT, APTT and INR dynamically. Adverse events such as line/filter coagulation, rupture and bleeding were also investigated and compared due to frequency and severity between the two groups.Result:1. There were forty-five patients received MARS treatment from August 2009 to August 2010, thirty-two cases of which met the inclusion criteria were recruited. Single treatment lasted for about 6 hours. The whole 18 cases in low-dose heparin group finished the treatment successfully, while there were four cases out of the fourteen cases reached experiment termination, one in which for severe coagulation and the other three cases for clotting.2. Patients in both groups were deep jaundice. Serum protein levels, RBC, Hb, and BPC counts were significant lower than normal before treatment in both groups. Coagulation index such as PT, TT and APTT were significantly prolonged in both groups with PTA≤40%. However, there was no difference between the two groups in basic situation.3. Protein binding toxins and water-soluble toxins such as Tbil, DbiL BUN, SCR were significantly depressed in both groups, and there was no significant difference between them.4. The RBC amount and Hb in low-dose heparin group were 3.210±0.778×10^12/l and 102.523±21.586 g/L before treatment, while 3.018±0.808×10^12/l and 97.076±22.734 g/L after treatment, respectively, indicating no significant differences between the two. Similarly, the RBC amount and Hb in no heparin group were 3.494±0.658×10^12/l and 102.50±35.240 g/L before treatment, while 3.284±0.636×10^12/l, and 107.10±15.445 g/L after treatment, respectively. No significant differences were observed. Further comparison between no heparin group and low-dose heparin group also indicated no significant differences.5. The BPC amount in low-dose heparin group was 107.86±104.54×109/L before MARS while 94.86±108.26×109/L after MARS treatment, no significant difference in decline was obtained (t=1.826, P=0.083). However, in no heparin group it was significantly decreased from 86.70±52.37×109/Lto 60.60±32.78×109/L(t=2.782, P=0.021)6. Eight time points (0min,30min, 1h,2h,3h,4h,5h and 6h in treatment) were selected to observe coagulation changes of PT, PTA, TT, APTT and INR dynamically. There was no difference on PT, PTA, INR between the two groups, but significant differences were observed on APTT and TT and Fbg.APTT:The APTT level in low-dose heparin group was increased rapidly after first given dose of anticoagulant heparin and reached the peak within 30min. While APTT level in no heparin group increased slowly. Further analyse showed that median APTT level at each time point was statistically significant different between the two groups (t 2.201, P= 0.036).TT:The TT level in low-dose heparin group was also increased rapidly, reaching the first peak at the time point of 30min and the second peak at the time point of 4h. In the end of the treatment it was still significantly higher than basic level. However, the TT level in no heparin group maintained a steady state during the whole treatment. And median TT level at each time point was statistically significant different between the two (t= 3.287, P= 0.003).Fbg:A significant difference on Fbg level was obtained between the two groups. In low-dose heparin group it was stabilized and increased slightly at the end of treatment. While in no heparin group it was decreased gradually and reached a ravine at the end of treatment. However, a curve was observed in the treatment of 2.5h between the two groups(F= 3.630, P= 0.001). 7. There were two cases of bleeding, seven cases of clotting in degree I and one case of clotting in degree II in the heparin group; while six cases of clotting in degree I and one case of clotting in degree III in no heparin group. And no case of hypersensitiveness was found in both groups. Thus no signficant difference was observed on complications between the two groups (P=0.845)Conclusion:1. Both low-dose heparin and no heparin systems are likely to cause declining on BPC in MARS treatment of liver failure. However, more obvious was obtained in no heparin group.2. PTA is an important but not the only indicator of blood coagulation in patients with liver failure. Comprehensive analysis of BPC, FDP, D-dimer and clinical symptoms is critical and required to determine the coagulation status to select an anticoagulation system before MARS.3. The use of low dose heparin in MARS improves the disorder of hypercoagulable state during high coaguation period; while no heparin during low coagulation period could effectively prevent the occurrences of bleeding and improve the mechanism of blood coagulation by reducing heparin-like substance in blood.更多还原