亚低温治疗对不同程度缺氧缺血性脑病新生儿凝血功能的影响

Effects of hypothermia therapy on coagulopathy in neonates with hypoxic - ischemic encephalopathy of different degrees

目的研究亚低温治疗对不同程度缺氧缺血性脑病（HIE）新生儿凝血功能的影响。方法通过振幅整合脑电图（aEEG）监测结果将25例患儿分为重度异常组（11例）和中度异常组（14例），监测2组患儿亚低温治疗前及亚低温治疗24h、48h、72h后血小板（PLT）计数、活化部分凝血活酶时间（Am）、血浆凝血酶原时间（r-r）、凝血酶时间（1Tr）、纤维蛋白原（17bg）、国际标准化比率（INR）水平，并采用重复测量方差分析比较亚低温治疗对不同程度脑损伤患儿凝血功能影响的差异。结果与中度异常组患儿亚低温治疗前凝血功能比较，重度异常组患儿APTT（t=2．239，P〈0．05）、PT（t=2．453，P〈0．05）明显延长，差异均有统计学意义。亚低温治疗后2组整体比较PLT、PT、AYI＇T、Fbg差异均无统计学意义（均P〉O．05），2组间INR（F=12．470，P〈0．05）、Tr（F：8．275，P〈0．01）比较差异均有统计学意义。4个时间点间Fbg比较差异无统计学意义iP〉0．05），4个时间点间PLT（F=32．420，P〈0．01）、PT（F=9．377，P〈0．01）、APTT（F=15．420，P〈0．01）、1Tr（F=7．326，P〈0．01）、INR（F=12．699，P〈0．01）比较差异均有统计学意义。PLT、INR、Fbg在脑损伤程度分组和时间之间无交互作用（均P〉0．05），町（F=3．374，P〈0．05）、APTT（F=4．227，P〈0．05）、TT（F=3．585，P〈0．05）在脑损伤程度分组和时间之间有交互作用，说明2组患儿PT、APTT、TT变化趋势不同，重度异常组患儿亚低温治疗24h后PT、APTT、TT升高的幅度明显大于中度异常组。重度异常组冷沉淀输注率高于中度异常组，但2组比较差异无统计学意义（P〉0．05）。结论亚低温治疗会影响脑损伤患儿的凝血功能，对重度脑损伤患儿凝血功能影响更大，而对中度脑损伤患儿凝血功能影响相对较小，重度脑损伤患儿在亚低温治疗后面临的出血风险更大，因此对不同程度HIE患儿凝血功能应进行分层干预，对重度脑损伤患儿进行更加积极的干预，以降低出血风险。

Objective To study the effects of hypothermia therapy on coagulopathy in neonates with hypoxic - ischemic encephalopathy（HIE） of different degrees. Methods Twenty - five newborns with HIE were divided into 2 groups （moderate HIE group and severe HIE group） by amplitude integrated electroencephalogram（aEEG）. The platelet （PLT） count,activated partial thromboplastin time （APTT） ,prothrombin time（PT） ,thrombin time（TT） ,fibrinogen （Fbg） and international normalized ratio （INR） were measured before hypothermia therapy and those after 24 hours, 48 hours ,72 hours after hypothermia therapy were collected. Tbe hematological parameters of 2 groups were analyzed by repeated measurement analysis of variance. Results The APTT（t =2.239,P〈0.05）and PT（t =2.453,P〈0.05） of severe HIE group were significantly longer than those of moderate HIE group and significantly different. PLT, PT, APTT and Fbg（ all P 〉 0.05 ） showed no statistically significant difference between 2 groups after hypothermia therapy. The differences in INR （ F = 12. 470, P 〈 0.05 ）, TT （ F = 8. 275, P 〈 0.01 ） between 2 groups were significant. Fbg at different time points showed no significant difference （ P 〉 0.05） between 2 groups. The differences in PLT （ F = 32. 420, P 〈0.01 ） ,PT（F= 9. 377,P 〈0.01） ,APTT（F = 15. 420,P 〈0.01 ）,TT（F =7. 326,P 〈0.01）and INR（F = 12. 699, P 〈 0.01 ） at different time points were significant between 2 groups. The degree of brain injury and time had no interactive effects in PLT, INR and Fbg（ all P 〉 0.05 ）. But the degree of brain injury and time had interactive effects in IT（ F = 3. 374, P 〈 0.05 ）, APT（ F = 4. 227, P 〈 0.05 ） and Tr （ F = 3. 585, P 〈 0.05 ）. It indicated that the change trend in PT, APTT and TI＂ were different between 2 groups. The increase range of PT, APTr and Tr of severe HIE group was higher than moderate HIE group after hypothermia therapy for 24 hours. The percentages of severe HIE group who received transfusion with blood product were higher than those of moderate HIE group （ P 〉 0.05 ）. Conclusion The coagulopathy function is worse in neonates with severe HIE in hypothernfia therapy which may aggravate the hemorrhage risk. And the effect of hypothermia on neonates with moderate HIE is less evident. So hierarchical intervention on coagulopathy in neonates with HIE during hypothermia should be adopted to relieve the hemorrhage risk.