腹腔热灌注化疗联合肿瘤细胞减灭术对卵巢癌患者凝血功能及血小板参数的影响

Effect of hyperthermic intraperitoneal perfusion chemotherapy combined with cytoreductive surgery on coagulation function and platelet parameters in patients with ovarian cancer

目的观察腹腔热灌注化疗联合卵巢癌肿瘤细胞减灭术对卵巢癌患者凝血功能及血小板参数的影响。方法抽取2011年1月至2015年12月于河南省人民医院住院并行满意的肿瘤细胞减灭术的卵巢癌患者140例(卵巢癌组),按照治疗方法又将其分为腹腔热灌注化疗+静脉化疗组(80例,以下简称热灌注化疗组)和单纯静脉化疗组(60例,以下简称静脉化疗组)。另抽取同期住院的良性疾病(子宫肌瘤和子宫内膜异位症)患者80例作为良性疾病组。所有患者入院第2天清晨抽取空腹静脉血4 ml行血常规、凝血五项检验并记录结果,观察良性疾病组和卵巢癌组患者凝血功能[活化部分凝血酶时间(APTT)、凝血酶原时间(PT)、凝血酶时间(TT)、D-二聚体(D-D)、纤维蛋白原(FIB)]及血小板参数[血小板计数(PLT)、血小板分布宽度(PDW)、血小板平均体积(MPV)]的差异性。热灌注化疗组从术后第1天开始每天1次腹腔热灌注治疗,连续3 d,第3天加用顺铂,术后第5天给予紫杉醇注射液静脉化疗;静脉化疗组于术后第5天给予紫杉醇+卡铂化疗。抽取两组卵巢癌患者术后第1、4、8天清晨空腹静脉血4 ml进行血常规、凝血五项检查并记录结果,观察热灌注化疗对卵巢癌患者凝血功能、栓塞发生率及血小板参数的影响。结果卵巢癌组与良性疾病组术前APTT、PT、TT水平比较差异未见统计学意义(P>0.05),但卵巢癌组D-D、FIB、PLT、PDW、MPV水平均高于良性疾病组(P均<0.05)。术后第1天,热灌注化疗组与静脉化疗组各凝血指标及血小板参数比较差异未见统计学意义(P>0.05);术后第4、8天,热灌注化疗组与静脉化疗组APTT、PT、TT比较差异未见统计学意义(P>0.05),但热灌注化疗组D-D、FIB水平低于静脉化疗组(P<0.05);术后第4、8天,热灌注化疗组PLT、PDW、MPV水平均低于静脉化疗组(P均<0.05)。静脉化疗组下肢血栓的发生率(25.00%,15/60)高于热灌注化疗组(10.00%,8/80),P<0.05。结论与良性疾病患者相比,卵巢癌患者常存在高凝状态,血小板数目增多,活化的血小板占比增多,发生血栓的概率增加。热灌注化疗有助于改善卵巢癌患者的凝血功能,抑制血小板的释放并降低其活跃程度,减少血栓栓塞事件的发生。

Objective To observe the effect of hyperthermic intraperitoneal perfusion chemotherapy combined with cytoreductive surgery on coagulation function and platelet parameters in patients with ovarian cancer.Methods One hundred and forty ovarian cancer patients with satisfactory tumor cell reduction surgery who were hospitalized in Henan Provincial People’s Hospital from January 2011 to December 2015 were selected as ovarian cancer group;and they were further divided into hyperthermic intraperitoneal perfusion chemotherapy combined with intravenous chemotherapy group(80 cases,referred to as hyperthermic perfusion chemotherapy group)and intravenous chemotherapy alone group(60 cases,referred to as intravenous chemotherapy group)according to treatment method.Eighty patients with benign diseases(hysteromyoma and endometriosis)hospitalized during the same period were set as benign diseases group.On the morning of the 2nd day after admission,4 ml fasting venous blood was taken for blood routine and coagulation five-term examination,and the results were recorded.The difference of coagulation function assessed by activated partial thromboplastin time(APTT),prothrombin time(PT),thrombin time(TT),D-dimer(D-D)and fibrinogen(FIB),and platelet parameters including platelet count(PLT),platelet distribution width(PDW),and mean platelet volume(MPV)between benign disease group and ovarian cancer group were observed.The hyperthermic perfusion chemotherapy group was treated by hyperthermic intraperitoneal perfusion once a day from the 1st day after operation for 3 consecutive days;on the 3rd day,the chemotherapy protocol added cisplatin;on the 5th day,intravenous chemotherapy of paclitaxel injection was performed.Intravenous chemotherapy group was treated by paclitaxel combined with carboplatin chemotherapy on the 5th day after operation.On the morning of the 1st,4th and 8th days after operation,4 ml fasting venous blood was sampled from the two groups with ovarian cancer patients for blood routine and coagulation examination,and the results were recorded.The effect of hyperthermic perfusion chemotherapy on coagulation function,embolism incidence and platelet parameters of ovarian cancer patients was observed.Results There was no statistically significant difference in levels of APTT,PT and TT between the ovarian cancer group and the benign disease group before operation(P>0.05),however,the levels of D-D,FIB,PLT,PDW and MPV in the ovarian cancer group were higher than those in the benign disease group(all P<0.05).On the 1st day after operation,there was no significant difference in coagulation indexes and platelet parameters between the hyperthermic perfusion chemotherapy group and the intravenous chemotherapy group(P>0.05);on the 4th and 8th days after operation,there was no significant difference in levels of APTT,PT and TT between the hyperthermic perfusion chemotherapy group and the intravenous chemotherapy group(P>0.05),but the levels of D-D and FIB in the hyperthermic perfusion chemotherapy group were lower than those in the intravenous chemotherapy group(P<0.05).On the 4th and 8th days after operation,the levels of PLT,PDW and MPV in the hyperthermic perfusion chemotherapy group were lower than those in the intravenous chemotherapy group(all P<0.05).The incidence of lower limb thrombosis in the intravenous chemotherapy group was 25.00%(15/60),higher than the 10.00%(8/80)in the hyperthermic perfusion chemotherapy group(P<0.05).Conclusions Compared with patients with benign diseases,patients with ovarian cancer often have hypercoagulable state,a significant increase in the number of platelets,increase in the proportion of activated platelets and the probability of thrombosis.Hyperthermic perfusion chemotherapy is helpful to improve the coagulation function of patients with ovarian cancer,inhibit the release of platelets and reduce their activity,and reduce the incidence of thromboembolic events.