低分子量肝素联合华法林治疗晚期肺癌合并急性肺栓塞临床研究

目的 观察低分子量肝素联合华法林治疗晚期肺癌合并急性非大面积肺栓塞的疗效及对呼吸困难症状的影响.方法 2008年7月至2010年6月收治ⅢB～Ⅳ期肺癌合并肺栓塞患者15例,所有患者均经螺旋CT动脉造影(SCTPA)确诊为急性非大面积肺栓塞.给予依诺肝素(1mg/kg体重)每12 h皮下注射1次(7～14 d),并在应用依诺肝素48 h后加用华法林,调整华法林剂量使国际标准化比值(INR)维持在2.0～3.0.监测患者治疗前和治疗后4、7、14d的呼吸困难分级(MRC分级)、动脉血气分析等指标的变化,观察疗效.结果 2例合并下肢深静脉血栓形成(DVT)患者因并发多器官功能衰竭分别于治疗第6天和第11天死亡,其余13例患者治愈6例,显效5例,好转2例,中位生存期9.2个月.治疗后4、7、14d患者的MRC分级由(3.1±0.5)级降低至(1.9±0.8)、(1.5±0.5)、(0.6±0.6)级,动脉血氧分压(PaO2)由(60.5±7.2) mm Hg(1 mm Hg=0.133 kPa)升高至(76.1±9.7)、(81.6±9.2)、(86.2±7.5) nn Hg,血浆D-二聚体由(9.44±5.29) mg/L降低至(4.33±3.34)、(0.88±0.32)、(0.41±0.17) mg/L,肺泡-动脉血氧分压差[(P(A-aO2)由(38.5±6.7)mm Hg降低至(35.5±5.1)、(29.3±3.2)、(24.1±4.1) mm Hg,其中PaO2、MRC分级、血浆D-二聚体治疗后4、7、14d与治疗前比较差异均有统计学意义(P＜0.05),而P(A-a)O2治疗后7、14d与治疗前比较差异有统计学意义(P＜0.05).在抗凝治疗期间无一例患者出现危及生命的大出血及血栓栓塞.结论 低分子量肝素联合华法林治疗晚期肺癌合并急性非大面积肺栓塞可显著改善患者的呼吸困难症状,不良反应少,安全性较高.

Clinical study of low-molecular-weight heparin combined with warfarin in advanced lung cancer patients with acute pulmonary embolism

Objective To investigate the efficacy of low-molecular-weight heparin (LMWH)combined with warfarin in advanced lung cancer patients with acute non-massive pulmonary embolism (PE) and the effect on dyspnea symptom.Methods Fifteen (stage Ⅲ B-Ⅳ ) lung cancer patients with PE from July 2008 to June 2010 were enrolled.All the patients were diagnosed as acute non-massive PE according to spiral computed tomography pulmonary angiography (SCTPA).Enoxaparin (1 mg/kg) was injected with subcutaneous injection twice a day for 7-14 days.Oral warfarin was added once a day 48 h after enoxaparin injection and the dosage was adjusted according to international normalized ratio (INR) level(maintain 2.0-3.0).The medical research council (MRC) grade,results of arterial blood gas analysis and adverse reactions were observed.Results Six patients were accompanied with deep venous thrombosis (DVT)according to vascular Doppler ultrasound,2 patients were died at the 6th day and 11th day due to multiple organ dysfunction syndrome.Six patients were cured.5 patients were good,2 patients were improved.The median survial time was 9.2 months.Thirteen patients' MRC grade was decreased trom (3.1 ± 0.5 ) grades to ( 1.9 ± 0.8 ),( 1.5 ± 0.5 ),(0.6 ± 0.6) grades,arterial oxygen pressure (PaO2) was raised from (60.5 ± 7.2)mm Hg (1 mm Hg=0.133 kPa) to (76.1 ±9.7),(81.6±9.2),(86.2±7.5) mm Hg,plasma D-dimer was decreased from (9.44 ± 5.29 ) mg/L to (4.33 ± 3.34 ),(0.88 ± 0.32 ),( 0.41 ± 0.1 7 ) mg/L and alveolar-arterial oxygen tension gradient [ P( A-a)O2 ] was increased from ( 38.5 ± 6.7 )mm Hg to ( 35.5 ± 5.1 ),(29.3 ± 3.2),(24.1 ± 4.1 ) mm Hg after 4,7,14 days of the treatment.There were significant differences in PaO2,MRC grade,plasma D-dimer before and after 4,7,14 days of the treatment (P ＜ 0.05),there was significant difference in P ( A-a)O2 before and after 7,14 days of the treatment (P＜ 0.05).There was no patient with big hemorrhage and thromboembolism during anticoagulant therapy.Conclusions For advanced lung cancer patients,the combination therapy with LMWH and warfarin for acute non-massive PE appears to be safe and effective on improving dyspnea symptom and hypoxemia.Adverse reaction is seldom.