一种新型心室辅助装置植入术后抗凝治疗管理
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摘要
目的通过对左心辅助羊术后抗凝的药物管理,摸索行之有效的抗凝治疗方案。方法 6例雄性成年绵羊,(80.0±5.0) kg,分别植入同一型号的左心室辅助装置(left ventricular assist device,LVAD)。术后前2周,每日清晨采血1次;之后,每周采晨血1次。术后每日口服华法林,检测凝血全项,持续观察10周,对抗凝效果做出评价。结果 6例实验动物的生理状态下的国际标准化比率(international normalized ratio,INR)为1.265±0.146,活化部分凝血活酶时间(activated partial thromboplastin time,APTT)为(41.017±12.530)s,乳酸脱氢酶(lactate dehydrogenase,LDH)为(411±119)U/L。术后1～3 d,应用肝素和口服华法林,控制INR和APTT分别为基值的1.4和1.7倍。待实验动物可以平稳进食后,停止使用肝素。持续监测INR,调整华法林用量。术后2周内,使用华法林(7.96±5.45)mg/d,测得INR为1.89±0.53。术后10周内,使用华法林(11.44±7.80)mg/d,测得INR为2.01±0.91;LDH为(509±92)U/L。在研究过程中,6例HeartCon均未出现泵内血栓,实验动物未见消化道出血等迹象。结论术后早期应用肝素抗凝是必要的。在不改变饮食结构的前提下,两周内基本可以制定每例个体的抗凝治疗标准。单一使用华法林,可以达到预期的抗凝效果。
Objective To determine an effective anticoagulant treatment program by the management of anticoagulants after the implantation of a new left ventricular assist device(LVAD) in sheep. Methods Six male healthy sheep weight 80±5 kg were implanted with the same type of LVAD. Blood was collected once a day in the first two weeks and once a week thereafter. The sheep were observed and evaluated for 10 weeks. Results The physiological state of the six experimental animals: the international normalized ratio(INR) was 1.265±0.146; activated partial thromboplastin time(APTT) was 41.017±12.530 s; lactate dehydrogenase(LDH) level was 411±119 U/L. One to three days after operation, the control of INR and APTT by heparin and warfarin were 1.4 and 1.7 times higher. Heparin was stopped when the animal could eat again. INR was monitored continuously and the warfarin dosage was adjusted. Two weeks after operation, warfarin 7.96±5.45 mg/d was used and the INR was 1.89±0.53. Ten weeks after operation, warfarin 11.44±7.80 mg/d was used, the INR was 2.01±0.91 and the level of LDH was 509±92 U/L. During the study, no thrombus caused by the pump was found, and no gastrointestinal bleeding was found in experimental animals. Conclusions It is necessary to apply heparin early after the operation. Under the premise of not changing the diet structure, the anticoagulant treatment standard for each individual is established within 2 weeks. The use of warfarin only can achieve the expected anticoagulant effect.
Objective To determine an effective anticoagulant treatment program by the management of anticoagulants after the implantation of a new left ventricular assist device(LVAD) in sheep. Methods Six male healthy sheep weight 80±5 kg were implanted with the same type of LVAD. Blood was collected once a day in the first two weeks and once a week thereafter. The sheep were observed and evaluated for 10 weeks. Results The physiological state of the six experimental animals: the international normalized ratio(INR) was 1.265±0.146; activated partial thromboplastin time(APTT) was 41.017±12.530 s; lactate dehydrogenase(LDH) level was 411±119 U/L. One to three days after operation, the control of INR and APTT by heparin and warfarin were 1.4 and 1.7 times higher. Heparin was stopped when the animal could eat again. INR was monitored continuously and the warfarin dosage was adjusted. Two weeks after operation, warfarin 7.96±5.45 mg/d was used and the INR was 1.89±0.53. Ten weeks after operation, warfarin 11.44±7.80 mg/d was used, the INR was 2.01±0.91 and the level of LDH was 509±92 U/L. During the study, no thrombus caused by the pump was found, and no gastrointestinal bleeding was found in experimental animals. Conclusions It is necessary to apply heparin early after the operation. Under the premise of not changing the diet structure, the anticoagulant treatment standard for each individual is established within 2 weeks. The use of warfarin only can achieve the expected anticoagulant effect.
引文
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[13] Akin S,Soliman OI,Constantinescu AA,et al.Haemolysis as a first sign of thromboembolic event and acute pump thrombosis in patients with the continuous-flow left ventricular assist device HeartMate Ⅱ[J].Neth Heart J,2016,24(2):134-142.
[14] Rimsans J,Sylvester KW,Connors JM.Direct thrombin inhibitor for LVAD thrombosis:a closer look [J].Clin Appl Thromb Hemost,2017,23(5):405-409.
[15] Bartoli CR,Zhang D,Kang J,et al.Clinical and in vitro evidence that subclinical hemolysis contributes to LVAD thrombosis [J].Ann Thorac Surg,2018,105(3):807-814.
[16] Martinez BK,Yik B,Tran R,et al.Meta-analysis of time in therapeutic range in continuous-flow left ventricular assist device patients receiving warfarin [J].Artif Organs,2018,42(7):700-704.
[17] Ghodsizad A,Badiye A,Zeriouh M,et al.Pump thrombosis following HeartMate II left ventricular assist device implantation in a patient with aspirin and plavix resistance [J].Heart Surg Forum,2016,19(6):E284-E285.
[18] Bergh WMVD,Lansink-Hartgring AO,Duijn ALV,et al.Thromboembolic stroke in patients with a HeartMate-II left ventricular assist device-the role of anticoagulation[J].J Cardiothorac Surg,2015,10:128.
[19] Yoshioka D,Toda K,Hidaka T,et al.Anticoagulation therapy for a LVAD patient with acquired warfarin resistance[J].J Artif Organs,2017,20(3):260-262.
[20] Bitar A,Vijayakrishnan R,Lenneman A,et al.The use of eptifibatide alone or in combination with heparin or argatroban for suspected thrombosis in patients with left ventricular assist devices [J].Artif Organs,2017,41(12):1092-1098.
[21] Boehme AK,Pamboukian SV,George JF,et al.Anticoagulation control in patients with ventricular assist devices [J].ASAIO J,2017,63(6):759-765.
[22] Welden CV,Truss W,Mcgwin G,et al.Clinical predictors for repeat hospitalizations in left ventricular assist device (LVAD) patients with gastrointestinal bleeding [J].Gastroenterol Res,2018,11(2):100-105.
[2] Combes A.Mechanical circulatory support for end-stage heart failure[J].Metabolism,2017,69:30-35.
[3] Lara-Pezzi E,Menasché P,Trouvin JH,et al.Guidelines for translational research in heart failure[J].J Cardiovasc Transl Res,2015,8(1):3-22.
[4] 姜洋,高航,王伟,等.磁液悬浮式离心血泵实验研究[J].北华航天工业学院学报,2012,22(6):4-6.
[5] 张杰民,刘晓程,刘志刚,等.磁液双悬浮离心血泵左心辅助的动物实验[J].中华医学杂志,2014(22):1740-1743.
[6] 刘天文,张杰民,刘志刚,等.磁液悬浮离心式心室辅助装置实验研究[J].中华生物医学工程杂志,2015,21(3):242-246.
[7] 姜洋,王伟,苏静静,等.Percutaneous guide line traction device of artificial assisted heart,CN 103623473 A[P].2014.
[8] 姜洋,王伟,苏静静,等.人工辅助心脏经皮导线牵引装置,Artificial heart percutaneous wire traction device,CN 103623473 B[P].2016.
[9] 刘晓程,张杰民,李翼鹏,等.左心室缝合环,CN202620331U[P].2012.
[10] 姜洋,刘晓程,许剑,等.一种外科手术用开孔钻头,CN203506831U[P].2014.
[11] Saeed D,Fukamachi K.In vivo preclinical anticoagulation regimens after implantation of ventricular assist devices[J].Artif Organs,2010,33(7):491-503.
[12] Gavalas MV,Breskin A,Yuzefpolskaya M,et al.Discriminatory performance of positive urine hemoglobin for detection of significant hemolysis in patients with continuous-flow left ventricular assist devices[J].J Heart Lung Transplant,2017,36(1):59-63.
[13] Akin S,Soliman OI,Constantinescu AA,et al.Haemolysis as a first sign of thromboembolic event and acute pump thrombosis in patients with the continuous-flow left ventricular assist device HeartMate Ⅱ[J].Neth Heart J,2016,24(2):134-142.
[14] Rimsans J,Sylvester KW,Connors JM.Direct thrombin inhibitor for LVAD thrombosis:a closer look [J].Clin Appl Thromb Hemost,2017,23(5):405-409.
[15] Bartoli CR,Zhang D,Kang J,et al.Clinical and in vitro evidence that subclinical hemolysis contributes to LVAD thrombosis [J].Ann Thorac Surg,2018,105(3):807-814.
[16] Martinez BK,Yik B,Tran R,et al.Meta-analysis of time in therapeutic range in continuous-flow left ventricular assist device patients receiving warfarin [J].Artif Organs,2018,42(7):700-704.
[17] Ghodsizad A,Badiye A,Zeriouh M,et al.Pump thrombosis following HeartMate II left ventricular assist device implantation in a patient with aspirin and plavix resistance [J].Heart Surg Forum,2016,19(6):E284-E285.
[18] Bergh WMVD,Lansink-Hartgring AO,Duijn ALV,et al.Thromboembolic stroke in patients with a HeartMate-II left ventricular assist device-the role of anticoagulation[J].J Cardiothorac Surg,2015,10:128.
[19] Yoshioka D,Toda K,Hidaka T,et al.Anticoagulation therapy for a LVAD patient with acquired warfarin resistance[J].J Artif Organs,2017,20(3):260-262.
[20] Bitar A,Vijayakrishnan R,Lenneman A,et al.The use of eptifibatide alone or in combination with heparin or argatroban for suspected thrombosis in patients with left ventricular assist devices [J].Artif Organs,2017,41(12):1092-1098.
[21] Boehme AK,Pamboukian SV,George JF,et al.Anticoagulation control in patients with ventricular assist devices [J].ASAIO J,2017,63(6):759-765.
[22] Welden CV,Truss W,Mcgwin G,et al.Clinical predictors for repeat hospitalizations in left ventricular assist device (LVAD) patients with gastrointestinal bleeding [J].Gastroenterol Res,2018,11(2):100-105.