ACT肝素反应斜率在体外循环中的应用

心脏外科的广泛开展，使体外循环直视手术常遇见具有不同凝血状态的复杂患者，激活全血凝固时间(ACT)监测已广泛用于体外循环指导肝素抗凝及鱼精蛋白对抗。本文就本院近两年来68例体外循环在ACT肝素反应斜率指导下使用肝素的总剂量及鱼精蛋白拮抗量作一总结并报道如下。     

低剂量鱼精蛋白拮抗肝素围体外循环期血浆肝素浓度变化与凝血功能损害

目的：探讨低剂量鱼精蛋白拮抗肝素围体外循环(CPB)期血浆肝素浓度变化的规律及其与术后凝血功能损害的关系。方法：采用发光底物法测定25例风湿性心脏瓣膜病瓣膜置换手术病人低剂量鱼精蛋白拮抗肝素下围CPB期血浆肝素浓度，并同时检测凝血功能指标：激活凝血时间(ACT)、血浆凝血酶原时间(PT)和活化部分凝血活酶时间(APTT)。结果：CPB结束时血浆肝素平均水平(11．06U／mL)显著地降低到肝素化初期浓度(13．16U／mL)的0．84左右(P<0．05)，低剂量鱼精蛋白拮抗肝素后5h内血浆肝素水平基本上稳定在CPB前水平(P>0．05)；当鱼精蛋白中和肝素后，ACT值迅速接近至术前水平(P>0．05)，并稳定于术前水平，而PT、APTT则仍显著异常高于正常水平(P<0．05)，但有明显恢复至正常的趋势。结论：CPB结束时采用低剂量鱼精蛋白拮抗肝素(0．8mg鱼精蛋白：100U肝素)能充分有效地中和血中肝素：CPB后凝血功能并不立即恢复正常，主要原因不是肝素中和不足，而是CPB本身使凝血功能受到损害。     

体外循环后控制性机血回输的临床研究

【目的】观察体外循环后控制性机血回输对胸液量和激活全血凝血时间（ACT）的影响。【方法】112例心脏瓣膜置换病人随机分为A、B两组,A组为机血通过中心静脉1～3h输完,并常规每100mI。机血给5mg鱼精蛋白中和。B组为体外循环（CPB）停机鱼精蛋白中和后10min内肝素血主动脉管输完,残余管道部分弃置。两组的麻醉、病人体外循环及停机后体内肝素中和方法相同。观测CPB后ACT值、关胸止血时间及术后24h胸液量。【结果】B组比A组ACT更接近生理值（P〈0．05）,关胸止血时间明显缩短（P〈0．01）,且胸液量明显减少（P〈0．01）。【结论】心脏手术中鱼精蛋白中和后10min内肝素血输完,能明显缩短手术时间,减少术后胸液渗量,减少库血的应用,临床操作方便和实用。     

体外循环后鱼精蛋白拮抗肝素两种方法的临床比较

目的比较两种鱼精蛋白拮抗肝素方法对体外循环后肝素中和效果及不良反应的影响。方法选择100例成年换瓣心脏手术患者,ASAⅡ～Ⅲ级,随机分为两组:Ⅰ组为常规肝素中和组,停机后一次予鱼精蛋白(鱼精蛋白/肝素比率为1.2:1),必要时根据ACT结果追加;Ⅱ组为负荷小剂量+微泵维持组,停机后先予鱼精蛋白/肝素为0.8:1中和,再微泵维持(50mg/h)。记录两组手术时间、关胸时间;测定中和后10min、30min、术毕ACT时间;记录术中出血量、输血量、鱼精蛋白中和肝素比例、术后24h胸腔引流量、鱼精蛋白中和后不良反应情况。结果鱼精蛋白中和肝素比例两组无统计学差异(P>0.05);中和前、中和后10min、术毕ACT两组差异无统计学意义(P>0.05),中和后30minⅠ组ACT明显较Ⅱ组延长(P=0.000);术中出血、输血量、关胸时间Ⅰ组优于Ⅱ组;术后6h胸腔引流量、输血量无统计学差异;中和后Ⅱ组轻度不良反应发生率低于Ⅰ组(P=0.000),Ⅰ组中、重度不良反应5例,Ⅱ组无重度不良反应发生,但无统计学差异(P=0.07)。结论负荷小剂量+微泵维持鱼精蛋白中和肝素策略使关胸时间明显缩短、术中出血量、用血量、鱼精蛋白不良反应均减少。     

一氧化氮在小儿体外循环时的关系变化

体外循环是进行心内直视手术必须的技术，同时又是一个非生理性的控制性休克阶段。在体外循环过程中涉及血液和血管壁的众多细胞及其分泌的细胞因子。一氧化氮（NO）是内皮细胞分泌的扩血管因子，也是体内最重要的气体信使之一。探讨NO用于儿童心内直视手术的目的在于通过其血管舒张作用改善其血流动力学，增强和保护血小板，加强心肌保护，从而进一步减少体外循环引起的炎症反应。研究者们应用NO时，在选取观察对象，NO使用剂量，样本的量，肝素及鱼精蛋白用量，体外循环（CPB）预充及输血指征等方面差异很大。作者对NO的生化特性和功能，及其在小儿CPB过程中的特殊性进行综述。     

激活全血凝固时间在体外循环455例中的应用

激活全血凝固时间(ACT)是体外循环、(CPB)时指导肝素抗凝和鱼精蛋白(PRTM)拮抗的监测手段。由于按常规方法计算给予肝素，个体之间相差达3倍。ACT在400秒以下可出现纤维蛋白原单体，说明有轻度凝血。ACT在600秒以上为肝素抗凝过份，不仅损害以血小板为媒介的止血，同时使肝素难以拮抗。本文对455例病人ACT监测总结如下。     

体外循环心内直视手术中大剂量国产抑肽酶的止血作用及机制：？…

目的：探讨体外循环中大剂量国产抑肽酶的止血作用及机制。方法：１２０例体外循环心内直视手术病人随机分为抑肽酶组和对照组。实验组抑肽酶剂量６万ＫＩＵ／ｋｇ,选点测定血中ＰＣ、Ｆｉｂ、ＦＤＰ等指标的变化并观察术中术后的出血量和输血量。结果：用药组出血量和输血量分别比对照减少５０％左右。ＦＤＰ较对照组降低（Ｐ〈０．０５）,Ｆｉｂ较对照组增高（Ｐ〈０．０５）。结论：大剂量国产抑肽酶有明显的止血效果,抑制纤溶     

体外循环心脏直视术中鱼精蛋白毒性反应的临床防治

目的：探讨体外循环心脏直视术中鱼精蛋白毒性反应的临床特点及防治对策，方法：回顾性分析连续1727体外循环心脏直视术病例，参照Oe及Weiler标准将其分为有反应组（鱼精蛋白毒性反应组）和无反应组，并将有反应组分为轻度和中重度反应组，分析其临床特点，结果：发生鱼精蛋白毒性反应者43例，发生率2．48％，其中轻度反应者35例（81．39％，35／43），中重度反应者8例（18．61％，8／43），有反应组与反应组临床一般情况无明显差别，中重度反应组转流时间及反应持续时间明显较轻度反应组长（P＜0．05）。中重度反应组死亡2例。结论：体外循环心脏直视术中鱼精蛋白毒性反应的发生难以预料；中重度反应者后果严重；临床上应充分认识鱼精蛋白毒性反应的特点，对转流时间较长的患者的应高度警惕鱼精蛋白毒性反应的发生；低浓度缓慢静脉给药可减少毒性反应的发生，发生严重毒性反应者应立即停药，迅速肝素化并再转机辅助循环，有利于对中重度毒性反应的救治。     

浅低温心脏不停跳心内直视手术215例临床分析

目的：总结215例浅低温体外循环下不停跳心内直视手术的临床应用经验。方法：215例行心脏不停跳心内直视手术病例,并行循环者阻断上下腔静脉而不阻断升主动脉,不使用心脏停跳液;逆行灌注者,阻断升主动脉后经冠状静脉窦逆行持续灌注机器氧合血,鼻咽温度在（33±1）℃,均在心脏空跳下完成心内直视手术。结果：心脏手术完毕后顺利停机,术后血液动力学平稳,低心输出量综合征发生率低,无1例发生神经系统并发症及空气栓塞,早期死亡率0．93％（2／215）。结论：浅低温体外循环下不停跳心内直视手术技术安全可行,是一种接近生理状态的心肌保护方法,可应用于绝大部份心内直视手术。     

心内直视术中鱼精蛋白的毒性反应分析

肝素的应用以及鱼精蛋白的中和作用 ,使现代心脏外科得到飞速发展。近年来 ,随着外科技术和体外循环的提高 ,手术死亡率明显下降。但鱼精蛋白所引起的严重毒性反应成为心内直视手术患者死亡的重要原因之一。我院自 2 0 0 0 - 0 8～ 2 0 0 3- 0 1行各种心内直视手术 2 4 6例中 ,发生鱼精蛋白毒性反应 14例 ,发生率为 4 .8%。美国从 1984～ 1991年 ,鱼精蛋白的毒性反应发生率由 0 .0 6 %上升至 0 .7% ,说明这种术中反应并不少见 ,现分析如下。1　对象和方法1.1　对象　本组男 175例 ,女 71例 ,男∶女为 2 .5∶ 1。年龄 9月龄～ 81岁。其中各种…     

长托宁在CPB体外循环瓣膜置换术鱼精蛋白不良反应中的应用

[目的]评价长托宁对体外循环瓣膜置换术(CPB-VR)鱼精蛋白不良反应的临床疗效.[方法]择期成人行CPB-VR中患者59例,随机分为两组:长托宁组 (A组,n=28),对照组(B组,n=31).麻醉诱导前10 min两组分别给予长托宁0.02 mg/kg和等体积生理盐水.观察各组鱼精蛋白不良反应发生情况,记录注射即刻...     

Anticoagulation management in patients undergoing open heart surgery by activated clotting time and whole blood heparin concentration

OBJECTIVE: To investigate the changes in perioperative anticoagulation management using a heparin-concentration-based system (HMS), and its effect on postoperative outcome. METHODS: A total of 39 patients undergoing elective primary open heart surgery were randomly assigned to a heparin-concentration-based system approach (study group: 17 patients) or a standard ACT-based anticoagulation system (control group: 22 patients). MEASUREMENTS AND MAIN RESULTS: Patients in the study group received a statistically significant higher dose of heparin (median 29000 IU with IQR 22 500-33 500 IU versus median 19 000 IU with IQR 17 775-21 500 IU; p < 0.001) and a smaller dose of protamine (median 170 mg with IQR 145-190 mg versus median 200 mg with IQR 180-250 mg; p = 0.008) compared to the control group. Postoperative platelet count was significantly higher in the study group (164 +/- 45 x 10(9)/L versus 125 +/- 27 x 10(9)/L, p = 0.002). None of the study patients, but six patients in the control group required transfusion of blood products (p = 0.02). No differences were recorded in postoperative antithrombin activity, bleeding, and other clinical outcomes. CONCLUSION: The HMS system, by facilitating maintenance of a stable heparin concentration, and by determining an appropriate dose of protamine, is associated with reduced platelet consumption and does not increase AT-III consumption and postoperative bleeding.     

Assessing heparin neutralization following cardiac surgery: sensitivity of thrombin time-based assays versus protamine titration methods.

Adequate assessment of heparin neutralization following cardiac surgery is critical in reducing the patient's exposure to protamine. Both excessive protamine and residual heparin have been associated with postoperative bleeding and poor patient recovery. The activated clotting time (ACT) is the preferred intraoperative heparin monitor, while both protamine titration (i.e. a protamine-containing ACT) and thrombin time methods have been used to detect circulating residual heparin after protamine administration. Following initial protamine dosing using the protamine response test (PRT), postoperative monitoring was employed in the operating room prior to transport of the patient to intensive care. Two point-of-care assays, the thrombin time (TT) and the protamine dose assay (PDA), were evaluated to determine their relative heparin sensitivity and their usefulness to quantitate protamine dose. The PDA, which is based on the ACT, was shown in laboratory and clinical studies to detect residual heparin above 0.25 units/ml and to quantify additional minidoses of protamine (as low as 25 mg) required to obtain complete heparin neutralization. Differential evaluation of the TT and heparin neutralized thrombin time (HNTT) was shown in laboratory studies to be more sensitive to small amounts of residual heparin than the ACT. Clinical evaluations confirmed that additional protamine is required in approximately 12% of cardiac surgical cases managed using the PRT system. Both the PDA and TT/HNTT provided useful postoperative assessment of the adequacy of heparin neutralization. The TT/HNTT had slightly improved heparin sensitivity even in the presence of significant fibrinogen loss. These point-of-care assays provide the opportunity to optimize heparin and protamine management in the cardiac surgery patient.     

Comparison of two methods for heparin monitoring: A semi-automated heparin monitoring device and activated clotting time during extracorporeal circulation

Two methods of heparin monitoring, semi-automated in-vivo heparin protamine titration (HPT) and activated clotting time (ACT), were compared in each of sixteen adult patients undergoing extracorporeal circulation (ECC) for coronary artery bypass surgery. The HPT method determined the initial and maintenance level of heparin for ECC, as well as, the amount of protamine needed for neutralization of heparin. ACT determinations were made in parallel to calculate heparin levels, heparin sensitivity, and protamine requirements. ACT determinations increased from 502±31 seconds after heparinization to 739±49 seconds (p<0.05) five minutes after the start of ECC. The HPT method determined heparin sensitivity to be 153±17 secs/mg/kg and this did not change after the institution of ECC. The increase in ACT observed after the start of ECC resulted in an increase in heparin sensitivity from 151±13 secs/mg/kg initially, to 247±17 secs/mg/kg after the institution of ECC (p<0.01). During ECC, the HPT method reported heparin levels which remained near the initial value of 2.40±0.12 mg/kg. The ACT method's initial heparin level of 2.66±0.12 mg/kg rose after the start of ECC to 4.39±0.55 mg/kg (p<0.05). The HPT method adequately predicted protamine requirements, 2.66±0.15 mg/kg protamine vs. 3.47±0.14 mg/kg actual dose while the ACT method predicted excess: 5.02±0.34 mg/kg (p<0.01). In-vivo heparin-protamine titration method provided more consistent information during ECC and directed a significantly smaller dose of protamine for heparin neutralization.     

Changing systems for measuring activated clotting times: impact on the clinical practice of heparin anticoagulation during cardiac surgery

BACKGROUND: The activated clotting time (ACT) is a standard monitor for heparin anticoagulation during cardiopulmonary bypass (CPB). This study determines the effect of upgrading our ACT system on our clinical practice with regards to the conduct and safety of heparin anticoagulation during cardiopulmonary bypass. METHODS: We compared the intraoperative heparin doses required for all adult cardiac surgery patients (n=1240) and postoperative bleeding for a subset of primary aortocoronary bypass (CABG) surgery procedures (n=285) from cohorts before and after the change in ACT systems. RESULTS: The heparin dose needed to exceed our target ACT of 480 sec for the duration of CPB was higher (45000 vs. 40000 units; p<0.0001), and the mean ACT during CPB was lower (557 vs. 618 sec; p<0.05) using the new ACT system. Furthermore, this coincided with decreased postoperative bleeding in the CABG subset (median value of 417 vs. 575 ml over 12 h; p<0.0005). CONCLUSIONS: We demonstrated that the introduction of the Actalyke ACT system significantly altered our clinical practice by increasing the heparin dose required to exceed our target ACT during CPB. Prospective study to determine the effect of Actalyke ACT system monitoring on hemostasis after cardiac surgery is merited.     

局部肝素抗凝在高危出血倾向患者行血液透析中的应用及护理

目的探讨鱼精蛋白中和的局部肝素化在高危出血倾向患者血液透析中临床应用的有效性和安全性。方法采用自身对照法将44例高危出血倾向的血液透析患者按治疗单、双日分为观察组和对照组。观察组采用鱼精蛋白中和的局部肝素化抗凝血液透析治疗56例次,对照组采用传统的无肝素生理盐水冲洗法血液透析治疗39例次,比较两组患者的出血情况、透析器和静脉壶的凝血情况、治疗时间和超滤量以及透析前后的各项生化指标。结果两组无1例诱发或加重出血,观察组的透析器和静脉壶的凝血情况、治疗时间和超滤量以及透析前后生化指标差值明显优于对照组(P<0.05)。结论鱼精蛋白中和的局部肝素抗凝应用于高危出血倾向患者行血液透析安全有效。     

Heparin–protamine balance after neonatal cardiopulmonary bypass surgery

Essentials

• Heparin‐protamine balance (HPB) modulates bleeding after neonatal cardiopulmonary bypass (CPB).
• HPB was examined in 44 neonates undergoing CPB.
• Post‐operative bleeding occurred in 36% and heparin rebound in 73%.
• Thrombin‐initiated fibrin clot kinetic assay and partial thromboplastin time best assessed HPB.

Summary

Background

Neonates undergoing cardiopulmonary bypass (CPB) are at risk of excessive bleeding. Blood is anticoagulated with heparin during CPB. Heparin activity is reversed with protamine at the end of CPB. Paradoxically, protamine also inhibits blood coagulation when it is dosed in excess of heparin.

Objectives

To evaluate heparin–protamine balance in neonates undergoing CPB by using research and clinical assays, and to determine its association with postoperative bleeding.

Patients/Methods

Neonates undergoing CPB in the first 30 days of life were studied. Blood samples were obtained during and after surgery. Heparin–protamine balance was assessed with calibrated automated thrombography, thrombin‐initiated fibrin clot kinetic assay (TFCK), activated partial thromboplastin time (APTT), anti‐FXa activity, and thromboelastometry. Excessive postoperative bleeding was determined by measurement of chest tube output or the development of cardiac tamponade.

Results and Conclusions

Of 44 neonates enrolled, 16 (36%) had excessive postoperative bleeding. The TFCK value was increased. By heparin in neonatal blood samples, but was only minimally altered by excess protamine. Therefore, it reliably measured heparin in samples containing a wide range of heparin and protamine concentrations. The APTT most closely correlated with TFCK results, whereas anti‐FXa and thromboelastometry assays were less correlative. The TFCK and APTT assay also consistently detected postoperative heparin rebound, providing an important continued role for these long‐established coagulation tests in the management of postoperative bleeding in neonates requiring cardiac surgical repair. None of the coagulation tests predicted the neonates who experienced postoperative bleeding, reflecting the multifactorial causes of bleeding in this population.

     

降低预防性血小板输注剂量对慢性血小板减少症患者出血风险的影响

目的 探讨降低预防性血小板输注剂量对慢性血小板减少症(chronic thrombocytopenia)患者出血的影响.方法 选择2008年10月至2010年12月在本院住院的80例因造血干细胞移植(hematopoietic stem cell transplantation,HSCT)、血液系统肿瘤和实体瘤化疗引起...