大剂量抑肽酶对血浆肝素浓度和凝血的影响

目的研究体外循环（ＣＰＢ）中大剂量抑肽酶对血浆肝素浓度和凝血的影响。方法选择成人房室间隔缺损修补术病人２０例,随机分为对照组（１０例,未用抑肽酶）和抑肽酶组（１０例,应用大剂量抑肽酶）。分别测定血浆肝素浓度、ＡＰＴＴ、ＴＴ和ＡＣＴ,并记录术后出血量。结果肝素浓度及ＴＴ组间比较无显著差别。抑肽酶组：ＡＣＴ和ＡＰＴＴ均显著延长（Ｐ＜０．０１）,术后６小时出血量明显减少（Ｐ＜０．０５）,但单独应用抑肽酶及肝素被中和后,ＡＣＴ与对照组无显著差别（Ｐ＞０．０５）。结论抑肽酶对肝素浓度及肝素中和无影响,它抑制内源性凝血途径,具有抗凝作用。抑肽酶明显减少ＣＰＢ术后出血量。     

大剂量抑肽酶对血浆肝素浓度和凝血的影响

目的 研究体外循环（ＣＰＢ）中大剂量抑肽酶对血浆肝素浓度和凝血的影响。方法 选择成人房室间隔缺陷修补术病人２０例，随机分为对照组（１０例，未用抑肽酶）和抑肽酶组（１０例，应用大剂量抑肽酶）分别测定血浆肝素浓度，ＡＰＴＴ，ＴＴ和ＡＣＴ，并记录术后出血量。结果 肝素浓度及ＴＴ组间比较无显著差别，抑肽酶组ＡＣＴ和ＡＰＴＴ均显著延长（Ｐ〈０．０１），术后６小时出血量明显减少（Ｐ〈０．０５）但单独应用抑肽酶     

抑肽酶在体外循环心脏外科的临床应用

通过在体外循环心脏手术中应用抑肽酶的临床研究（对照组ｎ＝２０；抑肽酶组ｎ＝５０）结果显示：抑肽酶能有效地保护血小板的功能，避免血小板在体外循环转流时的活化释放及损耗，并减轻血小板数量的下降；抑肽酶还可抑制纤溶系统的激活，与肝素有协同作用，使ＡＣＴ延长，并可减少肝素及鱼精蛋白的用量，最终达到明显减少术后失血量（６３％）及术后输血量（５４％）与输血浆量（４２％）之目的。     

体外循环中肝素、鱼精蛋白对血小板的激活及抑肽酶的抑制作用

目的研究在体外循环中肝素化及鱼精蛋白中和时血小板的激活以及应用抑肽酶对这种激活的抑制作用。方法２０例心脏瓣膜置换术患者随机等分为两组：对照组和抑肽酶组，分别于肝素化及应用鱼精蛋白前后检测血小板胞浆游离钙浓度，磷脂酶Ａ２活性及血浆血栓素水平。结果上述指标在肝素化及鱼精蛋白中和后均显著升高，其中鱼精蛋白中和时升高幅度更大，应用抑肽酶对肝素及鱼精蛋白所引起的上述改变均有显著抑制作用。结论抑肽酶对肝素和鱼精蛋白所致的血小板激活有显著抑制作用，这可能与抑肽酶在体外循环中的止血作用有关。     

氨甲苯酸和抑肽酶对体外循环中肝素抗凝作用的影响

目的为探讨氨甲苯酸和抑肽酶的止血疗效。方法将３４例成人心脏手术患者分为３组，Ａ组于体外循环（ＣＰＢ）前、中、后给予氨甲苯酸共７５０ｍｇ；Ｂ组ＣＰＢ中给予抑肽酶２００万Ｕ；并设一对照组。结果氨甲苯酸使ＣＰＢ中激活全血凝固时间（ＡＣＴ）明显缩短，追加肝素量较另两组显著增加（Ｐ＜０．０５），２４小时胸液量较对照组减少２３％（Ｐ＞０．０５）。抑肽酶使ＣＰＢ中ＡＣＴ略延长，与对照组相比无统计学意义，对肝素用量无影响，２４小时胸液减少３５％（Ｐ＜０．０５）。两用药组术中术后库血用量均显著减少（Ｐ＜０．０１），术后胸液量相似（Ｐ＞０．０５）。结论氨甲苯酸止血疗效弱并缩短ＡＣＴ及明显增加肝素用量，不如抑肽酶疗效可靠。     

小剂量抑肽酶在体外循环中保护血小板作用及减少术后出血

为评估小剂量抑肽酶（１．５×１０６ＫＩＵ）对血小板功能的保护及止血作用，用药组（Ａ组ｎ＝２０）体外循环（ＣＰＢ）预充液中一次性加抑肽酶，对照组（Ｂ组ｎ＝２０）加入同容积生理盐水。检测结果Ａ组较Ｂ组血小板计数、血小板聚集率均增高；血栓烷Ｂ２下降；ＡＣＴ延长但中和效果佳；术中止血时间缩短；术后失血量和输血量明显降低。结论：小剂量抑肽酶减轻血小板膜受体在ＣＰＢ中的损害、增强其聚集功能、减轻血小板数量下降；抑肽酶与肝素有协同作用并竞争性抑制肝素对血小板功能抑制；明显减少手术后失血和输血量。     

鱼精蛋白引起暴发性非心源性肺水肿1例

鱼精蛋白引起暴发性非心源性肺水肿１例里成荣，李天成，高百顺，姚忠喜病儿男，４岁。１９９１年ＩＩ月在中度低温体外循环下行室间隔缺损修补、三尖瓣环环缩术，手术经过顺利。术中ＡＣＴ常规监测，鱼精蛋白中和肝素后ＡＣＴ值９８ｓ（生理值８５ｓ）。在准备止血关胸时...     

心脏直视术中大剂量抑肽酶对肝素,鱼精蛋白作用的影响

３０例行心脏直视术患者随机分对照组和抑肽酶用药组，于肝素化前，肝素化后１０分钟，给鱼精蛋白前、给鱼精蛋白后１０分钟，分别观察ＡＣＴ，血小板计数，血小板聚集率，肺动脉平均压，肺血管阻力，ＴＸＢ２的变化，结果表明：心脏直视术中大剂量抑肽酶对肝素的抗凝有协同作用，但不影响鱼精蛋白对肝素的拮抗，其机制与保护血小板功能有关，同时抑肽酶可减轻鱼精蛋白应用后肺血管阻力增加和肺动脉压升高，其机制可能与其减少鱼精蛋     

氨甲苯酸和抑肽酶对体外循环中肝素抗作用的影响

目的 为探讨氨甲苯酸和抑肽肽酶的止血疗效。方法 将３４例成人心脏手术患者分为３组，Ａ组于体外量环（ＣＰＢ）前、中、后给予氨甲苯酸共７５０ｍｇ；Ｂ组ＣＰＢ中给予抑肽酶２００万Ｕ；并设一对照组。结果 氨甲苯酸使ＣＰＢ中激活全血凝固时间（ＡＣＴ）明显缩短，加肝素量较另两组显著增加（Ｐ〈０．０５），２４小时胸液量较对照组减少２３％（Ｐ〉０．０５）。抑肽酶使ＣＰＢ中ＡＣＴ略延长，与对照组相比无统计学意义，对     

小儿体外循环中应用ACT监测的体会

小儿体外循环中应用ＡＣＴ监测的体会王振喜１谷兴琳２我院自１９８１年后开展了小儿心内直视手术中应用激活全血凝固时间（ＡＣＴ）来监测体外循环（ＣＰＢ）中肝素抗凝及转流结束鱼精蛋白中和肝素情况，现将有关经验体会报道如下。临床资料本组１００例，男６３例，女３...     

In vitro effect of fresh frozen plasma on the activated coagulation time in patients undergoing cardiopulmonary bypass

The in vitro effect of fresh frozen plasma (FFP) on the whole blood activated coagulation time (ACT) was examined in 18 patients undergoing cardiopulmonary bypass (CPB) during coronary artery bypass graft surgery. The addition of FFP to whole blood in vitro, after systemic heparinization, significantly prolonged the ACT from 451 +/- 21 seconds (mean +/- SE) to 572 +/- 41 seconds (P less than 0.05). There was no significant correlation between the plasma antithrombin III activity and the prolongation in ACT after systemic heparinization, with or without addition of FFP. The addition of FFP to whole blood in three of the six patients who exhibited heparin resistance (ACT less than 400 seconds after administration of 350 unit/kg heparin) did not prolong the ACT to greater than 400 seconds. These observations suggest that infusion of FFP will further prolong the ACT after heparin administration in most patients including some with initial heparin resistance.     

The effect of temperature and aprotinin during cardiopulmonary bypass on three different methods of activated clotting time measurement

The activated clotting time (ACT) is used frequently for monitoring blood anticoagulant response with heparin before, during, and after cardiopulmonary bypass (CPB). Many cardiac procedures involving CPB require reduction of the patient's blood temperature and use of the serine protease inhibitor, aprotinin. Three different methods of ACT measurement were compared to show the effects of different CPB temperatures and the presence of aprotinin. A total of 42 patients were included in the study: 14 received CPB at 28 degrees C, 14 received CPB at 32 degrees C, and 14 normothermic (37 degrees C) CPB. Within each temperature group, seven received aprotinin. The ACT in each group of patients was measured by a celite activator (C-ACT), a kaolin activator (K-ACT), and a celite, kaolin and glass activator (MAX-ACT). All three methods of ACT measurement showed significant increases (p < .05) in clotting times at hypothermic CPB compared with normothermic groups. During heparinization the C-ACT was significantly increased (p < .05) in the presence of aprotinin. Comparability between the 3 ACT measurement methods showed a very high correlation between C-ACT and K-ACT clotting times (R2 = .8962), and slightly lower correlation between MAX-ACT and C-ACT (R2 = .7780), and MAX-ACT and K-ACT (R2 = .7827). All ACT measurements are affected by changes in blood temperature. The C-ACT measurement is prolonged with aprotinin, whereas the MAX-ACT and K-ACT method of measurement in the presence of aprotinin are not significantly altered. It appears that the MAX-ACT produces lower values and may necessitate additional heparin therapy for ACT target values considered safe during CPB. Further study is required from these additional findings.     

Fresh frozen plasma: a solution to heparin resistance during cardiopulmonary bypass

The reasons for the highly variable response of patients to heparin remain incompletely understood. Empirical maintenance of the activated clotting time (ACT) at levels of 400 to 480 seconds appears to be safe for cardiopulmonary bypass (CPB). For patients with ACT responses lower than predicted for initial heparin doses, titration with additional heparin has been customary. In 44 patients undergoing cardiopulmonary bypass, 20 patients were identified as having initial ACTs of 300 seconds or less after receiving 300 units per kilogram of heparin. In 11 of them, ACTs were titrated to 400 to 480 seconds with additional heparin. Nine were given 2 units of fresh frozen plasma shortly after institution of CPB. In this group, there was significant augmentation of the ACT immediately after infusion of plasma. No differences in total heparin dosages given during CPB were found between 24 control patients with initially acceptable ACTs and the group receiving fresh frozen plasma. In contrast, more heparin was necessary in the patients with a low ACT titrated with heparin alone. Data also indicated that protamine sulfate requirements were substantially lower after administration of plasma than were those in either the control or the heparin-titrated, low ACT group. Fresh frozen plasma appears to "normalize" the heparin-ACT dose-response curve in heparin-resistant patients and to lessen total heparin requirements during CPB.     

Lack of correlation between activated clotting time and plasma heparin during cardiopulmonary bypass.

The activated clotting time (ACT) with a Hemochron system for determining heparin requirements during cardiopulmonary bypass surgery, (CPB) accompanied by hemodilution and hypothermia was evaluated using plasma heparin levels as a standard. In 28 patients who were administered a standard heparin regimen (300 units/kg prebypass, 8000 units in the pump prime and 100 units/kg hourly during CPB) mean prebypass plasma heparin was 4 units/ml, and ACT was 493 seconds. During CPB mean plasma heparin decreased significantly (p < 0.001) to 3.1 units/ml, whereas mean ACT increased significantly (p < 0.001) to 674 seconds. The mean protamine requirement predicted from ACT was significantly higher (43%) than predicted from plasma heparin levels or actual protamine administered. The ACT neither accurately reflected plasma heparin during CPB nor predicted protamine requirements. The fixed-dose regimen employed, however, prevented both intraoperative thrombosis, assessed clinically in all patients, and clotting on six arterial line filters, as determined by scanning EM, despite wide variations in ACT and plasma heparin levels during surgery.     

High dose thrombin time versus the activated clotting time during cardiopulmonary bypass

In this study we compared the High Dose Thrombin Time (HiTT) with the Activated Clotting Time (ACT) during cardiopulmonary bypass (CPB) in non-aprotinin treated patients. On the advice of the HiTT test manufacturer each institution should perform comparative ACT/HiTT assays in the cardiac surgery population. In previous tests our target ACT value of 480 seconds corresponds with a mean HiTT value of 190 seconds. Our results showed that after heparinization (300-400 IU/kg body weight) 8 out of 20 patients did not reach the target ACT of 480 seconds, while the HiTT results in those 8 patients were higher than our target time of 190 seconds. Four heparin pretreated patients who received 400 IU/kg heparin, had relatively low ACT values (467 +/- 14 sec.) and high HiTT values (324 +/- 47 sec.). Before and during CPB there was a poor correlation between the HiTT and ACT (r = 0.38). The results of this study show that for the individual patient the target HiTT of 190 seconds is no guarantee for reaching an adequate ACT of 480 seconds. Although the HiTT may be a very useful assay for monitoring heparin effects during CPB, the determination of the target time can be a point of discussion. In contrast of the advice of the manufacturer we therefore suggest that comparative ACT/HiTT assay should be done in every individual patient to determine a safe target HiTT time, instead of the whole group of patients.     

Adequate anticoagulation during cardiopulmonary bypass determined by activated clotting time and the appearance of fibrin monomer.

The adequacy of anticoagulation during 2 hours of cardiopulmonary bypass at 30 degrees C in 9 rhesus monkeys was determined by measuring the whole-blood activated clotting time (ACT) and by noting the appearance of thrombin-altered fibrin (fibrin monomer) and the relative consumption of clotting factors. Factor V and VIII, the heparin cofactor, antithrombin III, prothrombin time, partial thromboplastin time, ACT, platelets, hematocrit, fibrinogen, and fibrin monomer were determined prior to heparinization and after protamine. In 6 of 9 experiments, fibrin monomer became positive in the plasma during cardiopulmonary bypass (CPB), indicating that active coagulation was occurring. In 5 of the 6 animals, initial ACT was less than 400 seconds, and fibrin monomer appeared within the first 30 minutes of bypass. In 1 animal with an initial ACT of 439 seconds, fibrin monomer appeared after 60 minutes of bypass, at which time the ACT was less than 400 seconds. An abnormal level of fibrin monomer was not detected in 5 pediatric patients with an ACT greater than 450 seconds during CPB. Our experimental study and clinical data suggest that the lower limit, as measured by the ACT, for anticoagulant effect to provide coagulation-free CPB is at least 400 seconds.     

Monitoring activated clotting time for combined heparin and aprotinin application: in vivo evaluation of a new aprotinin-insensitive test using Sonoclot.

OBJECTIVE: Kaolin-based activated clotting time assessed by HEMOCHRON (HkACT) is a clinical standard for heparin monitoring alone and combined with aprotinin during cardiopulmonary bypass (CPB). However, aprotinin is known to prolong not only celite-based but also kaolin-based activated clotting time. Overestimation of activated clotting times implies a potential hazardous risk of subtherapeutic heparin anticoagulation. Recently, a novel 'aprotinin-insensitive' activated clotting time test has been developed for the SONOCLOT analyzer (SaiACT). The aim of our study was to evaluate SaiACT in patients undergoing CPB in presence of heparin and aprotinin. METHODS: Blood samples were taken from 44 elective cardiac surgery patients at the following measurement time points: baseline (T0); before CPB after heparinization (T1 and T2); on CPB, before administration of aprotinin (T3); 15, 30, and 60 min on CPB after administration of aprotinin (T4, T5, and T6); after protamine infusion (T7). On each measurement time point, activated clotting time was assessed with HkACT and SaiACT, both in duplicate. Furthermore, the rate of factor Xa inhibition and antithrombin concentration were measured. Statistical analysis was done using Bland and Altman analysis, Pearson's correlation, and ANOVA with post hoc Bonferroni-Dunn correction. RESULTS: Monitoring anticoagulation with SaiACT showed reliable readings. Compared to the established HkACT, SaiACT values were lower at all measurement time points. On CPB but before administration of aprotinin (T3), SaiACT values (mean+/-SD) were 44+/-118 s lower compared to HkACT. However, the difference between the two measurement techniques increased significantly on CPB after aprotinin administration (T4-T6; 89+/-152 s, P=0.032). Correlation of ACT measurements with anti-Xa activity was unchanged for SaiACT before and after aprotinin administration (r2=0.473 and 0.487, respectively; P=0.794), but was lower for HkACT after aprotinin administration (r2=0.481 and 0.361, respectively; P=0.041). On CPB after administration of aprotinin, 96% of all ACT values were classified as therapeutic by HkACT, but only 86% of all values were classified therapeutic if ACT was determined by SaiACT. Test variability was comparable for SaiACT and HkACT. CONCLUSIONS: The use of SaiACT may result in more consistent heparin management that is less affected by aprotinin and a corresponding increase in heparin administration for patients receiving aprotinin.     

Kaolin-based activated coagulation time measured by sonoclot in patients undergoing cardiopulmonary bypass

OBJECTIVES: In vivo data for the kaolin-based ACT test from the Sonoclot Analyzer (SkACT, Sienco Inc, Arvada, CO) are lacking. The aim of this study was to compare SkACT with an established kaolin-based ACT from Hemochron (HkACT) and anti-Xa activity in patients undergoing cardiopulmonary bypass (CPB). DESIGN: Prospective observational study. SETTING: Community hospital. PARTICIPANTS: Fifty patients scheduled for elective cardiac surgery. INTERVENTIONS: Blood samples were taken before CPB at baseline (T0) and after heparinization (T1 and T2), on CPB after administration of aprotinin (5, 15, 30, 60 minutes; T3-T6), and at the end after protamine infusion (T7). MEASUREMENTS AND MAIN RESULTS: A total of 375 blood samples were analyzed. ACT measurements were comparable for SkACT and HkACT at each measurement time point. Overall bias +/- standard deviation between SkACT and HkACT was -19 +/- 75 seconds (-2.4% +/- 11.7%). Mean bias between SkACT and HkACT at each time point ranged from -35 to 3 seconds (-4.5% to 2.6%) and showed no statistical significance over time. Heparin sensitivity of SkACT and HkACT, defined as (ACT(Tx)-ACT(T0))/(anti-Xa(Tx)-anti-Xa(T0)), significantly increased for measurements during CPB (p < 0.001) but without significant difference between the 2 methods. Test variability was comparable for both ACT measurement techniques. Overall test variability was 7.5% +/- 7.4% for SkACT and 7.8% +/- 11% for HkACT. CONCLUSIONS: Accuracy and performance of SkACT and HkACT were comparable for heparin monitoring in patients undergoing CPB for elective cardiac surgery. However, both tests were affected significantly after initiating CPB and aprotinin infusion.     

Maintenance of blood heparin concentration rather than activated clotting time better preserves the coagulation system in hypothermic cardiopulmonary bypass

In cardiopulmonary bypass (CPB), despite heparin regimens in which the activated clotting time (ACT) is kept at more than 400 s, there is biochemical evidence of thrombin generation indicating activation of the coagulation system and increased fibrinolytic activity. Therefore, to reduce the coagulant activation has been one of the main issues in the improvement of CPB. The purpose of this study was to compare the heparin concentration with the ACT and to evaluate the effect of keeping higher heparin concentration on the coagulation and fibrinolytic systems during hypothermic CPB, employing moderate hypothermia (MHT) or deep hypothermic circulatory arrest (DHT). Heparin was either administered to maintain an ACT >400 s (ACT group) or to maintain a whole blood heparin concentration of 3 mg/kg (heparin group). At the lowest core temperature during CPB, the ACT and the heparinase ACT (unrelated to heparin concentration) were increased the most whereas the whole blood heparin concentration was less than half the initial concentration in both ACT groups of MHT and DHT. The thrombin-antithrombin III (TAT) content just after CPB in both MHT and DHT was significantly lower in the heparin group than in the ACT group. In conclusion, ACT does not reflect the whole blood heparin concentration during hypothermic CPB. Furthermore, maintenance of the higher heparin concentration during hypothermic CPB may suppress the activation of the coagulation system via thrombin inhibition. That effect was more remarkable in deep hypothermic CPB. Therefore, we believe that anticoagulation management during hypothermic CPB should be based on the maintenance of the higher blood heparin concentration.     

An investigation of a new activated clotting time "MAX-ACT" in patients undergoing extracorporeal circulation

Activated clotting time (ACT) is a test used in the operating room for monitoring heparin effect. However, ACT does not correlate with heparin levels because of its lack of specificity for heparin and its variability during hypothermia and hemodilution on cardiopulmonary bypass (CPB). A modified ACT using maximal activation of Factor XII, MAX-ACT (Actalyke MAX-ACT; Array Medical, Somerville, NJ), may be less variable and more closely related to heparin levels. We compared MAX-ACT with ACT in 27 patients undergoing CPB. We measured ACT, MAX-ACT, temperature, and hematocrit at six time points: baseline; postheparin; on CPB 30, 60, and 90 min; and postprotamine. Additionally, we assessed anti-Factor Xa heparin activity and antithrombin III activity at four of these six time points. With institution of CPB and hemodilution, MAX-ACT and ACT did not change significantly but had a tendency to increase, whereas concomitant heparin levels decreased (P = 0.065). Neither test correlated with heparin levels. ACT and MAX-ACT did not differ during normothermia but did during hypothermia, and ACT was significantly longer than MAX-ACT (P = 0.009). At the postheparin time point, ACT-heparin sensitivity (defined as [ACT postheparin - ACT baseline]/[heparin concentration postheparin - heparin concentration baseline]) was greater than MAX-ACT-heparin sensitivity (analogous calculation for MAX-ACT; 520 [266 - 9366] s. U(-1). mL(-1) vs 468 [203 - 8833] s. U(-1). mL(-1); P = 0.022). IMPLICATIONS: MAX-ACT (a new activated clotting time [ACT] test) uses more maximal clotting activation in vitro and, although it is less susceptible to increase because of hypothermia and hemodilution than ACT, lack of correlation with heparin levels remains a persistent limitation.