Strategy for balancing anticoagulation and hemostasis in aortocoronary bypass surgery: blood conservation and graft patency

The minimal effective dose of aprotinin on hemostasis under normothermic perfusion, the influence of anticoagulant therapy on graft patency, and the thromboembolic and hemorrhagic events were investigated after aortocoronary bypass graft operation (CABG). One hundred CABG patients under normothermic perfusion were randomly divided into the following groups: (1) coumadin plus acetylsalicylic acid (ASA) (n=32); no aprotinin used during cardiopulmonary bypass (CPB); (2) minimal-dose, 10(6) KIU during CPB, aprotinin used, followed by ASA and coumadin (n=36); and (3) very low-dose, total of 2x10(6) KIU before CPB and during CPB; aprotinin used; anticoagulation therapy with heparin early after surgery and followed by replacement with ASA and coumadin (n=32). The patency of arterial grafts was 100% in all groups. The patency of vein grafts was 95-98% and there was no difference among the groups. The blood loss was significantly reduced in both aprotinin groups (groups 2 and 3) compared to the coumadin plus ASA group, although no difference existed between the 2 aprotinin groups. Postoperative thrombotic and hemorrhagic events were not observed in any group. From this study, it was concluded that 10(6) KIU aprotinin in pump-prime-only followed by oral ASA and coumadin was the recommendation from the benefit/cost consideration.     

Hemostatic effects of low-dose protamine following cardiopulmonary bypass

Twenty-eight patients undergoing cardiac surgery were prospectively studied and were assigned to two groups. The patients received 0.8- (Group L) or 2.0-fold (Group H) dose of protamine for the neutralization after cardiopulmonary bypass (CPB) which was determined by Hepcon HMS(R) assay system in which the reagent chamber containing the concentration of protamine that completely neutralized the heparin had the shortest clotting time. Mean dose of protamine was 1.60 +/- 0.50 mg kg(-1) in Group L, and 3.56 +/- 1.48 mg kg(-1), respectively. Activated clotting times (ACT) were comparable between the two groups through this study period. In Group H, platelet counts significantly decreased to 69% of that before protamine administration, and plasma platelet factor 4 level significantly increased to approximate 2-fold of that before protamine administration just after protamine administration, respectively. However, these phenomena were not observed in Group L. In addition, these hemostatic changes occurred transiently just after protamine administration. We conclude that the low-dose protamine may prevent transient platelet depletion following CPB. Low-dose protamine can neutralize anticoagulation effect of heparin sufficiently and may mitigate protamine-induced platelet dysfunction.     

Hemostasis management by use of Hepcon/HMS: increased bleeding without increased need for blood transfusion

BACKGROUND: Extracorporeal circulation forces complete anticoagulation, most frequently achieved by complete heparinization. Activated clotting time (ACT) is the gold standard for monitoring, although there is a lack of correlation between heparin plasma level and ACT. Several systems for the estimation of free heparin have been developed: in this study we focused investigating on the influence of the Hepcon/HMS system on postoperative bleeding and transfusion requirements. METHODS: 114 patients were randomly assigned to one group monitored by use of Hepcon/HMS (group hepcon) and another group by use of ACT (ACT group); 7 patients were excluded due to re-exploration. 12 patients did not receive aprotinin; this part of the study was stopped early due to massive increased bleeding. 46 and 49 patients of groups hepcon and ACT, respectively, received aprotinin. RESULTS: Using aprotinin, in group hepcon total administered heparin was elevated by 13 % in contrast to group ACT while administered protamine was reduced by 20%. The ratio of antagonization was 82 +/- 17 % and 51 +/- 12 %, respectively. Coagulation parameters were not influenced except for increased postoperative ACT and PTT in the hepcon group. Bleeding of patients in that group was significantly increased during the first 6 hours, which led to an increased autologous retransfusion. Need for substitution of other blood components was not increased postoperatively. CONCLUSIONS: Use of the Hepcon/HMS-system for monitoring of heparinization during extracorporeal circulation is possible without increased risk of thromboembolism. Postoperative blood loss was slightly but significantly increased but there was no need for more heterogenous transfusion.     

Efficacy of minimal dose aprotinin in open heart procedures

In a randomized double blind study, 30 patients posted for CABG surgery were assigned to 3 groups of 10 each. Group A received 140 mg (1,000,000 KIU) of aprotinin after induction of anaesthesia but before sternotomy, an equal amount in the pump prime and a maintenance dose of 70 mg/hr throughout cardiopulmonary bypass (standard dose). Group B received placebo after induction of anaesthesia, 70 mg (500,000 KIU) aprotinin in the pump prime with a placebo as a maintenance dose (minimal dose). Group C received a placebo after induction of anaesthesia, in the prime and as a maintenance dose (control group). The mean chest closure times were insignificantly lower in the aprotinin groups; 35.83 +/- 13.93 mins in group A and 37.5 +/- 10 mins in group B as against 57.25 +/- 26.54 mins in group C. Post-operative haemoglobin loss was significantly lower (P<0.01) in aprotinin groups, 5.42 +/- 1.6 gm in group A and 6.28 +/- 2.49 gms in group B, as against 39.77 +/- 27.51 gm in group C. Whole blood transfusion requirement was also significantly reduced from 4.12 +/- 1.79 units in the control group to 2.5 +/- 0.75 units in group A (p < 0.05) and 2 +/- 1.3 units (p<0.01) in group B. We conclude that a minimal dose of aprotinin 70 mg (500,000 KIU) is effective in reducing postoperative blood loss, blood transfusion requirement and is economical.     

Clinical use of heparin-coated cardiopulmonary bypass in coronary artery bypass grafting.

Clinical handling, risk and benefit of a heparin-coated cardiopulmonary bypass system combined with reduced systemic heparinization in coronary bypass surgery was investigated in a prospective, randomized clinical study. 243 patients (Pts.) were divided into 3 groups: group A (n = 83) had a standard uncoated extracorporeal circulation (ECC) set, and systemic heparin was administered in an initial dose of 400 IE/kg body weight. During ECC activated clotting time (ACT) was kept > or = 480 sec. Group B (n = 77) had the same ECC set completely coated with low-molecular-weight heparin; i.v. heparin was given in the same dose as in group A, ACT was kept at the same level. Group C (n = 83) had the same coated ECC set as group B, but i.v. heparin was reduced to 150 IE/kg, and was set to be > or = 240 sec during ECC ACT. The same circulatory components were used in all 3 groups including roller pumps, coronary suction and an open cardiotomy reservoir. In the postoperative clinical course, recovery was not significantly different between groups, especially with respect to organ dysfunction; but there was significantly reduced postoperative bleeding where heparin-coated ECC and low-dose systemic heparinization were both used. This circulatory technique was also associated with a distinctly lower need for postoperative blood replacement. We conclude that heparin-coated extracorporeal circulation combined with either full-dose or reduced systemic heparinization can be used effectively with the same standard equipment and procedures as in uncoated technology. Combination with low-dose i.v. heparin leads to significantly decreased blood loss and less need for blood replacement.     

Clinical effects of different protamine doses after cardiopulmonary bypass

The optimal dose of protamine needed to reverse the anticoagulant effect of heparin after cardiopulmonary bypass is still not known. In this retrospective cohort study, we investigated 3 different dose regimes in 300 patients undergoing coronary artery bypass grafting. Group A patients (n = 100) were given protamine in the ratio of 1.3 mg to 1 mg heparin, group B patients (n = 100) were given 0.75 mg protamine to 1 mg heparin, and group C patients (n = 100) were given protamine in fractionated doses of 1 mg + 0.15 mg + 0.15 mg to 1 mg heparin. The groups were comparable in all major clinical and operative variables. The heparin dose was almost identical in the groups. The rate of red cell transfusion was significantly higher in group B than in the other groups. A similar but nonsignificant trend was observed in the incidence of resternotomy for postoperative bleeding, mediastinal drainage, and postoperative hemoglobin loss. The study demonstrates that a single bolus dose of 1.3 mg protamine to 1 mg heparin is safe and efficient for neutralizing heparin after cardiopulmonary bypass.     

Major coagulation disorders when using aprotinin--observations on a case.

Intraoperative application of the proteinase inhibitor aprotinin allows to drastically reduce blood loss during and after cardiopulmonary bypass operation. The side effects of this therapy (if any) have not been systematically registered and a possible interaction with heparin is not excluded. Such an interaction seems to have occurred in one of our patients. He developed a resistance to heparin shortly after prophylactic administration of aprotinin and maintained it for about one hour after discontinuation of the aprotinin. Prophylactic and therapeutic implications of this observation are briefly exposed.     

Protamine dosage based on two titrations reduces blood loss after valve replacement surgery: a prospective, double-blinded, randomized study

Background

Postoperative hemorrhage following cardiopulmonary bypass in heart valve replacement patients may be caused by a mismatch of protamine and heparin. We hypothesized that a 2-titration-guided protamine dose would reduce protamine-heparin mismatch and bleeding in those patients.

Methods

Patients scheduled for elective cardiac valve replacement surgery (N = 60) were randomly divided into 3 groups. All patients received 2 titrations: the first at termination of cardiopulmonary bypass and the second at 5 minutes after the initial dose of protamine. In the control group, the initial protamine dose was based on the heparin dose received; the supplemental protamine dose was empirically determined. In the single-titration group, the initial dose was based on the first titration, while supplemental dose was empirically determined. In the 2-titration group, both initial and supplemental doses were based on titrations. Bleeding volumes were recorded from the time of first protamine dose to 24 hours after surgery.

Results

Most patients needed supplemental protamine according to second titrations. In the 2-titration group, 12 patients received supplemental protamine, whereas only 1 patient in the single-titration group and 6 in the control group received supplemental protamine (P = 0.003). The blood loss was significantly less in the 2-titration group (526 ± 131 mL) than in the control group (730 ± 385 mL; P = 0.019).

Conclusions

A higher dosage of protamine based on 2 titrations reduced blood loss after surgery, supporting the hypothesis that inadequate dosage of protamine contributes to hemorrhage after valve replacement surgery.     

Influence of the concomitant use of heparin on the effects of warfarin during catheter ablation for atrial fibrillation

Warfarin is widely used to perform catheter ablation for atrial fibrillation (AF). Heparin is usually administered during this procedure to prevent thromboembolic events, while protamine is used to reduce the incidence of bleeding complications. The purpose of this study was to investigate the influence of heparin and protamine administration on the effects of warfarin and its safety. The subjects included 226 AF patients (206 males, 54.9 ± 9.1 years, paroxysmal/persistent AF: 118/108) undergoing AF ablation with the discontinuation of warfarin administration over 2 days. Heparin was administered to achieve an activated clotting time (ACT) above 300 s during the procedure. Several parameters of the coagulation status, including the prothrombin time international normalized ratio (PT-INR) and ACT values, measured immediately before and after protamine infusion were compared. The mean value of PT-INR prior to ablation was 1.9 ± 0.6. At the end of the procedure, the mean ACT and PT-INR values were 348.0 ± 52.9 and 2.9 ± 0.7, respectively. Following the infusion of 30 mg of protamine, both the ACT and PT-INR values significantly decreased, to 159.6 ± 31.0 (p < 0.0001) and 1.6 ± 0.3 (p < 0.0001), respectively. No cases of symptomatic cerebral infarction were observed, although femoral hematomas developed in 17 (7.5 %) of the patients without further consequence. The concomitant use of heparin augments the effect of warfarin. Meanwhile, protamine administration immediately reverses both the ACT and PT-INR, indicating the applicability of protamine for AF ablation in patients under the mixed administration of heparin and warfarin.     

Mini-Dose Pump-Prime Aprotinin Inhibited Enhanced Fibrinolytic Activity and Reduced Blood Loss and Transfusion Requirements After Coronary Artery Bypass Surgery

Objectives: Low-dose aprotinin in the pump during cardiopulmonary bypass (CPB) has been shown to improve postoperative hemostasis and platelet preservation. This investigation was undertaken to evaluate the effects of mini-dose pump prime only aprotinin (70 mg) on the hemostatic parameters and blood transfusion requirements in patients undergoing on-pump coronary artery bypass surgery (CABG).Materials and Methods: We studied 86 patients who underwent CABG. Forty patients received mini-dose aprotinin (500.000 KIU [70 mg] in the pump), and a control group of 46 did not. D-dimer level, full blood count, postoperative blood loss, and transfusion requirements were analyzed before, after one hour operation and first day after operation.Results: Twenty-four-hour postoperative blood loss was significantly reduced in the aprotinin group (188± 51.5 ml vs. 818± 243.5 ml, [mean ± standard deviation] p < 0.01). Patients in the aprotinin group also received significantly less banked blood posoperatively than the control group (1.20 ± 0.52 vs. 3.33 ± 1.13 Units/per patient (p < 0.04). One hour after operation, and 24 hours after operation D-dimer level was significantly reduced in the aprotinin group (p < 0.008 and p < 0.017, respectively).Conclusions: Mini dose pump-prime aprotinin reduces postoperative blood loss, transfusion requirements and yet confers hemostatic improvement through reduced fibrinolysis in patients undergoing routine coronary artery bypass grafting.     

不同酸碱度对鱼精蛋白中和肝素的影响

目的:探讨心脏手术后患者不同酸碱度对鱼精蛋白中和肝素的影响。方法:我院2009年10月至2010年5月期间对352例心脏病患者行体外循环手术,麻醉后即测正常活化凝血时间(ACT)值,在打开心包后按2.5 mg/kg从中心静脉给予肝素,在体外循环结束时,鱼精蛋白的剂量从肝素的1.5倍开始在升主动脉根部给药,测量中和后的ACT值,并依此作为追加鱼精蛋白量的参考。按体外循环结束时其酸碱度不同分为3组,观察比较各组肝素与鱼精蛋白总量之比、中和后ACT值,并观测3组术后6 h、12 h及24 h引流量及术后总引流量。结果:在酸性环境下,鱼精蛋白中和肝素剂量及术后引流量高于其他2组,差异有统计学意义(P<0.05)。在非酸性环境下,鱼精蛋白和肝素比平均值为1.63∶1;在pH<7.31或剩余碱(BE)<-6时,鱼精蛋白的用量显著增加,鱼精蛋白和肝素比平均值为2.33∶1。结论:不同酸碱度对鱼精蛋白拮抗肝素有较大影响,酸性环境下鱼精蛋白的中和作用会减弱,鱼精蛋白用量增加,术后引流量也会增多。在体外循环结束时,测得pH<7.31或BE<-6时,建议纠正酸碱平衡的同时适量追加鱼精蛋白。     

Aprotinin in cardiopulmonary bypass--effects on the Hageman factor (FXII)--Kallikrein system and blood loss.

Aprotinin has been used in our hospital in open heart surgery for almost 20 years and recently published studies have revealed a reduction in postoperative blood loss under this therapy. In the present study patients undergoing aorto-coronary bypass operations received either 20,000 KIU aprotinin/kg body weight (group 2) or 60,000 KIU aprotinin/kg body weight (group 3). Another group of patients without aprotinin served as a control (group 1) and postoperative bleeding was more pronounced in these patients compared with the other groups. In parallel, slight reductions in kallikrein-like activity were observed in patients treated with aprotinin. Furthermore, we have shown that the main inhibitor of the contact phase, C1-esterase-inhibitor, loses some of its activity against beta-FXIIa in the presence of heparin. Aprotinin was able to partly antagonize this phenomenon. All studies dealing with the effect of aprotinin in extracorporeal circulation demonstrate hyperfibrinolysis in untreated patients. Aprotinin is known to inhibit plasmin at low concentrations and thus reduced the postoperative bleeding tendency (group 2). In addition, plasma kallikrein is inhibited by high aprotinin concentrations and is responsible for a reduced activation of the contact phase system. This effect led to a further reduction in blood loss (group 3).     

Reduction of homologous blood requirement in cardiac surgery by intraoperative aprotinin application--clinical experience in 152 cardiac surgical patients

The protease inhibitor aprotinin interacts with plasmin and kallikrein, which are generated in cardiac surgery during cardiopulmonary bypass (CPB). The influence of high-dose aprotinin application (2 million kallikrein inactivator units given i.v. at the beginning of anaesthesia followed by a 500,000 KIU/h infusion throughout the operation and additional 2 millions KIU added to the priming of the oxygenator) on perioperative blood loss and donor blood requirement was studied in 152 adult cardiac surgical patients. This group was compared to 317 patients having cardiac surgery without the application of aprotinin. Aprotinin reduced the homologous blood requirement by 43% (1783 +/- 100 vs 1015 +/- 131 ml, p less than 0.05), while the reduction of postoperative blood loss was 29% (1070 +/- 43 vs 761 +/- 51 ml, p less than 0.05). Fortytwo percent of the aprotinin treated patients completed their hospital stay without having any donor blood transfusion compared to 18% in the group without aprotinin. The blood saving effect was even more pronounced in operations with prolonged perfusion times. Intra- and postoperative complications were equally distributed in both groups. The blood-saving effect of aprotinin may be due to a platelet-preserving effect and/or kallikrein inhibition during CPB. There were no clinically relevant side effects related to aprotinin observed. It is concluded that high dose aprotinin therapy reduces both postoperative blood loss and homologous blood requirement, and therefore the routine application of aprotinin during cardiac surgical procedures is to be recommended.     

Low-dose aprotinin in heart valve reoperations

BACKGROUND AND AIM OF THE STUDY: Aprotinin is effective in promoting hemostasis, notably in cardiac surgery with cardiopulmonary bypass. Its efficacy has been shown in coronary bypass graft operations. However, few reports exist of aprotinin use in valve operations, and in those studies only the full dose was used. Thus, our aim was to evaluate the effects of low-dose aprotinin in patients undergoing heart valve reoperation. METHODS: Eighteen patients having reoperative valve surgery received 10(6) KIU aprotinin after induction of anesthesia, and a further 10(6) KIU in the pump prime. A group of 18 similar patients who were operated on but did not receive aprotinin were used as controls. RESULTS: A significant reduction in postoperative blood loss (approximately 470 ml) occurred in patients receiving aprotinin. These patients also presented less postoperative bleeding than untreated patients in 70.4% of cases. No adverse effects of the drug were noted, except for one case of allergic reaction. CONCLUSION: The systematic use of low-dose aprotinin should be considered in valve reoperation, except in cases of re-exposure to the drug, or allergic reaction.     

Heparin rebound phenomenon--much ado about nothing?

Significant postoperative bleeding following open-heart surgery is often ascribed to the so-called heparin 'rebound' phenomenon and as such is treated with additional empiric doses of protamine sulphate. However, inappropriate protamine administration has been reported to be associated with acute pulmonary hypertension. The efficacy of heparin reversal was investigated in 42 patients undergoing open-heart surgery. The standard heparin bolus of 3 mg/kg body weight (4.1 IU/ml blood) administered before cardiopulmonary bypass was countered at the end of bypass using an empirical equivalent (3 mg/kg) of protamine. This regimen resulted in complete heparin neutralization (measured by the Hepcon HMS [Hemotec Inc., Englewood, CO, USA]) 15 min after protamine administration in all 42 patients, but heparin levels (0.4 IU/ml) were transiently detectable (duration less than 1 h) in six (14%) of the 42 cases 2 h later. Twenty-four hour postoperative bleeding in these patients did not differ significantly from that seen in patients who did not exhibit heparin rebound. Similarly, the thrombelastographic profiles (at 15 min and 2 h post-operation) and coagulation screen (prothrombin time, activated partial thromboplastin time, activated clotting time and platelets) did not differ significantly from those of non-rebound patients. The significance, if any, of the phenomenon of heparin rebound following cardiac surgery remains to be elucidated, and, until such time, conservative administration of protamine in response to 'rebound' is recommended.     

Off-pump coronary artery bypass grafting using continuous heparin infusion

ObjectivesLevels of anticoagulation during off-pump coronary artery bypass grafting (OPCAB) remain controversial. Prolonged activated clotting time (ACT) during OPCAB increases blood loss during surgery and can also cause paradoxical increase in postoperative myocardial infarction. Shorter ACT can increase thrombotic complication. Maintaining a steady ACT level is challenging. We have used continuous heparin infusion after initial bolus during OPCAB to maintain a steady low target ACT. The objective of the present study was to assess the effectiveness and safety of heparin infusion in maintaining a steady target ACT level.MethodsThis was a prospective study of consecutive OPCAB patients. ACT was measured after initial bolus dose of heparin. Once ACT of more than 200 seconds was achieved, heparin infusion was started to maintain the required level of anticoagulation. CPK-MB was measured in operation room, 6 and 24 hours postoperatively to rule out ischemic complication.ResultsACT could be maintained in target range with heparin infusion in 80.1% patients (161/201). Of the 40 patients with one or more ACT reading less than 200 seconds, 38 patients were managed by increasing the dose of heparin infusion and only 2 patients required additional bolus dose of heparin.ConclusionsHeparin infusion maintains a steady target ACT level and avoids peaks and troughs associated with bolus doses. Lower level of anticoagulation using continuous heparin infusion does not increase ischemic complications. This is the first ever study of use of heparin infusion during OPCAB. We may conclude that heparin infusion is a safe anticoagulation strategy for OPCAB.     

Cardioprotective effect of aprotinin on myocardial ischemia/reperfusion injury during cardiopulmonary bypass.

BACKGROUND: Aprotinin is a serine protease inhibitor used extensively in cardiac operations to reduce postoperative bleeding. It also has cardioprotective effects in ischemia/reperfusion injury. In this study, the effects of aprotinin on the release of cardiac markers were evaluated in patients who had good ventricular function and were undergoing coronary artery bypass grafting with cardiopulmonary bypass (CPB). METHODS AND RESULTS: Eighty male patients with an ejection fraction >or=40%, were randomized into either an aprotinin (Group-I; n=40) or control (Group-II; n=40) group. Patients in the aprotinin group received the full Hammersmith doses of aprotinin (2 x 10(6) KIU pre-CPB, 2 x 10(6) KIU at pump prime, 500,000 KIU/h during CPB), whereas the patients in the control group received only saline solutions. Cardiac troponin-I (cTnI) levels were measured before surgery, immediately after surgery, and at postoperative 6(th), 12(th), 24(th) h and 5(th) day. Creatine kinase (CK)-MB measurements were performed at the same time except for the postoperative 5(th) day. Cardiac index (CI), mixed venous oxygen saturation and lactate dehydrogenase (LDH) measurements were also performed. CONCLUSION: Although all patients were in reasonable condition, less myocardial enzyme leakage occurred on the aprotinin group, suggesting that aprotinin has a protective effect on the myocardium beyond that achieved with blood cardioplegia and systemic hypothermia. Because of aprotinin's effects on multiple targets of metabolism, its protective value might increase in more complicated cases.     

Recombinant hirudin for cardiopulmonary bypass anticoagulation: a randomized, prospective, and heparin-controlled pilot study

BACKGROUND: Lepirudin, a recombinant hirudin, is a direct acting thrombin inhibitor that has been used as a heparin alternative in patients with heparin-induced thrombocytopenia requiring on-pump cardiac surgery. To evaluate the efficacy, safety, and clinical utility of lepirudin as a cardiopulmonary bypass (CPB) anticoagulant, we compared lepirudin with heparin in a routine CPB setting. METHODS: Twenty patients were randomly assigned to receive lepirudin (0.25 mg/kg b. w. bolus and 0.2 mg/kg b. w. added to the CPB priming) or heparin (400 U/kg b. w. bolus) with protamine reversal. Lepirudin and heparin anticoagulation during CPB was monitored using the ecarin clotting time or ACT, respectively and additional lepirudin (5 mg) or heparin (5000 U) boluses were administered. RESULTS: The CPB circuit was performed in both groups without thromboembolic complications. Median blood loss during the first 36 hours was statistically higher ( P = 0.007) in the lepirudin group (1.226 +/- 316 ml) compared to the heparin group (869 +/- 189 ml). One patient of the lepirudin group developed pulmonary embolism 24 hours after surgery. This patient was tested homozygous for the FV-Leiden mutation. CONCLUSION: Lepirudin provides effective CPB anticoagulation but induces a higher postoperative blood loss than heparin. Lepirudin should be restricted to patients undergoing CPB who cannot be exposed to heparin.     

Interaction of vitamin K antagonists with heparin affect monitoring by activated clotting times

Background

Unfractionated heparin is recommended during atrial fibrillation (AF) ablation to achieve activated clotting time (ACT) above 250–300 s to prevent clot. Many patients on therapeutic international normalised ratio (INR) undergo AF ablation procedures; however, it is unknown whether they require less heparin to achieve similar ACT levels.

Methods

During AF ablation, the ACT was measured before and 10 min after administration of i.v. unfractionated heparin in patients with and without anticoagulation. The association of INR, heparin, pre-procedure ACT and body weight with ACT after heparin administration was tested using multivariable linear regression models.

Results

The subjects of this study were 149 patients undergoing AF ablation, among them 40 (27%) with subtherapeutic INR?<?2, 79 (53%) with an INR between 2 and 3, and 30 (20%) patients with INR?>?3. Baseline ACT was associated with INR (r?=?0.33, p?<?0.001). After a mean of 8,685?±?2,015 U (range, 5,000–15,000 IU) unfractionated heparin, univariate predictors of ACT were baseline INR (p?<?0.001), heparin dose (p?=?0.012) and baseline ACT (p?=?0.027). In the multivariable model, baseline INR (part r?=?0.64, p?<?0.001) and heparin dose (part r?=?0.33, p?<?0.001) strongly predicted post-heparin ACT. Estimated from the regression model, the heparin dose reductions by approximately one third in those with an INR of 2–3 and by at least two thirds in those with an INR above 3 may be favourable. Over the following 3 months, no thromboembolism and acute bleeding were observed.

Conclusion

The INR was the strongest predictor of post-heparin ACT, even more important than the heparin dose itself. The reduction of heparin dose by one third if INR is between 2–3 and by two thirds if INR is above 3 may be favourable.     

不同剂量抑肽酶在心内直视手术的应用

减少心内直视手术出血及减少库血用量，可直接减少输血性肝炎和凝血机制紊乱等术后并发症。为减少术后渗血，我们将抑肽酶用于心脏直视手术中，以不同剂量和方法分为３组：Ｉ组抑肽酶总量５００万ＫＩＵ，ＩＩ组抑肽酶总量２５０万ＫＩＵ，ＩＩＩ组抑肽酶总量２００万ＫＩＵ。结果表明，术后２４小时渗血量实验组分别比对照组减少５６．４％、３５％、３７％，效果显著。