A Case of Antiphospholipid Syndrome Underwent Cardiac Surgery Performed Using Coagulation Management by Measuring Heparin Concentration during Extracorporeal Circulation / 日本心臓血管外科学会雑誌

A 72-year-old female was diagnosed with systemic lupus erythematosus and antiphospholipid syndrome (APS) in 2014 and was followed up. Severe mitral regurgitation coexisted with APS, but the case was nonsymptomatic, and surgery involved high risk. Therefore, the physicians continued their observation. In 2020, the patient experienced rheumatic severe mitral stenosis and shortness of breath on exertion. Paroxysmal atrial fibrillation and coronary stenosis were also detected. Therefore, we planned mitral valve replacement, tricuspid annuloplasty, coronary artery bypass, pulmonary vein isolation and left atrial appendage closure. During extracorporeal circulation (ECC), we performed coagulation management based on blood heparin concentration using HMS PLUS. Because the APS patient showed prolonged activated clotting time (ACT), and coagulation therapy based on ACT is unreliable. She was discharged from our hospital on postoperative day 23. No complications, including bleeding and thrombosis, were observed 2 years after the operation. We experienced a case of APS who underwent cardiac surgery and performed coagulation management by measuring heparin concentration during ECC. We targeted a 3.5 U/ml heparin concentration, and her clinical course was uneventful.

Explore solutions to the "grey zone" of activated partial thromboplastin time mixing study / 中华检验医学杂志

Objective:To explore solutions to the "grey zone" of activated partial thromboplastin time (APTT) mixing study, and establish the clinical application pathway of it.Methods:Patients treated in West China Hospital of Sichuan University from January 1, 2018, to December 31, 2019, with a prolonged APTT were included in this study. The ROC curve was used to analyze the"cut-off"of different methods and explore solutions to the "grey zone" by combination of the 1∶1 and 4∶1 mixing study. Similar samples from January 1, 2020 to December 31, 2020 were included to verify the diagnostic efficiency of the clinical application pathway.Results:The traditional Rosner index criterion had a low diagnostic accuracy in differentiating factor deficiencies from inhibitors. A total of 49 cases (15%) in the establishment group and validation group were located in the "grey zone". The optimal cut-off value of the Rosner index in our 1∶1 mixing study for determining factor deficiency was 5.0%, and inhibitor was 9.1%. The sample between 5.0% and 9.0% needed 4∶1 mixing studies, which could significantly improve the detection sensitivity of inhibitors. The percentage of extended time after incubation-P (1∶1 mixing>10.8% and 4∶1 mixing>13.5%) was better than the traditional criterion mentioned by"consensus"in determining whether the inhibitor was time-dependent. The sensitivity, specificity, positive predictive value and negative predictive value of combined the 1∶1 and 4∶1 mixing study in differentiating factor deficiencies from inhibitors all attained more than 90%. Only 7% (3/43)of inhibitors were incorrectly classified into the factor deficiency group by the combination, which was 20.9% (9/43) by traditional criterion. The specificity for detecting time-dependent inhibitor was increased from 54.2% to 100%, and accuracy was increased from 63.3% to 97.4%.Conclusions:The combination of 1∶1 and 4∶1 mixing study can better resolve the "grey zone". The established clinical application pathway is beneficial for the further promotion and clinical application of APTT mixing study.

The influence of different dosage of protamine neutralization heparin on perioperation of on-pump coronary artery bypass grafting / 天津医药

Objective To investigate the effect of different doses of protamine neutralizing heparin on perioperation of on-pump coronary artery bypass graftting (CABG).Methods A total of 180 on-pump CABG patients hospitalized from January 2015 to November 2016 were randomly divided into three groups,the protamine group l,protamine group 2 and protamine group 3,60 patients in each group.Heparin (3 mg/kg) was used before extracorporeal circulation.After intracardiac operation was over,protamine was used to neutralize the heparin to adjust the activated clotting time (ACT) in protamine group 1,which was 10％ higher than that of intubation.Meanwhile,protamine group 2 was neutralized to equal to the ACT before intubation,and protamine group 3 was 10％ lower than that before the intubation.The differences of intraoperative and postoperative parameters were compared between the three groups.Results No death was found in the three groups during hospitalization.Comparing with protamine group 1 and protamine group 2,the time of operation,the ACT before the leaving operation room,the ACT of the first hour after returning to ICU,the amount of bleeding during operation,the time of closing and the amount of red blood for transfusion were decreased in protamine group 3 (P ＞ 0.05).The total amount of protamine for neutralizing and the ratio of protamine and heparin were significantly increased in protamine group 3 (P ＜ 0.05).The heart dysfunction after operation,perioperative myocardial infarction,pulmonary edema,pulmonary infection,renal dysfunction,poor wound healing,neurological complications,and time of in hospital stay showed no significant differences between three groups (P＞0.05).Conclusion ACT below 10％ of preoperation is safe,after neutralization of heparin by protamine,which can obviously reduce the bleeding,the time of sternal closure and the amount of red blood cell transfusion,showing a positive clinical significance.

Clinical study of ginkgo biloba extract dripping pills on ACS patients after PCI and its effects on PAR, ACT and ATⅢ / 中国生化药物杂志

Objective To investigate curative efficacy of ginkgo biloba extract dripping pills in treatment of acute coronary syndrome(ACS) after percutaneous coronary intervention(PCI) and its effects on platelet aggregation rate(PAR), activated clotting time(ACT) and antithrombin(AT)Ⅲ. Methods 90 patients of ACS treated with PCI who received therapy from January 2014 to October 2016 in Zhejiang green town cardiovascular hospital were selected and randomly divided into the observation group and the control group , 45 cases in each group.The control group was treated with routine treatment after PCI, while the observation group was combined with ginkgo biloba extract dripping pills.After treatment of seven days, the changed of PAR, ACT, ATⅢ and adverse cardiovascular events were compared, after treatment three months, the seattle angina scale were compared. Results After treatment, the levels of PAR in the observation group were significantly lower than that of the control group, and the levels of ACT and ATⅢ were significantly higher than that of the control group, the difference was statistically significant (P<0.05), the total incidence of adverse cardiovascular events in the observation group was significantly lower than that of the control group , the difference was statistically significant ( P<0.05), in the seattle angina scale, the scores of stable state of angina pectoris, the attack of angina pectoris, physical activity limitation, treatment satisfaction in the observation group were significantly better than that of the control group, the difference was statistically significant (P<0.05). Conclusion Ginkgo biloba extract dripping pill is well for ACS after PCI, which can effectively relieve clinical symptoms, to improve the expression of PAR, ACT and ATⅢ, helps to reduce the incidence of adverse cardiovascular events.

Optimal Anticoagulation during Off Pump Coronary Artery Bypass in Patients Recently Exposed to Clopidogrel

PURPOSE: The aim of this study was to find an optimal range of activated clotting time (ACT) during off-pump coronary artery bypass surgery (OPCAB) yielding ischemic protection without the risk of hemorrhagic complications in patients with recent exposure to dual antiplatelet therapy. MATERIALS AND METHODS: Three hundred and five patients who received aspirin and clopidogrel within 7 days of isolated multi-vessel OPCAB were retrospectively studied. Combined hemorrhagic and ischemic outcome was defined as the occurrence of 1 of the following: significant perioperative bleeding (>30% of estimated blood volume), transfusion of packed red blood cell (pRBC) > or =2 U, or myocardial infarction (MI). This was compared in relation to the tertile distribution of the time-weighted average ACT-212-291 sec (first tertile), 292-334 sec (second tertile), 335-485 sec (third tertile). RESULTS: The amount of perioperative blood loss was 937+/-313 mL, 1014+/-340 mL, and 1076+/-383 mL, respectively (p=0.022). Significantly more patients in the third tertile developed MI (4%, 4%, and 12%, respectively, p=0.034). The incidence of significant perioperative blood loss and transfusion of pRBC > or =2 U were lower in the first tertile than those of other tertiles without statistical significance. In the multivariate analysis, the first tertile was associated with a 52% risk reduction of combined hemorrhagic and ischemic outcomes (95% confidence interval: 0.25-0.92, p=0.027). CONCLUSION: A lower degree of anticoagulation with a reduced initial heparin loading dose should be carefully considered for patients undergoing OPCAB who have recently been exposed to clopidogrel.

Perioperative Management for the Patient with May-Thurner Syndrome: A Case Report / 대한구급학회지

May-Thurner syndrome is an anatomic variant in which the left common iliac vein is compressed by the right common iliac artery. The most frequent clinical presentation is deep vein thrombosis of the left lower extremity. We report the perioperative management in a patient with May-Thurner syndrome undergoing an open reduction of a tibia fracture. The patient developed deep vein thrombosis of the left lower extremity and had an endovascular stent placed approximately 1 year earlier. An important aspect of the perioperative management in a patient with May-Thurner syndrome is to prevent deep vein thrombosis. We monitored the activated clotting time during the intraoperative period.

Fibrinogen Level and Its Influence on Cardiopulmonary Bypass in Surgery for Aortic Dissection / 日本心臓血管外科学会雑誌

For the purpose of reducing blood loss and blood transfusion, 100 cases of acute aortic dissection treated at this department were studied, focusing on surgery for aortic dissection and coagulation factors, fibrinogen in particular. In cases of aortic dissection, fibrinogen decreased at the acute stage, and showed concentrations significantly lower in Stanford Type A than in Stanford Type B, in extensive dissection (DeBakey Type I or Type III retrograde dissection) than in limited dissection (DeBakey Type II), and in open false lumen type than in closed false lumen type. In the assessment of 34 cases of acute Stanford Type A aortic dissection operated on within 24h of onset, it was found that a marked prolongation of activated clotting time (ACT≥1, 000s) during cardiopulmonary bypass causes an increase in blood transfusion. When ACT was maintained for 400s or longer, to inhibit the marked prolongation of ACT, by changing at any time the dose of heparin during cardiopulmonary bypass by 50-250units/kg on the basis of the preoperative fibrinogen level, instead of fixing it at 300units/kg, ACT decreased significantly, and was controlled at appropriate levels despite the low concentration of fibrinogen. As fibrinogen can be measured in the hospital, and the result obtained in a short time, it is considered to play an important role in controlling ACT to determine the dose of heparin based on its concentration.

Thromboelastography and Activated Clotting Time as Guides to Prediction of Postoperative Bleeding in Cardiac Patients with Administration of Aprotinin / 대한마취과학회지

BACKGROUND: Activated clotting time (ACT) and thromboelastography (TEG) are generally accepted as adequate measures of the coagulation system for monitoring of the cardiac system. Aprotinin is alleged to affect ACT and TEG. We performed this study to see if the determination of ACT and TEG can provide a basis for the assessment of coagulation and the prediction of postoperative hemorrhage in cardiac surgical patients treated with aprotinin. METHODS: Twenty patients undergoing cardiac operation were studied. The values (control) of ACT and TEG were obtained just after induction of anesthesia. Each patient was fully heparinized and received aprotinin, 2,000,000 KIU added to the prime solution. At the end of the procedure, protamine, 3 mg/kg was given for the neutralization of heparin. Measurement of ACT and TEG were made 20 minutes after the administration of protamine, at the end of surgery, and 1 hour after transfer to ICU. The values were compared with the amount of hemorrage collected by chest tubes 1 hour, 2 hours and 8 hours after transferred to ICU. RESULTS: The values of ACT at 20 minutes after protamine administration and at the end of surgery significantly (P < 0.05) increased compared with the values of control, but the values in ICU did not show significant change. All values of TEG significantly (P < 0.05) changed compared with the values of control. No single variable of ACT and TEG showed correlation with the amount of hemorrhage through chest tubing postoperatively. CONCLUSIONS: The results indicate that neither ACT nor TEG predict the amount of postperative hemorrhage in aprotinin-treated patients having cardiac surgery. Therefore the TEG results should be interpreted cautiously because of the high rate of unreliable results.

Safety of Aprotinin Under Hypothermic Circulatory Arrest / 대한흉부외과학회지

It was reported that use of aprotinin in elderly patients undergoing hypothermic circulatory arrest was associated with an increased risk of renal dysfunction, and myocardial infarction as a result of intravascular coagulation. We reviewed 20 patients who received high-dose aprotinin under deep hypothermic circulatory arrest with(NP group, n=11) or without selective cerebral perfusion(SP group, n=9). The activated clotting time was exceeded 750 seconds in all but 1 patient. After opening aortic arch, retrograde low flow perfusion was maintained through femoral artery to prevent air embolization to the visceral arteries. Four patients among 20 died during hospitalization due to bleeding, coronary artery dissection, pulmonary hemorrhage and multiple cerebral infarction. Postoperatively, cerebrovascular accidents occurred in two patients; one with preoperative carotid artery dissection and the other with unknown multiple cerebral infarction. In conclusion, use of aprotinin in young patients undergoing hypothermic circulatory arrest did not increase the risk of renal dysfunction or intravascular coagulation if ACT during circulatory arrest is maintained to exceed 750 seconds with low-flow perfusion.

Influence of Aprotinin on Kaolin and Celite on Activated Clotting Time in Cardiac Surgery / 대한마취과학회지

BACKGROUND: High-dose aprotinin appears to enhance the anticoagulant effects of heparin, as documented by increases in the activated clotting times (ACTs) during cardiopulmonary bypass. This increase of the ACT in the presence of aprotinin and heparin is due to the use of celite as surface activator. We compared celite and kaolin as surface activators for the measurement of the ACT in cardiac surgical patients treated with high dose aprotinin. METHODS: This study included 25 patients who were scheduled for coronary bypass graft surgery and reoperation of cardiac valvular surgery. The 2 million units of aprotinin were added to the pump prime of heart-lung machine. The dosage of heparin and protamine was 3 mg/kg respectively. Whole blood was sampled 10 minutes after induction, heparin administration, cardiopulmonary bypass(CPB), 10 minutes before the termination of CPB and 10 minutes after protamine administration. The ACT was measured with Hemochron 801 blood coagulation timer with 12 mg of either celite (C-ACT) or kaolin (K-ACT) used as surface activator. RESULTS: At 10 minutes after induction and heparin administration, celite and kaolin ACTs were l20+/-28, 541+/-247 seconds and 126+/-23, 559+/-267 seconds rcspectively. But 10 minutes after initiation of CPB and before the termination of CPB, celite ACTs were 941+/-238 and 787+/-277 seconds; kaolin ACTs were 605+/-182 and 499+65 seconds, which were consistently less than celite ACTs(p<0.01). At 10 minutes after protamine administration, celite ACT was 118+/-12 seconds and kaolin ACT was 142 56 seconds which was consistently more than celite ACT(p<0.05). CONCLUSIONS: We recommend the K-ACT rather than C-ACT when monitoring of heparin-induced anticoagulation in patients treated with high-dose aprotinin. It is also highly recommended that patients being added with aprotinin should receive the usual doses of heparin and that the ACT should be measured with kaolin as the activator.

Influence of Aprotinin on Kaolin and Celite on Activated Clotting Time in Cardiac Surgery / 대한마취과학회지

BACKGROUND: High-dose aprotinin appears to enhance the anticoagulant effects of heparin, as documented by increases in the activated clotting times (ACTs) during cardiopulmonary bypass. This increase of the ACT in the presence of aprotinin and heparin is due to the use of celite as surface activator. We compared celite and kaolin as surface activators for the measurement of the ACT in cardiac surgical patients treated with high dose aprotinin. METHODS: This study included 25 patients who were scheduled for coronary bypass graft surgery and reoperation of cardiac valvular surgery. The 2 million units of aprotinin were added to the pump prime of heart-lung machine. The dosage of heparin and protamine was 3 mg/kg respectively. Whole blood was sampled 10 minutes after induction, heparin administration, cardiopulmonary bypass(CPB), 10 minutes before the termination of CPB and 10 minutes after protamine administration. The ACT was measured with Hemochron 801 blood coagulation timer with 12 mg of either celite (C-ACT) or kaolin (K-ACT) used as surface activator. RESULTS: At 10 minutes after induction and heparin administration, celite and kaolin ACTs were l20+/-28, 541+/-247 seconds and 126+/-23, 559+/-267 seconds rcspectively. But 10 minutes after initiation of CPB and before the termination of CPB, celite ACTs were 941+/-238 and 787+/-277 seconds; kaolin ACTs were 605+/-182 and 499+65 seconds, which were consistently less than celite ACTs(p<0.01). At 10 minutes after protamine administration, celite ACT was 118+/-12 seconds and kaolin ACT was 142 56 seconds which was consistently more than celite ACT(p<0.05). CONCLUSIONS: We recommend the K-ACT rather than C-ACT when monitoring of heparin-induced anticoagulation in patients treated with high-dose aprotinin. It is also highly recommended that patients being added with aprotinin should receive the usual doses of heparin and that the ACT should be measured with kaolin as the activator.

Comparative Study of Heparinase Treated Activated Clotting Time with Hephrinase Treated Thromboelastography for Detecting Residual Heparin Effects Following Cardiopulmonary Bypass / 대한마취과학회지

Residual heparin effects after protamine reversal is a potential bleeding disorder associated with cardiopulmonary bypass(CPB). To differentiate this from the other multiple factors causing coagulopathy should be initialized in the setting of management. The purpose of this study was to compare simple activated clotting time(ACT) and thromboelastography(TEG) with heparinase treated ACT and TEG for detecting residual heparin effects to distinguish rapidly the presence of heparin from the effects of other factors because the enzyme heparinase specifically neutralized heparin. After institution approval, 20 patients who required open heart surgery were studied. Baseline kaoline ACT, heparinase ACT, TEG and heparinase TEG(Haemoscope) were obtained before CPB on the same blood sample. The repeated tests were performed on the same blood samples 20 minutes after protamine reversal following CPB. Differences between heparinase treated tests and untreated tests were also evaluated at the same time. Wilcoxon signed ranked test was used to compare the results between before and after bypass. None of patients had significant postoperative bleeding complication. All tests before bypass were normal. Twenty minutes after protamine reversal, 3 patients showed kaoline ACT were extended above 10% of the value of heparinase ACT but all of them remained within normal range. However, nearly all patients showed heparin effects on TEG. The heparin effects on TEG were defined as significant differences in all of parameters, especially in alpha angle and R+K time between simple TEG and heparinase TEG. In Conclusion, heparinase treated ACT and native ACT are not sensitive to residual heparin effects after CPB. Their normal results did not preclude residual heparin effects on heparinase modified TEG. However, it might be further investigated to need additional protamine in the case of residual heparin effects on TEG.