The influence of the duration of cardiopulmonary bypass on coagulation, fibrinolysis and platelet function.

BACKGROUND: The duration of cardiopulmonary bypass (CPB) might influence blood coagulation. This appears particularly relevant in the light of new, less invasive techniques that propose smaller incisions at the expense of a possible prolongation of time on CPB. METHODS: The time-dependent effects on coagulation, fibrinolysis and platelet function were investigated in 94 patients scheduled for elective coronary artery bypass grafting. Tests on coagulation, fibrinolysis, and platelet function (flow cytometric assay of expression densities of glycoprotein IIb/IIIa and P-selection were performed the day before surgery and after completion of surgery. RESULTS: A significant correlation was found between the duration of CPB and parameters of increased coagulation, decrease of platelet counts during CPB and platelet function. Longer duration of CPB led to an increased need for transfusion of red blood cells. CONCLUSIONS: The duration of CPB affects thrombin formation as well as platelet count and function, but not the fibrinolytic system. This may prove to be a disadvantage when employing minimally invasive techniques that prolong the duration of CPB.     

Factor XIIIA and clot strength after cardiopulmonary bypass.

Reduced factor XIIIA levels and decreased clot strength have been associated with increased bleeding after cardiopulmonary bypass (CPB). The purpose of this study was to evaluate the relationship between hemostatic factors, including factor XIIIA, and clot strength before, during and after CPB. Factor XIIIA antigen, platelet counts, fibrinogen, factor V activity, tissue plasminogen activator and clot strength (by thromboelastograph) were measured at baseline, after 45 min of CPB, at the end of CPB and 4 h post-operatively in 34 patients. Baseline factor XIIIA antigen was 5.2 +/- 1.4 mg/l. On average, factor XIIIA levels dropped to 64% and clot strength to 77% of baseline values after 45 min on CPB and remained below baseline during the immediate post-operative period. Clot strength was significantly correlated (r = 0.81) with platelet count and fibrinogen but not plasma factor XIIIA levels. Addition of 10 mg/l recombinant factor XIII[a2] significantly increased clot strength. Postoperative bleeding at 2 h was inversely correlated with platelet count, factor XIIIA antigen and clot strength measured at the end of CPB. Maintenance of adequate platelet counts and factor XIIIA levels at the end of CPB may play a role in maintaining clot strength and reducing blood loss.     

Reduced erythrocyte deformability and hypercoagulability in idiopathic sudden sensorineural hearing loss

OBJECTIVE: Sudden sensorineural hearing loss is a frequent disease whose aetiology is still unknown in about 80% of patients. Aim of this study was to evaluate if haemorheological changes and some indexes of hypercoagulability and hypofibrinolysis are associated with idiopathic sudden sensorineural hearing loss (ISSHL). METHODS: We studied 63 patients with ISSHL and 67 healthy control subjects, matched for age, sex and traditional cardiovascular risk factors. Haemorheological studies were performed by assessing whole blood viscosity (WBV) at 0.512 s(-1) and 94.5 s(-1), plasma viscosity (PLV) and erythrocyte deformability index (DI). To assess whole blood coagulation Sonoclot analysis was performed. Sonoclot variables studied were Sonoclot activated clotting time (SonACT), clot rate and time to peak. Fibrinogen, PAI-1 antigen (ag) and factor VIII:C plasma levels were also measured. RESULTS: WBV, PLV, SonACT, clot rate, time to peak, PAI-1ag and factor VIII:C were significantly altered in patients in comparison with controls (p<0.05). A multivariate analysis (adjusted for traditional cardiovascular risk factors, hematocrit, fibrinogen, haemostatic and haemorheological variables) indicated that WBV at 94.5 s(-1), DI, SonACT, clot rate, PAI-1ag plasma levels and factor VIII:C activity were independently associated with ISSHL (p<0.05). CONCLUSIONS: The observed changes in viscosity, blood clotting and fibrinolysis may contribute, at least in part, to the pathophysiological mechanism of ISSHL.     

Postoperative bleeding after coronary revascularization. Comparison between tranexamic acid and epsilon-aminocaproic acid

BACKGROUND: Microvascular bleeding after Cardiopulmonary bypass (CPB) is mainly due to consumption of clotting factors, platelets damage, and hyperfibrinolysis. Aprotinin, the only antifibrinolytic drug effective in preserving platelets, is no longer available; an alternative regimen based on pure antifibrinolytic drugs has been proposed, since hyperfibrinolysis is known to contribute both to clot lysis and platelet dysfunction. In this study the efficacy of two antifibrinolytic drugs, Tranexamic acid (TA) and epsilon-aminocaproic acid (EACA), was tested in patients undergoing cardiopulmonary bypass (CPB), for primary myocardial revascularization. METHODS: Forty-eight consecutive patients were randomized to receive prophylactically equipotent doses of EACA (group A) or TA (Group B). Platelet count, prothrombin time, fibrin digestion products, blood loss and transfusion requirements recorded after 6 and 24 hours from the end of surgery were compared. RESULTS: The two groups were comparable for length of CPB and numbers of grafts; no significant difference was observed in the coagulation parameters considered. Blood losses were less in group B (TA) than in group A (EACA), both at 6 and 24 hours after surgery; homologous blood transfused was also less in group B, but no difference was statistically significant. No adverse effect was observed. CONCLUSIONS: In coronary patients, TA and EACA exhibit the same effects on blood loss and requirements after CPB; either drug can be safely used in cardiac surgery.     

Monitoring fondaparinux with the Sonoclot.

Fondaparinux is a new anticoagulant that interacts with antithrombin III and activated coagulation factor X resulting in an inhibition of the coagulation system. It has been successful in doses of 2.5 mg for thromboprophylaxis as well as in higher therapeutic doses of 5-7.5 mg. No optimal method for monitoring the effects of fondaparinux has been proposed. The aim of the present study was to investigate whether a viscoelastic coagulation analyzer, the Sonoclot (Sienco, Denver, Colorado, USA), could be used for in-vitro monitoring of fondaparinux. Different concentrations of fondaparinux were added in vitro to whole blood taken from eight volunteers. The blood samples mixed with the various amounts of fondaparinux were analyzed using the Sonoclot. The whole-blood activated partial thromboplastin time with the Hemochron Jr (ITC, Edison, New Jersey, USA) was used as the reference coagulation analysis. All analyses were started expeditiously, within 30 s from sampling, and were performed at 37 degrees C. The values of the Sonoclot parameter clot rate, which measures the rate of fibrin formation, fibrin polymerization and platelet-fibrin interactions, were significantly correlated to increasing concentrations of fondaparinux (R = -0.90). The Sonoclot parameters of activated coagulation time, time to peak and clot retraction had weaker, but still significant, correlations to fondaparinux concentrations. At prophylactic doses (0.38 microg/ml blood) the clot rate decreased 15% compared with the initial unanticoagulated value, whereas at therapeutic doses (1.53 microg/ml blood) there was a 27% decrease. In conclusion, the Sonoclot parameter clot rate could be of clinical value to individualize the fondaparinux dosage, especially the higher, therapeutic, dosages.     

Sonoclot血栓监测指标对经皮冠状动脉介入治疗围手术期心肌梗死的预测作用

目的经皮冠状动脉介入治疗(percutaneous coronary intervention,PCI)围手术期心肌梗死的发生与术前抗栓治疗关系密切,但至今还没有理想的临床指标评价PCI术前的抗栓治疗效果。Sonoclot是一种以血液黏度为基础体外实时监测凝血功能和血小板功能的方法。本研究拟入选急性冠状动脉综合征(ACS)患者,PCI术前进行Sonoclot检测,评价Sonoclot指标与PCI围手术期心肌梗死发生的相关性,寻找可以评价PCI术前抗栓疗效的指标。方法前瞻性连续入选2009年9月至2010年7月收住在北京大学第一医院心内科、临床诊断为非ST段抬高急性冠脉综合征并接受冠状动脉造影及介入治疗的患者。收集一般临床资料,根据PCI术后心肌标记物升高至正常值上限3倍以上与否判断患者是否发生围手术期心肌梗死,使用Sonoclot凝血及血小板功能分析仪(Sonoclot coagulation&platelet function analyzer,SCA,SIENCO,Inc,USA)完成ACT(activited clotting time,激活凝血时间)、CR(clot rate,凝血速率)、PF(platelet function,血小板功能)等指标的检测。结果共入组患者246例,其中,男性163例(66.3%),女性83例(33.7%),年龄分布于27～87岁之间,平均(64.3±11.2)岁。其中119例(48.4%)发生围手术期心肌梗死,与未发生者相比,性别、术中肝素用量、多支血管病变比例差异具有统计学意义。另外,经Sonoclot测得的肝素化前CR(gbCR)在两组间差异存在统计学意义(21.32比19.83,t=-2.000,P<0.05)。进一步按照gbCR的75%分位数(gbCR=24)将患者分为两组,结果显示,gbCR高于四分位数患者围手术期心梗风险明显增加(OR:1.94,95%CI:1.05～3.59,P=0.04)。对性别、年龄、BMI、多支血管病变、肝素用量、PT值、FIB值、gbCR等多个因素进行Logistic回归分析显示,gbCR是PCI围手术期心梗的独立预测因素(OR=2.36,95%CI:1.05～5.28)。结论肝素化前CR值与PCI围手术期心肌梗死具有显著相关性,提示对该指标的监测可能会预测PCI围术期心肌梗死的发生风险。     

Cerebrovascular events in young adults after surgical repair of tetralogy of Fallot

Increasing numbers of children who have undergone intracardiac repair of tetralogy of Fallot have survived to adulthood, but often have residual haemodynamic and/or electrical abnormalities. We report the unusual observation of 4 instances of cerebrovascular accidents in young adults subsequent to surgical repair of tetralogy of Fallot.     

Whole blood aggregation and coagulation in db/db and ob/ob mouse models of type 2 diabetes

Type 2 diabetes in humans is associated with a significant hypercoagulable state; however, the effects of this on stroke and cardiovascular disease are not completely understood. The genetic mutations in db/db and ob/ob mice produce metabolic abnormalities similar to type 2 diabetes, but little is known about their platelet or coagulation properties. The objective of this study was therefore to examine platelet function and coagulation in db/db and ob/ob mice to determine the degree of alteration induced by type 2 diabetes. Male db/db and ob/ob mice, 8-16 weeks old, and their respective genetic control mice were used for all experiments. To examine platelet function and coagulation, we measured ADP-induced whole blood aggregation at baseline and after inhibition with aspirin and fucoidan, whole blood coagulation by thromboelastography, and platelet CD61 expression by flow cytometry. Both db/db and ob/ob mice demonstrated significantly less ADP-induced whole blood aggregation compared with control mice (db/db mice, P < 0.001; ob/ob mice, P < 0.01). Aggregation was significantly inhibited with aspirin in all groups; however, fucoidan inhibited aggregation only in control mice. The db/db and ob/ob mice demonstrated significantly less maximal clot strength compared with control mice (P < 0.01), and ob/ob mice demonstrated premature clot fibrinolysis measured by thromboelastography. In conclusion, the db/db and ob/ob type 2 diabetes mouse models do not demonstrate a hypercoagulable state similar to humans with this disease. We caution their use for studying cardiovascular and cerebrovascular disease in the setting of type 2 diabetes.     

A Comparison of Hemostatic Parameters in Hypothermic Versus Normothermic Cardiopulmonary Bypass

Ten patients who underwent PCPS (group A) at our institution were evaluated for hemostatic abnormalities and compared to an age matched population undergoing open CPB (group B) to study the effects of CPB independent of the effects of hypothermia. Both groups had hemostatic parameters measured prior to, 1 hour after, and 16–24 hours following completion of the procedure. The mean duration of perfusion for group A was 53.7 ± 13.5 minutes and group B 108.1 ± 26.5 minutes (P < 0.0001). There were no significant differences in hemoglobin, platelet count, coagulation factors, and tests of in vitro platelet function between groups A and B at the different time points. While bleeding times for group B returned to baseline within an hour following bypass, they remained significantly prolonged in group A 24 hours later (P = 0.02). Conclusion: Normothermic bypass used during PCPS results in platelet function abnormalities similar to open hypothermic CPB suggesting the dominant role of the membrane oxygenator over hypothermia in inducing the platelet dysfunction .     

Activation of Coagulation and Fibrinolysis During Coronary Artery Bypass Grafting: A Comparison Between On-Pump and Off-Pump Techniques

Coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB) is associated with intense activation of hemostatic mechanisms. But the precise knowledge of the effects of eliminating CPB in patients undergoing off-pump coronary artery bypass grafting (CABG) are not well established. The present study was carried out to compare and document the changes in selected coagulation and fibrinolysis variables in patients undergoing on-pump and off-pump CABG (OPCAB). A total of 42 patients of on-pump and 31 patients of off-pump CABG were selected for the study. Platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), Fibrinogen and D-dimer levels were measured immediately, 24 h and 7 days after operation and compared with the baseline preoperative values. Statistical analysis was done by mixed ANOVA for repeated measures and Post-hoc tests using the Bonferroni correction, Chi square and unpaired t test. All the parameters were significantly changed (P < 0.05) with the time. Platelet counts, fibrinogen and D-dimer levels were significantly different between on-pump and off-pump CABG patients on immediate and 24 h postoperative period and attained almost same level after 7 days of operation. Fibrinogen level and platelet counts were increased after a sharp fall in the immediate post-operative period whereas D-dimer levels were persistently increased with a sharp peak of rise in the immediate post-operative period in on-pump group. On-pump surgery was associated with excessive fibrinolytic activity immediately after operation. The off-pump group demonstrated less activation of coagulation and fibrinolysis and delayed postoperative response that became almost equal to the on-pump group in the later postoperative period.     

Diagnosis of overt disseminated intravascular coagulation in critically Ill adults by Sonoclot coagulation analysis

Disseminated intravascular coagulation (DIC) diagnosis is hampered by the limited availability of reliable clinical or laboratory tests. Currently available tests are time consuming and expensive. We investigated whether coagulation and platelet function analyses using the Sonoclot system were suitable for overt DIC diagnosis in critically ill adults. This was an observational diagnostic study performed in 498 patients presenting with an underlying disorder associated with DIC. Overt DIC patients were identified according to an International Society on Thrombosis and Hemostasis (ISTH) score of >5. Coagulation and platelet parameters were analyzed using the Sonoclot system, and compared with ISTH as the gold standard. Receiver operating characteristic curves and area under the curves were used to evaluate the value of the Sonoclot parameters. There were no differences for age or gender between the groups. Significant correlations were observed between activated clotting time (ACT) and ISTH score (r = 0.7; P < 0.001), clot rate (CR) and ISTH score (r = 0.5; P < 0.001), platelet function (PF) and ISTH score (r = ?0.6; P < 0.001), and PF and platelet count (r = 0.5; P < 0.001). An ACT cut-off value of 213.5 s alone or combined with CR presented good sensitivity (76.7 and 86.8 %, respectively) and specificity (96.2 and 93.3 %, respectively). Sonoclot analysis can be performed using a point-of-care device that effectively discriminates low and high ISTH scores, and that effectively predicts coagulation dysfunction in patients with overt DIC.     

Latex D-dimer signal in in situ femoral vein thrombus in swine and effect of minidose exogenous tissue plasminogen activator bolus

STUDY OBJECTIVES: We created in situ femoral vein thrombi in swine to investigate the response of the latex d-dimer signal to acute in situ venous thrombosis, and to determine the minimum dose of exogenous bolus tissue plasminogen activator (t-PA) required to significantly elevate the d-dimer signal. STUDY DESIGN: We studied seven swine (20 to 22 kg) under pentobarbital anesthesia. A 6-cm segment of the proximal femoral vein was surgically exposed and briefly ligated. Thrombin, 250 U, was then injected into the isolated femoral vein segment to create an in situ clot. After clot formation was documented to be complete between the ligatures, they were then released. D-dimer levels were then measured every 15 min for 1 h before and 1 h after clot formation with ligatures released. Time-response curves to establish timing of peak t-PA effect were performed, and then escalating dose-response curves of d-dimer level to minidose t-PA were plotted. RESULTS: After formation of the clot, the release of ligatures resulted in no change in d-dimer levels over 1 h (p = 0.62) in all swine. When a time-response curve to exogenous t-PA bolus in the presence of femoral clot was plotted, there was a maximal increase in d-dimer signal at 30 min after bolus t-PA administration. The subsequent dose-response curves for escalating fivefold boluses of minidose t-PA showed an increase in d-dimer signal at doses of 0.8 mg (p = 0.03) and 4 mg (p = 0.003). CONCLUSION: We conclude the following: (1) in situ femoral vein clot formation does not elevate d-dimer signal for 1 h after ligature release; (2) minidose t-PA boluses of 0.8 mg and 4 mg significantly elevated the latex d-dimer signal above baseline; and (3) there is a potential role of minidose t-PA in enhancing the d-dimer signal in in situ deep venous thrombosis.     

Quality of life after repair of tetralogy of Fallot

OBJECTIVE: To determine the quality of life in individuals with corrected tetralogy of Fallot. METHODS AND SUBJECTS: Questionnaires concerning quality of life were sent to all 87 surviving patients aged between 16 and 40 years who had undergone intracardiac repair of tetralogy of Fallot and follow-up in the Wessex Cardiothoracic Unit, and to 87 age and sex matched controls, with medically treated haemodynamically insignificant ventricular septal defects. RESULTS: The only significant difference found between the cases and controls was in requirements for schooling, where those with tetralogy of Fallot were more likely to require additional educational help at school (p = 0.044). For all other aspects of quality of life examined by the questionnaire, including social and genetic history, exercise ability, and health related quality of life, no significant differences were found. Different operative techniques, such as transjunctional patching, right ventriculotomy, and previous palliative shunting, did not affect the quality of life of our population with Tetralogy of Fallot, on average twenty years after their surgery, although the range of operative techniques was limited. Neither age at surgery, nor time since surgery, was correlated with measurements of quality of life. CONCLUSIONS: Those who have undergone surgical correction of tetralogy of Fallot have a normal quality of life, with few differences compared to controls.     

Centrifugal and roller pumps — are there differences in coagulation and fibrinolysis during and after cardiopulmonary bypass?

Summary A number of hemostatic parameters reflecting the activation of coagulation and fibrinolysis were investigated in a prospective study of 24 patients undergoing cardiopulmonary bypass (CPB) during heart surgery. The patients were randomized to a group in which either a roller (group 1) or a centrifugal pump (group 2) was used. Blood samples were taken preoperatively, at the onset of and every 20min during CPB, after the administration of protamine, and 4, 20, 44, and 68 h postoperatively. The groups did not differ significantly in hematocrit, fibrinogen, factor XIII, and antithrombin III. Significant differences in favor of group 2 during and after CPB were found in prothrombin fragment F1+2, plasmin-antiplasmin complex (PAP), thrombin-antithrombin complex (TAT), and D-dimer (F1+2P < 0.01 after 80-min CPB, PAPP < 0.005 after 40-min CPB, TAT and D-dimerP < 0.05 after 100-min CPB, D-dimer and PAPP < 0.05 after protamine administration, TAT and F1+2 4h after CPB).These findings indicate the activation of fibrinolysis preceding thrombin generation during cardiopulmonary bypass. In addition, we conclude that centrifugal blood pumping is beneficial in avoiding excessive activation of both coagulation and fibrinolysis.     

The influence of beta-adrenergic blockade upon baseline blood coagulation and fibrinolytic activity and upon the responses to venous occlusion.

Twenty volunteers were assessed for baseline coagulation (Thrombelastography, Factor VIII and platelet count) and fibrinolytic (Euglobulin Lysis Time and Fibrin(ogen) Degradation Products) activity two hours after ingestion of 60 mgm propranolol or an identical placebo administered on a double blind basis. The responses of these parameters to a fifteen minute period of venous occlusion was also assessed. Beta adrenergic blockade reduced baseline FDP titres but did not affect other parameters, nor the local response to venous occlusion. During occlusion no significant change in coagulation activity could be detected in the non-occluded arm, but a small but statistically significant shortening of ELT was observed. Since this effect was prevented by propranolol it is probably mediated through adrenergic mechanisms. Adrenergic stimuli appear to influence episodes of coagulation and fibrinolysis during everyday activity, but do not contribute to baseline levels of coagulation or fibrinolytic function.     

五例尸检法乐氏四联症的解剖形态观察

本文报告5例未经心内手术矫治的法乐氏四联症,对其心脏解剖形态及合并畸形,作了详细的观察和描述。     

Pulmonary artery sling associated with tetralogy of fallot

We describe a rare case of pulmonary artery sling occurring simultaneously with tetralogy of Fallot. This report describes the successful concomitant repair of both intracardiac anomalies.     

法鲁四联症体外循环手术对血浆内皮素的影响

对２１例法鲁四联症患儿体外循环手术前后血浆内皮素的变化进行动态检测，并以单纯室间隔缺损２３例作为对照。结果显示，除术后１年外．法鲁四联症组各期内皮素值均较室缺组为高。术后１小时两组内皮素值均达最高峰，室缺组术后３天恢复，四联症组术后７天仍高于术前。内皮素值与体外循环时间及主动脉阻断时间在四联症组呈高度相关。文章讨论了体外循环期间内皮素变化的原因及临床意义。     

Pharmacological manipulation of gastric juice: thrombelastographic assessment and implications for treatment of gastrointestinal haemorrhage.

The impairment of formation and maintenance of a formed fibrin clot contributes to the prolonged bleeding and high incidence of rebleeding in upper gastrointestinal haemorrhage. To investigate the basis for the use of drug therapy in gastric bleeding, this study used thrombelastography to determine the effects of pharmacological manipulation of gastric juice on coagulation and fibrinolysis. The thrombelastograph is a mechanical device that provides a visual assessment of all stages of coagulation and fibrinolysis. The effects of fresh and pharmacologically changed gastric juice was assessed after its addition to fresh whole blood in the thrombelastograph cuvette. Pharmacological manipulation was achieved through alkalisation or through addition of tranexamic acid, aprotinin, or sucralfate. Fresh gastric juice delayed clot formation, decreased maximum clot amplitude, and stimulated clot lysis. Alkalisation inhibited the lytic effects of fresh gastric juice and improved the induced abnormalities in coagulation. Tranexamic acid partially inhibited gastric juice induced clot lysis but did not exhibit a beneficial effect on coagulation. Sucralfate, and to a lesser extent aprotinin significantly inhibited fibrinolysis but exacerbated the detrimental effect of gastric juice on the parameters of coagulation. Alkalisation of gastric juice reduces the adverse effect on coagulation and fibrinolysis. Tranexamic acid, aprotinin, and sucralfate can all reduce or inhibit clot lysis, but the adverse effects on clot formation may outweigh any potential benefit in the treatment of gastrointestinal bleeding.     

The surgical decision in tetralogy of Fallot: weighing risks and benefits with decision analysis

The preferred management of the symptomatic infant less than 2 years of age with tetralogy of Fallot remains unsettled. In this study decision analysis was used to assess the risks and benefits of three courses of action: (1) primary intracardiac repair; (2) palliative operation in infancy and delayed intracardiac repair; and (3) treatment with propranolol in infancy and delayed intracardiac repair. For each action the likelihood was determined of three possible outcomes for the patient: (1) death, (2) poor surgical result, or (3) good surgical result. Each outcome was associated with an estimated life expectancy. The best action was defined as that resulting in the longest life expectancy. With use of previously reported data and those from experience at one institution, a range of probabilities was estimated for death before operation, surgical mortality, success of propranolol treatment and hemodynamic result of operation. The choice of action was affected most by the mortality of primary intracardiac repair and the likelihood of a good hemodynamic result from intracardiac repair. Less important factors were the outcome of a palliative operation and the likelihood of success with propranolol therapy. It was found that in the institution studied if the mortality rate of primary intracardiac repair is 10 percent or less, intracardiac repair should be performed; otherwise propranolol treatment, which allows delay in intracardiac repair, should be selected. Both alternatives are preferable to palliative operation. With decision analysis, the clinician can use probabilities and life expectancy appropriate to a given clinical setting in determining the best management for the infant with tetralogy of Fallot.