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L Shore-Lesserson

Publications and source records attributed to L Shore-Lesserson.

At least 19 recordsLinked to original sources
PubMed2001

The balance of concurrent aggregation and deaggregation processes in platelets is linked to differential occupancy of ADP receptor subtypes.

Deaggregation, the partial reversal of the initial aggregation of platelets is observed following low, but not higher, micromolar ADP concentrations. This study tested the hypothesis that deaggregation results from a balance between concurrent, opposing, aggregation and deaggregation processes which are ADP (adenosine 5'-diphosphate) receptor occupancy-dependent. Aggregation of human platelet-rich plasma (PRP) prepared in r-hirudin was assayed in a 96-well plate reader over 20 min by measurement of the optical density (OD) at 580 nm. Aggregation and the time to reach peak aggregation were directly proportional to ADP receptor occupancy. The magnitude and time course of the response to ADP were comparable to those previously reported with standard aggregometry. The rate constant of platelet deaggregation, as assessed by a four-compartment kinetic model, was inversely proportional to agonist concentration. The ratio of the rate constants of aggregation and deaggregation was receptor occupancy-dependent and directly proportional to aggregation. Consequently, platelet aggregation was proportional, and deaggregation inversely proportional, to ADP receptor occupancy. We propose that the response of PRP to ADP and to 2-MeS-ADP (2-methylthioadenosine-diphosphate), in vitro, consists of at least two active, concurrent processes, aggregation and deaggregation. Incremental occupancy of the P2T ADP receptor subtype attenuates deaggregation and governs the balance between these two processes.

Adenosine Diphosphate↗
PubMed2001

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

UNLABELLED: 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.

Anticoagulants↗
PubMed2001

Use of intraoperative transesophageal echocardiography to predict atrial fibrillation after coronary artery bypass grafting.

BACKGROUND: Postoperative atrial fibrillation in coronary artery bypass graft surgery occurs in 10-40% of patients. It is associated with a significant degree of morbidity and results in prolonged lengths of stay in both the intensive care unit and hospital. METHODS: The authors prospectively evaluated patients undergoing coronary artery bypass with detailed transesophageal echocardiography examinations conducted before and after cardiopulmonary bypass to study whether risk factors for atrial fibrillation could be identified. Demographic and surgical parameters were also included in the analysis. Selected variables were subjected to univariate and subsequent multivariate analyses to test for their independent or joint influence on atrial fibrillation. RESULTS: Seventy-nine patients had assessable transesophageal echocardiography examinations. Significant univariate predictors of atrial fibrillation included advanced age (P = 0.002), pre-cardiopulmonary bypass left atrial appendage area (P = 0.04), and post-cardiopulmonary bypass left upper pulmonary vein systole/diastole velocity ratio (P = 0.03). When these three factors were considered together in a multiple logistic regression analysis, left upper pulmonary vein systole/diastole velocity ratio was a significant predictor (P < 0.05), as was the joint effect of age plus pre-cardiopulmonary bypass left atrial appendage area (P = 0.005). The probability of developing atrial fibrillation for the combination of age = 75 yr, post-cardiopulmonary bypass left upper pulmonary vein systole/diastole velocity ratio = 0.5, and left atrial appendage area = 4.0 cm was 0.83 (95% confidence interval, 0.51-0.96). CONCLUSIONS: Early identification of patients at risk for postoperative atrial fibrillation may be feasible using the parameters identified in this study.

Age Factors↗
PubMed2000

Anticoagulation for cardiac surgery in patients receiving preoperative heparin: use of the high-dose thrombin time.

UNLABELLED: Patients receiving heparin infusions have an attenuated activated clotting time (ACT) response to heparin given for cardiopulmonary bypass (CPB). We compared patients receiving preoperative heparin (Group H) to those not receiving heparin (REF group) with respect to ACT, high-dose thrombin time (HiTT), and markers of thrombin generation during CPB. Sixty-five consecutive patients (33 Group H, 32 REF group) undergoing elective CPB were evaluated. ACT and HiTT were measured at multiple time points. Plasma levels of thrombin-antithrombin III complex and fibrin monomer were determined at baseline, during CPB, and after protamine administration. Transfusion requirements and postoperative blood loss were measured and compared. ACT values after heparinization increased less in Group H and were significantly lower than those in the REF group (P < 0.01). HiTT values did not differ significantly between the two groups. Blood loss and transfusion requirements were not significantly different between the two groups. Plasma levels of thrombin-antithrombin III complexes and fibrin monomer also did not differ between groups at any time, despite a lower ACT in Group H after heparinization and during CPB. Our data suggest that thrombin formation and activity are not enhanced in patients receiving heparin therapy, despite a diminished ACT response to heparin. The utility of ACT and the threshold values indicative of adequate anticoagulation for CPB are relatively undefined in patients receiving preoperative heparin. HiTT should be investigated as a safe and accurate monitor of anticoagulation for CPB in patients receiving preoperative heparin therapy. IMPLICATIONS: The diminished activated clotting time response to heparin, in patients receiving preoperative heparin therapy, poses difficulties when attempting to provide adequate anticoagulation for cardiopulmonary bypass. Current data suggest that heparin resistance is not observed when high-dose thrombin time is used to monitor anticoagulation and that a lower activated clotting time value in these patients may be safe.

Anticoagulants↗
PubMed2000

Myocardial injury in cardiac surgery: the role of transfusion.

The approach to minimizing transfusion therapy in the cardiac surgical patient entails an understanding of the unique physiology of CPB. A comprehensive blood conservation program will promote autologous reinfusion techniques and pharmacologic agents that preserve hemostasis. The institution of therapy-directed algorithms using appropriately selected tests will ultimately reduce empiric transfusions and will improve specificity of transfusion therapy. The use of technologies and drugs that attenuate inflammation will reduce consumption and the activation of leukocytes and platelets. This approach should be a multifaceted one that will ultimately lead to better preservation of end-organ function after cardiac surgery.

Antifibrinolytic Agents↗
PubMed1999

Thromboelastography-guided transfusion algorithm reduces transfusions in complex cardiac surgery.

UNLABELLED: Transfusion therapy after cardiac surgery is empirically guided, partly due to a lack of specific point-of-care hemostasis monitors. In a randomized, blinded, prospective trial, we studied cardiac surgical patients at moderate to high risk of transfusion. Patients were randomly assigned to either a thromboelastography (TEG)-guided transfusion algorithm (n = 53) or routine transfusion therapy (n = 52) for intervention after cardiopulmonary bypass. Coagulation tests, TEG variables, mediastinal tube drainage, and transfusions were compared at multiple time points. There were no demographic or hemostatic test result differences between groups, and all patients were given prophylactic antifibrinolytic therapy. Intraoperative transfusion rates did not differ, but there were significantly fewer postoperative and total transfusions in the TEG group. The proportion of patients receiving fresh-frozen plasma (FFP) was 4 of 53 in the TEG group compared with 16 of 52 in the control group (P < 0.002). Patients receiving platelets were 7 of 53 in the TEG group compared with 15 of 52 in the control group (P < 0.05). Patients in the TEG group also received less volume of FFP (36 +/- 142 vs 217 +/- 463 mL; P < 0.04). Mediastinal tube drainage was not statistically different 6, 12, or 24 h postoperatively. Point-of-care coagulation monitoring using TEG resulted in fewer transfusions in the postoperative period. We conclude that the reduction in transfusions may have been due to improved hemostasis in these patients who had earlier and specific identification of the hemostasis abnormality and thus received more appropriate intraoperative transfusion therapy. These data support the use of TEG in an algorithm to guide transfusion therapy in complex cardiac surgery. IMPLICATIONS: Transfusion of allogeneic blood products is common during complex cardiac surgical procedures. In a prospective, randomized trial, we compared a transfusion algorithm using point-of-care coagulation testing with routine laboratory testing, and found the algorithm to be effective in reducing transfusion requirements.

Aged↗
PubMed1999

Platelet-activated clotting time does not measure platelet reactivity during cardiac surgery.

BACKGROUND: Platelet dysfunction is a major contributor to bleeding after cardiopulmonary bypass (CPB), yet it remains difficult to diagnose. A point-of-care monitor, the platelet-activated clotting time (PACT), measures accelerated shortening of the kaolin-activated clotting time by addition of platelet activating factor. The authors sought to evaluate the clinical utility of the PACT by conducting serial measurements of PACT during cardiac surgery and correlating postoperative measurements with blood loss. METHODS: In 50 cardiac surgical patients, blood was sampled at 10 time points to measure PACT. Simultaneously, platelet reactivity was measured by the thrombin receptor agonist peptide-induced expression of P-selectin, using flow cytometry. These tests were temporally analyzed. PACT values, P-selectin expression, and other coagulation tests were analyzed for correlation with postoperative chest tube drainage. RESULTS: PACT and P-selectin expression were maximally reduced after protamine administration. Changes in PACT did not correlate with changes in P-selectin expression at any time interval. Total 8-h chest tube drainage did not correlate with any coagulation test at any time point except with P-selectin expression after protamine administration (r = -0.4; P = 0.03). CONCLUSIONS: The platelet dysfunction associated with CPB may be a result of depressed platelet reactivity, as shown by thrombin receptor activating peptide-induced P-selectin expression. Changes in PACT did not correlate with blood loss or with changes in P-selectin expression suggesting that PACT is not a specific measure of platelet reactivity.

Adult↗
PubMed1998

Heparin and protamine titration do not improve haemostasis in cardiac surgical patients.

PURPOSE: Weight-based heparin and protamine dosing strategies for cardiopulmonary bypass (CPB) do not take into account interpatient variability in drug sensitivity and may result in bleeding complications. We compared the Hemochron RxDx heparin and protamine titration system with standard weight based management with regard to heparin dose, protamine dose, and perioperative bleeding. METHODS: One hundred and thirty-five cardiac surgical patients were randomised into four groups. Group 1 received standard heparin and protamine management: Group 2 received heparin and protamine by in vitro titration. Group 3 had the heparin dose titrated, and group 4 had the protamine dose titrated. Coagulation tests, bleeding, and transfusion requirements were measured. RESULTS: The initial heparin bolus predicted by the titration was < 300 U.kg-1 in all patients. Group 2 received a lower heparin bolus for the initiation of bypass but total heparin doses were not different among groups (group 1 = 365 +/- 43, group 2 = 348 +/- 73 U.kg-1, group 3 = 394 +/- 86 U.kg-1, group 4 = 376 +/- 60; P = 0.06). Groups 2 and 4 received a lower initial and a lower total protamine dose (total dose group 1 = 4.03 +/- 0.65 mg.kg-1, group 2 = 3.56 +/- 1.11 mg.kg-1, group 3 = 4.22 +/- 0.90 mg.kg-1, group 4 = 3.38 +/- 0.98 mg.kg-1, P = 0.001). The incidences of incomplete heparin neutralisation (P = 0.14) and heparin rebound (P = 0.1) were not different among groups. Postoperative bleeding and transfusion requirements did not differ. CONCLUSION: In cardiac surgical patients, heparin and protamine titration did predict a lower protamine dose but did not result in a measurable improvement in haemostasis during the perioperative period.

Analysis of Variance↗
PubMed1998

Intraoperative transesophageal echocardiography during noncardiac surgery.

OBJECTIVE: To investigate the use and impact of transesophageal echocardiography (TEE) during noncardiac surgery. DESIGN: Retrospective study. SETTING: A university teaching hospital. PARTICIPANTS AND INTERVENTIONS: The medical records and the videotapes of 123 intraoperative TEE examinations were reviewed. MEASUREMENTS AND MAIN RESULTS: TEE was used for non-consultative indications in 68 patients and in consultation in 55 patients. Information that would not have been detected intraoperatively by other means included intracardiac defects, valvular and aortic pathology, the presence or absence of ventricular dysfunction or intracardiac thrombi, and embolization during surgery. Findings during the initial TEE examination and the TEE evaluation of intraoperative events resulted in a major impact on patient management in 15% of patients. The majority of patients in whom TEE had any impact (the sum of major, minor, and limited impact groups) were classified as American Society of Anesthesiologists (ASA) class 3 or 4. Patients in whom TEE had any impact were significantly older than patients in whom TEE had no impact (66.5 +/- 13.4 years v 58.1 +/- 16.2 years; p < 0.05). No patient experienced a complication related to intraoperative TEE. CONCLUSION: It appears that TEE in patients undergoing noncardiac surgery is efficacious in rapidly disclosing new findings and information during periods of hemodynamic instability. It may have a significant impact on intraoperative patient management and may be beneficial in patients older than 66 years of age.

Adolescent↗
PubMed1996

Tranexamic acid reduces transfusions and mediastinal drainage in repeat cardiac surgery.

The administration of tranexamic acid (TA) prior to cardiopulmonary bypass (CPB) has been associated with reduced bleeding during and after cardiac surgery. In a prospective, randomized, controlled, double-blind clinical trial, adult patients undergoing repeat open heart surgery received TA (n = 17) or an equal volume of saline placebo (n = 13). In the TA group, a 20-mg/kg intravenous (IV) initial dose of TA at akin incision was followed by an infusion of 2 mg.kg-1.h-1, which continued for the duration of the surgical procedure. Identical transfusion guidelines were followed in both groups. Routine coagulation tests, D-dimer levels, mediastinal tube drainage, and transfusion requirements were compared. Cumulative postoperative mediastinal tube drainage measured at 24 h was 649 +/- 391 mliter (mean +/- SD) in the TA group compared with 923 +/- 496 mliter in the placebo group (P < 0.01). Forty-eight-and 72-h mediastinal tube drainage were also significantly less in the TA group (P < 0.01). Seven of 17 TA patients received to transfusion of allogeneic blood products compared with 1 of 13 placebo patients (P = 0.047). The incidence and volumes of platelet and fresh frozen plasma transfusion in the TA group were not significantly different in comparison with the placebo group. The perioperative increase in D-dimer levels (post-CPB minus pre-CPB) in the placebo group (median difference = 675 ng/mliter, range 125-1648) was significantly more than in the TA group (median difference = 182 ng/mliter, range -426-1950; P = 0.003). Sternal closure occurred in 41 +/- 21 min in the TA group and 61 +/- 49 min in the placebo group (P = 0.14), and the subjective bleeding score was less in the TA group than in the placebo group (2.38 +/- 0.78 vs 3.08 +/- 1.04; P = 0.045). The data from the current study support the prophylactic use of TA in patients undergoing repeat cardiac surgery. TA administered prior to CPB reduced the incidence of allogeneic transfusions and postoperative mediastinal tube drainage, and improved the subjective assessment of post-CPB hemostasis in a group of patients at moderately high risk for perioperative bleeding.

Adult↗