The role of desmopressin acetate in patients undergoing coronary artery bypass surgery. A controlled clinical trial with thromboelastographic risk stratification.

The role of desmopressin acetate in attenuating blood loss and reducing homologous blood component therapy after cardiopulmonary bypass is unclear. The purpose of this investigation was to identify a subgroup of patients that may benefit from desmopressin acetate therapy. One hundred fifteen patients completed a prospective randomized double-blind, placebo-controlled trial designed to evaluate the effect of desmopressin acetate (0.3 microgram.kg-1) on mediastinal chest tube drainage after elective coronary artery bypass grafting surgery in patients with normal and abnormal platelet-fibrinogen function as diagnosed by the maximal amplitude (MA) on thromboelastographic (TEG) evaluation. The 115 patients evaluated were divided into two groups based on the MA of the post-cardiopulmonary bypass TEG tracing. Group 1 (TEG:MA greater than 50 mm) consisted of 86 patients, of whom 44 received desmopressin and 42 received placebo. Twenty-nine patients had abnormal platelet function (TEG:MA less than 50 mm) and were designated as group 2. In group 2, 13 received desmopressin and 16 placebo. During the first 24 h after cardiopulmonary bypass, the placebo-treated patients in group 2 had significantly greater mediastinal chest tube drainage when compared to placebo patients in group 1 (1,352.6 +/- 773.1 ml vs. 865.3 +/- 384.4 ml, P = 0.002). In addition to increases in blood loss, group 2 placebo patients also were administered an increased number of blood products (P less than 0.05). The desmopressin-treated patients in group 2 neither experienced increased mediastinal chest tube drainage nor received increased amounts of homologous blood products when compared to those in group 1.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of viscoelastic measures of coagulation after cardiopulmonary bypass

Postoperative hemorrhage remains a major cause of morbidity after cardiopulmonary bypass (CPB). Treatment remains empiric because of the need for immediate correction and the lack of availability of rapid intraoperative coagulation monitoring (except for ACT) at most institutions. Thrombelastography (TEG) and Sonoclot analysis (SCT) are measures of viscoelastic properties of blood which allow rapid intraoperative evaluation of coagulation factor and platelet activity as well as overall clot integrity from a single blood sample. Routine coagulation tests (RCT) including activated clotting time (ACT), prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen level (FIB), and platelet count (PLT) were determined and compared to TEG and SCT to assess which best predicted clinical hemostasis after CPB. Forty-two patients prospectively felt to be at high risk for excessive post-CPB bleeding had blood obtained for RCT, TEG, and SCT analysis before systemic heparinization and 30 min after protamine administration. Nine of 42 patients had excessive chest tube drainage, but no reoperations were required. After CPB, mean values for RCT were normal, but there were abnormalities in TEG and SCT parameters that reflect platelet-fibrin interaction. Both TEG and SCT were 100% accurate in predicting bleeding in these nine patients and, overall, both tests were significantly better predictors of postoperative hemorrhage than RCT. We conclude that viscoelastic determinants of clot strength may be abnormal after CPB and that SCT and TEG are, therefore, more useful than RCT for the detection and management of coagulation defects associated with CPB.     

A prospective, randomized platelet-function study of heparinized oxygenators and cardiotomy suction

OBJECTIVE: The purpose of this study was to determine if substitution of a heparin-coated oxygenator and salvaged autologous blood for cardiotomy suction would improve platelet function. DESIGN: A prospective, randomized trial. SETTING: A large academic medical center. PARTICIPANTS: Sixty adult patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass (CPB). INTERVENTIONS: Patients were randomized into 1 of 4 groups in a 2 x 2 factorial design by oxygenator (heparinized v nonheparinized) and blood salvage during CPB (cardiotomy suction v salvaged autologous blood). MEASUREMENTS AND MAIN RESULTS: Primary outcome measures were platelet function, glass-bead retention, platelet dense-body adenosine triphosphate secretion, platelet-rich plasma (PRP) aggregometry, Plateletworks platelet-function analyzer (Helena Laboratories Corp, Allen Park, MI), and platelet count. Secondary outcome measures were chest-tube drainage and allogeneic blood transfusion requirements. All platelet-function tests except thrombin-receptor activator peptide-induced PRP aggregometry showed a reduction in platelet function during and immediately after CPB (all p < 0.05). The only statistically significant difference in platelet-function tests between the groups was the glass-bead assay at 5 minutes before discontinuation of CPB (p < 0.05). This difference resolved 10 minutes after protamine administration. There were no differences between the groups in the amount of blood transfused, chest-tube drainage, and routine laboratory test results. CONCLUSIONS: The authors concluded that the effects of these changes to the CPB circuit were small and inconsequential in this cohort of patients.     

Heparin-coated versus uncoated extracorporeal circuit in patients undergoing coronary artery bypass graft surgery

OBJECTIVE: To assess the effect of heparin-coated circuits on bleeding, transfusion, and platelet count in patients undergoing primary coronary artery bypass grafting with full heparinization. DESIGN: Randomized, double-blind study. SETTING: Tertiary-care academic medical center. PARTICIPANTS: Eighty-eight patients undergoing coronary artery bypass grafting requiring cardiopulmonary bypass (CPB) without previous sternotomy. INTERVENTIONS: Subjects received either a heparin-coated or an uncoated extracorporeal circuit for CPB. Heparin, 300 micro/kg, was administered, and supplemental amounts were administered to maintain an activated coagulation time of greater than 480 seconds. Platelet counts were determined during CPB. Mediastinal chest tube drainage was collected in the intensive care unit for 24 hours. MEASUREMENTS AND MAIN RESULTS: The mean platelet counts were similar between the groups during CPB. There was no significant difference in 24-hour mediastinal chest tube drainage (mean +/- standard deviation; median) between the heparin-coated (n = 44, 1096 +/- 401, 1015 mL) and uncoated group (n = 44, 1150 +/- 548, 1040 mL; p = 0.91). The heparin-coated group received less allogeneic packed red blood cells (0.9 +/- 1.6, 0.0 v 1.5 +/- 1.8, 1.0 U; p = 0.04). CONCLUSIONS: The use of a heparin-coated or uncoated cardiopulmonary bypass circuit and full heparinization marginally reduced only red blood cell transfusion but was not associated with platelet sparing or reduced perioperative bleeding.     

Evaluation of the platelet function analyzer (PFA-100) vs. the thromboelastogram (TEG) in the parturient

BACKGROUND: The platelet function analyzer (PFA-100) is a bedside test of coagulation designed to evaluate platelet function. It measures the time required for whole blood to occlude a membrane impregnated with either epinephrine (EPI) or adenosine 5'diphosphate (ADP). The results are reported as closure time (CT-EPI or CT-ADP) in seconds. The thromboelastogram (TEG) measures whole blood clotting and the maximum amplitude (MA) correlates with platelet count and function. We wished to establish whether there is a correlation between the CT and platelet count, between the CT and MA, and between the MA and platelet count. METHODS: Platelet count, CT, and MA were measured in blood drawn from 172 healthy term parturients using the PFA-100. RESULTS: We were unable to detect a significant correlation between the CT-EPI and platelet count (r=-0.1, P=0.21), or the CT-ADP and platelet count (r=-0.02, P=0.83). We also did not find a correlation between the CT-EPI and MA (r=-0.13, P=0.12) or between the CT-ADP and MA (r=-0.11, P=0.19). However, we found a significant correlation between platelet count and MA (r=0.33, P<0.001). CONCLUSIONS: We conclude that the CT does not correlate with the platelet count or MA in the parturient, but the TEG does. Therefore the TEG may be a better tool to evaluate coagulation in the parturient with thrombocytopenia.     

A comparison of Plateletworks and platelet aggregometry for the assessment of aspirin-related platelet dysfunction in cardiac surgical patients

OBJECTIVE: To compare the assessment of aspirin-related platelet dysfunction using Plateletworks (Helena Laboratories, Beaumont, TX), a new point-of-care platelet function analyzer, with turbidometric platelet aggregometry, in cardiac surgical patients. DESIGN: Prospective observational study. SETTING: University-affiliated teaching hospital. PARTICIPANTS: Fifty consecutive adult patients undergoing elective cardiac surgery for coronary artery bypass grafting or cardiac valve replacement. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Platelet function was assessed by Plateletworks and turbidometric platelet aggregometry before the commencement of anesthesia. Collagen, 10 microg/mL, was used as the agonist for both techniques. The area under the receiver-operator curve for the identification of recent aspirin ingestion (or=72 hours) using Plateletworks was 0.58 (95% confidence interval [CI] 0.42-0.75) versus 0.77 (95% CI 0.61-0.95) for turbidometric platelet aggregometry. The Spearman correlation coefficient (rho) between preoperative Plateletworks trade mark and postoperative mediastinal blood loss was 0.07 (p = 0.58), and between preoperative turbidometric platelet aggregometry and postoperative mediastinal blood loss was -0.31 (p = 0.03). On completion of surgery, the correlation coefficients were 0.14 (p = 0.34) and -0.29 (p = 0.08), respectively. CONCLUSION: These findings suggest that Plateletworks is of limited use for the detection of aspirin-related platelet defects in cardiac surgical patients.     

The kaolin-activated Thrombelastograph predicts bleeding after cardiac surgery

OBJECTIVE: The objective of this study was to determine the relationship of the kaolin-activated Thrombelastograph (TEG) with postoperative bleeding and laboratory tests of coagulation in the setting of cardiac surgery with the routine use of -aminocaproic acid. DESIGN: Prospective observational study. SETTING: An adult heart center at a tertiary referral, university hospital. PARTICIPANTS: Thirty adult cardiac surgical patients. INTERVENTIONS: The kaolin-activated TEG, platelet counts, prothrombin times, activated partial thromboplastin times, and fibrinogen levels were measured before induction of anesthesia, during cardiopulmonary bypass, and on arrival in the intensive care unit. Mediastinal and thoracostomy drainage were measured every hour for 4 hours after arrival in the intensive care unit. MEASUREMENTS AND MAIN RESULTS: Correlation and multivariate linear regression modeling were used to describe relationships among coagulation tests, TEG parameters, and early postoperative bleeding. The TEG maximum amplitude (MA) parameter correlated well with postoperative bleeding (r = -0.6, p = 0.0018), more so than platelet count (r = -0.45, p = 0.02), fibrinogen level (r = -0.40, p = 0.06), or prothrombin time (r = 0.43, p = 0.02). The receiver operating characteristic curve c-index describing MA as a predictor for postoperative bleeding is 0.78. Abnormalities in all the laboratory test results were associated with an abnormal MA. CONCLUSIONS: In conclusion, the kaolin-activated TEG is associated with early coagulopathic bleeding. It may reflect the severity of a global coagulopathy affecting both platelets and coagulation factors and be a guide to incremental prohemostatic therapy in this setting.     

Optimization of thromboelastography-guided platelet transfusion in cardiovascular surgery

Objectives  

Platelet dysfunction is a major cause of bleeding complications in patients undergoing cardiovascular surgery under cardiopulmonary bypass (CPB). Thromboelastography (TEG) can be used to assess post-CPB coagulopathy, but its utility in guiding platelet transfusion (PT) after CPB is unclear. This study assessed the utility of a TEG-guided PT protocol in patients undergoing cardiovascular surgery under CPB.     

Effects of hypothermia on thrombelastography in patients undergoing cardiopulmonary bypass

Thrombelastography (TEG) correlates with postoperative chest drain output in patients undergoing cardiopulmonary bypass (CPB). In vitro incubation with heparinase allows TEG monitoring during CPB, despite heparin anticoagulation. Hypothermia impairs coagulation, but these effects cannot be assessed by standard coagulation tests performed at 37 degrees C. The aim of this study was to assess the effects of hypothermia on TEG. Therefore, we have compared normothermic and temperature-adapted TEG in 30 patients undergoing CPB. Our data showed significantly impaired reaction time (r), kinetic time (k), and angle alpha (alpha) in temperature-adapted compared with normothermic TEG. Maximum amplitude (MA), reflecting absolute clot strength, was not affected at temperatures of 33-37 degrees C. These findings indicate a decrease in the speed of clot formation, but not absolute deterioration in clot quality. Furthermore, heparinase-modified TEG indicated that there were nine cases in which heparin effects persisted after heparin reversal with protamine, providing a rational guide to protamine therapy.      

Blood loss in elective coronary artery surgery: a comparison of centrifugal versus roller pump heads during cardiopulmonary bypass

OBJECTIVES: To compare the effects of centrifugal pumps versus roller pumps for cardiopulmonary bypass (CPB) in routine cardiac surgery on hematologic parameters in the context of modern practice. DESIGN: Prospective, randomized, partially blinded. SETTING: University teaching hospital. PARTICIPANTS: Elective coronary artery surgery patients (n = 113) INTERVENTION: Patients were randomized to be perfused with either a roller head (group R, n = 56) or a centrifugal head (group C, n = 57) pump. Patients received epsilon-aminocaproic acid before and during CPB. Core body temperatures were allowed to drift down to approximately 32 degrees C. MEASUREMENTS AND MAIN RESULTS: Postoperative chest tube blood loss, blood product requirements, hemoglobin, and platelet counts were assessed. There were no significant differences in preoperative or intraoperative parameters, including CPB time, complexity of procedure, and minimum core temperature. There were the expected reductions in hemoglobin and platelet levels post-CPB in both groups to a similar extent. Chest tubes remained in situ for similar durations, and the final volume of drainage was not significantly different (group C, 1300 +/- 92 mL; group R 1117 +/- 83 mL; p = 0.14). Allogeneic blood was given to 23% of patients in group C and 18% in group R (p = 0.63). Aspirin was associated with an increase in early chest tube drainage. CONCLUSIONS: In this surgical and perfusion environment, the authors were unable to show an advantage, from the hematologic point of view, in the routine use of a centrifugal pump head in elective coronary artery surgical patients. The use of antifibrinolytic agents and mild hypothermia may have effects on hemostasis that overshadow the influence of pump head design in this type of surgery.     

Use of abciximab-modified thrombelastography in patients undergoing cardiac surgery.

Thrombelastography (TEG) is a reliable coagulation monitoring system that can guide blood product transfusion in cardiac surgery. The maximum amplitude (MA) of TEG measures clot strength, which is dependent on both fibrinogen level and platelet function. Inhibition of platelet function with abciximab-fab is suggested to permit quantitative assessment of the contribution of fibrinogen to clot strength. We hypothesized that abciximab-modified TEG permits prediction of plasma fibrinogen levels and that the difference of standard MA and abciximab-modified MA (deltaMA) is a correlate for platelet function. We correlated abciximab-modified MA with plasma fibrinogen levels and deltaMA with platelet count in patients undergoing coronary revascularization. Correlation between plasma fibrinogen levels and abciximab-modified MA was significant (adjusted r2: 0.8; P < 0.0001). Correlation of deltaMA with platelet count was not significant when calculated in millimeters (adjusted r2: 0.04; P = 0.73). However, when deltaMA was calculated in dynes per square centimeter (deltaGMA), it correlated significantly with platelet count (adjusted r2: 0.51; P < 0.0001). We conclude that abciximab-modified TEG may therefore help to discriminate between hypofibrinogenemia and platelet dysfunction as a cause of decreased MA. IMPLICATIONS: We examined the use of abciximab-modified thrombelastography in patients undergoing cardiac surgery. Modification of thrombelastography with abciximab-fab allows prediction of fibrinogen levels, despite coagulation altered by cardiac surgery. The difference of standard maximum amplitude and abciximab-modified maximum amplitude correlates with platelet function when expressed in dynes per square centimeter.     

A comparison of hemodynamic indices derived by invasive monitoring and two-dimensional echocardiography

Intraoperative two-dimensional echocardiography (2D-echo) is useful for monitoring global and regional left ventricular function. The 2D-echo view most frequently utilized during intraoperative monitoring is the short-axis view at the level of the papillary muscles. To determine whether hemodynamic data can be derived from this single 2D-echo short-axis view, 12 patients undergoing coronary artery bypass grafting (CABG) were studied. All patients had normal left-ventricular function preoperatively (ejection fraction = 64% +/- 12%). Echo-data were obtained before and after cardiopulmonary bypass (CPB) by epicardial placement of a 5 MHz echo-transducer. The correlation between thermodilution and echo-derived cardiac indices was good (r = 0.8), and not significantly different from the correlation between stroke indices (r = 0.68). A strong positive correlation was established between end-diastolic volume index and echo cardiac index (CIE) (r = 0.93 before CPB; r = 0.91 after CPB) and end-diastolic area index and CIE (r = 0.94 before CPB; r = 0.91 after CPB). The pulmonary capillary wedge pressure was not a determinant of cardiac index before or after cardiopulmonary bypass. No correlation was observed between systemic vascular resistance and echo-derived wall stress. These findings demonstrate that, in patients with good left-ventricular function undergoing CABG surgery, 2D-echo provides a better index of left-ventricular preload than conventional invasive hemodynamic monitoring.     

Is platelet function as measured by Thrombelastograph monitoring in whole blood affected by platelet inhibitors?

Platelet inhibitors, especially the glycoprotein (GP) IIb/IIIa receptor antagonists, have demonstrated their effectiveness in reducing the acute ischemic complications of percutaneous coronary intervention (PCI) and in improving clinical outcomes in patients with acute coronary crisis. Three common platelet inhibitors observed in emergent cardiopulmonary bypass (CPB) for failed PCI are abciximab, eptifibatide, and tirofiban. An in vitro model was constructed in two parts to determine whether platelet aggregation inhibition induced by platelet inhibitors would be demonstrated by the Thrombelastograph (TEG) monitor when compared with baseline samples with no platelet inhibitor. In part A, 20 mL of fresh whole blood was divided into four groups: group I = baseline, group A = abcix-imab microg/mL, group E = eptifibatide ng/mL, and group T = tirofiban ng/mL. Platelet inhibitor concentrations in whole blood were derived starting with reported serum concentrations with escalation to achieve 80% platelet inhibition using the Medtronic hemoSTATUS and/or Lumi-aggregometer. A concentration range determined by our in vitro tests were chosen for each drug using concentrations achieving less than, equal to, or greater than 80% platelet inhibition. In part B, TEG analysis was then performed using baseline and concentrations for each drug derived in part A. Parameters measured were clot formation reaction time (R), coagulation time (K), maximum amplitude (MA) and alpha angle (A). Groups E1000 and E2000 extended R over control by 37% and 23%, respectively (p = 0.01 and 0.03). Groups E1000 and E2000 increased K times by 45% and 58% (p = .02 and .04). T160 samples prolonged K by 20% (p = 0.01). The angle or clot strength (A) was decreased in groups T160 and E1000 by 23% (+ 7.06 SD) and 18% (+ 11.23 SD), respectively (p = 0.001 and 0.01). The MA decrease was statistically significant in the T160, E1000 and E2000 by 9%, 6% and 13% respectively (p = 0.01). Samples treated with abciximab were comparable to control values for all parameters measured. Although statistical significance could be demonstrated with some parameters, sensitivity was only observed at increased doses and was not seen with all agents tested. In our in vitro model, the TEG monitor was unable to demonstrate clinically significant differences in platelet function and may not be reflective of platelet function in samples which have been treated with these GP IIb/IIIa inhibitors.     

5-year incidence of thrombocytosis and the effect on heparin dose response and heparin requirements

Thrombocytosis has been shown to be associated with heparin resistance. Contact activation of platelets results in release of Platelet Factor 4 from alpha granules present in the platelet cytoplasm. Platelet Factor 4 is a cationic substance that neutralizes heparin. This could result in inadequate heparinization during cardiopulmonary bypass (CPB). Inability to adequately anticoagulate patients with thrombocytosis could result in a poor clinical outcome. A retrospective review of pump records from 1991 to 1996 was used to assess the frequency of thrombocytosis, describe the demographic characteristics of patients with thrombocytosis, and determine the effects on patient heparin dose response (HDR) and additional heparin requirements. A platelet count of 400,000/mm3 was chosen as a cut-off for thrombocytosis. Of the 3281 patients undergoing CPB during this time period, a total of 571 patients were included in this review: 99 had high platelet counts. The over-all prevalence of thrombocytosis during this time period was 3.0%. Patients with thrombocytosis tended to be younger (p = .02), have lower preoperative HCT (p < .001), and weigh less (p < .001). These patients had lower post-heparin loading dose ACTs, lower HDR, required more additional heparin to reach an ACT of 480 sec before CPB, and required more heparin on CPB to maintain the ACT > 480 sec (p < .05). Multiple linear regression was performed and concluded that age, use of NTG and heparin drip preoperatively, and platelet count were significant predictors of the heparin dose response. Use of plasmapheresis to remove platelet-rich plasma (PRP) before CPB was performed in 22 patients, six of whom had high platelet counts. In these patients, removal of PRP resulted in no difference in the amount of additional heparin required pre-CPB to reach an ACT of 480 sec. (p = NS) Additional studies are needed to determine whether use of plasmapheresis is a cost-effective and clinically useful option in patients with thrombocytosis.     

Platelet-rich plasma sequestration, with therapeutic platelet yields, reduces allogeneic transfusion in complex cardiac surgery

Platelet dysfunction is the most common cause of nonsurgical bleeding after cardiopulmonary bypass (CPB). We hypothesized that reinfusion of a therapeutic quantity of platelets sequestered before CPB would decrease the need for allogeneic platelet transfusion, as well as decrease bleeding and total allogeneic transfusion, in cardiac surgery patients at moderately high risk for bleeding. Fifty-five patients undergoing either reoperative coronary artery bypass (CABG) or combined CABG and valve replacement were randomized to control or platelet-rich plasma sequestration (pheresis) groups. All patients received intraoperative epsilon-aminocaproic acid infusions. There was no significant difference between groups with respect to preoperative characteristics, duration of CPB, or target postoperative hematocrit. Mean platelet yields were 6.2 +/- 2.1 units (3.1 x 10(11) platelets). Mean pheresis time was 44 min. Allogeneic platelets (range = 6-12 units) were transfused to 28% of control patients, compared with 0% of pheresis patients (P < 0.01). Allogeneic packed red blood cells were transfused to 45% of control patients (1.2 units per patient) versus 31% of pheresis patients (0. 7 unit per patient) (P = 0.35). Total allogeneic units transfused were significantly reduced in the pheresis group (P < 0.02). Mediastinal chest tube drainage was not significantly decreased in the pheresis group. In this prospective, randomized study, therapeutic platelet yields were obtained before CPB. In contrast with recent studies with low platelet yields, these data support the conclusion that platelet-rich plasma sequestration is effective in reducing allogeneic platelet transfusions and total allogeneic units transfused in cardiac surgery patients at moderately high risk for post-CPB coagulopathy and bleeding. IMPLICATIONS: Transfusion of allogeneic blood products, including platelets, is common during complex cardiac surgical procedures. In the present prospective, randomized study, a significant reduction in allogeneic platelet transfusion and total allogeneic units transfused was observed after the reinfusion of a therapeutic quantity of autologous platelets sequestered before cardiopulmonary bypass.     

Reproductibilité et interchangeabilité du Thromboélastographe®, Sonoclot® et du temps de coagulation activé (Hémochron®), en chirurgie cardiaque

PURPOSE: Despite their common use in cardiac surgery, few studies have evaluated the reproducibility of the Thromboelastograph (TEG), of the Sonoclot (SCT), and of the activated coagulation time with celite (ACT-C) or kaolin (ACT-K) measured with the Hemochron, in clinical conditions of on-site monitoring of hemostasis. This study determined the reproducibility of those measurements, and evaluated the ability of various devices to substitute for the ACT-C. METHODS: Blood samples collected from 20 volunteers and 21 patients undergoing myocardial revascularization were analyzed in the two channels of the TEG, in two SCT and four Hemochron analyzers. The overall of TEG and SCT coagulation profiles were analyzed by a computerized TEG and an experienced observer respectively. The variation rate (V%) was calculated for each variable. The ability of ACT-K and SCT to substitute for ACT-C under different clinical conditions was evaluated. RESULTS: ACT-C and ACT-K V% ranged between 5.6% and 10.8% and between 6.7% and 12.4% respectively. TEG and SCT V% ranged between 3.1% and 9.5% and between 5.8% and 33.6% respectively, according to different conditions and parameters. In volunteers and non-heparinized patients, the ACT-C and ACT-K were interchangeable. No other test can substitute for the ACT-C when patients are heparinized during cardiopulmonary bypass (CPB). CONCLUSIONS: In the clinical conditions of use, on-site hemostasis monitoring devices providing the most reproducible measurements are, in decreasing order, the TEG, the Hemochron and the SCT. In heparinized patients and during CPB, results from different tests are not interchangeable, stressing the importance of establishing appropriate instrument-specific values for monitoring anticoagulation during cardiac surgery.     

Does hemodilution enhance coagulability?

Recent publications reported enhanced coagulability in hemodilution determined by TEG. In contrast, earlier reports have shown prolongation of in-vivo bleeding time in anemia. In order to take a closer look at this discrepancy undiluted and diluted anticoagulated blood samples (20 % with saline solution, hydroxyl-ethyl starch 6 % (HES), autologous platelet poor plasma (PPP)) were investigated by TEG (n = 10), ball (n = 10), and hook coagulometer (n = 15) as well as tests simulating primary hemostasis ex vivo (Platelet Function Analyzer PFA-100, n = 10). RESULTS: Dilution with plasma changed TEG parameters in a way, when started by recalcification of the blood sample, which is characteristic of enhanced coagulability (r decreased in all and k in 8 of 10 samples, maximal amplitude increased in 9 out of 10). With HES, changes in TEG parameters mainly indicated reduced coagulability (k increased in 7 out of 10, MA decreased in 10 out of 10). When the coagulation was additionally activated by PTT reagent (InTEG) the TEG parameters also mainly showed hypocoagulation with the three dilution solutions. Coagulation times with ball and hook coagulometers were significantly prolonged by dilution especially with saline (+ 25 % and + 17 %, p < 0.001). Dilution always significantly (often abnormally) prolonged closure time in PFA-100 (saline + 41 +/- 18 %, PPP + 37 +/- 20 %, HES + 69 +/- 24 %) demonstrating disturbance of primary hemostasis, particularly with HES. Conclusions: From the results obtained it can be concluded that the changes in the classical TEG (without addition of PTT-reagent), suggesting an enhanced coagulability, may be caused methodically as they are also found with autologous PPP. On the other hand, a disturbance of the primary hemostasis in hemodilution has to be taken into account from the results seen with the PFA-100 and a number of published data.     

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.     

Hematological assessment of patients undergoing plasmapheresis during cardiac surgery

Methods of reducing patient exposure to homologous blood transfusions include the technique of intraoperative plasmapheresis for the production of platelet rich plasma (PRP). The present study was designed to determine the patient benefits of PRP by examining hemostatic changes in coagulation screens and viscoelastic whole blood monitoring (Thrombelastography, [TEG]). One hundred fifteen patients undergoing elective cardiac surgery were prospectively randomized into a blinded study. Sixty-three patients had 20 percent of the circulating plasma volume sequestered prior to heparinization and pheresed into PRP, which was reinfused 10 minutes following heparin reversal with protamine. The control (CTR) group of 52 patients were exposed to no sequestration procedure. Patients were followed to discharge and 112 parameters, including anthropometric, operative, and postoperative factors, were measured. There were no significant differences between patient groups in preoperative, cardiopulmonary bypass (CPB), or surgical parameters. Average PRP volume was 600+/-100 ml with a total platelet yield of 1.1 billion platelets per patient. TEG indices were determined at four distinct times during the surgical procedure. The CTR group had significantly higher pre-CPB TEG indices of 2.3+/-1.2 and 2.1+/-1.2 (mean+/-SD), vs. 1.8+/-1.5 and 1.4+/-1.7 in the PRP group (p less than .04). Following heparin reversal, pre-PRP reinfusion TEG values were similar between groups, although both groups had significantly decreased indices when compared to pre-CPB values. Thirty minutes post-PRP infusion the treatment group had significantly improved TEG recovery when compared to the CTR group, 1.0+/-1.2 vs. 0.3+/-1.7 (p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)     

In vivo comparison study of FDA-approved surface-modifying additives and poly-2-methoxyethylacrylate circuit surfaces coatings during cardiopulmonary bypass

The purpose of this double-blind prospective and randomized study was to examine the effects of surface-modifying additives (SMAs) and poly-2-methoxyethylacrylate (PMEA) circuits on platelet count, platelet function (Sonoclot), postoperative chest tube drainage volume, peri- and postoperative blood product use, extubation time, and intensive care time. Terumo noncoated, Terumo-coated (PMEA), Cobe noncoated, and Cobe coated (SMA) circuits were evaluated to find the most cost-effective way to improve patient outcomes. We aimed to find if an additional charge for a coated CPB circuit would be recovered by reducing other patient costs (blood transfusions, intensive care unit time, and bring back postoperative bleeding). An initial literature review revealed the comparison of PMEA circuits vs. noncoated circuits and SMA circuits vs. noncoated circuits in both adult and porcine models. Both SMA- and PMEA-coated circuits decreased platelet consumption, platelet factor release, and the overall perioperative inflammatory response while on cardiopulmonary bypass (CPB). The question not answered in an initial search was simply, "which coated circuit is best for the patient: SMA or PMEA?" Research comparing the above coated circuits each other was not found. The study was approved by the Institutional Review Board. Thirty patients were scheduled for elective coronary artery bypass grafting and/ or valvular repair or replacement surgery. These 30 patients were randomized as 10 patients to Terumo X-Coating (PMEA surface coating) (CT), 10 patients to Cobe Smart-X coating (SMA surface coating; CC), 5 patients to Terumo noncoated tubing (NCT), and 5 patients to Cobe noncoated tubing (NCC). Informed consent was obtained from each patient before surgery. The data showed no statistically significant relationship between platelet counts, platelet function (Sonoclot), postoperative chest tube drainage volume, peri- and postoperative blood products, intensive care unit time, or total hospital length of stay. Analysis revealed statistically significant clinical associations of extubation time and protamine dose with treatment group. This study provided evidence that SMA- and PMEA-coated circuits do not improve platelet consumption or decrease blood product use for patients undergoing CPB. There was statistical significance with a reduction in extubation time and total protamine requirement needed to return activated clotting time (ACT) to baseline post-CPB. Although the use of SMA and/or PMEA circuits during CPB has clinical benefit to the CPB patient, an additional charge for the specialty circuit may not be realized.