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Objectives Use of viscoelastic testing, such as thromboelastography (TEG), is recommended in cardiac surgery to monitor coagulation and to guide the transfusion of blood products. The Quantra QPlus System is a novel point-of-care platform that uses ultrasonic pulses to characterize dynamic changes in viscoelastic properties of a blood sample during coagulation. Despite the ability to assess similar aspects of clot formation, limited studies addressing the interchangeability of viscoelastic testing parameters exist. The primary aim of the present study was to assess the correlation and agreement between Quantra and TEG5000 results using blood samples from cardiac surgery patients. Design Tertiary care, academic medical center. Setting Prospective observational study. Participants Twenty-eight patients undergoing elective cardiac surgery undergoing cardiopulmonary bypass were evaluated. Measurements and Main Results Perioperative blood samples were collected and assessed using Quantra, and results were compared with TEG and conventional coagulation testing. Method comparison analysis demonstrated that Quantra parameters (Quantra clot time, clot stiffness, and fibrinogen contribution to clot stiffness) significantly correlated with TEG R and TEG G after induction of anesthesia, during cardiopulmonary bypass, and after rewarming (rs = 0.83, rs = 0.84, and rs = 0.73, respectively). However, Quantra parameters demonstrated poor agreement compared with equivalent TEG5000 parameters. Conclusions The Quantra QPlus System significantly correlated with TEG5000, suggesting that this test may be used in a similar clinical context. Despite the strength of correlation between Quantra and TEG parameters, measurements are not interchangeable.

Objectives Coagulation point-of-care tests for the diagnosis and management of bleeding commonly are used in cardiac surgery. Recently, a new viscoelastic point-of-care device, Quantra (HemoSonics, Charlottesville, VA), which is based on sonic estimation of elasticity via resonance sonorheometry, entered the market. Prior studies have compared the Quantra parameters with conventional coagulation tests and thromboelastography or rotational thromboelastography, but no study has assessed the correlation of the platelet-derived Quantra parameter platelet contribution to stiffness (PCS) with platelet function assays. The present study compared the Quantra-derived coagulation parameters with conventional coagulation tests, rotational thromboelastography–derived parameters, and platelet function measured using multiplate aggregometry. Design Prospective cohort study. Setting University research hospital. Participants The study comprised 30 cardiac surgery patients before and after cardiopulmonary bypass. Interventions None. Measurements and Main Results Quantra clot stiffness showed a very strong correlation with the EXTEM maximum clot firmness before and after cardiopulmonary bypass and in the overall samples (r values 0.94-0.96). Quantra fibrinogen contribution to stiffness was compared with the corresponding FIBTEM and Clauss fibrinogen levels, which also showed a strong level of correlation (r values between 0.74 and 0.87). Quantra PCS strongly correlated with platelet count (r = 0.71) in the overall samples and moderately with adenosine diphosphate–dependent platelet function (r = 0.67). In a multivariable model, both the adenosine diphosphate test value and the platelet count remained independently associated with Quantra PCS. Conclusions Fibrinogen-dependent clot stiffness properties are well-reflected by the Quantra fibrinogen contribution to stiffness parameter, and PCS incorporates platelet count and function.

This is the second annual review in the Journal of Cardiothoracic and Vascular Anesthesia to cover highlights in coagulation for cardiac surgery. The goal of this article is to provide readers with a focused summary from the literature of the prior year's most important coagulation topics. In 2020, this included a discussion covering allogeneic transfusion, antiplatelet and anticoagulant therapy, factor concentrates, coagulation testing, mechanical circulatory support, and the effects of coronavirus disease 2019.

Currently, hemostasis is one of the most widely researched topics in perioperative medicine. As investigators learn more about the complexity of coagulation, developing tests with the ability to rapidly monitor coagulation and guide targeted therapy is the key to optimizing hemostasis management. There is mounting evidence that algorithmic transfusion using point-of-care (POC) testing can reduce red cell and platelet transfusions and major bleeding after cardiac surgery. Integrating these tests during cardiac surgery and trauma management is especially important because these groups use the most blood products within a health system and the risks of transfusion are well documented. Currently, numerous POC tests are available for evaluating hemostasis. The purpose of this review is to provide a comprehensive evaluation of the current evidence surrounding the most common POC testing devices in practice for managing coagulation.

Objective Lung transplantation is associated with high rates of bleeding and frequent blood transfusion. The authors aimed to determine if point-of-care coagulation testing (POCCT) reduced transfusion requirements. Design, Settings, and Participants A before-and-after cohort analysis conducted at a single tertiary referral center. Ninety-three sequential adult patients between January 2010 and January 2014 undergoing isolated lung transplant without preoperative extracorporeal support were analyzed. Intervention ROTEM and multi-plate POCCT were introduced on July 1, 2012, with an associated algorithm based on the results. Measurements and Main Results Statistically significant decreases in the proportion of patients receiving PRBCs (87% v 65%; p = 0.015), FFP (72% v 30%; p v 37%; p = 0.002) were found after the intervention. There were small decreases in median chest tube blood loss at 2 hours (300 mLs v 215 mLs; p = 0.03) and 4 hours (440 mLs v 350 mLs; p = 0.050) but not at 12 hours postoperatively. There were no changes in reoperation for bleeding (9% v 4%; p = 0.158) or in-hospital mortality (6% v 2%; p = 0.617). The cost of blood products administered decreased from a median of $3,935.00 to $991.00 (p Conclusions Use of POCCT in lung-transplant surgery is associated with significant reductions in blood product use and cost. There were no detectable changes in outcome aside from a small decrease in early postoperative bleeding.

Children with congenital heart defects are at increased risk for perioperative bleeding and postoperative thrombosis. In this study, the authors sought to develop a predictive model for postoperative thrombotic complications that integrates intraoperative bleeding and the requirement for allogenic blood products in addition to known patient and surgical characteristics.Retrospective cohort.Pediatric hospital.Neonates and children who underwent surgery with cardiopulmonary bypass (CPB).None MEASUREMENTS AND MAIN RESULTS: Demographic, laboratory, point-of-care coagulation, surgical, and perioperative transfusion data were collected. Among the 369 participants included in the study, 67 (18%) developed postoperative thrombotic complications. From multivariable logistic regression analyses, preoperative oxygen saturation85% (odds ratio [OR] 2.06, 95% confidence interval [CI] 1.10-3.85; p = 0.024), surgery in the neonatal period (OR 2.16, 95% CI 1.02-4.55; p = 0.044), use of preoperative antiplatelet or anticoagulation therapy (OR 3.34, 95% CI 1.61-6.96; p = 0.001), and the volume of blood product transfused post-CPB (80 mL/kg [OR 5.72, 95% CI 1.73-18.91; p = 0.004] and 15-80 mL/kg [OR 3.06, 95% CI 1.24-7.53; p = 0.015]) were independently associated with an increased incidence of thrombotic complications. No statistical differences were observed in available preoperative coagulation tests between children who developed postoperative thrombosis and those who did not.This observational cohort study found that cyanosis, surgery in neonates, preoperative anticoagulation or antiplatelet therapy, and the volume of post-CPB transfusion are important predictors of postoperative thrombotic complications in children undergoing cardiac surgery. Additional studies are required to explore the relationship between hypoxia, coagulopathy, and postoperative thrombosis.

Objective Protamine is used to neutralize heparin after patient separation from cardiopulmonary bypass (CPB). Different bedside tests are used to monitor the adequacy of heparin neutralization. For this study, the interchangeability of the activated coagulation time (ACT) and thromboelastometry (ROTEM; Tem Innovations GmbH, Basel, Switzerland) clotting time (CT) ratios in children undergoing cardiac surgery was assessed. Design Single-center, retrospective, cohort study between September 2010 and January 2012. Setting University children’s hospital. Participants The study comprised children 0 to 16 years old undergoing elective cardiac surgery with CPB. Exclusion criteria were preoperative coagulopathy, Jehovah’s witnesses, and children in a moribund condition (American Society of Anesthesiologists score 5). Interventions None. Measurements and Main Results After heparin neutralization with protamine, the ratio between ACT, with and without heparinase, and the CT measured with INTEM/HEPTEM (intrinsic test activated with ellagic acid was performed without heparinase [INTEM] and with heparinase [HEPTEM]) using tests of ROTEM were calculated. Agreement was evaluated using Cohen’s kappa statistics, Passing-Bablok regression, and Bland-Altman analysis. Among the 173 patients included for analysis, agreement between both tests showed a Cohen’s kappa statistic of 0.06 (95% CI: -0.02 to 0.14; p = 0.22). Bland-Altman analysis showed a bias of 0.01, with a standard deviation of 0.13, and limits of agreement between -0.24 and 0.26. Passing-Bablok regression showed a systematic difference of 0.40 (95% CI: 0.16-0.59) and a proportional difference of 0.61 (95% CI: 0.42-0.86). The residual standard deviation was 0.11 (95% CI: -0.22 to 0.22), and the test for linearity showed p = 0.10. Conclusion ACT, with or without heparinase, and the INTEM/HEPTEM CT ratios are not interchangeable to evaluate heparin reversal after pediatric patient separation from CPB. Therefore, the results of these tests should be corroborated with the absence/presence of bleeding and integrated into center-specific treatment algorithms.

Objective: Perioperative coagulation testing often is performed with arterial samples even though device reference ranges typically are established in venous samples. Although limited studies exist comparing coagulation parameters across sampling sites, viscoelastic testing devices have demonstrated some differences. The objective of this study was to compare coagulation parameters determined using the Quantra System for venous and arterial samples. Design: Prospective, observational study. Setting: Tertiary care university hospital. Participants: The study comprised 30 adult patients undergoing cardiac surgery. Interventions: Paired arterial and venous samples were obtained at 2 of the following time points: baseline, during bypass, or after protamine reversal of heparin. Quantra measurements included Clot Time (CT), Heparinase Clot Time (CTH), Clot Time Ratio (CTR), Clot Stiffness (CS), and Fibrinogen (FCS) and Platelet (PCS) Contributions to clot stiffness. Measurements and Main Results: The relationship and agreement between matched data pairs were established and statistical analysis was performed via paired t tests. CTR, CS, FCS, and PCS were unaffected by the sampling site, whereas CT and CTH demonstrated statistically significant differences between arterial and venous samples (p < 0.001). Arterial clot times were prolonged relative to the venous ones with a mean percent error of 14.2 % and 11.9 %, respectively. These results are in general agreement with those reported for other viscoelastic testing devices. Conclusions: This study demonstrates that Quantra clot stiffness-based parameters (CS, FCS, PCS) are unaffected by sampling site, whereas the clot time parameters (CT and CTH) show good correlation in the presence of a bias. CTR, a ratio of CT and CTH, also is unaffected.

Introduction Heparin induced thrombocytopenia (HIT) is frequent in patients under extracorporeal membrane oxygenation (ECMO) or ventricular assist device support (VAD). Therapeutic plasma exchange (TPE) and use of direct thrombin inhibitors (DTI) as argatroban have proven to be useful. However, monitoring its effect can be difficult as activated clotting time (ACT) or standard coagulation tests (prothrombin time (PT) and activated partial thromboplastin time (aPTT)) lack enough reliability. Coagulation assessment during surgery may be challenging, especially during heart transplantation (HT) where there is narrow margin to metabolize DTI. Methods A 51-year-old male presented a myocardial infarction with cardiac arrest and arrhythmic storm requiring support with ECMO and VAD. The patient needed HT and was anticoagulated with intravenous argatroban for 3 weeks before surgery because of HIT (31000 thrombocytes/μL). Four TPE were performed and four intravenous doses of specific gammaglobulin (1g/kg) were given achieving negative values of anti-PF-4 antibodies. Argatroban infusion was stopped 6 hours before surgery. Results The coagulation test pre-surgery showed 98000 thrombocytes/μL, PT 39%, aPTT 55,1s fibrinogen 3,5g/L, haemoglobin 93g/L. Intraoperative anticoagulation was established with full dose unfractionated heparin and tranexamic acid was given (20mg/kg bolus+6mg/kg/h infusion). After coming off by-pass, anticoagulation was reverted with protamine and 2 units of PRBC, 1000mL fresh frozen plasma (FFP), two platelet pools and 1200IU 4-factor-prothrombin-complex-concentrate (PCC; Prothromplex®: 1200IU factor II, 1000IU factor VII, 1200IU factor IX and 1200IU factor X) were administered empirically. Despite being ACT back to baseline, significant diffuse bleeding was clinically noticed. ROTEM was performed showing prolonged EXTEM, INTEM and HEPTEM clotting time (CT). A second dose of PCC was administered and one unit of PRBC was transfused. Because no improvement was noticed, a second ROTEM was performed showing increased CT in all tests, with no heparin contribution (table 1). A litre of FFP was then administered with significant reduction of bleeding, allowing for chest closure. No further significant blood loss was observed in intensive care. The patient was weaned from mechanical ventilation on day 4 and discharged from the ward after 21 days. No thrombotic/bleeding events were noticed during the hospital stay. Discussion ROTEM was useful detecting coagulation factors deficiency in an appropriate time. Unexpected prolongation of CT after PCC administration may suggest residual thrombin inhibition by argatroban, that was neutralized with FFP administration.

OBJECTIVE Preparing hydroxyethyl starch (HES) in a plasma-adapted solution is supposed to improve safety with regard to coagulation. The influence of a new plasma-adapted HES preparation on coagulation was studied. DESIGN Operator-blinded, randomized study. SETTING Laboratory in vitro study. PARTICIPANTS Fifteen healthy young men scheduled for blood donation. INTERVENTIONS Blood was diluted by 10%, 30%, and 50% using either a plasma-adapted or nonplasma-adapted (prepared in saline solution) potato-derived 6% HES 130/0.42. Only the composition of the solvent of the 2 HES preparations was different. MEASUREMENTS AND MAIN RESULTS Rotation thromboelastometry (ROTEM; Pentapharm, Munich, Germany) was used to assess changes in coagulation; whole blood aggregometry with 3 inducers was used to assess effects of dilution with HES on platelet function. Clotting time (CT) and clot formation time were significantly prolonged by 30% and 50% dilution, showing significantly longer times in the non-plasma-adapted than in the plasma-adapted HES group (eg, intrinsic CT at the 30% dilution level: plasma-adapted HES 228 +/- 26 seconds [within normal range] v 269 +/- 29 seconds in the nonplasma-adapted HES group). Clot strengthening and clot firmness were significantly reduced by the non-plasma-adapted HES at the 30% dilution level. Platelet aggregation was significantly more reduced by the non-plasma-adapted HES at the 30% and 50% dilution levels. CONCLUSIONS Dilution with the nonplasma-adapted HES 130/0.42 was associated with more negative effects on thromboelastometry and platelet aggregation than the same HES 130/0.4 dissolved in a plasma-adapted solution. The benefits of using a plasma-adapted modern HES preparation on blood loss and use of blood/blood products in cardiac surgery need to be studied.

Objective Recombinant activated factor VII (rFVIIa) is being increasingly used in cardiac surgical patients with refractory hemorrhage. In this study, the authors assessed the ability of thromboelastography (TEG) in guiding rFVIIa therapy in this setting. Design Retrospective study. Setting Tertiary care university hospital. Participants Thirty-eight consecutive patients who received rFVIIa for refractory hemorrhage after cardiac surgery and had a complete coagulation profile including TEG within 30 minutes before and after rFVIIa. Interventions Standard coagulation (prothrombin time, partial thromboplastin time, platelet number, and fibrinogen) and TEG measurements (r time, k time, α angle, and maximum amplitude) before and after rFVIIa therapy were compared between responders and nonresponders (determined retrospectively based on clinical records). Measurements and Results Twenty-eight patients (74%) were classified as responders. There were no consistent changes in standard coagulation and TEG measurements before and after rFVIIa therapy. The number of abnormalities in pretreatment coagulation tests was related to response rates; odds of response were 11-fold (95% confidence interval [CI]) and 33-fold (95% CI) greater among patients with 0 or 1 abnormality in standard coagulation tests and TEG measures, respectively, than those with 2 or more abnormalities. Conclusions TEG may be a useful tool for predicting response to rFVIIa in the setting of refractory hemorrhage after cardiac surgery.

p ON WILLEBRAND DISEASE (VWD) was first described by Erik von Willebrand in 1926. It is caused by quantitative nd/or qualitative defects of the von Willebrand factor (VWF). WF is a multimeric plasma protein composed of 250 kilodalon subunits and a multimer fraction that shows a wide range in ize from 500 kilodaltons to 10 million daltons. High–moleclar-weight (HMW) VWF multimers mediate platelet adhesion longside vascular injury by binding to connective tissue and to latelets. VWF also binds and stabilizes coagulation factor FVIII.1 herefore, patients’ bleeding symptoms may refer to platelet dysunction and/or deficiency of FVIII. VWD is classified as 3 main ypes: type 1 (VWF moderately reduced), type 3 (VWF absent), nd type 2 (VWF antigen in normal range, but qualitative defect). ype 2 VWD is divided into subtypes, with type 2A showing ecreased platelet adhesion resulting from the deficiency of mulimer fractions, type 2B with increased affinity for platelet glycorotein Ib, type 2M with reduced platelet adhesion despite relaively normal multimer fraction, and type 2N with decreased ffinity for FVIII and low FVIII levels.1 Inherited VWD is the ost frequent bleeding disorder, showing an autosomal dominant r recessive inheritance pattern in most cases, and the majority of atients exhibit mild-to-moderate mucocutaneous bleeding sympoms.2 In contrast, acquired von Willebrand syndrome (AVWS) is rare nd occurs in patients without a bleeding history. It is summarized nder VWS type 1 if associated with hypothyroidism or Wilm’s umor, or more commonly as VWS type 2A because of a lack of r decrease in the HMW VWF paralleled by a decrease in plateletependent functions.3 AVWS is associated with several underlyng diseases (eg, lymphoproliferative disorders, myeloproliferative isorders, neoplasias, hypothyroidism, thrombocythemia, immuologic diseases, and cardiovascular diseases4); with drugs like iprofloxacin, griseofulvin, valproic acid, and hydroxyethyl starch; nd with various pathogenic mechanisms including developing utoantibodies to VWF, adsorption of VWF onto tumor cells or ctivated platelets, increased proteolysis, and mechanical destrucion of HMW VWF multimers under high shear stress.5 It is well known that neither routine coagulation tests nor hromboelastometric measurements enable exact diagnosis of VWS. Testing for AVWS includes patient (lifelong mucocutaeous, postoperative bleeding) and family bleeding history, creening procedures (eg, platelet count, partial thromboplastin ime, concentration of FVIII [FVIII:C], platelet function analyzer PFA-100; Dade Behring, Marburg, Germany]), and confirming ests (eg, VWF antigen [VWF:Ag], VWF ristocetin cofactor acivity [VWF:RCo], VWF collagen-binding activity [VWF:CB], istocetin-induced platelet aggregation [RIPA], and analysis of WF multimers by gel electrophoresis).3 All these tests are time onsuming, and several are available only in specialized laboral

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 ϵ-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.

Objective: Thromboelastographic evaluation of the influence of fibrinolysis on blood loss and blood product transfusions in children during cardiac surgery. Design: Prospective study. Setting: University-affiliated, pediatric medical center. Participants: Two hundred seventy-eight consecutive children undergoing cardiac surgery. Interventions: Blood sampling for coagulation tests, including native and protamine-modified thromboelastography. Measurements and Main Results: Blood coagulation tests were measured before, during, and after cardiopulmonary bypass (CPB). Demographic data, perioperative blood loss, and blood product transfusions were prospectively recorded. Fibrinolysis was defined as thromboelastography of A30/MA less than 0.85 (MA, maximum amplitude; A30, amplitude 30 minutes after MA) and was noted in 3% of children pre-CPB, 16% during CPB, and 3% post-CPB. Fibrinolysis before CPB was associated with poor cardiac output. Fibrinolysis during CPB occurred in young children (aged 350 ± 836 days) undergoing complex surgery with prolonged CPB (119 ± 48.8 minutes) and deep hypothermia (25.6°C ± 4.7°C). These patients received blood products after CPB and were not fibrinolytic after transfusion. They incurred similar blood loss (in mL/kg) and received similar volumes of blood products (mL/kg) as age-matched and surgery-matched patients without fibrinolysis. Conclusion: A group of children at risk for fibrinolysis during CPB was identified. However, fibrinolysis during CPB did not influence blood loss or the total volume of blood products transfused.

Objective: To assess the risk of hemorrhagic complications associated with epidural anesthesia in patients undergoing coronary artery bypass grafting. Design: A prospective study. Setting: A cardiac surgical center associated with a university. Participants: Five hundred fifty-eight consecutive patients scheduled for coronary artery bypass surgery. Interventions: A Tuohy 18G epidural catheter was inserted the day before surgery in all patients. Measurements and Main Results: Preoperative coagulation tests, such as platelet count and prothrombin time, were performed. No patient was on oral anticoagulation therapy or had coagulation disorders. Four hundred three (72%) patients were on antiplatelet therapy, which was terminated at least 1 week before surgery. The epidural catheter was left in situ for up to 5 days. All patients were observed daily for signs of spinal cord compromise, such as radicular back pain or progressive sensory or motor deficits. There were no documented spinal hematomas. Conclusion: By following certain guidelines, the risk for the development of epidural hematoma is not increased in patients undergoing epidural anesthesia during cardiac surgery.

Hemorrhage remains one of the leading causes of trauma-related deaths. Uncontrolled diffuse microvascular bleeding in the course of initial care is common, potentially resulting in exsanguination. Early and aggressive hemostatic intervention increases survival and reduces the incidence of massive transfusion. Thus, timely diagnosis of the underlying coagulation disorders is mandatory. It has been shown that standard coagulation tests do not sufficiently characterize trauma-induced coagulopathy (TIC). This has led to increasing interest in alternatives, such as the viscoelastic test, to diagnose TIC and to provide the basis for a goal-directed hemostatic therapy. The concept of damage control resuscitation (DCR) has been introduced widely in trauma patients with severe bleeding. This strategy addresses important confounders of the coagulation process such as hemodilution, hypothermia, and acidosis; DCR is based on a damage control surgical approach, permissive hypotension, and improvement of hemostatic competence. Many studies have shown benefit in mortality when using high ratios of fresh frozen plasma (FFP) to red blood cells (RBC) as early treatment. However, there is increased awareness that coagulation factor concentrate could be beneficial in the treatment of trauma-induced coagulopathy.

m e r l a a a w p r FOR MAJOR BLEEDING related to severe trauma, major surgery, or chronic anticoagulation, a rapid assessment of hemostatic function is crucial so that optimal fluid replacements and blood transfusion can be administered without delays.1-6 Although the safety of blood products with regard to viral transmission risks has improved in recent years,7,8 transfusions of allogeneic erythrocyte and plasma products have been implicated in serious adverse events, including nosocomial infections, acute lung injury, and organ dysfunction.9-12 Obtaining conventional laboratory tests, such as the prothrombin time (PT), activated partial thromboplastin time (aPTT), and fibrinogen level, during acute bleeding is difficult because of a long turn-around time ( 30 min).13,14 Furthermore, laboatory PT/international normalized ratio and aPTT may not be articularly useful in predicting bleeding after trauma or invaive procedures.15,16 The prime example of bleeding management is preemptive transfusions of fresh-frozen plasma (FFP) and platelet concentrates according to the erythrocyte requirement in major trauma cases.17,18 This so-called “damage control resuscitation” (DCR; able 1) originally was advocated for battlefield resuscitation n which laboratory testing and transfusion resources were imited. However, plasma product transfusion according to CR became increasingly popular in US civilian trauma ceners and operating rooms.17,19 The prevention of trauma-induced coagulopathy and subsequent nonsurgical bleeding is a major advantage of DCR,20 but the DCR approach lacks a specific target for replacement and a consideration for interindividual variability in coagulation factor levels and vascular (endothelial) responses. Implementing transfusion algorithms based on point-of-care (POC) coagulation testing can be effective in decreasing transfusion requirements in elective or urgent cardiac surgical settings.2,5,21-23 In this review, the practical use of thromboelastometry is discussed relating to the diagnosis of coagulopathy and optimizing hemostatic interventions.

Objectives To evaluate the in vitro effects of high concentrations of heparin and its reversal with protamine on routine laboratory parameters as well as on modified thromboelastogram (ROTEM; TEM International, Munich, Germany) and impedance aggregometry (MULTIPLATE; Dynabyte, Munich, Germany). Design An observational, nonrandomized in vitro study. Setting A single-center, university hospital. Participants Ten healthy volunteers. Interventions Heparinization of whole blood to levels of 2, 4, 6, and 8 IU/mL of heparin and reversal with protamine. For MULTIPLATE measurements, heparin levels up to 20 IU/mL were tested. Measurements and Main Results The present results show that the prothrombin time (PT) and fibrinogen measurements are altered significantly by heparin concentrations above 2 IU/mL. Protamine reversal also affected coagulation tests except for the fibrinogen. The INTEM test using the ROTEM system was influenced significantly by heparin concentrations of 2 IU/mL or higher, whereas EXTEM measurements remained stable up to 4 IU/mL. The findings for the FIBTEM test were stable up to 6 IU/mL but then declined to values less than 50% of baseline at 8 IU/mL. HEPTEM results remained valid under all concentrations of heparin tested. The effect of protamine on ROTEM was seen mainly in the INTEM and HEPTEM measurements. Heparin concentrations up to a level of 20 U/mL had no effect on MULTIPLATE measurements. Effects of protamine on MULTIPLATE became significant at heparin-to-protamine ratios below 1:1 and were more pronounced for adenosine diphosphate than for thrombin receptor-activated protein testing. Conclusions Neither fibrinogen (Clauss) nor derived fibrinogen or FIBTEM testing is valid in the setting of high concentrations of heparin unless antagonized by heparinase. Reversal of heparin with protamine worsens platelet function at all ratios as detected by aggregometry (MULTIPLATE) and thromboelastography (ROTEM), starting at a 1:1 ratio. Therefore, appropriate coagulation testing under cardiopulmonary bypass conditions should be selected carefully according to heparin levels. In particular, fibrinogen values are falsely low at heparin levels of 2 IU/mL and above. Therefore, newer algorithms promoting the correction of fibrinogen levels on cardiopulmonary bypass should be based on appropriate testing.

Background & Aim. Visco-elastic point-of-care tests such as TEG and ROTEM are increasingly used to guide haemostatic therapy after cardiac surgery. Their use during cardiopulmonary bypass (CPB) has the potential advantage of earlier information about haemostasis allowing the preparation of blood products. However, testing during CPB might be affected by heparinization and its reversal with protamine and has not been validated (1). The aim of this study was to assess the clinical utility of visco-elastic coagulation tests during cardiopulmonary bypass to predict post-bypass coagulation status and to guide therapy. Methods. In this prospective study, TEG and ROTEM tests were performed in fifty-two adult patients undergoing elective cardiac surgery at two time points: near the end of cardiopulmonary bypass (on-CPB) and after heparin reversal with protamine (post-protamine). Clotting times (R-time, CT) and clot strength (MA, MCF) were compared between the two time points for each test assay. The 95% confidence intervals of the mean difference were compared to a pre-specified clinical important limit of þ/-20% of the post-protamine value. Correlation between TEG and ROTEM and visco-elastic and corresponding laboratory values (Clauss Fibrinogen, PT, aPTT) was also assessed. Results. Both visco-elastic fibrinogen assays were well within the pre-specified clinically important limit (Z79% of patients). Fibrinogen assays correlated well between the analysers (Pearson r1⁄40.69) but had a bias (Bland-Altman) of 5.4mm. The laboratory Clauss fibrinogen was much lower during cardiopulmonary bypass than after protamine (mean difference 1.2g/L, 95% CI 1.03 1.4, po0.01), which was well outside a clinically acceptable difference. For intrinsically activated tests, clotting times were different and outside the pre-specified limit on TEG (po0.01) but not on ROTEM (p1⁄40.67), while clot strength was well within the clinical limit on both devices (Z94% of patients). For extrinsically activated tests, clotting time was different on ROTEM (po0.01) but not on TEG (p1⁄40.24), but both were within the clinical limit. The clot strength was different on TEG (po0.01) but not on ROTEM (p1⁄40.57) while both were within the pre-specified limit in 98% of patients. Conclusion. Results from TEG and ROTEM tests performed towards the end of cardio-pulmonary-bypass are clinically comparable to results after reversal of heparin. Amplitudes indicating clot-strength were the most stable parameters across all tests whereas clotting times showed more variability. In contrast laboratory testing of fibrinogen using the Clauss assay was essentially invalid during cardiopulmonary bypass.

Objectives: The Thromboelastogram (TEG; Haemoscope Corporation, Niles, IL) and the ROTEM thromboelastometry analyzer (Pentapharm GmbH, Munich, Germany) are coagulation monitors that measure the viscoelastic changes accompanying whole-blood coagulation generation and lysis. It is not clear whether TEG and ROTEM transfusion algorithms suggest similar blood component intervention. This study aims to report the extent to which administration of platelets, fresh frozen plasma, and cryoprecipitate would be indicated using protocol-dictated interventions by the Rotem, TEG, and conventional coagulation screens during orthotopic liver transplantation (OLT).Design: Prospective observational study.Setting: University hospital.Participants: Twenty patients undergoing orthotopic liver transplantation.Interventions: Coagulation was managed with native TEG protocols. Additional samples for kaolin TEG, kaolin heparinase TEG, Rotem in-TEM, Rotem hep-TEM, Rotem fib-TEM, full blood count, prothrombin time, and Clauss fibrinogen assays were taken at 5 fixed operative stages.Measurements and Main Results: Results were reviewed and protocol-indicated interventions recorded. There was moderate agreement between Clauss fibrinogen and Rotem fib-TEM assays about fulfilling fibrinogen transfusion criteria (kappa = 0.42, p

Objective: To compare the ability of thromboelastography, when done at either 10 or 60 minutes after protamine reversal of heparin, to predict excessive bleeding after coronary artery bypass graft (CABG) surgery and to investigate, with the use of heparinase, whether heparin contamination was responsible for the difference, if any. Design: Prospective study. Setting: University hospital, single institution. Participants: Patients undergoing elective CABG surgery (n = 40). Interventions: Blood samples for thromboelastography and routine coagulation tests were collected before induction of anesthesia and at 10 and 60 minutes after protamine reversal of heparin. Blood loss and blood product use were recorded postoperatively. Measurements and Main Results: Of 40 patients undergoing elective CABG surgery, 10 fulfilled the criteria for excessive postoperative bleeding. The sensitivity of thromboelastography to identify patients who bled was better at 60 minutes than at 10 minutes after protamine reversal of heparin (100% v 70%). There was greater specificity (83% v 40% at 10 minutes; 73% v 20% at 60 minutes) and positive predictive value (58% v 28% at 10 minutes; 55% v 29% at 60 minutes) when heparinase was added. At both times, thromboelastography showed only moderate correlation with total blood loss and the use of fresh frozen plasma or platelets or both. Conventional coagulation tests did not predict excessive postoperative bleeding. Conclusion: This study suggests that timing and the use of heparinase influence the predictive ability of thromboelastography, but its usefulness as a sole predictor of post–CABG surgery bleeding is limited. Copyright 2002, Elsevier Science (USA). All rights reserved.

Objectives: To examine whether coagulation tests, sampled before and during cardiopulmonary bypass (CPB), are related to blood loss and blood product transfusion requirements, and to determine what test value(s) provide the best sensitivity and specificity for prediction of excessive hemorrhage. Design: Prospective. Setting: University-affiliated, pediatric medical center. Participants: Four hundred ninety-four children. Interventions: Coagulation tests. Measurements and Main Results: Demographic, coagulation test, blood loss, and transfusion data were noted in consecutive children undergoing cardiac surgery. Laboratory tests included hematocrit (Hct), prothrombin time, partial thromboplastin time (PTT), platelet count, fibrinogen concentration, and thromboelastography. Stepwise linear regression analysis indicated that platelet count during CPB was the variable most significantly associated with intraoperative blood loss (in milliliters per kilogram) and 12-hour chest tube output (in milliliters per kilogram). Other independent variables associated with blood loss were thromboelastography maximum amplitude (MA) during CPB, preoperative PTT, preoperative Hct, and preoperative thromboelastography angle and shear modulus values. Thromboelastography MA during CPB was the only variable associated with total products transfused (in milliliters per kilogram). Of all tests studied, platelet count during CPB (≤108,000/μL) provided the maximum sensitivity (83%) and specificity (58%) for prediction of excessive blood loss (receiver operating characteristic analysis). Blood loss was inversely related to patient age; neonates received the most donor units (median, 8 units; range, 6 to 10 units). Conclusions: During cardiac surgery, coagulation tests (including thromboelastography) drawn pre-CPB and during CPB are useful to identify children at risk for excessive bleeding. Platelet count during CPB was the variable most significantly associated with blood loss.

Objectives: Pyridoxalated hemoglobin-polyoxyethylene (PHP) is a prototypical red cell substitute approved for phase I studies. Peripheral blood smears of human blood mixed with PHP in 1 to 4 g/dL concentrations showed dose-dependent red cell aggregation and rouleaux. Whether this aggregation limits interpretation of blood compatibility testing and whether the intense coloration of serum or plasma containing PHP affects routine coagulation and clinical chemistry measurements was tested. Design: In vitro studies. Setting: University hospital laboratory. Participants: Four healthy volunteers, blood types A, B, AB, and O. All were Rh+. Measurements and Main Results: ABO typing, Rh typing, and antibody screening and coagulation studies were performed on blood: PHP admixtures having final concentrations of 1, 2, and 4 g/dL. For clinical chemistry interference studies, known concentrations of analytes were added to a serum matrix containing PHP ABO (forward) and Rh typing showed no interference in the three concentrations tested. Reverse ABO typing and antibody screening showed rouleaux at 4 g/dL, which corrected with routine saline replacement. Partial thromboplastin time (PTT), prothrombin time (PT), and fibrinogen showed no clinically significant differences from the controls. Results for electrolytes, renal function analytes, and markers of cardiac injury were acceptable by standard laboratory methods. However, results of liver function tests were unacceptable in PHPcontaining specimens. Conclusions: PHP-induced aggregation was observed with high PHP concentration; however, compatibility testing was not affected because agglutination was corrected by saline replacement, which is standard practice. Although routine blood banking, coagulation, and most clinical chemistry analytes can be measured reliably, alternative methods and strategies are needed for assessing liver function in the presence of PHP.

Objective: To determine the effects of red cell separation and ultrafiltration on heparin concentration. Design: Prospective study. Setting: University-affiliated, pediatric medical center. Participants: Thirty-one children undergoing cardiac surgery. Interventions: Blood sampled for heparin concentration and coagulation tests. Measurements and Main Results: Thirteen infants underwent modified veno-venous ultrafiltration (UF) after cardiopulmonary bypass (CPB). In addition, residual blood in the CPB circuit was hemoconcentrated by UF and reinfused (UF group). Heparin concentration increased from 2.0 ± 0.6 to 2.5 ± 0.8 U/mL, following modified UF; while activated coagulation time (ACT) decreased from 701 ± 177 to 627 ± 107 seconds. Heparin concentration of CPB circuit residual increased from 1.9 ± 0.7 to 3.1 ± 1.0 U/mL. In 18 children (older than 1 year old), the residual blood in the CPB circuit was hemoconcentrated by cell separation (CS) and reinfused (CS group). Heparin concentration of CPB circuit residual decreased from 2.6 ± 0.6 to 0.3 ± 0.2 U/mL. After reinfusion, patient heparin concentration remained unchanged at Conclusions: The plasma concentration of heparin increased after veno-venous modified UF of the patient. Heparin concentration also increased after UF of residual CPB circuit blood. In contrast, circuit blood hemoconcentrated by CS contained minimal heparin, and, when infused, did not increase patient's heparin concentration. ACT and thrombin time did not correlate with heparin concentration.

Objectives: To assess the benefits of withdrawn autologous plasma, the objective of this study was to investigate whether withdrawal of acutely performed platelet-rich or platelet-poor plasmapheresis allays changes in the protein C-thrombomodulin and fibrinolytic systems after retransfusion secondary to cardiopulmonary bypass (CPB). In addition, the study attempted to determine the influence of acute plasmapheresis (APP) on the protein C-thrombomodulin and fibrinolytic systems as well as on homologous blood consumption and perioperative blood loss in elective aortocoronary bypass patients. Design: The investigation was scheduled as a prospective, randomized, unblinded study. Setting: This single investigation was conducted in the Department of Anaesthesiology and Intensive Care Medicine at a university in Germany. The study protocol was approved by the Ethics Committee of the hospital, and informed consent was obtained. Participants: Sixty male patients scheduled for elective coronary artery bypass grafting with extracorporeal circulation were included in the study. Interventions: APP was performed between induction of anesthesia and incision, collecting either 10 mL/kg of autologous platelet-poor plasma (PPP patients, group 1; n = 20) or the same amount of platelet-rich plasma (PRP patients, group 2; n = 20). Patients of group 3 ( n = 20) had no APP (control group). All patients were maintained on their usual regimen of cardiac drugs until the morning of surgery. To preserve hemodynamic stability and restore the intravascular oncotic pressure, the separated plasma was replaced by infusion of an equal amount of hydroxyethyl starch solution (HES) (6% HES, molecular weight 2 × 10 5 , substitution rate 0.5%). In all operations, the same surgical procedure was chosen. For all patients, induction and maintenance of anesthesia were similar, consisting of weight-related doses of fentanyl (35 μg/kg), midazolam (0.65 mg/kg), and pancuronium bromide (0.15 mg/kg). The lungs of all patients were mechanically ventilated during the first 5 hours after the end of the operation. Measurements and Main Results: All patients had serial coagulation studies including antithrombin (AT) III-activity, prekallikrein, factor XII, and immunologic tests such as thrombin-antithrombin III (TAT), fibrinopeptide A (FPA), protein C and S (PC and PS), thrombomodulin (TM), tissue-plasminogen-activator (t-PA), plasminogen-activator-inhibitor (PAI 1), fibrinopeptide Bβ 15–42 (FPBβ 15–42), D-dimers, and hemoglobin and platelet counts determined intraoperatively and postoperatively. Chest tube drainage and transfusion requirements were recorded. APP had no negative effects on the quality of PPP and PRP plasma. The platelet count of the withdrawn plasma was 28 ± 12 × 10 9 /L (PPP group) and 245 ± 36 × 10 9 /L (PRP group). At the end of the operation (after retransfusion of autologous plasma) and on the morning of the first postoperative day, platelet counts were significantly higher ( p > 0.05) in the PRP than in the PPP and control groups. Plasma concentrations of TAT and FPA increased (ranging from +185% to +340% from baseline values) and AT III-activity, PC, PS, and TM antigen decreased (ranging from −8% to −55% from baseline values) to a different extent for all three groups throughout CPB. t-PA-activity increased with a maximum at the end of CPB (PPP group, 6.9 ± 1.5 IU/mL; PRP group, 3.8 ± 0.8 IU/mL; control group, 10.9 ± 2.8 IU/mL). Fibrin and fibrinogen degradation markers such as D-dimers and FPBβ 15 to 42 occurred in peak concentrations after neutralization of heparin by protamine. Only PRP patients showed baseline concentrations of coagulation parameters the next morning ( p p p Conclusions: The results suggest that in cases of elective cardiac surgery, heparin cannot prevent generation of both thrombin and fibrin throughout CPB and postoperatively. The APP procedure had no negative effect on the quality of autologous plasma. APP-withdrawn PRP did not only increase platelet count effectively but also improved an altered hemostatic system after retransfusion. Because of the beneficial effects of APP-withdrawn PRP, it appears to be an attractive technique, especially in patients in whom withdrawal of autologous whole blood cannot be performed, as well as to reduce allogeneic blood usage and perioperative blood loss.

Objective: Hetastarch has been studied as a volume expander in adults after cardiopulmonary bypass (CPB) and in recommended dosages has not altered coagulation studies or increased clinical bleeding. Hetastarch was compared with albumin in children after CPB to determine whether hetastarch use was associated with increased clinical bleeding or alteration of coagulation studies. Design: Randomized double-blinded study. Setting: University-affiliated children's hospital. Participants: Forty-seven children age 1 year or greater (mean 72.8 months; range 12 months to 15.5 years) scheduled for repair of congenital heart disease with moderate hypothermia were randomized to receive hetastarch or albumin as a postoperative volume expander during the first 24 hours after surgery. Interventions: Thirty-eight children required colloid replacement therapy. Blood pressure, central venous pressure, urine output, and chest tube drainage were used to determine colloid requirement. Measurements and Main Results: Clinical bleeding and laboratory studies of coagulation were evaluated as were requirements for colloid, crystalloid, and blood products. Twenty children received 6% hetastarch, and 18 received 5% albumin. No differences were found in the amount of replacement fluids required, or in coagulation parameters in children receiving 20 mL/kg or less of either colloid replacement therapy. An increase in prothrombin time was demonstrated in children who received greater than 20 mL/kg of 6% hetastarch ( p = 0.006); however, no difference in clinical bleeding or blood product requirement was demonstrated between the hetastarch or albumin groups receiving more than 20 mL/kg. Conclusion: This study demonstrated that 6% hetastarch is safe and an effective plasma volume expander in the postoperative management of children, using volumes up to 20 mL/kg. Close laboratory monitoring and careful evaluation of clinical bleeding are suggested when larger doses of hetastarch are administered because of prolongation of the prothrombin time with more than 20 mL/kg of hetastarch.

Introduction. In normal controls, female gender and low-normal haematocrit levels have pro-coagulant effects. We utilized Thromboelastography® (TEG) to assess, I) effects of gender on coagulation, and II) relationship with standard coagulation tests (SCT). In contrast to SCT, TEG® measures clot formation, strength, and lysis in whole blood under low shear forces resembling physiologic venous flow. TEG parameters usually measured are R time, K time, Angle, and MA or Maximum Amplitude. ”Shorter R and K time, and larger Angle and MA are indicative of accelerated coagulation”. [Reference values for R 2-8 min, K 1-3 min, Angle 55-78°, MA 51-69 mm]. Method. Retrospectively, records of 146 adult CABG surgery patients were reviewed. Baseline preoperative kaolin heparinase TEG® parameters R, K, Angle, and MA were recorded. Adults with pre-existing coagulation abnormalities, liver failure, or renal failure were excluded. Results. Preoperatively, there was no gender differences in SCT i.e. [platelet count (P 0.39), PT (P 0.32), PTT (P 0.35)] and baseline creatinine (P 0.15). But females were older (P 0.001), had lower BSA (P 0.0001) and lower preoperative haematocrit (P 0.0001). Females demonstrated accelerated coagulation status compared to men, shorter R [7.67 1.77 vs. 6.65 1.69 min (P 0.003)], shorter K [1.94 0.59 vs. 1.59 0.45 min (P 0.002)], larger Angle [63.61 6.33 vs. 67.74 5.90 ° (P 0.001) and larger MA [63.13 6.33 vs. 67.74 67.63 mm (P 0.0002). Gender specific TEG® data was further analysed by percentiles into 4 sub-groups [ P25, P25-P50, P50-75, and P75]. Compared to males, fewer females had R values 75 (86.87% vs. 61.11%) [P 0.0067], more females had K values P25 (22.77% vs. 50.0%) [P 0.0038], Angle values P75 (5.88% vs. 22.22%) [P 0.0138], and MA values P75 (52.94% vs. 86.11%) [P 0.0045]. Relationship of individual TEG parameters with SCT: a) TEG R, directly to pre-op PTT (P 0.04)] and no relation with pre-op PT, platelet count and haematocrit (P 0.05). b) TEG K, inversely to pre-op platelet count (P 0.03)], directly to haematocrit (P 0.0001) and no relation with pre-op PT and PTT (P 0.05). c) TEG Angle, inversely to pre-op haematocrit (P 0.0001)], no relation with Pre-op PT, PTT, and platelet count (P 0.05). d) TEG MA, directly to pre-op platelet count (P 0.003), inversely to pre-op haematocrit (P 0.0001) and no relation with PT and PTT (P 0.05). Conclusions. Despite no gender differences in baseline SCT in adult CABG surgery patients, TEG® demonstrated female gender and low-normal haematocrit were associated with accelerated coagulation.

Cephalosporin antibiotics are used prophylactically in cardiothoracic surgery to prevent postoperative infection. In 30 patients undergoing primary elective coronary artery bypass grafting, the whole blood coagulation system was prospectively evaluated before, and 10 and 30 minutes after administration of 1 g of cephapirin (Cefadyl, Bristol Laboratory, Evansville, IN). All patients had normal preoperative coagulation studies and had not received anticoagulant or antiplatelet therapy within 7 days of surgery. At 10 minutes after cephapirin administration, 23 of 30 patients had a significant change in all phases of whole blood coagulation as monitored by thromboelastography (TEG). Thirty minutes after cephapirin administration there was no statistical difference compared with the baseline TEG. It is concluded that cephapirin can cause a significant but transient change in the viscoelastic properties of blood. Coagulation parameters of the TEG should be measured prior to cephapirin administration to prevent errors in establishing baseline values prior to cardiopulmonary bypass.