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Background: Bleeding after cardiac surgery is common and continues to require 10–20% of the national blood supply. Transfusion of allogeneic blood is associated with increased morbidity and mortality. Excessive protamine in the absence of circulating heparin after weaning off CPB can cause anticoagulation and precipitate bleeding. Hence, adequate dose calculation of protamine is crucial yet under evaluated. Study Design: Retrospective cohort study. Methods: We conducted a retrospective bi‐institutional analysis of cardiac surgical patients who underwent cardiopulmonary bypass (CPB)‐assisted cardiac surgery to assess the impact of protamine dosing in transfusion practice. Total 762 patients were identified from two institutions using electronic medical records and the Society of Thoracic Surgery (STS) database who underwent cardiac surgery using CPB. Patients were similar in demographics and other baseline characteristics. We divided patients into two groups based on mg of protamine administered to neutralize each 100 U of unfractionated heparin (UFH)—low‐ratio group (Protamine: UFH ≤ 0.8) and high‐ratio group (Protamine: UFH > 0.8). Results: We observed a higher rate of blood transfusion required in high‐ratio group (ratio >0.8) compared with low‐ratio group (ratio ≤0.8) (p <.001). The increased requirement was consistently demonstrated for intraoperative transfusions of red blood cells, plasma, platelets, and cryoprecipitate. Conclusion: High protamine to heparin ratio may cause increased bleeding and transfusion in cardiac surgical patients. Protamine to heparin ratio of 0.8 or lower is sufficient to neutralize circulating heparin after weaning off cardiopulmonary bypass. [ABSTRACT FROM AUTHOR]

Enhanced recovery after cardiac surgery (ERACS) has been gaining rapid acceptance after multiple studies have demonstrated promising results in improved outcomes of enhanced recovery after surgery in other surgical fields (eg, colorectal, orthopedic, thoracic, etc). Cardiac surgery has several unique challenges, including sternotomy, cardiopulmonary bypass and associated coagulopathy, blood transfusion, and postoperative intensive care requirement. Nonetheless, selective cardiac surgical patients can still benefit from ERACS. Guidelines for perioperative care in cardiac surgery, previously published by the ERACS Society, are weighted heavily in preoperative and postoperative management without much focus on intraoperative care provided by anesthesiologists. To address this gap and to explore anesthesiology's contribution in achieving ERACS, the study authors' cardiac anesthesiology division, in collaboration with cardiac surgery, introduced the ERACS protocol in their institution in February 2020. The cardiac anesthesiology division, in collaboration with cardiac surgery, introduced the ERACS protocol consisting of multimodal opioid-sparing analgesia, including the introduction of regional blocks, hemostasis management protocol, reversal of neuromuscular blockade, and administration of antiemetics in the authors' institution in February 2020. They have conducted a retrospective chart review study comparing patients who have received ERACS measures with a similar historic cohort who underwent cardiac surgery prior to initiation of an ERACS protocol. The primary outcomes of the study were to determine patients' time to extubation, postoperative opioid consumption, intensive care unit (ICU) length of stay (LOS), and incidence of postoperative complications (eg, postoperative nausea vomiting [PONV], bleeding, ICU readmission, delirium. The ERACS patients showed reduced opioid consumption (intraoperative fentanyl; postoperative fentanyl, as well as oxycodone, in the first 6 hours postoperatively), lesser mechanical ventilation (2.5 hours less), shorter ICU stays (5 hours less), shorter hospital LOS (1 day), and lesser incidence of PONV. None of the ERACS patients required blood transfusion. The study authors performed an anonymous survey among the anesthesiologists and ICU providers to assess providers' satisfaction, which showed 92% of survey takers agreed that the ERACS protocol should be continued for future cardiac patients, and 61% of survey takers reported superior pain control in ERACS group of patients while managing those patients. The ERACS is achievable after the careful implementation of a series of measures. It does not signify only fast-track extubation and opioid-sparing analgesia, and must be implemented in the entire perioperative period beginning from preoperative clinic to postoperative rehabilitation. Cardiac anesthesiologists play a vital role in execution of intraoperative ERACS measures. Both providers and patients themselves are key stakeholders. A larger randomized prospective trial is warranted to solidify the inference. [ABSTRACT FROM AUTHOR]

Viscoelastic coagulation tests have been increasingly used for hemostasis management in cardiac surgery. The ClotPro system is a novel viscoelastic device based on principles of rotational thromboelastometry. We aimed to compare ClotPro with ROTEM and plasma coagulation assays in cardiopulmonary bypass (CPB) patients. Blood samples were collected from 25 CPB patients at (1) baseline, (2) start of CPB, (3) end of CPB, and (4) end of surgery. The EX-test, IN-test, HI-test, FIB-test parameters on ClotPro were compared with corresponding ROTEM assay (EXTEM, INTEM, HEPTEM, and FIBTEM). Standard plasma coagulation assays and endogenous thrombin generation (TG) were simultaneously evaluated. Pearson correlation analyses showed moderate correlations between clotting times (CTs) (r = 0.63–0.67; p < 0.001, respectively), and strong correlations with maximal clot firmness (MCF) (r = 0.93–0.98; p < 0.001, respectively) between ClotPro and ROTEM. EX-test and IN-test MCF parameters were interchangeable with acceptable percentage errors (EX-test MCF: 7.3%, IN-test MCF: 8.3%), but FIB-test MCF (27.0%) and CT results were not (EX-test CT: 44.7%, IN-test CT: 31.4%). The correlations of PT/INR or peak TG with EX-test CTs were higher than with EXTEM CTs (PT/INR: r = 0.80 and 0.41, peak TG: 0.43 and 0.18, respectively). FIB-test MCF has strong correlation with plasma fibrinogen and factor XIII level (r = 0.84 and 0.66, respectively). ROC analyses showed that ClotPro was capable of emulating well-established ROTEM thresholds (area under curves: 0.83–1.00). ClotPro demonstrated strong correlations in MCF parameters of ROTEM in CPB patients. It may be reasonable to modify ROTEM-based transfusion algorithm pertaining to MCF parameters to establish cut-off values for ClotPro device. [ABSTRACT FROM AUTHOR]

Background: Acute normovolemic hemodilution (ANH) is a blood conservation strategy in cardiac surgery, predominantly used in coronary artery bypass graft (CABG) and/or valve procedures. Although higher complexity cardiac procedures may benefit from ANH, concerns for hemodynamic instability, and organ injury during hemodilution hinder its wider acceptance. Laboratory and physiological parameters during hemodilution in complex cardiac surgeries have not been described. Study design and methods: This observational cohort (2019–2021) study included 169 patients who underwent thoracic aortic repair, multiple valve procedure, concomitant CABG with the aforementioned procedure, and/or redo sternotomies. Patients who received allogeneic blood were excluded. Statistical comparisons were performed between ANH (N = 66) and non‐ANH controls (N = 103). ANH consisted of removal of blood at the beginning of surgery and its return after cardiopulmonary bypass. Results: Intraoperatively, the ANH group received more albumin (p =.04) and vasopressor medications (p =.01), while urine output was no different between ANH and controls. Bilateral cerebral oximetry (rSO2) values were similar before and after hemodilution. During bypass, rSO2 were discretely lower in the ANH versus control group (right rSO2p =.03, left rSO2p =.05). No differences in lactic acid values were detected across the procedural continuum. Postoperatively, no differences in extubation times, intensive care unit length of stay, kidney injury, stroke, or infection were demonstrated. Discussion: This study suggests hemodilution to be a safe and comparable blood conservation technique, even without accounting for potential benefits of reduced allogenic blood administration. The study may contribute to better understanding and wider acceptance of ANH protocols in high‐risk cardiac surgeries. [ABSTRACT FROM AUTHOR]

Hemophilia is an X-linked, recessive bleeding disorder. Improvements in factor replacement therapy and overall approach to hemophilia management have increased the lifespan and quality of life for patients with hemophilia. Thus, they are presenting for cardiac surgery related to age-related atherosclerosis, vascular disorders, and degenerative valvular disease. Although challenging, cardiac surgery can be performed safely with appropriate planning, using a multidisciplinary approach. This article provides a narrative review and framework for the perioperative management of patients with hemophilia A and B undergoing cardiac surgery. [ABSTRACT FROM AUTHOR]

• Four-factor prothrombin complex concentrate (4F-PCC) is increasingly utilized in various critical bleeding situations. • Most of these uses are currently considered as "off-label" in the United States. • Existing retrospective studies and a limited number of prospective randomized studies support its hemostatic efficacy. • Thromboembolic events are the most feared complications after 4F-PCC administration but data are insufficient to fully assess its potential risk in different patient populations. • Optimal dosing and monitoring of 4F-PCC need to be further investigated. Four-factor prothrombin complex concentrate (4F-PCC) is the term used to describe a pathogen-reduced, lyophilized concentrate that contains therapeutic amounts of at least 4 coagulation factors: Factor II (FII), Factor VII (FVII), Factor IX (FIX), and Factor X (FX). 4F-PCC has proven to be an effective hemostatic agent compared to plasma transfusion in several prospective randomized trials in acute warfarin reversal. In recent years, 4F-PCC has been used in various acquired coagulopathies including post-cardiopulmonary bypass bleeding, trauma-induced coagulopathy, coagulopathy in liver failure, and major bleeding due to anti-FXa (anti-Xa) inhibitors (eg, rivaroxaban and apixaban). As transfusion of frozen plasma (FP) has not been found efficacious in the above critical bleeding scenarios, there is increasing interest in expanding the use of 4F-PCC. However, efficacy, safety, and clinical implications of expanded use of 4F-PCC have not been fully elucidated. Prothrombin time and international normalized ratio are commonly used to assess dose effects of 4F-PCC. Prothrombin time/international normalized ratio are standardly use for warfarin titration, but they are not suited for real-time monitoring of complex coagulopathies. Optimal dosing of 4F-PCC outside of the current approved use for vitamin K antagonist reversal is yet to be determined. In this review, we will discuss the use of 4F-PCC in four critical bleeding settings: cardiac surgery, major trauma, end-stage liver disease, and oral anti-Xa reversal. We will discuss recent studies in each area to explore the dosing, efficacy, and safety of 4F-PCC. [ABSTRACT FROM AUTHOR]

Vasodilatory shock is a serious medical condition that increases the morbidity and mortality of perioperative and critically ill patients. Norepinephrine is an established first-line therapy for this condition, but at high doses, it may lead to diminishing returns. Oftentimes, secondary noncatecholamine agents are required in those whose hypotension persists. Angiotensin II and vasopressin are both noncatecholamine agents available for the treatment of hypotension in vasodilatory shock. They have distinct modes of action and unique pharmacologic properties when compared to norepinephrine. Angiotensin II and vasopressin have shown promise in certain subsets of the population, such as those with acute kidney injury, high Acute Physiology and Chronic Health Evaluation II scores, or those receiving cardiac surgery. Any benefit from these drugs must be weighed against the risks, as overall mortality has not been shown to decrease mortality in the general population. The aims of this narrative review are to provide insight into the historical use of noncatecholamine vasopressors and to compare and contrast their unique modes of action, physiologic rationale for administration, efficacy, and safety profiles. [ABSTRACT FROM AUTHOR]

Background: Acute normovolemic hemodilution is recommended as a technique to reduce allogeneic red blood cell (RBC) transfusions in cardiac surgery, but its efficacy to reduce non-RBC transfusion has not been consistently demonstrated. We hypothesized that intraoperative large-volume autologous whole blood (AWB) collection and reinfusion improves viscoelastic coagulation parameters.Study Design and Methods: Prospective observational study of cardiac surgery patients at the University of Maryland Medical Center between December 2017 and August 2019. Rotational thromboelastometry parameters were compared between AWB and control groups (n = 25 in each group) at three time points: T1, baseline; T2, on cardiopulmonary bypass (CPB) after the cross-clamp removal; and T3, 30-60 minutes after protamine administration. The study's primary outcomes were whole blood viscoelastic coagulation parameters that included EXTEM clotting time (CT), FIBTEM amplitude at 10 minutes, and EXTEM amplitude at 10 minutes (EXTEM-A10 ). Chest tube drainage and allogeneic transfusion were secondary outcomes.Results: Reinfusion of AWB after CPB resulted in a significantly shorter EXTEM CT; mean difference, -11.4 seconds (-21.4 to -1.4; P = .03). It also resulted in a greater percentage increase in EXTEM A10 from T2 to T3; mean difference, 7.8% (95% CI, 1.1%-14.5%; P = .02). Statistical significance was not found in 24-hour chest tube drainage.Conclusion: Large-volume AWB collection and reinfusion are feasible in selected cardiac surgical patients, and may be associated with prohemostatic effects according to thromboelastometry, warranting further investigation with a prospective randomized study. [ABSTRACT FROM AUTHOR]

Objective: To investigate the pharmacokinetics and pharmacodynamics of an ε-aminocaproic acid (EACA) regimen designed for cardiac surgery with cardiopulmonary bypass (CPB). Design: Prospective observational study requiring blood sampling to measure EACA concentrations and fibrinolysis markers (fibrinogen, D-dimer, α 2 -antiplasmin, and tissue plasminogen activator-plasminogen activator inhibitor [tPA-PAI-1] complex). Setting: Single-center, tertiary medical center. Participants: Patients who underwent cardiac surgery with CPB between 2018 and 2019 for aortic or mitral valve replacement/repair or coronary artery bypass grafting. Previous sternotomy patients were included. Intervention: None. Measurements and Main Results: The pharmacokinetics of EACA, during CPB, were described by a 3-compartment disposition model. EACA concentrations were greater than 130 mg/L in all patients after CPB and in most patients during CPB. The D-dimer level trended up and reached a peak median level of 1.35 mg/L of fibrinogen equivalence units (FEU) at 15 minutes after protamine administration. The median change in D-dimer (ΔD-dimer) from baseline to 15 minutes after protamine was 0.34 (–0.48 to 3.81) mg/L FEU. ΔD-dimer did not correlate with EACA concentration intraoperatively, urine output, body weight, glomerular filtration rate, cell salvage volume, and ultrafiltration volume. The median 24-hour chest tube output was 445 (180-1,011) mL. Conclusion: This regimen provided maximum EACA concentrations near the time of protamine administration, with a total perioperative dose of 15 g. Most patients had EACA concentrations greater than the target during CPB. ΔD-dimer did not correlate with EACA concentration. The median 24-hour chest tube output compared well to similar studies that used higher doses of EACA. [ABSTRACT FROM AUTHOR]

Therapeutic plasma exchange (TPE) has a number of applications in cardiac surgical patients and has been used increasingly in high-risk heart and lung transplant patients. In this narrative review, the authors describe TPE principles, complications, and specific indications for TPE, including thrombotic thrombocytopenic purpura, heparin-induced thrombocytopenia, induction of immunotolerance in heart and lung transplant patients, and treatment of antibody-mediated rejection in heart and lung transplant patients. The review is based on published literature and the authors' institutional experience with perioperative TPE in cardiac surgical patients. [ABSTRACT FROM AUTHOR]

Low-dose tranexamic acid (TXA) has been recently recommended for cardiopulmonary bypass (CPB) to reduce associated complications. Although point-of-care laboratory tests for TXA concentrations are unavailable, a novel TPA-test on the ClotPro® system can measure TXA-induced inhibition of fibrinolysis. We evaluated the performance of the TPA-test in vitro and in patients undergoing surgery requiring CPB. Blood samples were obtained from six volunteers for in vitro evaluation of tissue plasminogen activator (tPA)-triggered fibrinolysis and the effects of TXA. This was followed by an observational study in 20 cardiac surgery patients to assess clinical effects of TXA on the TPA-test. Hyperfibrinolysis induced by tPA was inhibited by TXA ≥2 mg L−1 in a concentration-dependent manner, and was completely inhibited at TXA ≥10 mg L−1. In patients undergoing CPB, antifibrinolytic effect was detectable on TPA-test parameters after a 0.1 g bolus of TXA at the end of CPB, and complete inhibition of fibrinolysis was obtained with TXA ≥0.5 g. The antifibrinolytic effects of 1 g TXA on TPA-test parameters were gradually attenuated over 18 h after surgery. However, the fibrinolytic inhibition continued in four patients with estimated glomerular filtration rate (eGFR) ≤30 ml min−1 1.73 m−2. The eGFR had strong correlations with TPA-test parameters at 18 h after surgery (r=0.86–0.92; P <0.0001). The TPA-test is sensitive to low concentrations of TXA and serves as a practical monitoring tool for postoperative fibrinolytic activity in cardiac surgery patients. This test might be particularly useful in patients with severe renal impairment. [ABSTRACT FROM AUTHOR]

Background: Perioperative use of allogeneic blood products is associated with higher morbidity, mortality, and hospital costs after cardiac surgery. Blood conservation techniques such as acute normovolemic hemodilution (ANH) report variable success. We hypothesized that large-volume ANH with limited hemodilution would reduce allogeneic blood transfusion compared to the standard practice.Study Design and Methods: Retrospective observational study of cardiac surgery patients at the University of Maryland Medical Center between January 2014 and September 2017. Using the institutional Society of Thoracic Surgeons database 91 autologous and 981 control patients who underwent coronary artery bypass grafting, aortic valve replacement, or both were identified. After propensity matching of 13 preoperative characteristics, 84 autologous and 84 control patients were evaluated. Our primary endpoint was avoidance of blood transfusion during index hospitalization, and secondary endpoints were postoperative bleeding and major adverse outcomes.Results: The median harvest volumes in the ANH and control groups were 1100 mL and 400 mL, respectively. Of the ANH group, 25% received any transfusion versus 45.2% of the control group after propensity score matching (p < 0.006). When controlling for preoperative platelet count, the transfusion rate ratios for ANH were 0.58 (95% confidence interval, 0.39-0.88) for RBCs and 0.63 (0.44-0.89) for non-RBC components, which were both found to be statistically significant. There was no difference found in major adverse events.Conclusion: These results suggest that large-volume ANH is beneficial in reducing both RBC and non-RBC component usage in cardiac surgery. A further prospective validation is warranted. [ABSTRACT FROM AUTHOR]

Prostacyclin (prostaglandin I2 [PGI2]) is an eicosanoid lipid mediator produced by the endothelial cells. It plays pivotal roles in vascular homeostasis by virtue of its potent vasodilatory and antithrombotic effects. Stable pharmacological analogues of PGI2 are used for treatment of pulmonary hypertension and right ventricular failure. PGI2 dose dependently inhibits platelet activation induced by adenosine-5'-diphosphate, arachidonic acid, collagen, and low-dose thrombin. This property has led to its use as an alternative to direct thrombin inhibitors in patients with type II heparin-induced thrombocytopenia (HIT) undergoing cardiac surgery. The aims of this review are the following: (1) to review the pharmacology of PGI2 and its derivatives, (2) to present the evidence for their use in pulmonary hypertension and right heart failure, and (3) to discuss their utility in the management of HIT in cardiac surgery. [ABSTRACT FROM AUTHOR]

Objective To determine the relationships between hypothermia and pH at surgery end and postoperative red blood cell (RBC) transfusion in massively transfused adult cardiac surgery patients. Design Retrospective cohort study. Setting Single tertiary care, academic medical center. Participants A total of 395 adult patients having cardiac surgery with cardiopulmonary bypass who were massively transfused during an 8-year period. Patients were excluded if they did not receive an antifibrinolytic drug during surgery. Interventions None. Measurements and Main Results Body temperature and pH at surgery end were recorded. Postoperative RBC transfusion, a surrogate for postoperative bleeding, was the study’s primary outcome. Secondary outcomes were postoperative fresh frozen plasma (FFP) transfusion, postoperative platelet transfusion, reoperation for bleeding, and mortality. Patients with hypothermia did not have more postoperative RBC transfusion (p = 0.56), but patients with acidosis or alkalosis received more RBCs after surgery (p = 0.04). There were no differences in secondary outcomes between groups. In multivariate analysis, both acidosis and alkalosis were independently associated with postoperative RBC transfusion (p = 0.01 and p < 0.0001). Conclusion Hypothermia at surgery end has no association with postoperative RBC transfusion in massively transfused cardiac surgery patients, but pH derangements are associated with increased postoperative transfusion. Thus, normalization of blood pH may be important in reducing postoperative bleeding in massively transfused cardiac surgery patients. [ABSTRACT FROM AUTHOR]

Perioperative management of cardiovascular surgical procedures requiring cardiopulmonary bypass (CPB) in patients with hemophilia A poses a clinical challenge in coagulation management. Use of CPB requires the administration of an anticoagulant, usually unfractionated heparin, and also causes dilutional coagulopathy, platelet dysfunction or platelet consumption coagulopathy. Hypothermia and activation of the inflammatory cascade also affect coagulation. The effects of CPB on circulating levels of factor VIII have not been clearly defined. In this review, the effects of CPB and hemodilution on FVIII are shown in a case presentation, and perioperative laboratory testing in patients with hemophilia A having cardiac surgery is discussed along with perioperative and postoperative coagulation management. [ABSTRACT FROM AUTHOR]

Bleeding complications after cardiac surgery are common and are associated with increased morbidity and mortality. Their etiology is multifactorial, and treatment decisions are time sensitive. Point-of-care (POC) testing has an advantage over standard laboratory tests for faster turn-around times, and timely decision on coagulation intervention(s). The most common POC coagulation testing is the activated clotting time (ACT), used to monitor heparin therapy while on cardiopulmonary bypass. Viscoelastic coagulation tests including thromboelastometry (ROTEM) and thromboelastography (TEG) have been recommended for the treatment of postoperative bleeding after cardiac surgery because the ROTEM/TEG-guided treatment algorithms reduced the use of blood products. Other POC tests are commercially available, but there is sparse evidence for their routine use in cardiac surgery. These devices include heparin management systems, POC prothrombin time and activated partial thromboplastin time, POC fibrinogen assay, and whole blood platelet function tests. There are multiple confounding elements and conditions associated with cardiac surgery, which can significantly alter test results. Anemia and thrombocytopenia are regularly associated with deviations in many POC devices. In summary, POC coagulation testing allows for rapid clinical decisions in hematological interventions, and, when used in conjunction with a proper transfusion algorithm, may reduce blood product usage, and potentially complications associated with blood transfusion. [ABSTRACT FROM AUTHOR]

Achieving hemostasis after complex cardiovascular and transplant surgical procedures is one of the greatest challenges anesthesiologists face. Preoperative coagulation disturbances due to underlying disease or antithrombotic therapy are common, and they are worsened by intraoperative blood loss and fluid replacement. The coagulation reactions in vivo are incredibly complex interactions among blood cells, proteins, and vasculature, standing in sharp contrast to rather simple treatment options including transfusion of platelets, plasma, and cryoprecipitate. The long turnaround time of laboratory coagulation testing, and intraoperative heparin use also make timely coagulation assessment difficult during cardiopulmonary bypass, and thus, hemostatic components are often empirically ordered and administered without knowing their actual need or efficacy. However, increasing clinical experience with viscoelastic coagulation testing in cardiac and transplant anesthesia has introduced a paradigm shift, enabling clinicians to obtain clinically relevant coagulation data in a timely fashion and to treat a specific element of coagulation that is dysfunctional. Viscoelastic coagulation testing may facilitate an optimal use of blood components and other hemostatic agents, but its application is often practice specific (ie, type of surgery), and there are technical limitations and learning curves. The aims of this review are thus to summarize recent clinical data on viscoelastic coagulation testing and to provide practical examples of its use in complex cardiac surgical and transplant cases. [ABSTRACT FROM AUTHOR]

Background: Cardiac transplantation can be complicated by refractory hemorrhage particularly in cases where explantation of a ventricular assist device is necessary. Recombinant activated factor VII (rFVIIa) has been used to treat refractory bleeding in cardiac surgery patients, but little information is available on its efficacy or cost in heart transplant patients.Methods: Patients who had orthotopic heart transplantation between January 2009 and December 2014 at a single center were reviewed. Postoperative bleeding and the total costs of hemostatic therapies were compared between patients who received rFVIIa and those who did not. Propensity scores were created and used to control for the likelihood of receiving rFVIIa in order to reduce bias in our risk estimates.Results: Seventy-six patients underwent heart transplantation during the study period. Twenty-one patients (27.6%) received rFVIIa for refractory intraoperative bleeding. There was no difference in postoperative red blood cell transfusion, chest tube output, or surgical re-exploration between patients who received rFVIIa and those who did not, even after adjusting with the propensity score (P = 0.94, P = 0.60, and P = 0.10, respectively). The total cost for hemostatic therapies was significantly higher in the rFVIIa group (median $10,819 vs. $1,985; P < 0.0001). Subgroup analysis of patients who underwent redo-sternotomy with left ventricular assist device explantation did not show any benefit for rFVIIa either.Conclusions: In this relatively small cohort, rFVIIa use was not associated with decreased postoperative bleeding in patients undergoing heart transplantation; however, it led to significantly higher cost. [ABSTRACT FROM AUTHOR]

Background: Prothrombin complex concentrate (PCC) is increasingly used for acute warfarin reversal. We hypothesized that computational modeling of thrombin generation (TG) could be used to optimize the timing and dose of PCC during hemodilution induced by cardiopulmonary bypass (CPB). Methods: Thrombin generation patterns were modeled in anticoagulated patients ( n = 59) using a published computational model. Four dosing schemes were evaluated including single full dose (median, 41.2 IU/kg) of PCC before or after CPB, ½-dose before and after CPB, or 1/3-dose before CPB plus 2/3-dose after CPB. Hemodilution was modeled as 40 or 60 % dilution of factors from baseline. The lag time (s) of TG, and peak thrombin level (nM) were evaluated. Results: Prolonged lag time, and reduced peak TG were due to low vitamin K-dependent (VKD) factors, and pre-CPB PCC dose-dependently restored TG to near-normal or normal range. After 40 % dilution, TG parameters were similar among 4 regimens at the end of therapy. The recovery of VKD factors was less when PCC was given before CPB after 60 % dilution, but TG parameters were considered hemostatically effective (>200 nM) with any regimen. Withholding the full dose of PCC until post-CPB resulted in severely depressed TG peak (median, 47 nM) after 60 % dilution, and some supra-normal TG peaks after treatment. Conclusions: Pre-CPB administration of full or divided doses of PCC prevents extremely low TG peak during surgery, and maintains hemostatic TG peaks in both 40 and 60 % hemodilution models. Although PCC's hemostatic activity appears to be highest using the full dose after CPB, hypercoagulability may develop in some cases. [ABSTRACT FROM AUTHOR]

Reduced aspirin responsiveness (i.e. persistent high platelet reactivity in platelet function testing) might be associated with increased risk of myocardial ischemia and cardiac mortality in patients with coronary disease. However, the impact in patients undergoing coronary artery bypass grafting (CABG) is unclear. The aim of this prospective cohort study was to evaluate the predictive value of reduced aspirin responsiveness on cardiac and thromboembolic events in patients undergoing elective isolated CABG surgery with aspirin intake until at least two days before surgery. We included 304 patients in this prospective single-center cohort study. Impedance platelet aggregometry (Multiplate®) was performed directly before and on the first day after surgery. Reduced aspirin responsiveness was defined as area under the curve in ASPItest (AUCASPI) ≥300 U. The primary outcome was a composite of all-cause mortality and/or major adverse cardiac or thromboembolic events within 1 year. Reduced aspirin responsiveness was found in 13 and 24% of patients pre and postoperatively, respectively. There was no difference in the outcomes between patients with normal and reduced aspirin responsiveness in the preoperative measurement (log-rank test,p = 0.540). Multivariate analysis including logistic EuroSCORE I and postoperative troponin T levels did not show any association of reduced aspirin responsiveness with adverse outcome (hazard ratio, 0.576; (95% CI 0.128–2.585;p = 0.471). Similarly, postoperative reduced aspirin responsiveness was not associated with adverse events. To conclude, reduced aspirin responsiveness as evaluated by Multiplate® platelet function analyzer was not associated with increased incidence of major adverse cardiac and thromboembolic events and mortality after CABG surgery. [ABSTRACT FROM PUBLISHER]

Objective: Aprotinin, once used to reduce allogeneic blood product transfusion during cardiac surgery, was withdrawn from the market in late 2007 over concerns of causing increased mortality. This study was undertaken to determine what, if any, the impact of changing antifibrinolytic agents (from aprotinin to tranexamic acid) for deep hypothermic circulatory arrest cases would have on blood bank resource utilization. Design: This a retrospective review. Setting: All cases were performed at a single university hospital. Participants: All patients underwent cardiac surgical procedures requiring deep hypothermic circulatory arrest performed by a single cardiac surgeon between January 2006 and November 2008. Intervention: All patients prior to November 15, 2007 received aprotinin as antifibrinolytic therapy, while those after that date received tranexamic acid for antifibrinolytic therapy. Measurements and Main Results: Blood transfusion data and recombinant factor VIIa use during the pre- and immediate postoperative period was collected for all patients during the study time period. There were no significant differences between the aprotinin (n = 82) and tranexamic acid (n = 78) groups with regard to baseline coagulation status or operative characteristics. Patients treated with tranexamic acid required more fresh frozen plasma (2.5 units, p < 0.001), platelets (0.5 units, p < 0.01), and cryoprecipitate (25 units, p < 0.001), and had a higher incidence of recombinant factor VIIa use (34.6% v 12.2%, p < 0.01) compared with patients in the aprotinin group. Conclusions: Patients treated with tranexamic acid required more clotting factors than the control group receiving aprotinin. [ABSTRACT FROM AUTHOR]

The cardiopulmonary bypass (CPB) used in heart surgery has a deleterious effect on hemostasis. The aim of our study was to assess by means of standard laboratory and point-of-care methods changes induced by CPB in coagulation parameters, particularly in platelet function, and to determine whether these changes differ depending on the type of heart–lung machine (HLM) used: minimal extracorporeal circulation system (MECC) and standard HLM. The study enrolled 88 patients scheduled for coronary artery bypass surgery performed on pump. Forty-four interventions were performed with MECC and 44 with standard HLM. Blood was sampled preoperatively, after 30 min on CPB, after weaning from CPB, and 24 h postoperatively. Coagulation and platelet function were assessed using multiple electrode aggregometry (MEA), rotation thromboelastometry, as well as standard laboratory tests. Rotation thromboelastometry and standard laboratory reflected significantly impaired hemostasis after weaning from CPB but no significant differences between the two groups at different time points. Aggregation decreased significantly in both groups as early as 30 min after the institution of CPB ( P < 0.05, Mann–Whitney U-test) and recovered within the first 24 h postoperatively, without reaching the preoperative level. Intraoperatively, aggregometry values reflected a significantly more severe reduction of platelet function in standard HLM group than in the MECC group ( P < 0.01, ProcMixed test). Our findings suggest that MEA and thromboelastometry reflect impairment of coagulation in cardiac surgery performed on different types of HLM and that platelet function is less affected by MECC than by standard HLM. [ABSTRACT FROM AUTHOR]

In Jehovah''s Witness patients, the use of red blood cells, platelets, and fresh frozen plasma is not optional. Various blood conservation techniques are available, but complex cardiac surgery remains a major challenge. The feasibility of fractions of “primary components” has not been fully considered in published case reports. For Jehovah''s Witness patients who preoperatively give consent, factor IX concentrates may be acceptable for hemostatic therapy. We hereby describe a combination of “secondary components” to prevent excessive bleeding in a Jehovah''s Witness patient undergoing complex replacement of the aortic arch. [Copyright &y& Elsevier]

Andexanet alfa is a Gla-domainless mutant (S195A) factor Xa (GDXa) approved for acute reversal of oral factor Xa inhibitors. Cardiac surgery patients exposed to andexanet before cardiopulmonary bypass often exhibit severe heparin resistance. There is a paucity of data on the effectiveness and optimal dosage of antithrombin use in this setting. The objective of this study was to evaluate the in vitro effect of increased heparin with antithrombin levels on attenuating heparin resistance induced by GDXa. Heparinised normal pooled plasma and cardiopulmonary bypass plasma were spiked with GDXa 4 μM. Tissue factor-activated thrombin generation was used to assess heparin reversal effects of GDXa and restoration of anticoagulation with additional heparin with and without antithrombin. Serum thrombin–antithrombin complex, antithrombin activity, and tissue factor pathway inhibitor were also measured in tissue factor-activated, recalcified cardiopulmonary bypass plasma spiked with GDXa. In normal pooled plasma, GDXa-induced heparin reversal was mitigated by maintaining a high heparin concentration (12 U ml−1) and supplementing antithrombin (1.5–4.5 μM) based on peak and velocity of thrombin generation. Heparin reversal by GDXa was also demonstrated in cardiopulmonary bypass plasma, but supplementing both heparin (8 U ml−1) and antithrombin (3 μM) attenuated GDXa-induced changes in peak and velocity of thrombin generation by 72.5% and 72.2%, respectively. High heparin and antithrombin levels attenuated thrombin–antithrombin complex formation in tissue factor-activated, GDXa-spiked cardiopulmonary bypass plasma by 85.7%, but tissue factor pathway inhibitor remained depleted compared with control cardiopulmonary bypass plasma. Simultaneous supplementation of heparin and antithrombin mitigate GDXa-induced heparin resistance by compensating for the loss of tissue factor pathway inhibitor. [ABSTRACT FROM AUTHOR]

Background: Epsilon-aminocaproic acid is a plasmin inhibitor that potentially reduces perioperative bleeding when administered prophylactically to cardiac surgery patients. To evaluate the efficacy of ε-aminocaproic acid, a prospective placebo-controlled trial was conducted in patients undergoing primary coronary artery bypass grafting surgery. Study design: One hundred patients were randomly assigned to receive either ε-aminocaproic acid (100 mg/kg before skin incision followed by 1 g/hour continuous infusion until chest closure, 10 g in cardiopulmonary bypass circuit) or placebo, and the efficacy of ε-aminocaproic acid was evaluated by the reduction in postoperative thoracic-drainage volume and in donor-blood transfusion up to postoperative day 12. Results: Postoperative thoracic-drainage volume was significantly lower in the ε-aminocaproic acid group compared with the placebo group (ε-aminocaproic acid, 649 ± 261mL; versus placebo, 940 ± 626mL; p=0.003). There were no significant differences between the ε-aminocaproic acid and placebo groups in the percentage of patients requiring donor red blood cell transfusions (ε-aminocaproic acid, 24%; versus placebo, 18%; p=0.62) or in the number of units of donor red blood cells transfused (ε-aminocaproic acid, 2.2 ± 0.8 U; versus placebo, 1.9 ± 0.8 U; p=0.29). Epsilon-aminocaproic acid did not reduce the risk of donor red blood cell transfusions compared with placebo (odds ratio: 1.2, 95% confidence interval; 0.4 to 3.2, p=0.63). Conclusions: Prophylactic administration of ε-aminocaproic acid reduces postoperative thoracic-drainage volume by 30%, but it may not be potent enough to reduce the requirement and the risk for donor blood transfusion in cardiac surgery patients. This information is useful for deciding on a therapy for hemostasis in cardiac surgery. [Copyright &y& Elsevier]