Search

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-A 10 ). 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 A 10 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., (© 2021 AABB.)

Hereditary angioedema (HAE) is a rare autosomal dominant disorder mostly due to the deficiency of C1-esterase inhibitor (C1-INH). Reduced C1-INH activity below ~38% disrupts homeostasis of bradykinin (BK) formation by increasing kallikrein activation and causes recurrent angioedema attacks affecting the face, extremities, genitals, bowels, oropharynx, and larynx. HAE symptoms can be debilitating and potentially life-threatening. The recent clinical developments of biological and pharmacological agents have immensely improved acute and long-term care of patients with moderate-to-severe HAE. The therapies are given as on-demand and/or prophylaxis, and self-administration is highly recommended and performed with some agents via intravenous or subcutaneous route. Perioperative clinicians need to be familiar with the symptoms and diagnosis of HAE as well as available therapies because of the potential need for airway management, sedation, or anesthesia for various medical and surgical procedures and postoperative care. Cardiovascular surgery using cardiopulmonary bypass is a unique condition in which heparinized blood comes into direct contact with an artificial surface while pulmonary circulation, a major reserve of angiotensin-converting enzyme (ACE), becomes excluded. These changes result in systemic kallikrein activation and BK formation even in non-HAE patients. The objectives of this review are (1) to review pathophysiology of HAE and laboratory testing, (2) to summarize pertinent pharmacological data on the prophylactic and on-demand treatment strategies, and (3) to discuss available clinical data for perioperative management in cardiovascular surgery.

Generation of plasma-free hemoglobin (pfHb) and activated complement during complex cardiac surgery contributes to end-organ dysfunction. This prospective, multicenter REFRESH I (REduction in FREe Hemoglobin) randomized controlled trial evaluated the safety and feasibility of CytoSorb hemoadsorption therapy to reduce these factors during prolonged cardiopulmonary bypass (CPB). Eligible patients underwent elective, nonemergent complex cardiac surgery with expected CPB duration ≥3 hours. Exclusions included single procedures including primary coronary artery bypass graft, single valves, transplant, and left ventricular assist device extraction. TREATMENT used 2 parallel 300 mL CytoSorb hemoadsorption cartridges in a side circuit during CPB. CONTROL was standard of care. Of 52 enrolled patients, 46 underwent surgery (Safety group, n = 23 vs Control, n = 23), and 38 were evaluated for pfHb reduction (EFFICACY group, n = 18 vs CONTROL, n = 20). Type and number of serious adverse events (44 vs 43 CONTROL) were similar, as was 30-day mortality. Transient reduction in platelets during CPB was observed in both groups, especially TREATMENT, but returned to pretreatment levels after CPB without bleeding. Peak pfHb was positively correlated with CPB length (P = 0.01) but the high variability of pfHb, due to the broad surgical procedure mix, prevented detection of changes in pfHb in the overall EFFICACY population. However, the valve replacement surgery subgroup (8 vs 10 CONTROL) had the highest peak pfHb levels, and TREATMENT demonstrated significant pfHb reductions vs CONTROL (P ≤ 0.05) in CPB ≥3 hours. In the EFFICACY group, C3a and C5a were significantly reduced by treatment throughout surgery. Intraoperative hemoadsorption with CytoSorb was safe and feasible in this randomized, controlled pilot study during complex cardiac surgery. Treatment with CytoSorb resulted in significant reductions in pfHb during valve replacement surgery and reductions in C3a and C5a in the overall EFFICACY group. Future studies will target complex cardiac surgery patients with prolonged CPB to assess hemoadsorption effect on end-organ dysfunction and outcomes., (Copyright © 2019. Published by Elsevier Inc.)

Objective: Point-of-care (POC) devices allow for prothrombin time/international normalized ratio (PT/INR) testing in whole blood (WB) and timely administration of plasma or prothrombin complex concentrate during cardiopulmonary bypass surgery. This study evaluated the sensitivities of a new POC PT test, a dry-hematology method with heparin neutralization technology (DRIHEMATO PT-S [DRI PT-S]; A&T Corporation, Kanagawa, Japan), and compared it with other POC tests currently available., Design: Prospective, observational study., Setting: University hospital, single center., Participants: Healthy volunteers and warfarin-treated and cardiac surgical patients., Measurement and Main Results: In WB samples obtained from 6 healthy volunteers, PT-INR results of DRI PT-S were not affected by an in vitro addition of heparin <6.0 U/mL. In warfarin-treated samples (n = 88, PT/INR 0.98-3.87), PT-INR with DRI PT-S showed acceptable correlation with the laboratory method (r 2 = 0.85, p < 0.001). In blood samples obtained from cardiac surgical patients (n = 72), heparin prolonged the PT/INR with the laboratory assay, dry-hematology method with non heparin neutralization technology (DRI PT), Coaguchek XS (Roche Diagnostics, Basel, Switzerland), and Hemochron Jr. (Accriva Diagnostics, Edison, NJ), but DRI PT-S was not affected by heparin anticoagulation. In nonheparinized samples, different methods between DRI PT-S and the laboratory method yielded acceptable correlations (r 2 = 0.76, p < 0.0001). There was a moderate correlation between factor levels and the PT-INR with DRI PT-S (factor [F]II: r 2 = 0.63, FVII: r 2 = 0.47, FX: r 2 = 0.67; p < 0.0001)., Conclusions: This study demonstrated that PT/INR can be accurately assessed using the dry-hematology method in WB under therapeutic heparin levels. Currently available other POC PT/INR tests are affected by heparin, and thus they are not recommended for coagulation monitoring during cardiopulmonary bypass., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Intracardiac thrombosis (ICT) and pulmonary thromboembolism (PE) after cardiopulmonary bypass (CPB) are life-threatening events, but pathological mechanisms are not yet well defined. The aim of this review is to provide an update of case literature of a postbypass hypercoagulable state. Case commonalities among 48 ICT/PE events included congestive heart failure (50%), platelet transfusion (37.5%), CPB duration greater than 3 hours (37.5%), and aortic injury (27.1%). Preexisting thrombophilia was rarely reported, and 16.7% had low activated clotting time, ≤400 seconds during CPB. Mortality rate was very high (85.4%), despite attempted thrombectomy and supportive therapy. Thrombolytic therapy was infrequently used (5 of 48 times), but its efficacy is questionable due to common use of antifibrinolytic therapy (77.1% of cases). Acute ICT/PE events appear to rarely occur, but common features include prolonged CPB, depressed myocardial function, major vascular injury, and hemostatic interventions. Further efforts to elucidate pathomechanisms and optimize anticoagulation during CPB and hemostatic interventions after CPB are warranted.

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.

Background: Bleeding is a serious complication after pediatric cardiopulmonary bypass (CPB) that is associated with an increase in perioperative morbidity and mortality. Four-factor prothrombin complex concentrates (4F-PCCs) have been used off-label to supplement transfusion protocols for bleeding after CPB in adults; however, data on their use in neonates are limited. In this study, we hypothesized that 4F-PCCs administered ex vivo to neonatal plasma after CPB will increase thrombin generation., Methods: Fifteen neonates undergoing complex cardiac repairs requiring CPB were enrolled in this prospective study. Arterial blood was obtained after anesthesia induction but before CPB (baseline), after CPB following heparin reversal, and after our standardized transfusion of a quarter of a platelet apheresis unit (approximately 20 mL·kg) and 3 units of cryoprecipitate. Kcentra (CSL Behring), a 4F-PCC with nonactivated factor VII (FVII), and factor 8 inhibitor bypassing activity (FEIBA; Baxter Healthcare Corporation), a 4F-PCC with activated FVII, were added ex vivo to plasma obtained after CPB to yield concentrations of 0.1 and 0.3 IU·mL. Calibrated automated thrombography was used to determine thrombin generation for each sample., Results: The addition of Kcentra to plasma obtained after CPB resulted in a dose-dependent increase in the median (99% confidence interval) peak amount of thrombin generation (42.0 [28.7-50.7] nM for Kcentra 0.1 IU·mL and 113.9 [99.0-142.1] nM for Kcentra 0.3 IU·mL). The rate of thrombin generation was also increased (15.4 [6.5-24.6] nM·min for Kcentra 0.1 IU·mL and 48.6 [29.9-66.6] nM·min for Kcentra 0.3 IU·mL). The same was true for FEIBA (increase in peak: 39.8 [27.5-49.2] nM for FEIBA 0.1 IU·mL and 104.6 [92.7-124.4] nM for FEIBA 0.3 IU·mL; increase in rate: 17.4 [7.4-28.8] nM·min FEIBA 0.1 IU·mL and 50.5 [26.7- 63.1] nM·min FEIBA 0.3 IU·mL). In the posttransfusion samples, there was a significant increase with Kcentra in the median (99% confidence interval) peak amount (41.1 [21.0-59.7] nM for Kcentra 0.1 IU·mL and 126.8 [106.6- 137.9] nM for Kcentra 0.3 IU·mL) and rate (18.1 [-6.2 to 29.2] nM·min for Kcentra 0.1 IU·mL and 53.2 [28.2-83.1] nM·min for Kcentra 0.3 IU·mL) of thrombin generation. Again, the results were similar for FEIBA (increase in peak: 43.0 [36.4-56.7] nM for FEIBA 0.1 IU·mL and 109.2 [90.3-136.1] nM for FEIBA 0.3 IU·mL; increase in rate: 25.0 [9.1-32.6] nM·min for FEIBA 0.1 IU·mL and 59.7 [38.5-68.7] nM·min for FEIBA 0.3 IU·mL). However, FEIBA produced in a greater median reduction in lag time of thrombin generation versus Kcentra in samples obtained after CPB (P = 0.003 and P = 0.0002 for FEIBA versus Kcentra at 0.1 and 0.3 IU·mL, respectively) and in samples obtained after transfusion (P < 0.0001 for FEIBA versus Kcentra at 0.1 and 0.3 IU·mL)., Conclusions: After CPB, thrombin generation in neonatal plasma was augmented by the addition of 4F-PCCs. The peak amount and rate of thrombin generation were enhanced in all conditions, whereas the lag time was shortened more with FEIBA. Our findings suggest that the use of 4F-PCCs containing activated FVII may be an effective adjunct to the initial transfusion of platelets and cryoprecipitate to augment coagulation and control bleeding in neonates after CPB.

The techniques and equipment of cardiopulmonary bypass (CPB) have evolved over the past 60 years, and numerous numbers of cardiac surgical procedures are conducted around the world using CPB. Despite more widespread applications of percutaneous coronary and valvular interventions, the need for cardiac surgery using CPB remains the standard approach for certain cardiac pathologies because some patients are ineligible for percutaneous procedures, or such procedures are unsuccessful in some. The ageing patient population for cardiac surgery poses a number of clinical challenges, including anemia, decreased cardiopulmonary reserve, chronic antithrombotic therapy, neurocognitive dysfunction, and renal insufficiency. The use of CPB is associated with inductions of systemic inflammatory responses involving both cellular and humoral interactions. Inflammatory pathways are complex and redundant, and thus, the reactions can be profoundly amplified to produce a multiorgan dysfunction that can manifest as capillary leak syndrome, coagulopathy, respiratory failure, myocardial dysfunction, renal insufficiency, and neurocognitive decline. In this review, pathophysiological aspects of CPB are considered from a practical point of view, and preventive strategies for hemodilutional anemia, coagulopathy, inflammation, metabolic derangement, and neurocognitive and renal dysfunction are discussed., (© The Author(s) 2014.)

Purpose: Intrapulmonary or intracardiac thrombosis is a rare but catastrophic event following complex cardiothoracic surgery. Although there have been multiple cases reported in the literature, the causes of these events are largely unknown. In this retrospective review, we attempt to identify risk factors and propose possible mechanisms of thromboses after cardiopulmonary bypass (CPB)., Methods: A literature search was conducted using the MEDLINE and EMBASE with these keywords: (intra)pulmonary thrombosis, pulmonary embolism, pulmonary infarction, lung embolism, (intra)cardiac thrombosis, cardiac thrombi, in combination with CPB, extracorporeal membrane oxygenation, deep hypothermic circulatory arrest, or cardiac surgery. Putative risk factors were compiled from reported cases., Results: We identified 34 cases of massive intrapulmonary and/or intracardiac thromboses. All but 2 cases (94.1%) were fatal. Clinical presentations were systemic hypotension and/or pulmonary hypertension, right ventricular failure, and cardiogenic shock in 32 (94.1%) cases. The timing was immediate (<10 min) following hemostatic intervention in 16 cases (47.1%), within 45 min in 8 cases (23.5%), and not reported in the rest. Putative risk factors included antifibrinolytic use (88.2%), congestive heart failure (55.9%), prolonged CPB use (>2 h) (41.1%), and low activated clotting time (<400 s) after initial heparinization (20.6%). The administration of tissue plasminogen activator in 5 cases was ineffective., Conclusions: Massive thrombosis following cardiac surgery is a highly lethal event with limited treatment options. Particular attention should be paid to the status of thrombin regulatory proteins before protamine and other hemostatic interventions in patients undergoing complex cardiac surgery with antifibrinolytic agents.

A method for the determination of tranexamic acid (TXA) in human plasma and cerebral spinal fluid (CSF) was developed. Analyses were performed by ultra performance liquid chromatography with tandem mass spectrometry detection (UPLC-MS/MS) using ɛ-aminocaproic acid (ACA) as an internal standard. TXA and ACA were extracted from a 50 μL sample of plasma or CSF using a methanol protein crash protocol, and chromatographic separation was performed on an ACQUITY™ TQD mass spectrometer using a UPLC C18 BEH 1.7 μm column with a water and methanol gradient containing 0.1% formic acid. The detection and quantitation was performed by positive ion electrospray ionization using the multiple reaction monitoring (MRM) mode. The method was linear over the concentration range of 0.1-10.0 μg/mL, with lower limit of quantitation of 0.1 μg/mL for TXA. The intra- and inter-assay precision was less than 12% and 13% respectively at the plasma and CSF TXA concentrations tested. The present method provides a relatively simple and sensitive assay with short turn-around-time. The method has been successfully applied to assess the plasma and CSF concentrations of tranexamic acid achieved with only one dosing regimen of tranexamic acid in patients undergoing cardiopulmonary bypass surgery (CPB)., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: Antithrombin (AT) levels decrease during cardiopulmonary bypass (CPB), particularly when combined with deep hypothermic circulatory arrest (DHCA). Low AT levels might lead to imbalance of pro- and anticoagulant factors promoting systemic thrombotic events. We hypothesized that low levels of AT might lead to increased in vitro thrombin generation when procoagulant factors are added to the patient's plasma after CPB., Methods: Blood samples were obtained before heparinization and after separation from CPB from five patients undergoing cardiac surgery with DHCA. AT levels were determined by chromogenic assay and expressed as a percent of normal activity. The balance between procoagulant and anticoagulant elements was manipulated in the patients' plasma by adding normal donor plasma, AT-deficient plasma, or purified AT. The Thrombinoscope system was used to evaluate thrombin generation with and without AT supplementation., Results: AT levels (median, range) were 82.0% (71.0, 109) and 37.0% (34.0, 41.0) of normal before and after separation from CPB, respectively (P < 0.05). Peak thrombin generation (median, range) was 56.6 nM (42.1, 61.0) in plasma after CPB, and it remained at 61.1 nM (54.9, 64.5) when a donor plasma with normal AT (105%) was added. When AT-deficient plasma was added to the patient's plasma, peak thrombin generation (median, range) was increased from 56.6 nM (42.0, 61.0) to 117 nM (95.0, 188) (P < 0.05 versus control). After the addition of purified AT, the peak thrombin generation was reduced to 12.2 nM (9.0, 29.3) (P < 0.05 versus control)., Conclusion: Plasma AT activity is severely decreased after CPB with DHCA. Our data suggest that the administration of coagulation factor components without AT repletion may lead to excessive thrombin generation, which clinically, may potentially lead to a hypercoagulable state.

Background: Changes in the Jehovah's Witness (JW) blood refusal policy now give members the personal choice to accept certain processed fractions of blood, such as factor concentrates and cryoprecipitate., Methods: Two JW patients undergoing complex aortic surgery who developed severe microvascular bleeding after prolonged use of cardiopulmonary bypass were treated with recombinant activated factor VII, cryoprecipitate, and antithrombin concentrate., Results: Cardiopulmonary bypass-induced coagulopathy was successfully treated, allowing chest closure without evidence of thrombotic complications., Conclusions: Processed blood fractions can be a valuable adjuvant to drugs when treating bleeding in JW patients.

Purpose: The Sonoclot Analyzer provides a functional test of whole blood coagulation by measuring the viscous property of the blood sample. In this study, we used a modified Sonoclot assay, using cuvettes with a glass bead activator containing heparinase, and compared the Sonoclot data before and after cardiopulmonary bypass (CPB) to assess the usefulness in predicting postoperative hemorrhage., Methods: In 41 cardiac surgery patients, Sonoclot data were obtained immediately after heparin administration (pre-bypass) and just before protamine administration (post-bypass). Excessive bleeding was defined as chest tube drainage greater than 2 ml.kg(-1).h(-1) in 1 h during the first 4 h after surgery., Results: There were no significant differences in Sonoclot values before and after CPB in patients with acceptable bleeding (n = 29). In patients with excessive bleeding (n = 12), Sonoclot variables reflecting fibrin formation (activated clotting time [ACT], rate of fibrin formation [clot rate], and peak clot signal) were preserved after CPB; however, the variables reflecting platelet-fibrin interaction (time to peak, peak angle, and clot retraction rate) were significantly different from their respective pre-bypass values. Sonoclot analysis showed impairment of clot maturation after CPB in patients with excessive postoperative bleeding., Conclusion: Our results suggest that abnormal postoperative hemorrhage can be predicted by Sonoclot analysis with a new glass bead-activated heparinase test performed after CPB.

Inflammation in cardiac surgical patients is produced by complex humoral and cellular interactions with numerous pathways including activation, generation, or expression of thrombin, complement, cytokines, neutrophils, adhesion molecules, mast cells, and multiple inflammatory mediators. Because of the redundancy of the inflammatory cascades, profound amplification occurs to produce multiorgan system dysfunction that can manifest as coagulopathy, respiratory failure, myocardial dysfunction, renal insufficiency, and neurocognitive defects. Coagulation and inflammation are also closely linked through networks of both humoral and cellular components including proteases of the clotting and fibrinolytic cascades, including tissue factor. Vascular endothelial cells also mediate inflammation and the cross talk between coagulation and inflammation. Novel antiinflammatory agents inhibit these processes by several mechanisms such as preventing proteolysis of the protease-activated receptor (aprotinin), inhibiting complement-mediated injury (pexelizumab), or inhibiting contact activation (kallikrein inhibitors). Surgery alone also activates specific hemostatic responses, activation of immune mechanisms, and inflammatory response mediated by the release of various cytokines and chemokines. Novel agents are under investigation to further improve outcomes in cardiac surgical patients.

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]

This is an annual review to cover highlights in transfusion and coagulation in patients undergoing cardiovascular surgery. The goal of this article is to provide readers with a focused summary of the most important transfusion and coagulation topics published in 2022. This includes a discussion covering the management of anemia and red blood cell transfusion, the management of factor Xa inhibitors, updates in coagulation testing, updates in the use of factor concentrates, advances in platelet therapy, advances in anticoagulation management of patients on extracorporeal membrane oxygenation and other forms of mechanical circulatory support, and advances in the diagnosis and management of heparin-induced thrombocytopenia. [ABSTRACT FROM AUTHOR]

Introduction: Our study aim was to explore how different protamine-heparin ratios impacted enzymatic coagulation and acellular fibrin clot growth in plasma using an in vitro model. We hypothesized that a low protamine-heparin ratio would be associated with superior fibrin clot growth dynamics. Methods: We performed an in vitro study using 15 plasma samples from a commercial supplier. Different protamine-heparin ratios were added to each donor plasma sample: low ratio (0.7–1), traditional ratio (1–1), and high ratio (1.3–1) and clot formation dynamics were evaluated using a Thrombodynamics analyzer. Study outcomes were initial clot growth velocity and clot size at 30 min. Results: Plasma samples treated with a one-to-one protamine-heparin ratio had significantly lower mean initial clot growth velocity compared to samples treated with a low protamine-heparin ratio; mean difference −2.3 μm/min (95% CI = −4.0 to −0.7, p =.004). Plasma samples treated with a one-to-one protamine-heparin ratio also had significantly smaller mean clot size at 30 min compared to samples treated with a low protamine-heparin ratio; mean difference −54.0 μm (95% CI = −107.6 to −0.4, p =.048). There were no significant differences in mean initial clot growth velocity or clot size at 30 min between plasma samples treated with a high protamine-heparin ratio and those treated with a one-to-one or low protamine-heparin ratio (all p >.05). Conclusions: Plasma samples treated with a low protamine-heparin ratio had superior clot growth velocity and larger clot size at 30 min compared to a one-to-one ratio, supporting the notion that a low protamine-heparin ratio may optimize enzymatic coagulation after cardiopulmonary bypass. [ABSTRACT FROM AUTHOR]

The study aims were to evaluate current blood transfusion practice in cardiac surgical patients and to explore associations between preoperative anemia, body mass index (BMI), red blood cell (RBC) mass, and allogeneic transfusion. Multicenter retrospective study. Academic and non-academic centers. After Institutional Review Board approval, 26,499 patients who underwent coronary artery bypass grafting ± valve replacement/repair between 2011 and 2019 were included from the Maryland Cardiac Surgery Quality Initiative database. Patients were stratified into BMI categories (<25, 25 to <30, and ≥30 kg/m2), and a multivariable logistic regression model was fit to determine if preoperative hematocrit, BMI, and RBC mass were associated independently with allogeneic transfusion. Preoperative anemia was found in 55.4%, and any transfusion was administered to 49.3% of the entire cohort. Females and older patients had lower BMI and RBC mass. Increased RBC and cryoprecipitate transfusions occurred more frequently after surgery in the lower BMI group. After adjustments, increased transfusion was associated with a BMI <25 relative to a BMI ≥30 at an odds ratio (OR) of 1.26 (95% confidence interval [CI]: 1.08-1.39). For each 1% increase in preoperative hematocrit, transfusion was decreased by 9% (OR: 0.91; 95% CI: 0.90-0.92). For every 500 mL increase in RBC mass, there was a 43% reduction of transfusion (OR: 0.57; 95% CI: 0.55-0.58). Transfusion probability modeling based on calculated RBC mass eliminated sex differences in transfusion risk based on preoperative hematocrit, and may better delineate which patients may benefit from more rigorous perioperative blood conservation strategy. [Display omitted] [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]

To examine the pharmacokinetics (PK) and pharmacodynamics of a tranexamic (TXA) regimen designed for cardiac surgery with cardiopulmonary bypass (CPB). A pilot study quantifying TXA concentrations, fibrinolysis markers, and a plasmin- generation (PG) assay. For comparison, PG assay was performed on pooled normal plasma (PNP) with varying TXA concentrations. A single-center, tertiary, academic medical center. Twenty patients undergoing cardiac surgery with CPB for valve surgery and/or coronary artery bypass grafting. TXA 100 mg/h infusion for 5 hours starting before incision; 1 g TXA in CPB prime and 1 g TXA at CPB end prior to heparin reversal. The PK fit a 2-compartment disposition model. TXA concentrations were above 15 mg/L in all patients during CPB through 2 hours post-TXA infusion. During and after CPB, the TXA regimen decreased the median peak PG by 60% (95% confidence interval [CI], 56%-62%). Lowest median peak PG occurred 15 minutes postprotamine. Peak median D-dimer level of 1.24 (0.95-1.71; 95% CI) mg/L occurred at 15 minutes postprotamine and baseline-adjusted ΔD dimer correlated with increased CPB time (p = 0.004) and lower TXA level (p = 0.001). The median 24-hour chest tube output was 447 (330-664; 95% CI) mL. PG assay on PNP revealed a plateau inhibition at 5 mM TXA (786 mg/L). This regimen, with total perioperative dose of 2.5 grams, provided TXA concentrations above 15 mg/L for all patients from CPB initiation through 2 hours post-TXA. PG was significantly inhibited (p < 0.0001) during and after CPB, with maximum inhibition measured at 15 minutes after protamine administration. [ABSTRACT FROM AUTHOR]

Background: Heparin management in hemophilia A (HA) patients with a factor VIII (FVIII) inhibitor can be challenging due to severe activated clotting time (ACT) prolongations. It is important to better understand the impact of emicizumab, a FVIII mimetic on ACT, and tissue factor (TF)‐based coagulation assays. Methods: Whole blood from 18 patients undergoing cardiopulmonary bypass (CPB) were mixed in vitro with pooled normal plasma, FVIII‐deficient or FVIII‐inhibitor plasma to affect functional FVIII levels. ACTs and heparin concentration by protamine titration were measured in whole blood mixture with/without emicizumab (50‐100 μg/ml). Thrombin generation and plasmin generation were measured in the patient's plasma mixed with normal plasma or FVIII‐inhibitor plasma to assess the impact of emicizumab under low TF activation. Results: FVIII inhibitors prolonged ACTs by 2.2‐fold compared to those in normal plasma mixture at baseline. During CPB, ACTs in normal plasma mixture, and FVIII‐deficient mixture were in 400s, but ACTs reached 900s in FVIII‐inhibitor mixture. Emicizumab shortened ACTs by up to 100s in normal plasma mixture, and FVIII‐deficient mixtures. ACTs remained over 600s in FVIII‐inhibitor mixture, despite adding emicizumab at 100 μg/ml. Heparin concentration measured by TF‐based protamine titration was unaffected. Emicizumab enhanced thrombin peak in the presence of FVIII inhibitors, whereas plasmin generation was mainly affected by thrombin generation, and systemic use of ɛ‐aminocaproic acid. Conclusions: FVIII inhibitors extensively prolong ACTs in heparinized whole blood, and clinical levels of emicizumab partially reverse ACT values. Protamine titration should be considered for optimal heparin monitoring in emicizumab‐treated patients with FVIII inhibitors. [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]

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: Cardiopulmonary bypass (CPB) may cause platelet dysfunction, contributing to bleeding. There are no investigations of how CPB affects platelet mitochondrial respiration and what correlation this has with platelet aggregation and bleeding. Methods: We studied platelet mitochondrial respiration and aggregation in eighteen adult cardiac surgery patients having CPB. The relationships between respiration, aggregation and postoperative bleeding were analyzed. Results: Platelet respiration, reflected by the respiratory control ratio (RCR), was unchanged after CPB (mean difference in RCR= −0.02 (95% CI=−1.45 to 1.42), p=0.98). Further, there were no significant relationships between indexed adenosine diphosphate (ADP) or thrombin receptor-activating peptide (TRAP)-induced aggregation and the RCR (p=0.12 and p=0.41). Only post-CPB ADP - induced aggregation correlated with 24-hr chest tube output (p=0.04), but indexing for platelet count attenuated the effect (p=0.07). Conclusion: Platelet mitochondrial respiration is preserved after CPB and is not correlated with aggregation or bleeding. Only post-CPB, ADP-induced aggregation correlates with postoperative bleeding. [ABSTRACT FROM AUTHOR]

Background. Patients undergoing coronary artery bypass grafting (CABG) are at risk of postoperative bleeding because of decreased platelet function and cardiopulmonary bypass (CPB)-induced haemostatic impairment. Fibrinogen concentration decreases by 34-42% of the preoperative level by the end of CPB. An inverse relationship between perioperative plasma fibrinogen levels and postoperative bleeding has been reported in CABG patients. Administration of fibrinogen concentrate after weaning from CPB in patients with diffuse microvascular bleeding may help promote haemostasis. We compared patient outcomes following fibrinogen concentrate administration or transfusion of allogeneics in CABG patients with decreased platelet function. Methods. Thirty-eight patients with decreased preoperative platelet function in Multiplate aggregometry were included. Patients with bleeding after CPB received either fibrinogen concentrate (guided by the measurement of fibrin clot quality using the FIBTEM thromboelastometric test) or allogeneics. Results. Twenty-nine of 38 patients received haemostatic therapy (bleeding ++ fibrinogen group, n == 10; bleeding ++ allogeneics group, n == 19). Total transfusion (median (interquartile range)) was significantly lower in the bleeding ++ fibrinogen group (0 (0, 3.8) units), compared with the bleeding ++ allogeneics group (6 (5, 8) units, p == 0.0073). Bolus administration of fibrinogen concentrate increased FIBTEM maximum clot firmness from 10.5 (9.3, 11) mm after CPB to 20.5 (20, 21.8) mm at the end of surgery. Postoperative outcomes were similar in both groups. No treatment-related complications were observed after fibrinogen concentrate. Conclusions. In CABG patients with bleeding after CPB, FIBTEM-guided administration of fibrinogen concentrate resulted in overall decreased transfusion, compared with haemostatic therapy with allogeneics. Fibrinogen concentrate administration increased the fibrin clot quality and helped achieve haemostasis. [ABSTRACT FROM AUTHOR]

BACKGROUND: Coagulopathy after cardiopulmonary bypass (CPB) is caused by multiple perturbations in cellular and humoral elements of coagulation. A timely and comprehensive method to evaluate hemostasis would be helpful in the management of bleeding patients after CPB. The assessment of whole blood coagulation using rotation thromboelastometry (ROTEM) was compared to coagulation tests routinely performed during cardiac surgery. STUDY DESIGN AND METHODS: Blood was obtained from 26 patients undergoing CPB surgery at baseline, at 60 minutes on CPB, at the end of CPB, and on admission to intensive care unit. ROTEM tests (extrinsically activated [EXTEM], intrinsically activated [INTEM], specific clot formation [FIBTEM]), prothrombin time, activated partial thromboplastin time, platelet (PLT) count, fibrinogen, prothrombin level, antithrombin level, and thrombin generation (TG) measurement were performed. RESULTS: We observed strong correlations between FIBTEM-amplitude at 10 minutes (A10) and fibrinogen level (r = 0.87; p < 0.001) and between EXTEM/ INTEM-A10 variables and PLT count (r = 0.72 and 0.67, respectively; p < 0.001). Receiver operating characteristic analysis demonstrated that EXTEM-A10 and INTEM-A10 are predictive of thrombocytopenia below 80 × 109/L (area under the curve [AUC], 0.83 and 0.82, respectively), and FIBTEM-A10 was highly predictive of fibrinogen level below 200 mg/dL (AUC, 0.96). There were only weak correlations found between TG peak and clot formation time of EXTEM or INTEM (r = 0.30 and 0.29, respectively; p < 0.05). CONCLUSION: ROTEM variables demonstrated clinically relevant correlations with PLT counts and fibrinogen levels. In particular, decreasing levels of fibrinogen can be quickly determined (<15-20 min) using FIBTEM. [ABSTRACT FROM AUTHOR]

ntifibrinolytic agents have been prophylactically administered to patients undergoing cardiopulmonary bypass (CPB) to reduce postoperative bleeding due to plasmin-mediated coagulation disturbances. After the recent market withdrawal of aprotinin, a potent bovine-derived plasmin inhibitor, two lysine analogs, ε-aminocaproic acid and tranexamic acid are currently available for clinical use. Although the use of aprotinin recently raised major concerns about postoperative thrombosis and organ dysfunctions, there is a paucity of information on the potential complications related to lysine analogs. Using the available preclinical and clinical data, we present current perspectives on the hemostatic mechanism and potential harms of antifbirnolytic therapy related to cardiac surgery. Fibrin formation is the critical step for hemostasis at the site of vascular injury, and localized fibrinolytic activity counterbalances excess fibrin formation which might result in vascular occlusion. Inhibition of the endogenous fibrinolytic system may be associated with thrombotic complications in susceptible organs. It is thus important to understand CPB-related changes in endogenous fibrinolytic proteins (e.g., tissue plasminogen activator (tPA), plasminogen) and antifibrinolytic proteins (e.g., α-antiplasmin). [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]

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]