Blood Management Research Articles

Cardiac Surgery in Jehovah's Witnesses: 329 Consecutive Cases

This study aimed to describe the outcome of Jehovah's Witnesses (JWs) undergoing cardiac surgery at the authors' center. A single-center retrospective cohort study. At a cardiovascular center with a tertiary intensive care unit (ICU) and specific experience with cardiac surgery in JWs. The institutional protocol describing all perioperative care in JWs has been applied for 21 years. All JWs undergoing cardiac surgery in the Amphia Hospital from January 1, 2001 to January 31, 2022. None. The study cohort comprised 329 JWs undergoing cardiac surgery. Twenty-three patients (6.8%) were treated preoperatively for anemia. The mean European System for Cardiac Operative Risk Evaluation score was 5.1 (range 0-18). Coronary artery bypass grafting (53.2%) was performed most frequently, followed by aortic valve replacement (13.4%). Mean preoperative hemoglobin levels were 14.5 g/dL (range 9.8-18.5 g/dL), dropping to 11.6 g/dL (range 6.6-15.6 g/dL) at hospital discharge. Mean blood loss was 439 ± 349 mL in the first 12 hours postsurgery. Maximum mean postoperative troponin levels were 431 ± 424 ng/L. Resternotomy and postoperative myocardial infarction occurred in 3.6% and 4.2% of patients, respectively. On average, patients had an ICU stay of 1.4 ± 1.8 days and a hospital stay of 6.8 ± 4.2 days. Hospital mortality was 0.6% and was related to cardiac failure. This study demonstrated that cardiac surgery in JWs is safe when adhering to a strict perioperative patient blood management protocol.

An enhanced recovery programme significantly improves postoperative outcomes after surgical aortic valve replacement.

Evidence regarding the benefits of an enhanced recovery after cardiac surgery (ERACS) programme is lacking. The aim of this study was to analyse the impact of a systematic standardized ERACS programme for patients undergoing isolated elective surgical aortic valve replacement (SAVR) for aortic stenosis in terms of hospital mortality and morbidity, patient blood management and length of stay. Patients undergoing isolated elective SAVR for aortic stenosis between 2015 and 2020 were identified from our database (n = 941). The standardized systematic ERACS programme was implemented in November 2018. Propensity score matching indicated that 259 patients would receive standard perioperative care (control group) and 259 patients would receive the ERACS programme (ERACS group). The primary outcome was hospital mortality. The secondary outcomes were hospital morbidity, patient blood management and length of stay. Both groups had similar hospital mortality rates (0.4%). The ERACS group had a significantly lower troponin I peak level (P < 0.001), a larger proportion of improved perioperative left ventricular ejection fractions (P = 0.001), a lower incidence of bronchopneumonia (P = 0.030), a larger proportion of patients with mechanical ventilation <6 h (P < 0.001), a lower incidence of delirium (P = 0.028) and less acute renal failure (P = 0.013). The ERACS group had a significantly lower rate of red blood cell transfusions (P = 0.002). The intensive care unit stay was significantly shorter in the ERACS group than in the control group (P = 0.039). The standardized systematic ERACS programme significantly improved postoperative outcomes and should become the reference for the perioperative care pathway for patients undergoing SAVR.

Patient Blood Management in Liver Transplant—A Concise Review

Transfusion of blood products in orthotopic liver transplantation (OLT) significantly increases post-transplant morbidity and mortality and is associated with reduced graft survival. Based on these results, an active effort to prevent and minimize blood transfusion is required. Patient blood management is a revolutionary approach defined as a patient-centered, systematic, evidence-based approach to improve patient outcomes by managing and preserving a patient's own blood while promoting patient safety and empowerment. This approach is based on three pillars of treatment: (1) detecting and correcting anemia and thrombocytopenia, (2) minimizing iatrogenic blood loss, detecting, and correcting coagulopathy, and (3) harnessing and increasing anemia tolerance. This review emphasizes the importance of the three-pillar nine-field matrix of patient blood management to improve patient outcomes in liver transplant recipients.

Etablierung eines Patient Blood Managements als Behandlungsstandard

Anaemia is among the most common co-morbidity in surgical patients. However, it often remains unrecognized and untreated, which results in an increased requirement for allogeneic blood products and complications. Patient Blood Management offers patient-centred and evidence-based therapies and preventive measures for anaemia. Patient Blood Management is composed of 3 main pillars: pre-operative anaemia management, blood loss reduction and the rational use of allogeneic blood products. The World Health Organization demands the implementation of Patient Blood Management measures since 2010. However, a comprehensive implementation of Patient Blood Management as a standard-of-care is still not achieved. Here, we describe the need for a comprehensive Patient Blood Management implementation and highlight several specific Patient Blood Management measures.

Bloodless surgery in urologic oncology: A review of hematologic, anesthetic, and surgical considerations.

The urologic oncology patient who refuses blood transfusion can present unique challenges in perioperative blood management. Since blood loss and associated transfusion can be expected in many complex urologic oncology surgeries, a multidisciplinary approach may be required for optimal outcomes. Through collaboration with the hematologist, anesthesiologist, and urologist, various techniques can be employed in the perioperative phases to minimize blood loss and the need for transfusion. We review the risks and benefits of these techniques and offer recommendations specific to the urologic oncology patient.

Con: Artificial Intelligence–Derived Algorithms to Guide Perioperative Blood Management Decision Making

Artificial intelligence has the potential to improve the care that is given to patients; however, the predictive models created are only as good as the base data used in their design. Perioperative blood management presents a complex clinical conundrum in which significant variability and the unstructured nature of the required data make it difficult to develop precise prediction models. There is a potential need for training clinicians to ensure they can interrogate the system and override when errors occur. Current systems created to predict perioperative blood transfusion are not generalizable across clinical settings, and there is a considerable cost implication required to research and develop artificial intelligence systems that would disadvantage resource-poor health systems. In addition, a lack of strong regulation currently means it is difficult to prevent bias.

Haematological Trends and Transfusion during Adult Extracorporeal Membrane Oxygenation: A Single Centre Study.

Patient demographics, haematological and coagulation parameters, plasma haemoglobin and fibrinogen concentrations, platelet count, the international normalised ratio (INR), the activated partial thromboplastin time (APTT), and blood product transfusion data from 138 patients who received ECMO in a single high-volume centre were analysed. Ninety-two patients received venoarterial (VA) ECMO and 46 patients received venovenous (VV) ECMO. The median (IQR) duration of VA, and VV ECMO was 8 (5-13) days and 13 (8-23) days, respectively. There were significant reductions in haemoglobin, the platelet count, and the fibrinogen concentration upon initiation of ECMO. On average, over time, patients on VV ECMO had platelet counts 44 × 109/L higher than those on VA ECMO (p ≤ 0.001). Fibrinogen and APTT did not vary significantly based on the mode of ECMO (p = 0.55 and p = 0.072, respectively). A platelet count < 50 × 109/L or a fibrinogen level < 1.8 g/L was associated with 50% chance of PRBC transfusion, regardless of the ECMO type, and packed red blood cell (PRBC) transfusion was more common with VA ECMO. APTT was predictive of the transfusion requirement, and the decrement in APTT was discriminatory between VVECMO survivors and nonsurvivors. ECMO support is associated with reductions in haemoglobin, platelet count, and fibrinogen. Patients supported with VA ECMO are more likely to receive a PRBC transfusion compared to those on VV ECMO. Thrombocytopaenia, hypofibrinogenaemia, and anticoagulation effect the likelihood of requiring PRBC transfusion. Further research is needed to define optimal blood management during ECMO, including appropriate transfusion triggers and the anticoagulation intensity.

A patient blood management perspective on Anemia in the obese patient journey

Obesity and anemia are increasing prevalence around the globe. They can interplay and are both associated with high morbidity and poorer clinical outcomes. Inflammation and iron deficiency are important contributors to anemia in obese patients. Furthermore, obesity surgery can trigger high blood loss, increased demand for blood transfusions and long-term nutrient deficiency. Patient blood management programs have been crucial in improving patients' clinical results whilst minimizing costs in many different settings, such as orthopedic surgery, cardiovascular surgery, pregnancy and intensive care unit patients. In this mini-review, we will discuss applications of patient blood management principles in caring of obese individuals during the patient journey.

A novel predictive model of perioperative blood transfusion requirement in tuberculous spondylitis patientsundergoing posterior decompression and instrumentation.

Retrospective study. The aim of this study was to develop apredictive model for determining perioperative blood transfusion in tuberculous spondylitis patients undergoingposterior decompression and instrumentation. Tuberculous spondylitis is a common infection found in the spine. This condition may result in the need of surgical treatment, especially when there is a delay in diagnosis with inadequate antituberculosis drug treatment. The procedure results in high amount of bleeding on many occasions, leading to the higher rate of intraoperative transfusion.We develop a predictive model that can be used to determine blood transfusion requirement in spinal tuberculosis surgery. We reviewed the medical records of 83 tuberculous spondylitis patients who underwent posterior decompression and instrumentation. The clinical characteristics of the patients were analyzed using bivariate and multivariate regression test. The impact and strength of these variables was assessed to predict the probability of intraoperative red blood cell transfusion presence based on unstandardized beta, standard error, receiver operating characteristic, and confluence of sensitivity and specificity curve analyses. Furthermore, validation of this newly proposed predictive scoring system was performed using a set of 45 patients. The factors that significantly affect the need of blood transfusion during posterior spondylitis tuberculosis surgery were BMI (p = 0.005), pre-operative Hb (p < 0.001), number of affected segments (p = 0.042), and duration of surgery (p = 0.003). Our predictive model showed good sensitivity and specificity values based on a large area under the curve (0.913) and strong Pearson's r testing (correlation coefficient of 0.752). Validation set also resulted a large area under the curve (0.905) and strong correlation coefficient of 0.713. BMI, pre-operative Hb, number of affected segments, and duration of surgery became the significant factors which correlated to the presence of red blood cell transfusion in patients undergoing posterior spondylitis tuberculosis surgery. This predictive scoring system can be used to further adjust blood matching and inventory, determine intraoperative blood management, and ensure the safety of surgery in a comprehensive manner.

Enhanced Recovery after Surgery in patients undergoing total joint arthroplasty: A retrospective study.

Enhanced Recovery after Surgery (ERAS) protocol has been developed and practiced for various surgical procedures to improve outcomes in the postoperative period. We hereby present our experience of ERAS for a large cohort of patients undergoing total joint arthroplasty (TJA). We implemented the ERAS program at The Third Affiliated Hospital of Shanghai University from January 2020 and retrospectively compared outcomes of patients undergoing total knee or hip arthroplasty before and after the implementation of the program. ERAS protocol consisted of the use of patient education, blood management, multimodal analgesia, antiemetics, shorter fasting time, no patient-controlled analgesia, early physical therapy, and reduced use of catheters and drains. There were 94 patients in the study group (ERAS) and 113 patients in the control group (non-ERAS). We noted a statistically significant reduction in the incidence of postoperative nausea/vomiting, lowered pain scores, reduced length of hospital stay and better functional outcomes with both total knee and hip arthroplasties in our study cohort. ERAS protocol can bae effectively implemented for patients undergoing TJA. The use of ERAS leads to better postoperative outcomes and shortened hospital stay.

Application of cardiovascular interventions to decrease blood loss during hepatectomy: a systematic review and meta-analysis

BackgroundPerioperative bleeding and allogeneic blood transfusion are generally thought to affect the outcomes of patients. This meta-analysis aimed to determine the benefits and risks of several cardiovascular interventions in patients undergoing hepatectomy.MethodsIn this systematic review and meta-analysis, randomised controlled trials (RCTs) were searched in the Cochrane Library, Medline, Embase, and Web of Science to February 02, 2023. RCTs focused on cardiovascular interventions aimed at reducing blood loss or blood transfusion requirements during hepatectomy were included. The primary outcomes were perioperative blood loss amount, number of patients requiring allogeneic blood transfusion and overall occurrence of postoperative complications. The secondary outcomes were operating time, perioperative mortality rate, postoperative liver and kidney function and length of hospital stay.ResultsSeventeen RCTs were included in the analysis. A total of 841 patients who underwent hepatectomy in 10 trials were included in the comparative analysis between low central venous pressure (CVP) and control groups. The forest plots showed a low operative bleeding volume [(mean difference (MD): -409.75 mL, 95% confidence intervals (CI) -616.56 to -202.94, P < 0.001], reduced blood transfusion rate [risk ratio (RR): 0.47, 95% CI 0.34 to 0.65, P < 0.001], shortened operating time (MD: -13.42 min, 95% CI -22.59 to -4.26, P = 0.004), and fewer postoperative complications (RR: 0.76, 95% CI 0.58 to 0.99, P = 0.04) in the low CVP group than in the control group. Five and two trials compared the following interventions, respectively: ‘acute normovolaemic haemodilution (ANH) vs control’ and ‘autologous blood donation vs control’. ANH and autologous blood donation could not reduce the blood loss amount but greatly decreased the number of patients requiring allogeneic blood transfusion. No benefits were found in the rate of mortality and length of postoperative hospital stay in any of the comparisons.ConclusionLowering the CVP seems to be effective and safe in adult patients undergoing hepatectomy. ANH and autologous blood donation should be used as a part of blood management for suitable patients in certain circumstances.Trial registrationPROSPERO, CRD42022314061.

Perioperative management of pediatric patients undergoing juvenile angiofibroma resection. A case series and educational review highlighting patient blood management.

Juvenile nasopharyngeal angiofibromas are one of the most enigmatic, bloody tumors encountered by otorhinolarygnologists, head and neck surgeons, neurosurgeons, and anesthesiologists. Juvenile nasopharyngeal angiofibromas are rare, benign, highly vascular tumors with a propensity towards aggressive local invasion. Surgery, open or endoscopic, to remove the growth is the primary treatment of choice for Juvenile nasopharyngeal angiofibromas. Historically, surgical resection was associated with massive, rapid blood loss, traditionally managed by blood product transfusion and deliberate hypotension. Preventative management employing multimodal blood conservation strategies should be an essential standard of perioperative care for patients with Juvenile nasopharyngeal angiofibromas. We describe a contemporary and comprehensive approach in the management of patients with high grade Juvenile nasopharyngeal angiofibromas. This includes surgical strategies such as preemptive external carotid artery embolization, endoscopic surgical approach, and staged operations, as well as anesthetic strategies including antifibrinolytic therapy and acute normovolemic hemodilution. These surgeries, once synonymous with massive transfusion, may potentially be performed without allogeneic blood transfusion, or deliberate hypotension. Using a case series, the authors introduce a contemporary approach to multimodal, multidisciplinary blood conservation strategies for Juvenile nasopharyngeal angiofibromas surgery. Here in the authors report on an updated contemporary perioperative clinical approach to patients with Juvenile nasopharyngeal angiofibromas. From an anesthetic perspective, we describe the successful use of normal hemodynamic goals, restrictive transfusion strategy, antifibrinolytic therapy, autologous normovolemic hemodilution, and early extubation in the care of three adolescent males with highly invasive tumors. We demonstrate that new surgical and anesthetic strategies have yielded a significant decrease in intraoperative blood loss and eliminated the need for transfusion of autologous red blood cells, which enable improved outcomes. The perioperative approach to elective surgery for Juvenile nasopharyngeal angiofibromas management is presented from a multidisciplinary patient blood management perspective.

Preoperative hemoglobin levels, extended resections and the body mass index influence survival after pancreaticoduodenectomy

The negative influence of perioperative transfusion of packed red blood cells on the prognosis of various malignancies is the focus of recent research interest. The development of a propensity score for the prediction of perioperative transfusion of packed red blood cells (pRBCs) and the identification of independent risk factors for survival, that can either be known prior to or during surgery in patients undergoing pancreaticoduodenectomy for pancreatic head cancer are the two objectives of this study. Logistic regression analyses and Cox regression modeling were used to identify independent risk factors for perioperative transfusion of pRBCs and to determine individual risk factors for patient survival. A total of 101 adult patients who underwent surgery between 01/01/2016 and 12/31/2020 were investigated in a single-center retrospective analysis. Preoperative hemoglobin levels (OR: 0.472, 95%-CI: 0.312-0.663, p < 0.001) and extended resections (OR: 4.720, 95%-CI: 1.819-13.296, p = 0.001) were identified as independent risk factors for perioperative transfusion of pRBCs, enabling the prediction of pRBC transfusion with high sensitivity and specificity (AUROC: 0.790). The logit of the derived propensity model for the transfusion of pRBCs (HR: 9.231, 95%CI: 3.083-28.118, p < 0.001) and preoperative Body Mass Index (BMI) (HR, 0.925; 95%-CI: 0.870-0.981, p = 0.008) were independent risk factors for survival. Low preoperative hemoglobin levels, low BMI values, and extended resections are significant risk factors for survival that can be known and thus potentially be influenced prior to or during surgery. Patient blood management programs and prehabilitation programs should strive to increase preoperative hemoglobin levels and improve preoperative malnutrition.

"The Role of Plasma and Platelet Transfusion in Patient Blood Management – A Narrative Review"

Patient blood management (PBM) has been defined as the timely application of evidence-based medical and surgical concepts designed to maintain hemoglobin concentration, optimize hemostasis, and minimize blood loss in an effort to improve patient outcome.

Project S.T.O.P (Stop the Over-ordering of Platelets): An initiative to reduce platelet wastages for pediatric open-heart surgeries

IntroductionDue to a national policy change in the management of unused platelet units from September 2018, there was a drastic increase in the number of platelet units wasted in our institution. MethodsUsing Quality Improvement (QI) tools, platelet wastages from pediatric heart surgeries was identified as a priority area to work on. An intervention based on the creation of ‘Order Sets’ for pediatric open-heart surgeries was implemented, standardizing standby platelet orders based on type of surgery and patient weight. ResultsThis intervention led to a dramatic improvement in the number of platelets ordered on standby, and consequently a decrease in platelet wastage from 47.6% to 16.9% for pediatric open-heart surgeries, without any reported adverse events. ConclusionWith the creation of Order Sets and continuous education, it was possible to eradicate the practice of requesting unnecessary standby platelets for surgeries. This is an effective patient blood management (PBM) strategy resulting in a significant decrease in platelet wastage rate and substantial cost savings.

Perioperative Iron Deficiency in Patients Scheduled for Major Elective Surgeries: A French Prospective Multicenter Cross-Sectional Study.

The management of perioperative iron deficiency is a component of the concept of patient blood management. The objective of this study was to update French data on the prevalence of iron deficiency in patients scheduled for major surgery. The CARENFER PBM study was a prospective cross-sectional study in 46 centers specialized in orthopedic, cardiac, urologic/abdominal, or gynecological surgery. The primary end point was the prevalence of iron deficiency at the time of surgery (D-1/D0) defined as serum ferritin <100 µg/L and/or transferrin saturation (TSAT) <20%. A total of 1494 patients (mean age, 65.7 years; women, 49.3%) were included from July 20, 2021 to January 3, 2022. The prevalence of iron deficiency in the 1494 patients at D-1/D0 was 47.0% (95% confidence interval [CI], 44.5-49.5). At 30 days after surgery, the prevalence of iron deficiency was 45.0% (95% CI, 42.0-48.0) in the 1085 patients with available data. The percentage of patients with anemia and/or iron deficiency increased from 53.6% at D-1/D0 to 71.3% at D30 (P < .0001), mainly due to the increase of patients with both anemia and iron deficiency (from 12.2% at D-1/D0 to 32.4% at D30; P < .0001). However, a treatment of anemia and/or iron deficiency was administered preoperatively to only 7.7% of patients and postoperatively to 21.7% (intravenous iron, 14.2%). Iron deficiency was present in half of patients scheduled for major surgery. However, few treatments to correct iron deficiency were implemented preoperatively or postoperatively. There is an urgent need for action to improve these outcomes, including better patient blood management.

Blood Transfusions and Adverse Events after Colorectal Surgery: A Propensity-Score-Matched Analysis of a Hen–Egg Issue

Blood transfusions are considered a risk factor for adverse outcomes after colorectal surgery. However, it is still unclear if they are the cause (the hen) or the consequence (the egg) of adverse events. A prospective database of 4529 colorectal resections gathered over a 12-month period in 76 Italian surgical units (the iCral3 study), reporting patient-, disease-, and procedure-related variables, together with 60-day adverse events, was retrospectively analyzed identifying a subgroup of 304 cases (6.7%) that received intra- and/or postoperative blood transfusions (IPBTs). The endpoints considered were overall and major morbidity (OM and MM, respectively), anastomotic leakage (AL), and mortality (M) rates. After the exclusion of 336 patients who underwent neo-adjuvant treatments, 4193 (92.6%) cases were analyzed through a 1:1 propensity score matching model including 22 covariates. Two well-balanced groups of 275 patients each were obtained: group A, presence of IPBT, and group B, absence of IPBT. Group A vs. group B showed a significantly higher risk of overall morbidity (154 (56%) vs. 84 (31%) events; OR 3.07; 95%CI 2.13-4.43; p = 0.001), major morbidity (59 (21%) vs. 13 (4.7%) events; OR 6.06; 95%CI 3.17-11.6; p = 0.001), and anastomotic leakage (31 (11.3%) vs. 8 (2.9%) events; OR 4.72; 95%CI 2.09-10.66; p = 0.0002). No significant difference was recorded between the two groups concerning the risk of mortality. The original subpopulation of 304 patients that received IPBT was further analyzed considering three variables: appropriateness of BT according to liberal transfusion thresholds, BT following any hemorrhagic and/or major adverse event, and major adverse event following BT without any previous hemorrhagic adverse event. Inappropriate BT was administered in more than a quarter of cases, without any significant influence on any endpoint. The majority of BT was administered after a hemorrhagic or a major adverse event, with significantly higher rates of MM and AL. Finally, a major adverse event followed BT in a minority (4.3%) of cases, with significantly higher MM, AL, and M rates. In conclusion, although the majority of IPBT was administered with the consequence of hemorrhage and/or major adverse events (the egg), after adjustment accounting for 22 covariates, IPBT still resulted in a definite source of a higher risk of major morbidity and anastomotic leakage rates after colorectal surgery (the hen), calling urgent attention to the implementation of patient blood management programs.

Patient Blood Management, Anemia, and Transfusion Optimization Across Surgical Specialties.

Patient blood management (PBM) is a systematic, evidence-based approach to improve patient outcomes by managing and preserving a patient's own blood and minimizing allogenic transfusion need and risk. According to the PBM approach, the goals of perioperative anemia management include early diagnosis, targeted treatment, blood conservation, restrictive transfusion except in cases of acute and massive hemorrhage, and ongoing quality assurance and research efforts to advance overall blood health.

Intensivtherapie in der Herzchirurgie – alles anders?

With approximately 100000 operations performed in Germany per year, cardiac surgery is among the surgical specialties that require intensive care tratment most frequently. Although all therapeutic aspects of ICU treatment are of high importance among cardiac surgery patients, there is a focus on hemodynamics with the overarching goal of sufficient oxygen delivery. Patients undergoing cardiac surgery are particularily prone to hemodynamic instability and low cardiac output syndrome, potentially culminating into cardiogenic shock. This article presents an overview of essential elements of intensive care medicine in cardiac surgery, paying special attention to hemodynamic monitoring, low cardiac output syndrome, inotropy, cardiac arrhyhmia, perioperative myocardial infarction, and patient blood management.

Response to: Association of Intraoperative Red Blood Cell Transfusions With Venous Thromboembolism and Adverse Outcomes After Cardiac Surgery.

We are grateful for the interest and comments of Butt et al1 with regard to our recently published study.2 First, Butt et al1 noted that the overall exposure rate to intraoperative packed red blood cells (PRBCs) was 17.8% in our study compared to the reported rate of 12.8% to 60.3% in previous studies in similar patients. They then speculated that the relatively lower rate of intraoperative PRBC transfusion observed in our study was due to our decision to label missing information on intraoperative PRBC transfusion as “no transfusion.” In support of their argument, they cited a retrospective study of 8141 patients from 10 centers who had cardiac surgery between 2011 and 2014; these patients underwent either isolated coronary artery bypass grafting (CABG) surgery or aortic valve replacement, and Butt et al1 did not cite the risk-adjusted rate for intraoperative PRBC transfusion, which was found to be 4% to 59%.3 Thus, our reported rate of 17.8% is likely reflective of the more contemporary and average national rate of intraoperative PRBC transfusion for isolated CABG surgery. Furthermore, Butt et al1 highlighted that labeling missing data for intraoperative PRBC transfusions as “no transfusion” as justified in the methodology section of our manuscript, and omission of any postoperative transfusion before any hospital-acquired venous thromboembolic (HA-VTE) complications might have biased the association between intraoperative PRBC transfusion and HA-VTE complications. To address this, we performed a sensitivity analysis which indicated that after removing patients with missing data for intraoperative PRBC transfusion the association between intraoperative PRBC transfusion and HA-VTE remained (odds ratios [ORs] for 1, 2, 3, and ≥4 units of PRBC versus none: 1.16 [1.09 to 1.23], 1.19 [1.12 to 1.26], 1.59 [1.49 to 1.68], 1.49 [1.40 to 1.58]). Postoperative transfusion before any HA-VTE complications was not collected by the Society of Thoracic Surgeons Adult Cardiac Surgery Database and was not available for analysis. Second, Butt et al1 also indicated that a causality relationship between intraoperative PRBC transfusion and HA-VTE complications was not supported by the lower odds of HA-VTE complications in women. To address this comment, we reiterate the following: i) given the retrospective nature of our study it was not meant to definitively ascertain a causality, but rather reinforce a previously described association between intraoperative PRBC transfusion and HA-VTE complications in a large-scale national registry; ii) our propensity score-weighted, and covariate-adjusted analysis including adjusting for sex indicated that intraoperative PRBC transfusion was independently associated with HA-VTE complications after isolated CABG surgery; iii) only a small proportion of patients had missing data for height (0.03%) and weight (0.02%), and thus, the calculated body mass index (BMI) was observed in nearly all patients (missing, 0.03%). Therefore, our conditional imputation for 0.03% of the missing BMI is highly unlikely that it may have impacted the association of BMI and intraoperative PRBC transfusion in the development of the propensity score. We agree with Butt et al1 that it would have been potentially valuable to study the impact of geographic location on our selected patient- and procedure-related characteristics, but this information was not available through the participant user file research mechanism via which our study was approved. Third, we agree with the comment that delayed thromboprophylaxis during a prolonged hospital length of stay may also exacerbate HA-VTE complications independently or in combination with intraoperative and postoperative PRBC transfusions. As indicated by Butt and colleagues1 the Society of Thoracic Surgeons Adult Cardiac Surgery Database does not capture data on delayed thromboprophylaxis during a prolonged hospital length of stay, and thus we were not able to study its respective association with prolonged length of stay. Butt et al1 speculate that our approach of implementing a propensity score-weighted method using matching inverse probability of treatment weighting to account for potential confounding of the association between intraoperative PRBC transfusion and our outcomes may have been impacted by handling of extreme weights.4 To address the possibility of residual confounding, we considered the evidence for causality (E value),5 which is considered as an alternative approach to sensitivity analyses for potential unmeasured confounding, and were able to demonstrate that there was a low potential for unmeasured confounding significantly influencing the association between intraoperative PRBC transfusion and our primary outcome of HA-VTE. Finally, we agree with Butt et al1 that there is a need to better predict HA-VTE. We also strongly believe that there is a potentially unmet need for current and future “studies to explore interventions aimed at improving perioperative anemia and blood management while maintaining appropriate postoperative thromboprophylaxis, thereby significantly decreasing the need for PRBC transfusions in this setting and potentially decreasing the incidence of postoperative venous thromboembolism after cardiac surgery.”2