Antithrombin supplementation attenuates heparin resistance in plasma spiked with Gla-domainless factor Xa S195A in vitro.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Simultaneous supplementation of heparin and antithrombin mitigate GDXa-induced heparin resistance by compensating for the loss of tissue factor pathway inhibitor.

In vitro effects of Gla-domainless factor Xa analog on procoagulant and fibrinolytic pathways in apixaban-treated plasma and whole blood.

BACKGROUND: Andexanet alfa is a Gla-domainless FXa (GDXa) analog used as an antidote to FXa inhibitors. Despite its clinical use, laboratory monitoring for anti-Xa reversal and the effect of andexanet on fibrinolysis has not been explored. We used a GDXa with a serine-to-alanine mutation at position 195 (chymotrypsin numbering) to model the interaction between andexanet and apixaban. METHODS: Six batches of pooled plasma, and whole blood from healthy volunteers were treated with increasing concentrations of apixaban with/without GDXa. Thrombin generation and plasmin generation (TG and PG) were tested in plasma, and whole blood thrombus formation was tested using thromboelastometry or a flow-chamber system. FXa was also tested in isolation for its ability to support plasmin activation with/without apixaban and GDXa. RESULTS: Apixaban (250-800 nM) concentration-dependently decreased the velocity and peak of TG in plasma. Apixaban prolonged the onset of thrombus formation in thromboelastometry and flow-chamber tests. GDXa normalized apixaban-induced delays in TG and whole blood thrombus formation. However, GDXa minimally affected the low PG velocity and peak caused by apixaban at higher concentrations (500-800 nM). FXa promoted plasmin generation independent of fibrin that was inhibited by apixaban at supratherapeutic concentrations. CONCLUSIONS: This study demonstrated the feasibility of assessing coagulation lag time recovery in plasma and whole blood following in vitro apixaban reversal using GDXa, a biosimilar to andexanet. In contrast, GDXa-induced changes in plasmin generation and fibrinolysis were limited in PG and tPA-added ROTEM assays, supporting the endogenous profibrinolytic activity of FXa and its inhibition at elevated apixaban concentrations.

Trends and predictions of perioperative transfusion and venous thromboembolism in hepatectomy using a North American Registry.

BACKGROUND: Studies indicate a link between allogeneic blood transfusion and venous thromboembolism (VTE) post-major surgery. Analyzing trends and predictors of these outcomes after hepatectomy can inform risk management. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was used for a retrospective analysis. Primary outcomes were perioperative red blood cell (RBC) transfusion and VTE events within 30 days of hepatectomy. Seven-year trends and predictors were evaluated. RESULTS: Among 29,131 hepatectomy patients, transfusion rates showed no statistically significant decreasing trends (p = .122) from 2014 to 2020 (18.13%-16.71%), while VTE rates showed a downward trend over the 7 years (p = .021); 17.2% received RBC transfusion, with higher rates in surgeries lasting ≥282 min (median: 220 min). Calculated RBC mass [hematocrit (%) × body weight (kg) × 10-5 × 70/ √ (body mass index/22)] at or below 1.5 L substantially increased transfusion odds. VTE was reported postoperatively in 2.6% of cases more frequently in longer cases involving transfusions. The adjusted odds ratio (aOR) of VTE escalated from the shortest operative time to the longest (3.17; 95% confidence interval [CI], 2.37-4.22). The adjusted odds of VTE doubled for transfused patients compared to non-transfused patients (aOR, 2.19; 95% CI, 1.86-2.57). CONCLUSIONS: Rates of RBC transfusion and VTE rates hepatectomy have minimally changed in the recent years. VTE prevention is challenging in extended surgeries at increased risk of bleeding and RBC transfusions. Patient-level data on coagulation and thromboprophylaxis can potentially refine risk assessment for postoperative VTE.

Survey shows all surgical residents have exposure to robotic surgery yet no formalized curricula exist amongst programs: A Southwest Surgical Congress Survey.

BACKGROUND: Increased robotic surgery exposure during general surgery training occurs at many institutions without a formal education curriculum. Our study evaluates the current state of general surgery robotic training within programs represented by the Southwestern Surgical Congress (SWSC). METHODS: A web-based survey regarding robot-assisted surgery (RAS) and general surgery training was developed and sent to member institutions of the SWSC. General surgery program directors were asked to voluntarily complete the survey. Results were evaluated in aggregate. Descriptive analysis was used. RESULTS: In total, 28 programs responded. All reported resident exposure to RAS during training. Case mix was diverse with exposure to multiple general surgical subspecialties. 89% of programs reported the presence of a formal RAS curriculum, however, only 53% reported recognition of training completion. Case volumes also varied amongst programs with 46% of programs reporting residents logging 21-40 cases and 35% logging more than 40 cases in total. CONCLUSION: Exposure to RAS among SWSC residency programs is ubiquitous, however, there is significant variation between programs in case volumes, case types, and elements of RAS curricula.

Trends and Prediction of Surgical Site Infection After Elective Spine Surgery: An Analysis of the American College of Surgeons National Surgical Quality Improvement Project Database.

Background: Surgical site infection (SSI) is an infrequent but costly complication after elective spine surgery. Identification of important temporal changes and predictive factors may inform targeted prevention efforts. Patients and Methods: A retrospective study of elective spine surgery patients was performed using the National Surgical Quality Improvement Programs (NSQIP) database from 2011 and 2019. Temporal changes in SSI and related factors were examined descriptively. Recursive partitioning and bootstrap forest techniques were used to inform the development of predictive models for SSI. Results: A total of 6,038 (1.66%) of 363,754 patients had an SSI recorded. Peri-operative transfusion and preoperative anemia decreased over the nine-year period, however, obesity and diabetes mellitus increased, whereas the SSI rate remained essentially unchanged. A full model including 15 variables had an area under the curve (AUC) of 0.693 (95% confidence interval [CI], 0.686-0.700) whereas a reduced model with just nine variables had an AUC of 0.690 (95% CI, 0.683-0.697). Adjusted odd ratios (aOR) greater than two were noted for only three variables; a posterior approach (aOR, 2.32; 95% CI, 2.14-2.50), body mass index (BMI) >40 kg/m2 (aOR, 2.63; 95% CI, 2.39-2.90), and surgical duration longer than 350 minutes (aOR, 2.39; 95% CI, 2.14-2.67). Remaining retained variables included albumin <3.5 g/dL, inpatient procedure, peri-operative transfusion, diabetes mellitus (both insulin/non-insulin), anemia, and smoking. Conclusions: Surgical site infection rate remained unchanged over a nine-year period despite the lower rates of allogeneic blood transfusion. Class 3 obesity, long operative times, and a posterior approach mainly for thoracic/lumbar spine procedures seemed more pragmatic, but their predictive performance was only modest in our prediction models for SSI.

Blunt Cerebrovascular Injury in Pediatric Hanging Victims.

INTRODUCTION: Incidence of blunt cerebrovascular injury (BCVI) following hanging in the pediatric population is ill-defined. Current guidelines recommend screening imaging during the initial trauma evaluation. Necessity of screening is questioned given BCVI is considered rare after hanging, especially when asymptomatic. This study aims to elucidate the incidence of BCVI in pediatric hangings and determine the value of radiographic work-up. METHODS: A retrospective cohort study was performed of pediatric hangings reported to the National Trauma Data Bank (NTDB), 2017-2019. Imaging, diagnoses, and findings suggestive of BCVI, such as Glasgow Coma Scale (GCS) ≤8, presence of cervical injury, and soft tissue injury were considered. Statistical analysis was carried out to compare incidence. RESULTS: 197 patients met study criteria, with 179 arriving in the trauma bay with signs of life. BCVI incidence was 5.6% (10 of 179). Computed Tomography Angiography (CTA) of the neck was the only reported screening modality in this data set. A CTA was completed in 46% of the cases. DISCUSSION: BCVI incidence following pediatric hanging is more common than previously thought. Less than half of patients had a CTA reported in this cohort. This may result in an underestimate. Given the potentially devastating consequences of a missed BCVI, the addition of CTA to initial work-up may be worthwhile to evaluate for cervical vascular injury, but further studies into the outcomes of children who do receive prophylactic therapy are needed.

Relationships Between Body Mass Index, Allogeneic Transfusion, and Surgical Site Infection After Knee and Hip Arthroplasty Surgery.

BACKGROUND: Increased body mass index (BMI) is considered as an important factor that affects the need for total knee and hip arthroplasty (TKA/THA) and the rate of perioperative complications. Previous investigations have not fully established the relationship of BMI and perioperative transfusion with surgical site infection (SSI) or the relationship of BMI and perioperative transfusion after TKA or THA. METHODS: The National Surgical Quality Improvement Program database was used to perform a retrospective cohort study involving 333,223 TKA and 41,157 THA cases between 2011 and 2018. Multivariable regression assessed the associations of BMI (5 standard categories) and transfusion with SSI. Odds ratio (OR) of SSI was calculated relative to a normal BMI (18.5-24.9 kg/m 2 ) after adjustment of potential confounding factors. RESULTS: Perioperative transfusion decreased significantly over time for both TKA and THA; however, SSI rates remained steady at just under 1% for TKA and 3% for THA. In TKA, a higher OR for SSI was associated only with a BMI of 40+ (OR, 1.86; 95% confidence interval [CI], 1.60-2.18) compared to a referent BMI. In THA, increased ORs of SSI were seen for all BMI levels above normal and were highest for a BMI 40+ (OR, 3.08; 95% CI, 2.47-3.83). In TKA, ORs of transfusion decreased with increasing BMI and were lowest for a BMI 40+ (OR, 0.51; 95% CI, 0.47-0.54). In THA, ORs of transfusion began to increase slightly in overweight patients, reaching an OR of 1.36 (95% CI, 1.21-1.54) for a BMI 40+. CONCLUSIONS: SSI incidence remained unchanged despite continuous reductions in blood transfusion in TKA and THA patients over 8 years. In TKA, ORs for SSI increased, but ORs for transfusion decreased with increasing BMI above normal. Conversely, in THA, ORs for SSI and transfusion both increased for a BMI 40+, but only OR for transfusion increased in underweight patients. These findings suggest the importance of controlling obesity in reducing SSI following TKA and THA.