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.

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.

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.

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.

Temporal changes and predictors of perioperative blood transfusion in elective spine surgery: a retrospective analysis of a large surgical database.

BACKGROUND: Allogeneic blood transfusion used to be common in spine surgery. Patient blood management has been widely adopted, and it is important to reassess transfusion predictors in contemporary practice. METHODS: A retrospective study of inpatient spine surgery was performed using National Surgical Quality Improvement Program (NSQIP) data from 2011 to 2019. The primary outcome was perioperative transfusion within 72 h of surgery. Multivariable logistic regression and recursive partitioning were used to assess up to 15 variables including patient and surgical data, surgical specialty (orthopaedic surgery vs neurosurgery), and year of surgery. RESULTS: The study population included 251 971 US surgical patients; 6.9% of these patients received perioperative blood transfusion. Perioperative transfusions declined over time with the steepest decline from 2011 to 2015. The greatest reduction was seen among orthopaedic cases where the transfusion rate declined from 16.0% to 8.7% between 2011 and 2015. Eight variables were predictive factors in a reduced model: operative time, preoperative haemoglobin, vertebral level, number of vertebral levels, older age, surgeon specialty, arthrodesis, and year of surgery (area under the curve [AUC]=0.880; 95% confidence interval [CI], 0.878-0.883). Overall, longer operative time (>144 min) and greater numbers of vertebral levels had greater associations with transfusion than surgical specialty after adjustments. Prevalence of anaemia (15%) has not substantially declined. CONCLUSIONS: Perioperative blood transfusion rate in spine surgery has declined over the past decade. The extent and duration of surgery and preoperative haemoglobin level remain important factors associated with increased odds for perioperative blood transfusion.

Automatic implantable cardioverter defibrillator (AICD) within the abdomen as a cause of adhesive small bowel obstruction (ASBO): a case report.

Adhesive small bowel obstruction (ASBO) is commonly caused by intra-abdominal adhesions, usually from prior surgery. Conservative management is the mainstay of treatment, with adhesiolysis required for non-resolving obstruction. An unusual patient presentation of ASBO is presented here, where the cause is proposed as an automatic implantable cardioverter defibrillator (AICD) within the abdomen. Although the patient had several presentations of ASBO successfully treated with conservative management, a non-resolving obstruction required surgical management. At laparotomy, the AICD was found to be in close association with extensive matted adhesions to adjacent small bowel. Adhesiolysis was performed, with the AICD implanted in a subrectus pocket. The patient had an uncomplicated recovery, and at review 6 weeks following the operation was found to have a normal bowel habit with nil further episodes concerning for obstruction. This case highlights the importance of non-classical risk factors being a possible cause of ASBO.

Protocol Duodenal Graft Biopsies Aid Pancreas Graft Surveillance.

BACKGROUND: Histological evaluation of the pancreas graft is usually done on demand resulting in significant delays. This analysis reports on endoscopic protocol duodenal graft biopsies at regular intervals to determine feasibility, safety, and monitoring benefits. METHODS: Protocol duodenal graft biopsies in 27 consecutive pancreas transplants (10 simultaneous pancreas kidney [SPK], 17 pancreas after kidney [PAK]) with a follow-up of a minimum of 12 months were performed at days 14, 30, 90, 180, 360, 430. University of Pittsburgh Medical Center classification for intestinal rejection was used. C4d staining was performed when antibody-mediated rejection was suspected. RESULTS: Overall patient and pancreas graft survival was 100% and 93% at a mean follow-up of 2.8 years. One hundred sixty-seven endoscopic biopsy procedures were performed in 27 grafts without any complication. Biopsies revealed rejection in 3 (30%) SPK recipients and in 15 (82%) of PAK recipients as early as 14 days posttransplant. Two patients underwent PAK retransplantation diagnosed with acute rejection at day 180. All except 1 recipient being treated for rejection, showed histological improvement following antirejection treatment. Following transient treatment success, a total of 3 pancreas grafts were lost for immunological reason. One loss was immediate despite antirejection treatment, 1 secondary to nonresolving rejection at 7 months and the third due to recurrent rejection 15 months posttransplantation. Additionally, biopsies detected vascular (venous thrombosis) and overimmunosuppression (cytomegalovirus infection) complications. CONCLUSIONS: Protocol graft duodenal biopsies detect complications after whole-organ pancreas transplantation, are useful in guiding therapy, and carry potential for improving outcome.