Perioperative Bleeding Research Articles

Effect of fibrinogen replacement therapy on bleeding outcomes and 1-year mortality in patients undergoing thoracic aortic surgery: a retrospective cohort study.

This study aimed to examine the effect of fibrinogen replacement therapy with cryoprecipitate or fibrinogen concentrate on bleeding outcomes and 1-year mortality in patients undergoing thoracic aortic surgery. We retrospectively studied 439 consecutive patients who underwent thoracic aortic surgery with cardiopulmonary bypass between January 1st, 2010 and December 31st, 2019 and identified patients who received cryoprecipitate or fibrinogen concentrate (the fibrinogen replacement group) and those who did not (the control group). Multivariate analyses were performed to examine the associations of fibrinogen replacement therapy with perioperative major bleeding (i.e., excessive hemorrhage or blood transfusion), re-exploration for bleeding, and 1-year mortality. There were 285 patients in the fibrinogen replacement group who received 2.2 ± 1.0g of concentrated fibrinogen amount and 154 patients in the control group. The incidence of major bleeding in the fibrinogen replacement group was less than that in the control group in patients with fibrinogen level < 150mg/dL during cardiopulmonary bypass (49.7% versus 74.6%, p = 0.0007, multivariate odds ratio; 0.33, 95% confidence intervals; 0.12-0.91, p = 0.03), but not in patients with fibrinogen level ≥ 150mg/dL (25.0% versus 29.6%, p = 0.51). No significant difference was found in re-exploration for bleeding (1.0% versus 1.3%, p = 1.00) or 1-year mortality (10.4% versus 5.3%, multivariate Cox proportional-hazard ratio; 1.03, 95% confidence intervals; 0.82-1.31, p = 0.74) between the fibrinogen replacement group and the control group. The results of this study indicate that 2-3g of fibrinogen replacement reduces the incidence of major bleeding in patients with hypofibrinogenemia during cardiopulmonary bypass in thoracic aortic surgery.

The association between preoperative blood calcium and postoperative blood loss in patients undergoing heart valve replacement surgery.

Bleeding after heart valve surgery is a serious clinical challenge. Hypocalcemia has been associated with the extent of bleeding in patients with spontaneous intracerebral hemorrhage. However, the association between blood calcium levels and bleeding extent in heart valve replacement patients has not been clearly established. This study aimed at determining the association between blood calcium levels and perioperative hemorrhage after heart valve replacement therapy. Based on preoperative blood calcium levels, patients were grouped into the hypocalcemia group and normocalcemia group. Postoperative bleeding, blood product use, and complications were monitored during hospitalization. The association between blood calcium levels and major bleeding was determined by multivariable logistic regression models. In the first 12h after surgery, bleeding in hypocalcemia group was significantly larger than that of the normocalcemia group (338 ± 234mL vs 232 ± 96mL; p = .024). The outcome was the same when the overall chest tube output was considered (950 ± 447mL vs 738 ± 220mL; p = .038). The incidence of major bleeding was 65.91% in the hypocalcemia group and 18.97% in the normocalcemia group (p = .001). Postoperative complications in the two groups were similar. After adjusting for multiple covariates, the adjusted odds ratios (OR) for participants in hypocalcemia group was 10.01 (95% CI 3.35-34.82), compared with that in normocalcemia group (p < .001). In patients undergoing heart valve surgery, preoperative blood concentrations of calcium are associated with postoperative blood loss. Hypocalcemia before operation may increase the risk of postoperative bleeding. When patients with valvular heart disease present with hypocalcemia before surgery, prompt intervention may lead to better control of postoperative bleeding.

Efficacy and Safety of Tranexamic Acid for Reduction in Blood Transfusions in Patients Undergoing Major Non-Cardiac Surgeries: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background and Objective: Tranexamic Acid (TXA) is an anti-fibrinolytic agent that is effective in decreasing perioperative bleeding thus subsequently reducing the risk of blood transfusions in cardiac surgeries, however, there is limited data available on patients undergoing major non-cardiac surgeries. The primary objective of this meta-analysis is to elucidate the efficacy and safety of TXA in reducing the risk of blood transfusions in major non-cardiac surgeries where TXA is not standard of care. Method: A comprehensive literature search was carried on PubMed (Medline), EMBASE, CENTRAL (Cochrane Library) and Google Scholar from inception till May 2022. The inclusion criteria were randomized controlled trials (RCTs) in adults (≥18 years) undergoing major non-cardiac surgeries for which TXA was not standard of care. The treatment group included patients receiving perioperative IV(Intravenous) TXA. The control group included placebo, usual-care or active comparator (Aprotinin, EACA(epsilon-aminocaproic acid), rFVIIa(activated recombinant factor), Topical TXA, Oral TXA, batroxobin). Primary outcomes were proportion of patients that received blood transfusion and volume of PRBCs (Packed Red Blood Cells) transfused at the longest follow-up. Review Manager Software (RevMan, version 5.3) was employed for statistical analyses and forest plots were created to visually analyze the results. The Mantel-Haenszel random effect model was applied. Higgins I2 test was used to evaluate heterogeneity across the studies. The bias assessment was carried out via Cochrane risk of Bias tool (Rob-2) and GRADE methodology was utilized to assess the certainty of evidence. Results: A total of 82 RCTs, n=16,638 patients were included (TXA n= 8303 vs Non-TXA n=8335, TXA n=7986 vs Placebo n=7949, TXA n= 317 vs Comparator n=386). The mean age of included patients was 48.2 years and included surgery types were orthopedics, urology, plastic surgery, neurosurgery, general surgery, obstetrics, gynaecology, hepatobiliary and spine surgery. The pooled analysis of proportion of patients that received TXA showed a decreased need of transfusion (RR(Risk Ratio): 0.63, 95% CI;0.54,0.74, I2=75 %, P= <0.00001, low certainty) as compared to placebo or standard care or active comparator, however, the results were limited by significant heterogeneity (variable threshold for transfusion, ). The subgroup analysis according to baseline transfusion rate of 10-19% and ≥20%, trial size(≤50, 51-99,≥100) and risk of bias didn't report any significant difference in overall risk ratio or resolved statistical heterogeneity. TXA also reduces the volume of PRBCs transfused (mean difference)MD: -0.46, 95% CI; -0.85,0.07, I2=98%, P,0.00001, low certainty) and the length of stay in hospital (MD:-0.49, 95% CI;-0.91,-0.18,I2=82%, P= 0.002) as compared to control in patients undergoing major non-cardiac surgeries, however, TXA use was not found to be significantly associated with risk of deep vein thrombosis (RR: 1.05, 95% CI;0.78,1.40,I2=0 %, P= 0.76), pulmonary embolism (RR: 1.18, 95% CI;0.76,1.82,I2=0 %, P= 0.46), stroke (RR: 1.55, 95% CI;0.91,2.65,I2=0 %, P= 0.11), seizure(RR: 1.66, 95% CI;0.64,4.28,I2=0 %, P= 0.30), myocardial infarction (RR: 1.25, 95% CI;0.89,1.74,I2=0%, P= 0.19), all-cause mortality (RR: 1.02, 95% CI;0.77,1.36,I2=0 %, P= 0.88) and need for re-operation due to hemorrhage (RR: 0.80, 95% CI;0.58,1.11,I2=0 %, P= 0.18).Subgroup analysis based on trial size, baseline risk of transfusion and risk of bias didn't resolve statistical heterogeneity for the volume of PRBCs transfused. Conclusion: Perioperative TXA administration reduces the risk of PRBC transfusion needs for patients undergoing major non-cardiac surgeries for which TXA is not standard of care as compared to placebo, standard care or other active comparators. However, the results are limited by significant heterogeneity and low quality of evidence. TXA group was also found to be associated with decreased length of stay in hospital. However, there was no significant increased risk of any major thrombotic event. There is need of further high quality prospective RCTs to provide conclusive evidence. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

A comparative high-resolution physicochemical analysis of commercially available fibrin sealants: Impact of sealant osmolality on biological performance.

Fibrin sealants are well-established components of the surgical toolbox, especially in procedures that harbor a high risk of perioperative bleeding. Their widespread use as hemostats, sealants or tissue-adhesives in various surgical settings has shown that the choice of the appropriate sealant system affects the clinical outcome. While many studies have compared the hemostatic efficiency of fibrin sealants to that of other natural or synthetic sealants, there is still limited data on how subtle differences in fibrin sealant formulations relate to their biological performance. Here, we performed an in-depth physicochemical and biological characterization of the two most commonly used fibrin sealants in the US and Europe: TISSEEL™ ("FS") and VISTASEAL™/VERASEAL™ ("FS+Osm"). Our chemical analyses demonstrated differences between the two sealants, with lower fibrinogen concentrations and supraphysiological osmolality in the FS+Osm formulation. Rheological testing revealed FS clots have greater clot stiffness, which strongly correlated with network density. Ultrastructural analysis by scanning electron microscopy revealed differences between FS and FS+Osm fibrin networks, the latter characterized by a largely amorphous hydrogel structure in contrast to the physiological fibrillar network of FS. Cytocompatibility experiments with human fibroblasts seeded on FS and FS+Osm fibrin networks, or cultured in presence of sealant extracts, revealed that FS+Osm induced apoptosis, which was not observed with FS. Although differential sealant osmolality and amounts of fibrinogen, as well as the presence of Factor XIII or additives such as antifibrinolytics, may explain the mechanical and structural differences observed between the two fibrin sealants, none of these substances are known to cause apoptosis at the respective concentrations in the sealant formulation. We thus conclude that hyper osmolality in the FS+Osm formulation is the primary trigger of apoptosis-a mechanism that should be evaluated in more detail, as it may affect the cellular wound healing response in situ.

Association of liver dysfunction with outcomes after cardiac surgery-a meta-analysis.

To perform a meta-analysis of studies reporting outcomes in patients with liver dysfunction addressed by the model of end-stage liver disease (MELD) and Child-Turcotte-Pugh (CTP) scores undergoing cardiac surgery. A systematic literature search was conducted to identify contemporary studies reporting short- and long-term outcomes in patients with liver dysfunction compared to patients with no or mild liver dysfunction undergoing cardiac surgery (stratified in high and low score group based on the study cutoffs). Primary outcome was perioperative mortality. Secondary outcomes were perioperative neurological events, prolonged ventilation, sepsis, bleeding and/or need for transfusion, acute kidney injury, and long-term mortality. A total of 33 studies with 48,891 patients were included. Compared with the low score group, being in the high score group was associated with significantly higher risk of perioperative mortality (Odds ratio, OR 3.72, 95% confidence interval, CI 2.75-5.03, P < 0.001). High score group was also associated with a significantly higher rate of perioperative neurological events (OR 1.49, CI 1.30-1.71, P < 0.001), prolonged ventilation (OR 2.45, CI 1.94-3.09, P < 0.001), sepsis (OR 3.88, CI 2.07-7.26, P < 0.001), bleeding and/or need for transfusion (OR 1.95, CI 1.43-2.64, P < 0.001), acute kidney injury (OR 3.84, CI 2.12-6.98, P < 0.001), and long-term mortality (incidence risk ratio, IRR:, 1.29, CI 1.14-1.46, P < 0.001). The analysis suggests that liver dysfunction in patients undergoing cardiac surgery is independently associated with higher risk of short and long-term mortality and also with an increased occurrence of various perioperative adverse events.

Comparison of Clopidogrel, Prasugrel and Ticagrelor Response of Patients by PFA-100-Innovance Test Results.

Devices such as stents and flow diverters require the use of safe and fast antiplatelet therapy. We aimed to compare the responses to clopidogrel, prasugrel, and ticagrelor by assessing the Platelet Function Analysis (PFA-100)-Innovance test results of patients undergoing endovascular stenting to determine their resistance rates. Sixty-one women and 55 men, aged 18-87years, were included in this study. Patients were divided into three groups: clopidogrel treatment, prasugrel treatment, and ticagrelor treatment. The systemic diseases of the patients, especially hypertension and diabetes, were recorded. The test results were evaluated according to the results for the collagen/epinephrine (COL-EPI), collagen/adenosine (COL-ADP), and P2Y results. The PFA-100-Innovance results for COL-EPI and P2Y were significantly higher for patients treated with prasugrel and ticagrelor compared with patients treated with clopidogrel (COL-EPI, p = 0.001; P2Y, p = 0.001). Clopidogrel resistance was identified in 31 patients (26.7%), and prasugrel resistance was identified in 4 patients (3.4%). Ticagrelor resistance was not detected. Therefore, 30.1% of patients were classified as drug-resistant. Perioperative bleeding was not detected in any patient. Hypertension was the most common disease recorded for patients being treated for cerebral aneurysm, and diabetes was the most common disease recorded for patients who underwent peripheral artery stenting (p = 0.002). Potent antiplatelet agents, such as prasugrel and ticagrelor, have a low rate of resistance but are associated with an increased bleeding risk. Thus, the choice of a suitable drug during the treatment window remains a critical factor when determining treatment strategies.

ODP324 Internal Carotid aneurysm inside a pituitary macroadenoma: case study and literature review

Abstract BACKGROUND: Coexisting pituitary adenoma (PA) and intracranial aneurysms (IA) is relatively frequent. However, the finding of an aneurysm inside a PA is extremely rare. We report a patient with pituitary macroadenoma with an embedded internal carotid artery (ICA) aneurysm, who presented with anterior hypopituitarism. CLINICAL CASE: 73 y. o. black female presented after a fall secondary to orthostastic hypotension. In the ER her BP was 78/50 mmHg, HR 76/min sinus rhythm. She reported fatigue, presyncope, and 20 lbs weight loss in the preceding 3 months. CT head without contrast showed a sellar mass. Pituitary MRI confirmed a 20×24×29 mm sellar mass consistent with a macroadenoma extending laterally to both cavernous sinuses with bilateral encasement of ICAs, superiorly elevating optic chiasm, and mild extension to the left Meckel's cave. The study also incidentally showed a &amp;gt; 5 mm ICA aneurysm embedded within the macroadenoma. Diagnostic cerebral angiogram demonstrates a medially directed left superior hypophyseal ICA aneurysm measuring 5.4×4. 0 mm with a 3.5 mm neck. The patient denied headaches, peripheral vision loss, or polyuria. On examination her weight was 154 lbs, height 5'6", normal visual field testing, and no neurologic deficits. Endocrine testing was consistent with anterior hypopituitarism: ACTH 17 pg/mL (10-48), Cortisol 4.7 mcg/dL (6-18.4), TSH 1.4 mIU/L (0.4- 4. 0), FT4 0.7 (0.7-1.9 ng/dL), IGF1 7 ng/mL (55-162), Prolactin 38.3 ng/mL (4.8- 23.3), and FSH 6.6 IU/mL (20-138). Clinical improvement followed hydrocortisone and levothyroxine replacement. Patient was discharged home with a plan for outpatient endocrine follow up and subsequent endovascular intervention. Unfortunately, she presented a few weeks later with pulmonary embolism, for which she was treated with Eliquis. Given high risk of bleeding, the plan for endovascular embolization was postponed. Patient was educated about sick day rules and is set for routine endocrine visit and periodic MRI surveillance of the macroadenoma. DISCUSSION: intracranial aneurysms appear to occur more frequently in association with PAs than among the general patient population. In 2 cohort of patients with PA, 5.4-7.3% had coexisting IAs, the majority of which are outside the pituitary region. However, the presence of an aneurysm embedded within a PA, as in our case, is very rare, and most are discovered by accident. In such cases, although spontaneous aneurysm rupture or pituitary apoplexy is extremely rare, misdiagnosis of the embedded aneurysm can potentially result in catastrophic outcomes if it is not appropriately recognized and addressed prior to pituitary surgery. Cerebral angiography with embolization or coiling of the aneurysm prior to hypophysectomy can decrease the risk of perioperative rupture or bleeding. In our case, given the risk of bleeding while on anticoagulation therapy, the plan for endovascular intervention was postponed. Presentation: No date and time listed

Clinical analysis of three-dimensional surgical planning system for guiding robot-assisted selective artery clamping partial nephrectomy in completely endophytic renal tumor

Objective: To examine the safety and feasibility of three-dimensional (3D) surgical planning system for guiding robot-assisted selective artery clamping partial nephrectomy (RASPN) in completely endophytic renal tumor. Methods: Clinical data of 32 patients who suffered from completely endophytic renal tumor and underwent RASPN associated with 3D surgical planning system in Department of Urology, Sun Yat-Sen University Cancer Center from November 2018 to August 2021 were analyzed retrospectively. There were 21 males and 11 females, with the age (M (IQR)] of 45.0 (17.5) years (range: 30 to 68 years). Fifteen tumors were located on the left and 17 on the right. Maximum tumor diameter, R.E.N.A.L. Score and preoperative estimated glomerular filtration rate (eGFR) were 27.5 (13.0) mm (range: 14 to 50 mm), 10.0 (1.8) (range: 7 to 11), and 105.5 (15.7) ml·min-1·(1.73 m2)-1 (range: 71.1 to 124.8 ml·min-1·(1.73 m2)-1), respectively. The 3D reconstruction before RASPN was performed in all patients to formulate surgical planning, mainly including stereo localization of renal mass, confirmation of tumor feeding artery, and injury prediction of collecting system or vessel via "2 mm distance method" defined as probable damage of renal pelvis/calyx and artery/vein when these tissues were less than 2 mm away from tumor. Results: Totally 32 patients successfully underwent RASPN guided by 3D surgical planning system, without conversion to open operation or radical nephrectomy. Rapid location of tumor and selective clamping of artery were achieved in all cases and no one encountered global ischemia, with branch occlusion time of 24.5 (15.4) min (range: 12 to 60 min) and coincidence rate of 95.0% (57/60) between planned and actual clamping vessels. The sensitivity and specificity of 2 mm distance method for predicting the injury of collecting system were 13/15 and 17/17, respectively. The operating time of 185 (48) minuetes (range: 76 to 295 minutes) and estimated blood loss of 200 (350) ml (range: 20 to 800 ml) were observed, without intraoperative transfusion case. There was one patient performed with renal vein repair. Clavien-Dindo postoperative grade Ⅱ and Ⅲa bleeding complications occurred in 2 cases, and no postoperative urinary fistula was found. The length of hospitalization was 3 (0) days (range: 2 to 10 days). The pathological diagnosis demonstrated 4 chromophobe cell carcinomas and 2 angiomyolipomas, besides 26 clear cell carcinomas including one positive surgical margin. The postoperative latest eGFR was 103.9(18.5) ml·min-1·(1.73 m2)-1 (range: 75.8 to 122.3 ml·min-1·(1.73 m2)-1) and no tumor recurrence or metastasis was detected during the follow-up time of 15.4 (13.9) months (range: 3 to 35 months). Conclusion: For RASPN in completely endophytic renal tumor, 3D surgical planning system is contributed to determining mass position, defining tumor feeding artery, and predicting collecting system/vessel injury, which benefited precise tumor resection, postoperative renal function preservation, and perioperative urinary fistula and bleeding complication decrease.

The effect of anticoagulation therapy on perioperative bleeding risk in patients undergoing heart transplantation

The effect of anticoagulation therapy on perioperative bleeding risk in patients undergoing heart transplantation

Are Viscoelastic Tests Clinically Useful to Identify Platelet-Dependent Bleeding in High-Risk Cardiac Surgery Patients?

Postoperative use of platelet function testing to rule out microvascular bleeding due to platelet dysfunction after cardiac surgery still lacks strong reference data and reliable cutoff values, yielding a clinically adequate sensitivity and specificity. The present study aims to investigate the performance of two different point-of-care viscoelastic devices and platelet aggregometry in expressing surgery-dependent platelet dysfunction and anticipating postoperative major bleeding in a cohort of high-risk patients. Prospective cohort study of 50 adult patients who were on antiplatelet drugs discontinued for no more than 7 days (clopidogrel and prasugrel) or 5 days (ticagrelor) undergoing cardiac surgery with cardiopulmonary bypass (CPB). Coagulation and platelet function testing, including QUANTRA, ROTEM, and Multiplate, were assessed preoperatively and postoperatively. Chest drain blood loss was measured in the first 12 postoperative hours. Perioperative bleeding was assessed using a modified version of the Universal Definition of Perioperative Bleeding (UDPB) in cardiac surgery, modified to not consider anemia-correcting packed red cells transfusions in the absence of bleeding >600 mL/12 h. Major bleeding was identified as UDPB class II or higher. Multiplate adenosine diphosphate (ADPtest) was significantly ( P = .001) reduced after CPB, whereas TRAPtest was not. The platelet component (PC) as extrapolated by ROTEM data (EXTEM MCF-FIBTEM MCF) was unchanged after CPB, while the A10 PC (PC at 10 minutes) was significantly ( P = .001) reduced. The QUANTRA platelet contribution to clot stiffness (PCS) was significantly ( P = .001) reduced, as well. At the ROC analysis for the predictive ability of the post-CPB platelet function testing, the best discrimination was obtained by the QUANTRA PCS, with an area under the curve (AUC) (95% confidence interval [CI]) of 0.80 (0.66-0.91), P = .001, followed by the ROTEM A10 PC with AUC (95% CI) of 0.75 (0.51-0.99), P = .004, and PC with AUC (95% CI) of 0.74 (0.50-0.99), P = .009. The Multiplate ADPtest had an AUC (95% CI) of 0.67 (0.42-0.91), and the TRAPtest had an AUC (95% CI) of 0.62 (0.37-0.86). The cutoff values identified were 13 hPa for the QUANTRA PCS, 40 mm for the ROTEM A10, and 48.5 mm for the ROTEM PC, with negative predictive values of 84%, 81%, and 86%, respectively, and positive predictive values of 55%, 53%, and 69%, respectively. QUANTRA PCS, ROTEM A10 PC, and Multiplate ADPtest showed a significant decrease after CPB, whereas ROTEM PC and Multiplate TRAPtest did not. Major bleeding was predicted with a moderate to good discrimination by the post-CPB viscoelastic tests (PCS, PC, and A10 PC).

Removal of Apixaban during Emergency Cardiac Surgery Using Hemoadsorption with a Porous Polymer Bead Sorbent.

Background: Patients on direct oral anticoagulants are at high risk of perioperative bleeding complications. We analyzed the results of intraoperative hemoadsorption (HA) in patients undergoing cardiac surgery who were also on concurrent therapy with apixaban. Methods: we included 25 consecutive patients on apixaban who underwent cardiac surgery with the use of cardio-pulmonary bypass (CPB) at three sites. The first 12 patients underwent surgery without hemoadsorption (controls), while the next 13 consecutive patients were operated with the Cytosorb® (Princeton, NJ, USA) device integrated into the CPB circuit (HA group). The primary outcome was perioperative bleeding assessed by the Bleeding Academic Research Consortium (BARC) definition and secondary outcomes included 24 h chest-tube-drainage (CTD) and need for 1-deamino-8-d-arginine-vasopressin (desmopressin (DDAVP)) administration to achieve hemostasis. Results: Preoperative mean daily dose of apixaban was higher in the HA group (8.5 ± 2.4 vs. 5.6 ± 2.2 mg, p = 0.005), while time since last apixaban dose was longer in the controls (1.3 ± 0.9 vs. 0.6 ± 1.2 days, p < 0.001). No BARC-4 bleeding events and no repeat-thoracotomies occurred in the HA group compared with 3 and 1, respectively, in the controls. Postoperative 24 h CTD volume was significantly lower in the HA group (510 ± 152 vs. 893 ± 579 mL, p = 0.03) and there was no need for DDAVP compared to controls, who received an average of 10 ± 13.6 mg (p = 0.01). Conclusions: In patients on apixaban undergoing emergent cardiac surgery, the intraoperative use of hemoadsorption was feasible and safe. Compared to patients operated on without hemoadsorption, BARC-4 bleeding complications did not occur and the need for 24 h CTD and DDAVP was significantly lower.

Risk stratification of perioperative myocardial infarction/injury following noncardiac surgery in high risk patients

Abstract Background Perioperative myocardial infarction/injury (PMI) screening is increasingly recommended by current guidelines. PMI is often caused by type 2 myocardial infarction, and risk stratification tools for these patients are lacking. Purpose To derive and internally validate a risk prognostication model for PMI of likely type 2 infarction (lT2MI) Methods We included consecutive high-risk patients undergoing noncardiac surgery into this prospective multicenter study. Patients received a systematic routine PMI screening with pre- and postoperative measurement of cardiac troponin (cTn). PMI was prospectively defined as an absolute increase of cTn above the preoperative value. PMI etiology was centrally adjudicated and hierarchically classified by 2 independent physicians based on all clinical information obtained during index hospitalization and selected those with lT2MI for further analyses. To identify risk factors and allow risk stratification in lT2MI, we prespecified that only perioperative variables should be included into the model. We constructed a logistic binary regression model for major adverse cardiac events (MACE) within 120 days, including variables available at time of clinical evaluation: additional symptoms or ECG-criteria required according to the Universal Definition of Myocardial Infarction, absolute increase in cTn (categorized according to level of absolute increase 1–&amp;lt;2 times the 99th percentile, ≥2 to &amp;lt;4 times, and ≥4 times), urgency of procedure, perioperative bleeding (drop in haemoglobin &amp;gt;30g/L or deemed relevant for PMI by adjudicator), and ESC/ESA surgery risk (low, medium, high risk of cardiac events). Variables were omitted from the final model if the p-value was &amp;gt;0.05. Variable levels with similar odds ratios were grouped for simplification of the prognostic model. We constructed a calibration plot and calculated the area under the receiver-operating characteristics curve (AUC) and Brier Score. For internal validation we calculated the predicted probabilities and classified patients into low-risk (predicted event rate &amp;lt;10%), intermediate range (10–20%), and high-risk (&amp;gt;20%), and compared the predicted with the observed event rate. Results PMI occurred in 1016/7754 patients (13.1%) of which 750/1016 (73.8%) were adjudicated as lT2MI. MACE within 120 days occurred in 118/750 (15.7%) patients. The initial and final logistic prognostic model for 120-day MACE or death is shown in the table. Internal validation found a good fit of predicted and observed event rate following bootstrapping of 1000 iterations (Figure 1), a good AUC of 0.71 and a Brier score of 0.12. Conclusion The derived risk prognostication model for PMI of lT2MI can aid in the stratification of patients and support clinical decision making following noncardiac surgery. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Swiss National Science FoundationSwiss Heart Foundation

EFFICACY, EFFECTIVENESS, AND SAFETY OF PLASMA-DERIVED BLOOD COAGULATION FACTOR X CONCENTRATE FOR THE TREATMENT OF HEREDITARY FACTOR X DEFICIENCY: A SYSTEMATIC REVIEW

Hereditary factor X deficiency (FXD) leads to bleeding episodes that vary in intensity depending on the level of factor X in the blood. A novel plasma-derived blood coagulation factor X concentrate (Coagadex ® ; pdFX) was developed for use in patients with this disease and it is available in Brazil. To analyze the efficacy, effectiveness, and safety of pdFX in patients with hereditary FXD. A systematic search (PROSPERO approval: CRD42022303062) was conducted in accordance with the Cochrane search methods, using the following electronic databases: Embase, MEDLINE via PubMed, Cochrane Central Register of Controlled Trials, and Latin American and Caribbean Health Sciences Literature, as well as clinical trials databases such as ClinicalTrials.gov and the EU Clinical Trials Register , to identify studies that included patients of any age, both sexes, with any type of severity of FXD. Two reviewers independently screened references, selected the studies, extracted the data, and assessed the risk of bias using the ROBINS-I tool. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. A total of four studies involving 30 patients were included. Overall, the risk of bias was judged as serious. Across studies, pdFX was used to prevent bleeds (Ten01 and Ten02 studies), for perioperative bleeding management (Ten03), or for routine prophylaxis and on-demand treatment (Ten05). All studies included patients with severe or moderate severity. Only two participants with mild severity were included (Ten03). The efficacy of pdFX was rated “excellent”by the majority of investigators. No patients developed thrombotic events or factor X inhibitors, and no deaths or other serious adverse events were reported in any of the studies. The best available evidence was provided by three single-arm trials and one retrospective study with compassionate use, with an overall serious risk of bias. None of the included studies compared pdFX with the current treatment: prothrombin-complex concentrate or fresh-frozen plasma. No validated tool was used to evaluate the effectiveness of the intervention regarding the bleeding episodes, instead, the investigators rated them subjectively. The included studies were performed in different populations, using pdFX for different purposes. Overall, the results of this systematic review reveals several weaknesses in the currently available evidence. This systematic review showed that the currently available data regarding pdFX for the treatment of hereditary FXD is very uncertain, mainly due to the lack of comparator arms and the overall serious risk of bias in the included studies. Therefore, we cannot draw any conclusions as to whether factor X concentrate is associated with a higher incidence of AEs or whether it can impact on the incidence and severity of bleeding events compared to other treatments.

Initial experiences with the use of covered stents in endovascular treatment of aortoiliac stenoocclusive diseases

Introduction: Treatment for complex aortoiliac stenoocclusive disease traditionally is open surgical repair. Endovascular approach is associated with less perioperative stress for the patient, and is a reasonable solution. Covered stent implantation is an alternative treatment option in this patient population even in the case of aortobiiliac or aortobifemoral bypasses. Objective: Assessing outcomes of aortoiliac covered stent implantation at our vascular center. Method: We retrospectively analysed the data of 36 prospectively registered, consecutive patients who underwent aortoiliac covered stent implantations at our department between the 1th November 2019 and 30th September 2021. Medical records, perioperative complications, preoperative and postoperative Rutherford stages and ankle-brachial index were recorded. One-year survival and primary patency as primary endpoints were presented on Kaplan-Meier curve. Our secondary endpoints were change of the ankle-brachial index and Rutherford stage, and the incidence of the major amputation. Results: 36 patients were included in the study. Mean follow-up time was 12 +/- 6.9 months. TASC C-D aortoiliac lesions were the indication of the procedures in 72.2% (n = 26). Patients had critical limb ischaemia in 44% (n = 16). In 64% (n = 23), interventions were performed via percutaneous puncture. In-hospital stay was 5 +/- 7 days. Perioperative bleeding and reoperation occured in 4 (11.1%) and 6 (16.6%) cases, respectively. Perioperative mortality was zero. The one-year survival and primary patency were 94.3% and 91.4%, respectively. The postoperative Rutherford stage (3 [2] vs. 1 [1]; p < 0.001) and ankle-brachial index (0.4 [0.55] vs. 1 [0.4]; p < 0.001) improved significantly compared to the preoperative ones. Unplanned major amputation was not performed. Conclusion: Significant clinical improvement with low perioperative mortality, acceptable morbidity and high one-year primary patency and survival can be obtained by the use of covered stents in the treatment of aortoiliac stenoocclusive disease. This procedure can be an alternative to open surgical repair.

The Supply Side of Coagulation: Fibrinogen and Bleeding in Liver Disease and Transplantation.

In this issue of Transplantation, Carrier et al1 describe a study that assesses the effect of preoperative fibrinogen levels on perioperative bleeding and outcomes. In 613 patients with end-stage liver disease who underwent liver transplantation between 2008 and 2019, preoperative low fibrinogen levels were associated with more blood loss but not worse 1-y survival in univariate and multivariate statistical models. This effect was most prominent when fibrinogen levels were below 3 g/L before surgery. In any model of coagulation, fibrinogen is the substrate required to create an effective clot and provide hemostasis. Like most components of hemostasis, fibrinogen is synthesized by the liver and reduced in severe liver disease. Additionally, and maybe more commonly‚ dysfibrinogenemia occurs in liver disease resulting in defects of the fibrinogen structure with undetermined effects on hemostasis.2 The coagulation abnormalities associated with liver disease result in dysbalanced hemostasis that can cause impaired clot formation or excessive thrombosis. Conventional coagulation tests cannot detect this dysbalanced hemostasis‚ as they measure only (a part of) the procoagulant side of hemostasis. Viscoelastic testing, now routinely used in many transplant centers‚ may provide a better assessment of all aspects of clot formation by creating a visual representation of changes in the viscosity of blood when a clot forms. Viscoelastic testing can guide transfusion management in many clinical scenarios‚ including liver transplantation‚ but possibly, more importantly, allows us to identify patients who are hypercoagulable even when the conventional coagulation tests are abnormally high. The results of Carrier et al suggest that low preoperative fibrinogen levels may be an indicator that a patient is at risk for increased intraoperative bleeding. This may be particularly useful if perioperative viscoelastic testing is not used or available as with the study center. This risk of bleeding increased when fibrinogen levels were below 3 g/L before surgery, a level that is far higher than what has traditionally been considered a concerning threshold. Most experts and societies, for example, the review on perioperative coagulation management in liver transplant recipients by Bezinover et al here in Transplantation in 2018,3 recommend fibrinogen concentrate and/or cryoprecipitate transfusion for fibrinogen levels below 1.5 to 2 g/L. Although raising new questions, the present study does not provide enough evidence to change this recommendation at this time. An association with bleeding (even in a multivariate model) does not necessarily mean that replacing fibrinogen with levels over 3 g/L will reduce the risk of bleeding. The assumption is that fibrinogen levels that are below 3 g/L before surgery may decrease more during transplantation to a level that actually impairs hemostasis. Excessive transfusion of cryoprecipitate (and, to a lesser degree, fibrinogen concentrates) is not without risk and may increase the risk of thromboembolic complications.4 The results by Carrier et al are raising new questions about fibrinogen thresholds and may provide the impetus for future (prospective) studies but should not necessarily change our current management. The Centre Hospitalier de L’Universite de Montreal (CHUM) has demonstrated for many years with great success what can be achieved with a concerted effort to reduce blood transfusion5: More than 70% of the patients in the present study did not receive any red blood cell transfusion at all! The center undertakes a number of interventions to achieve these remarkable results. For example, over 50% of the patients in this study underwent phlebotomy at the beginning of surgery. I am not aware of any other center that implemented such a vigorous and successful program to reduce blood transplantation. Unfortunately, this also limits the generalizability of the present study (and reduces the statistical power of the study). Furthermore, because viscoelastic testing was not used in this study, we do not know if lower preoperative fibrinogen levels result in deficient fibrinogen contribution to clot strength later during surgery (assessed, for example, using fibrinogen assays such as FIBTEM with rotational thromboelastometry, ROTEM). In summary, Carrier et al provide important insight into the role of fibrinogen in achieving hemostasis during and good outcomes after liver transplantation. Their data encourage us to check for fibrinogen levels whenever we measure conventional or viscoelastic coagulation tests and design future randomized trials of fibrinogen replacement in liver transplantation.

Preoperative Fibrinogen Level and Bleeding in Liver Transplantation for End-stage Liver Disease: A Cohort Study.

Liver transplantation is a high-risk surgery associated with important perioperative bleeding and transfusion needs. Uncertainties remain on the association between preoperative fibrinogen level and bleeding in this population. We conducted a cohort study that included all consecutive adult patients undergoing a liver transplantation for end-stage liver disease in 1 center. We analyzed the association between the preoperative fibrinogen level and bleeding-related outcomes. Our primary outcome was intraoperative blood loss, and our secondary outcomes were estimated perioperative blood loss, intraoperative and perioperative red blood cell transfusions, reinterventions for bleeding and 1-y graft and patient survival. We estimated linear regression models and marginal risk models adjusted for all important potential confounders. We used restricted cubic splines to explore potential nonlinear associations and reported dose-response curves. We included 613 patients. We observed that a lower fibrinogen level was associated with a higher intraoperative blood loss, a higher estimated perioperative blood loss and a higher risk of intraoperative and perioperative red blood cell transfusions (nonlinear effects). Based on an exploratory analysis of the dose-response curves, these effects were observed below a threshold value of 3 g/L for these outcomes. We did not observe any association between preoperative fibrinogen level and reinterventions, 1-y graft survival or 1-y patient survival. This study suggests that a lower fibrinogen level is associated with bleeding in liver transplantation. The present results may help improving the selection of patients for further studies on preoperative fibrinogen administration in liver transplant recipients with end-stage liver disease.

Factor eight inhibiting bypass activity for refractory bleeding in acute type A aortic dissection repair: A propensity-matched analysis.

Perioperative bleeding and transfusion have been associated with adverse outcomes after cardiac surgery. The use of factor eight inhibiting bypass activity (FEIBA) in managing bleeding after repair of acute Stanford type A aortic dissection (ATAAD) has not previously been evaluated. We report our experience in utilizing FEIBA in ATAAD repair. A retrospective review was undertaken of all consecutive patients who underwent repair of ATAAD between July 2014 and December 2019. Patients were divided into two groups, dependent upon whether or not they received FEIBA intraoperatively: "FEIBA" (n= 112) versus "no FEIBA" (n= 119). From this, 53 propensity-matched pairs of patients were analyzed with respect to transfusion requirements and short-term clinical outcomes. Thirty-day mortality for the entire cohort was 11.7% (27 deaths), not significantly different between patient groups. Those patients who received FEIBA demonstrated reduced transfusion requirements for all types of blood products in the first 48 h after surgery as compared with the "no FEIBA" cases, including red blood cells, platelets, plasma, and cryoprecipitate (p< .0001). There was no significant difference in major postoperative morbidity between the two groups. The FEIBA cohort did not demonstrate an increased incidence of thrombotic complications (stroke, deep venous thrombosis, pulmonary thromboembolism). When used as rescue therapy for refractory bleeding following repair of ATAAD, FEIBA appears to be effective in decreasing postoperative transfusion requirements whilst not negatively impacting clinical outcomes. These findings should prompt further investigation and validation via larger, multi-center, randomized trials.

Development and validation of a model for surveillance of postoperative bleeding complications using structured electronic health records data

BackgroundPostoperative bleeding complications surveillance is done primarily through manual chart review. The purpose of this study was to develop and validate a detection model for postoperative bleeding complications using structured electronic health records data. MethodsPatients who underwent operations at 1 of 5 hospitals within our local health system between 2013 and 2019 and whose complications were reported by the American College of Surgeons National Surgical Quality Improvement Program were included. Electronic health records data were linked to American College of Surgeons National Surgical Quality Improvement Program data using personal health identifiers. Electronic health records predictors included diagnosis codes mapped to PheCodes, procedure names, and medications within 30 days after surgery. We defined bleeding events as the transfusion of red blood cell components within 30 days after surgery. The knockoff filter and the lasso were used to develop a model in a training set of operations from January 2013 to March 2017. Performance of each model was tested in a held-out data set of patients who underwent operations from March 2017 to October 2019. ResultsA total of 30,639 patients were included; 1,112 patients (3.6%) had a bleeding event. Eight predictor variables were selected by the knockoff filter. When applied to the test set, specificity was 94%, sensitivity was 94%, area under the curve was 0.97, and accuracy was 93%. Calibration was consistent in lower predicted risk patients, whereas the model slightly overpredicted risk in high-risk patients. ConclusionWe created a parsimonious, accurate model for identifying patients with bleeding complications. This model can be used to augment manual chart review for surveillance and reporting of perioperative bleeding complications, enabling inclusion of all surgeries in quality improvement efforts.

Preoperative treatment with clopidogrel and ticagrelor on bleeding complications in off-pump coronary artery bypass grafting

BackgroundDual antiplatelet therapy (DAPT) consisting of acetylsalicylic acid and clopidogrel or ticagrelor increased bleeding complications in patients undergoing coronary artery bypass grafting (CABG). We aimed to compare the bleeding risks between patients treated with clopidogrel and ticagrelor preoperatively and investigate the influence of discontinuation of clopidogrel and ticagrelor on bleeding risk in off-pump CABG (OPCABG). MethodsWe conducted a retrospective analysis of patients with DAPT who underwent OPCABG. The propensity score matching was performed given the baseline differences between clopidogrel- and ticagrelor-treated patients. Bleeding was assessed by chest tube drainage volume and universal definition of perioperative bleeding. ResultsThis study included 836 patients. Five hundred and fifty patients were treated with clopidogrel and 286 patients treated with ticagrelor before surgery. After matching, 275 patients treated with clopidogrel and 275 patients with ticagrelor were included. There were no significant differences in bleeding between clopidogrel and ticagrelor group. Patients who discontinued clopidogrel before surgery <3 d had a higher risk of severe perioperative bleeding compared with those who discontinued ≥5 d (16.4 % vs. 5.0 %, P = 0.045). By contrast, the risk of severe perioperative bleeding was comparable among patients who discontinued ticagrelor for <3 d, ≥3–5 d and ≥5 d preoperatively (16.2 % vs. 9.1 % vs. 10.1 %, P = 0.317). The multivariable analysis confirmed that time since discontinuation (<3 d vs. ≥5 d: OR = 2.732, 95 % CI: 1.332–5.605, P = 0.006) but not the types of P2Y12 receptor antagonist was an independent predictor for severe perioperative bleeding. ConclusionsThere were no significant differences in severe perioperative bleeding between clopidogrel and ticagrelor groups. Discontinuation of clopidogrel <3 d before OPCABG increased the risk of severe perioperative bleeding.

Bypassing the post-anaesthesia care unit after elective hip and knee arthroplasty: a prospective cohort safety study.

Following knee and hip arthroplasty, transfer to a recovery area immediately following surgery and before going to ward might be unnecessary in low-risk patients. Avoiding the recovery area in this way could allow for more targeted use of resources for higher risk patients, which may improve operating theatre flow and productivity. A prospective single-centre cohort study on the safety of criteria for bypassing the post-anaesthesia care unit in elective hip and knee arthroplasty was designed. Criteria were: ASA physical status < 3; peri-operative bleeding < 500 ml; low postoperative discharge-score (modified Aldrete-score); and an uncomplicated surgical and neuraxial anaesthesia procedure. The primary outcome was the number of patients in need of secondary readmission to the post-anaesthesia care unit. Events within the first 24 postoperative hours were recorded, along with readmission and complication rates. A total of 696 patients were included, with 287 (41%) undergoing total hip arthroplasty, 274 (39%) undergoing total knee arthroplasty and 135 (19%) undergoing unicompartmental knee-arthroplasty. Of these, 207 (44%) bypassed the post-anaesthesia care unit. Patients all received multimodal analgesia without peripheral nerve blockade. Only one patient in the ward group required secondary readmission to the post-anaesthesia care unit. Within 24 h, 151 events were reported, with 41 (27%) in the ward group and 110 (73%) in the post-anaesthesia care unit group. Two events in each group occurred within 2 hours of surgery. No complications were attributed to bypassing the post-anaesthesia care unit. The use of simple pragmatic criteria for bypassing the post-anaesthesia care unit for patients undergoing knee and hip arthroplasty with spinal anaesthesia is possible and associated with significant reduction of post-anaesthesia care unit admission and without apparent safety issues. Confirmation is needed from other studies and external validity should be interpreted cautiously in centres with different peri-operative regimens, organisational and staffing structures.