Low Preoperative Fibrinogen Research Articles

Development of machine learning models to predict perioperative blood transfusion in hip surgery

BackgroundAllogeneic Blood transfusion is common in hip surgery but is associated with increased morbidity. Accurate prediction of transfusion risk is necessary for minimizing blood product waste and preoperative decision-making. The study aimed to develop machine learning models for predicting perioperative blood transfusion in hip surgery and identify significant risk factors.MethodsData of patients undergoing hip surgery between January 2013 and October 2021 in the Peking Union Medical College Hospital were collected to train and test predictive models. The primary outcome was perioperative red blood cell (RBC) transfusion within 72 h of surgery. Fourteen machine learning algorithms were established to predict blood transfusion risk incorporating patient demographic characteristics, preoperative laboratory tests, and surgical information. Discrimination, calibration, and decision curve analysis were used to evaluate machine learning models. SHapley Additive exPlanations (SHAP) was performed to interpret models.ResultsIn this study, 2431 hip surgeries were included. The Ridge Classifier performed the best with an AUC = 0.85 (95% CI, 0.81 to 0.88) and a Brier score = 0.21. Patient-related risk factors included lower preoperative hemoglobin, American Society of Anesthesiologists (ASA) Physical Status > 2, anemia, lower preoperative fibrinogen, and lower preoperative albumin. Surgery-related risk factors included longer operation time, total hip arthroplasty, and autotransfusion.ConclusionsThe machine learning model developed in this study achieved high predictive performance using available variables for perioperative blood transfusion in hip surgery. The predictors identified could be helpful for risk stratification, preoperative optimization, and outcomes improvement.

Risk factors for lymphorrhea and lymphocele after radical prostatectomy: a retrospective case-control study.

To investigate the risk factors for postoperative lymphorrhea or/and lymphocele (PLL) in patients undergoing radical prostatectomy (RP). The clinical data of 606 patients were retrospectively collected. The receiver operating characteristic (ROC) curve was utilized to identify the optimal cutoff value. Multivariable logistic regression analysis was used to screen the independent predictors of PLL. Univariate analysis showed that nine factors differed between the PLL and non-PLL group. Multivariable logistic regression analysis showed that low preoperative fibrinogen level, extraperitoneal surgery, robot-assisted laparoscopic radical prostatectomy (RALRP), and hypoalbuminemia were risk factors and the use of fibrin glue was a protective factor. Correlation analysis showed that the scope of LN dissection (LND) and number of lymph nodes (LNs) dissected were positively correlated with PLL in the extraperitoneal approach, but were not significantly correlated with PLL in the transperitoneal approach. The use of fibrin glue was negatively associated with PLL in the overall procedure and the extraperitoneal approach, but not significantly so in the transperitoneal approach. Comparison of LNs clearance between the two surgical approaches revealed that the extent of LND and number of LNs dissected in the extraperitoneal approach were less than in the transperitoneal approach. During RALRP, more attention should be paid to fully clotting the broken end of lymphatic vessels. The use of fibrin glue could reduce the probability of PLL. The extent of LND or number of LNs dissected were positively correlated with PLL in the extraperitoneal approach.

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.

Post-operative uric acid: a predictor for 30-days mortality of acute type A aortic dissection repair

BackgroundHyperuricemia is associated with aortic dissection and cardiovascular diseases. The implication of high serum uric acid (UA) level after acute aortic dissection repair remains unknown. The aim of this study is to explore the role of peri-operative serum UA level in predicting 30-days mortality with acute type A aortic dissection (AAAD) patients, who underwent surgery.MethodsThis study retrospectively enrolled 209 consecutive patients with AAAD, who underwent surgery in Xiangya Hospital from 2017 to 2020. Post-operative laboratory examinations were measured within 24 h after surgery. Univariate analysis and logistic regression analysis were used for predictor finding.Results209 consecutive AAAD patients were included, 14.3% (n = 30) were dead within 30 days after surgery. By univariate analysis, we found AAAD repair patients with 30-days mortality had a higher prevalence of cerebral malperfusion, lower pre-operative fibrinogen, longer cardiopulmonary bypass and aortic crossclamp time, and higher post-operative day 1 (POD1) creatinine and urea levels. Both pre-operative (433.80 ± 152.59 vs. 373.46 ± 108.31 mmol/L, p = 0.038) and POD1 (559.78 ± 162.23 vs. 391.29 ± 145.19 mmol/L, p < 0.001) UA level were higher in mortality group than in survival group. In regression model, only cerebral malperfusion (OR, 7.938, 95% CI 1.252–50.323; p = 0.028) and POD1 UA level (OR, 2.562; 95% CI 1.635–4.014; p < 0.001) were independent predictors of 30-days mortality in AAAD repair patients. According to the ROC curve, the POD1 UA level provided positive value for 30-days mortality in AAAD repair patients with 0.799 areas under the curve. The optimum cutoff value selected by ROC curve was 500.15 mmol/L, with a sensitivity of 65% and a specificity of 86%.ConclusionPre- and post-operative hyperuricemia are potentially associated with worsened outcomes in AAAD surgery patients. The POD1 UA level has a predictive role in 30-days mortality in AAAD repair patients.

Combination of preoperative fibrinogen and D-dimer as a prognostic indicator in pancreatic ductal adenocarcinoma patients undergoing R0 resection.

BACKGROUNDPatients with malignant tumors frequently exhibit hyperactivation of the coagulation system and secondary increased fibrinolytic activity. Fibrinogen and D-dimer are common indicators that are crucial in the coagulation/fibrinolysis system. Both indicators have been verified to have predictive value in the overall survival (OS) of many patients with solid malignancies.AIMTo explore the prognostic significance of fibrinogen combined with D-dimer in pancreatic ductal adenocarcinoma (PDAC) patients undergoing radical R0 resection.METHODSWe retrospectively analyzed the clinical data of 282 patients with PDAC undergoing radical R0 resection in the Cancer Hospital, Chinese Academy of Medical Sciences, between January 2010 and December 2019. The surv_cutpoint function of R language was used to determine the optimal cutoff values of the preoperative fibrinogen concentration and preoperative D-dimer concentration. Enrolled patients were further divided into the any-high group (high preoperative fibrinogen concentration and/or high preoperative D-dimer concentration) and the low-low group (low preoperative fibrinogen and D-dimer concentrations) according to the optimal cutoff values.RESULTSThe optimal cutoff values of the preoperative fibrinogen concentration and preoperative D-dimer concentration were 3.31 g/L and 0.53 mg/L, respectively. Furthermore, multivariate Cox regression analysis showed that the preoperative fibrinogen concentration (HR: 1.603, 95%CI: 1.201-2.140, P = 0.001) and preoperative D-dimer concentration (HR: 1.355, 95%CI: 1.019-1.801, P = 0.036) exhibited obvious correlations with the OS of PDAC patients undergoing radical R0 resection. A prognostic analysis was further performed based on the subgroup results by using fibrinogen combined with D-dimer. The median OS duration of the low-low group (31.17 mo) was significantly longer than that of the any-high group (15.43 mo). Additionally, multivariate Cox regression analysis revealed that the degree of differentiation (P < 0.001), lymph node metastasis (HR: 0.663, 95%CI: 0.497-0.883, P = 0.005), preoperative CA19-9 level (HR: 1.699, 95%CI: 1.258-2.293, P = 0.001), adjuvant therapy (HR: 1.582, 95%CI: 1.202-2.081, P = 0.001) and preoperative combined grouping (HR: 2.397, 95%CI: 1.723-3.335, P < 0.001) were independent predictors of OS in PDAC patients undergoing radical R0 resection.CONCLUSIONPreoperative fibrinogen combined with D-dimer plays a predictive role in OS, and low preoperative fibrinogen and D-dimer concentrations can indicate prolonged OS in PDAC patients undergoing radical R0 resection.

Low preoperative fibrinogen level is risk factor for neurological complications in acute aortic dissection.

Aortic arch surgery in patients with acute aortic dissection is frequently complicated by neurological complications and coagulopathy. However, the relationship between the coagulation system and neurological complications in patients with acute aortic dissection has not been clarified. Thus, the aim of this study was to investigate the relationship between the coagulation system and neurological complications in patients with acute aortic dissection.From September 2014 to January 2016, a total of 126 patients with acute type A aortic dissection were enrolled. Perioperative characteristics and standard laboratory tests upon admission were analyzed using univariate and multivariate logistic regression analysis in this study. The primary outcome was the correlation between the coagulation system and neurological complications.Univariate logistic regression analysis showed that the neurological complications (+) group underwent more serious and complicated postoperative outcomes. Multivariable logistic regression analysis revealed serum creatinine level (OR, 1.049; 95% CI, 1.011–1.089; P = .01), white blood cell counts (OR, 1.581; 95% CI, 1.216–2.057; P = .001) and fibrinogen concentration upon admission (OR, 0.189; 95% CI, 0.060–0.596; P = .004) as predictors of neurological complications. However, we found that there was no association between the coagulation system and in-hospital mortality.Low preoperative fibrinogen level is the preferred marker for predicting clinical neurological complications in patients with acute type A aortic dissection treated with surgical repair.

Reexploration for Bleeding and Its Association With Mortality After Cardiac Surgery

Excessive bleeding after cardiac surgical procedures sometimes necessitates reexploration. This study described the associations between reexploration for bleeding and morbidity and mortality after cardiac surgical procedures. In addition, independent predictors of reexploration were identified. This retrospective observational study based on prospectively registered data included 5,392 consecutive cardiac surgical operations performed from 2009 through 2013. Reexplorations for bleeding within 24 hours of surgical procedures and perioperative morbidity and mortality (30-day, 90-day, and from 90 days until the end of follow-up) were registered. Factors independently associated with mortality, morbidity, and reexploration were identified with multivariable logistic or Cox regression models. Mean follow-up time was 2.4 years (range 0 to 5 years). In this study, 320 patients (6.0%) underwent surgical reexploration. These patients had higher unadjusted mortality at 30 days, 90 days, and more than 90 days (all p < 0.0001). The increased risk remained statistically significant after adjustment for other risk factors at 90 days (odds ratio [OR]: 1.82; 95% confidence interval [CI]: 1.13 to 2.93; p= 0.013) and at more than 90 days (hazard ratio: 1.72; 95% CI: 1.14 to 2.61; p= 0.010). Reexploration was, after adjustment, independently associated with prolonged stay in the intensive care unit (>24 hours), perioperative stroke, perioperative renal injury, need for dialysis postoperatively, prolonged mechanical ventilation (>72 hours), and postoperative mechanical circulation support. Independent risk factors for reexploration were low body mass index, high EuroSCORE, low preoperative fibrinogen plasma concentration, long extracorporeal circulation time, combined valve and coronary artery bypass operations, and dual antiplatelet therapy less than 5 days preoperatively. Excessive bleeding leading to reexploration is associated with a twofold increased early postoperative mortality rate. Reexploration for bleeding is also associated with mortality beyond 90 days after operation.

Preoperative plasma fibrinogen concentration, factor XIII activity, perioperative bleeding, and transfusions in elective orthopaedic surgery: A prospective observational study

BackgroundMajor orthopaedic surgery involves a calculated risk of bleeding. In other groups of surgical patients, low preoperative plasma fibrinogen concentration and factor XIII (FXIII) activity have been associated with an elevated risk of bleeding. In the present study we investigated the association between preoperative fibrinogen plasma concentration and FXIII activity on bleeding and transfusion requirements in patients undergoing a spinal fusion procedure or hip or knee arthroplasty. MethodsTwo hundred and forty-five adult patients undergoing spine fusion surgery (n=52), total unilateral primary hip arthroplasty (n=114), or total knee arthroplasty (n=79) were included in a prospective observational study. Blood samples were collected <24h before surgery and analysed for fibrinogen concentration and FXIII activity. Intraoperative and postoperative bleeding volume and transfusion requirements were recorded. ResultsSpinal fusion surgery patients with a low preoperative fibrinogen concentration (≤2.5g/L) had a greater total perioperative median bleeding volume than patients with fibrinogen>2.5g/L (2430 (400–6560) mL vs. 1390 (400–7420) mL, p=0.029). No significant association between low fibrinogen levels and perioperative bleeding volume was observed for arthroplasty patients. There was no association between low fibrinogen levels and transfusion requirements in any of the groups. Low FXIII activity was not significantly associated with bleeding volume and transfusion requirements in any group. ConclusionMeasurement of preoperative fibrinogen plasma concentration can identify spinal fusion patients with an increased risk of excessive perioperative bleeding. Measurement of FXIII activity cannot identify orthopaedic patients with elevated risk of bleeding.

Cardiac surgery and phenprocoumon therapy— Is preoperative normalization of the international normalized ratio necessary?

Objectives: Patients on phenprocoumon presenting for surgery are often converted to heparin preoperatively. We assessed the impact of this conversion on outcome in cardiac surgery patients. Methods: From November 2007 to September 2013, 115 patients with phenprocoumon therapy presented for surgery and were operated either before or after the international normalized ratio (INR) had normalized (group A, INR &gt; 1.3, n = 71; group B, INR ⩽ 1.3, n = 44 at day of surgery; group C, matched control cohort without preoperative phenprocoumon, INR ⩽ 1.3, n = 60). Results: Patients received a mix of cardiac surgical procedures (including valves, coronary artery bypass grafting, ventricular assist devices, and transplantation) without intergroup differences. Surgery was emergent in 11%, 2%, and 13% in groups A, B, and C, respectively (p = 0.2). Preoperative hospital stay was longest in group B (p &lt; 0.01). Hospital mortality was high with 26% in group A (EuroSCORE 22 ± 22), 13% in group B (EuroSCORE 17 ± 16), and 7% in group C (EuroSCORE 10 ± 15) p &lt; 0.01. Mean chest tube drainage (first 24 h) was lowest in group C (mean/min/max, A: 1096/350/4750 mL; B 1086/300/4100 mL; C 757/120/2170 mL, p = 0.03), and preoperative hemoglobin was highest (A: 7.5 ± 1.2, B: 7.5 ± 1.4, C: 8.1 ± 1.2 mmol/L, p = 0.01). If transfusion was required, patients in group A received more red blood cells (mean units, A: 4.5 ± 8; B: 3.5 ± 6; C: 1.5 ± 3, p = 0.02). By multivariate analysis, preoperative INR was not an independent predictor of postoperative bleeding (p = 0.8). Only low preoperative fibrinogen predicted increased chest tube drainage, independent of phenprocoumon (p = 0.01). Conclusion: Patients presenting for cardiac surgery with preoperative phenprocoumon represent a high-risk population. Bleeding complications for these patients are higher but do not seem to be influenced by preoperative INR. Our data question the need for conversion to heparin.

Low Preoperative Fibrinogen Plasma Concentration Is Associated With Excessive Bleeding After Cardiac Operations

Data from small selected patient populations suggest that the preoperative plasma concentration of fibrinogen influences postoperative blood loss and red blood cell transfusion after cardiac operations, but there are also conflicting reports. We assessed the importance of preoperative fibrinogen concentration for excessive bleeding and red cell blood transfusion in a large cohort of mixed cardiac surgical patients. We included 1,954 cardiac surgical patients in a prospective observational study. The fibrinogen plasma concentration was measured on the day before the operation. Blood loss (mediastinal drain volume) during the first 12 postoperative hours and red blood cell transfusion during the hospital stay were registered and related to fibrinogen concentration with logistic regression models. Excessive bleeding was defined as postoperative blood loss exceeding 1,000 mL/12 hours. The preoperative fibrinogen concentration was inversely proportional to the prevalence of excessive bleeding in univariate testing (odds ratio [OR], 0.75; 95% confidence interval [CI], 0.64 to 0.89 per g/L; p=0.001) and also in a multiple model adjusted for age, sex, body mass index, renal function, acuteness of the operation, cardiopulmonary bypass time, clopidogrel use less than 5 days before the operation, and type of operation (OR for fibrinogen, 0.82; 95% CI, 0.69 to 0.97; p=0.024). In contrast, the prevalence of red cell blood transfusion increased with increasing fibrinogen levels in univariate testing (OR, 1.36; 95% CI, 1.24 to 1.49; p<0.001) but not in a multiple model (OR, 1.10; 95% CI, 0.89 to 1.28; p=0.49). Preoperative plasma concentration of fibrinogen is independently associated with excessive bleeding after cardiac operations but not with red blood cell transfusion.

Preoperative Fibrinogen Levels as a Predictor of Postoperative Bleeding after Open Heart Surgery

Open heart surgery still involving major bleeding continues to be a major challenge after cardiac surgery and is also a significant cause of morbidity and mortality. Most hemostatic factors are intercorrelated with postoperative bleeding, and fibrinogen seems the most fundamental hemostatic risk factor for open heart surgery. The study included 97 patients who underwent elective coronary artery surgery (78 men and 19 women; mean age, 60.9 +/- 10.3). Preoperative blood samples were obtained and preoprative quantitative determination of plasma fibrinogen levels were measured by the clotting method of Clauss using the fibrinogen kit. Patients were operated on by the same team and the same technique. The total amount of drainage blood from chest tubes was recorded after termination of operation. There were statistical significance between the fibrinogen levels and the drainage (r = -0.897, P < .001). Chest drainage was a mean of 972 mL (range, 240-2445 mL) in the first 48 hours after sternotomy closure. Fibrinogen level and relation to age was statistically significant (P = .015). There was no statistical significance between fibrinogen levels and gender (male gender = 400.7 +/- 123.0 versus female gender = 395.6 +/- 148.1; P = .877) and between drainage and gender (male gender = 968.2 +/- 538.5 versus female gender = 990.0 +/- 554.7; P = .876). Two patients (2%) died early after the surgery. There were no significant differences between the postoperative bleeding and cardiopulmonary bypass time (P = .648) or cross-clamp time (P = .974). The results of this study suggested that low preoperative fibrinogen level appears to be a useful diagnostic marker to assess the activity of the coagulation system, and that its preoperative level may serve as a potential risk factor for postoperative bleeding after coronary artery bypass surgery.