Drop In Hematocrit Research Articles

P119. Does the use of IV tranexamic acid impact postoperative hemoglobin and hematocrit following anterior cervical discectomy and fusion?

<h3>BACKGROUND CONTEXT</h3> Spinal surgery is often complicated by significant blood loss which can lead to increased patient morbidity and mortality. Tranexamic acid (TXA) is a synthetic antifibrinolytic agent that has shown promise in decreasing blood loss as well as need for postoperative blood transfusion when given during surgery. <h3>PURPOSE</h3> Recent studies have begun to report on the benefits of TXA when given perioperatively during spinal surgery2. Few studies, however, have looked at the effects of TXA in patients undergoing anterior cervical discectomy and fusion (ACDF). In this study we aimed to evaluate the effectiveness of TXA in reducing intraoperative blood loss in a cohort of ACDF patients. <h3>STUDY DESIGN/SETTING</h3> Retrospective, single-surgeon study at academic medical center. <h3>PATIENT SAMPLE</h3> All patients who underwent primary ACDF during this time either with or without the augment of TXA were included. <h3>OUTCOME MEASURES</h3> The mean differences in intraoperative blood loss as well as the change from pre to post-surgical hemoglobin and hematocrit, measured at presurgical testing 1 week prior to surgery and on postop day 1 were analyzed in TXA-treated patients compared to non-TXA-treated patients. Additionally, the number of patients requiring postoperative drain and average drain output on postoperative day #1 were measured. Mean length of stay in between groups was also analyzed. This study was subject to IRB approval. <h3>METHODS</h3> Medical records for all patients who underwent primary ACDF with a single surgeon at a tertiary center over a 3-year period from September 2016-October 2019 were evaluated retrospectively. <h3>RESULTS</h3> A total of 83 patients underwent primary ACDF during the study period. Three additional patients who underwent revision of ACDF were excluded for the purposes of this study. Of the 83 patients who underwent primary ACDF, 14 received TXA perioperatively while 69 did not receive TXA. Preoperative diagnoses included spinal stenosis, disc herniation, and spondylolisthesis. Distribution of diagnoses was equal among study groups. Patient demographics and comorbidities including age, BMI, cardiovascular disease, respiratory disease, diabetes and smoking status were evaluated and there were no significant differences between groups. Patients who received TXA had significantly lower mean operative blood loss than the non-TXA patients (41.1mL vs 77.4mL p<.05). There was, however, no significant difference in postoperative drop in hemoglobin (0.7 vs 1.0, p=.332) or hematocrit (0.0, 1.8, p=.392) between the two groups. A total of 49 patients in the non-TXA group (71%) required drain placement while 6 patients in the TXA group (43%) had a drain placed (p=.062). There was a trend towards decreased drain output on postop day 1 in the TXA group compared to the non-TXA group (32.3mL vs 40.8mL, p=.056), however it was not significant. There was also no significant difference in average length of stay between TXA and non-TXA patients (3.2 vs 3.6 days, p=.564). <h3>CONCLUSIONS</h3> TXA has been reported as a useful perioperative tool to decrease bleeding associated with spinal surgery. We found in our patients who underwent ACDF that intraoperative use of IV TXA led to a significant decrease in intraoperative blood loss, however, there was no difference in the change in pre and postoperative hemoglobin and hematocrit between ACDF patients who received TXA and those who did not. There was also no difference in mean postoperative length-of-stay between the TXA and non-TXA groups. Additionally, while not significant, there was a trend towards TXA patients being less likely to require a drain postoperatively (p=.062) and those requiring a drain having less output in the early postoperative period (p=.056). While use of TXA perioperatively for ACDF was shown in this study to decrease operative blood loss, this change was not reflected in surgical hemoglobin change or overall length of stay. Further analysis of the benefits of TXA on bleeding in ACDF patients is warranted. <h3>FDA DEVICE/DRUG STATUS</h3> This abstract does not discuss or include any applicable devices or drugs.

Peri-operative Morbidity Associated with Bilateral Hip Arthroplasty for Inflammatory Arthritis: Results from a Consecutive Series of 168 Hips.

This study aims to assess the risks and peri-operative morbidity associated with a single-stage sequential bilateral hip arthroplasty (SBHA) when performed in patients with arthritis secondary to inflammatory arthropathy. Data of patients who underwent SBHA between 2012 and 2018 for inflammatory arthritis were extracted from a database, for peri-operative complications and functional improvement. SBHA for other causes was excluded. Data of 84 consecutive patients with a mean age of 34.5years were analyzed. The mean follow-up was 2.4years. 66% had ankylosing spondylitis, while 14% had rheumatoid arthritis. 50% of the patients had bilateral fusion of the hips, and 34% had flexion deformity > 30°.None of the patients had peri-operative cardiac or pulmonary complications. 2.4% had per-operative hypotension (MAP < 50mmHg) and 1.2% had desaturation (SpO2 < 90%). The mean drop in hematocrit was 9.3%. While 31% did not require blood transfusion, 35% required more than 1 unit of blood. Patients with pre-operative PCV of > 36% had a significantly lower risk of being transfused > 1 unit of blood (p = 0.02). ICU admission was 6%-mostly for post-operative monitoring. While one patient had a local hematoma that needed a wash-out, there were no infections, dislocations, or mortality in these patients. The modified Harris hip score improved from a mean of 26.5-85. The mean hip flexion improved post-operatively from 32° to 92°. SBHA for inflammatory arthritis can be performed with minimum complications in a multidisciplinary setting. Pre-operatively, PCV of > 36 is advised to reduce transfusion rates.

Investigation the Effects of Adding Intravenous Transoxalic Acid and Its Complications in the Prevention of Postpartum Hemorrhage after Vaginal Delivery in Patients Admitted to Ali-ibn-Abitaleb Hospital in Zahedan

Background: This study was designed to investigate the effect of tranexamic acid and its side effects in preventing postpartum hemorrhage in patients referred to Ali ibn Abitaleb Hospital in Zahedan during 2020-2021. Methods: Patients were divided into two groups of 85 patients. Vital signs as well as drug side effects related to tranexamicity are monitored and recorded every15 minutes in the first hour and every 30 minutes in the second hour. Also, blood samples are taken from patients to measure hemoglobin and hematocrit within6 hours after delivery. The number and weight difference of droschitis used during 2 hours after delivery are also measured. In addition, PPH (Postpartum hemorrhage) cases in both groups were checked by repeated examination of the uterine fundus during the first 2 hours and after 6 weeks. Results: There was no statistically significant difference between the two groups in terms of the number of deliveries and further decrease in hemoglobin levels in the control group compared to the intervention group. Nausea, vomiting, and dizziness were observed in the intervention group and thrombosis was not observed in any group. According to the independent samples t-test, there was a statistically significant difference between the mean blood volume lost between the two groups. The mean hematocrit drop was statistically significant between the two groups. No blood transfusion was observed in any of the patients. Conclusion: Tranxamic acid injections can effectively reduce postpartum hemorrhage and reduce maternal hemoglobin and hematocrit following this complication.

The CXCL12/CXCR4 and VEGF165/Nrp1 Pathways Have Differential Effects on Pathological Neo-Angiogenesis and Vascular Remodeling in Hemophilic Arthropathy

Introduction: Joint hypervascularity is characteristic to hemophilic arthropathy (HA), which is a hallmark complication in patients with hemophilia. Angiogenesis in the hemophilic joint is triggered by bleeding and results in excessive vascular remodeling with enlarged irregularly shaped vessels that appear fragile, potentially causing re-bleeding. Therefore, targeting angiogenesis may offer novel treatment avenues in HA. Vascular endothelial growth factor A (VEGF-A) is an important angiogenic mediator implicated in the pathogenesis of HA, but a complete blockade may cause vascular instability with more bleeding, or inhibition of anti-angiogenic isoforms, thereby decreasing therapeutic efficacy. An alternative approach may be to target the co-receptor Neuropilin 1 (Nrp1) that facilitates binding of the pro-angiogenic isoform VEGF165 to its signaling receptor, VEGFR2. Here, we determine whether blocking the binding of VEGF165 to Nrp1 can curb the pathological vascular remodeling associated with hemophilic joint bleeding.Methods and results: Joint bleeding was induced by subpatellar needle puncture in FVIII-/- mice, resulting in pronounced intra- and peri-articular bleeding, evidenced by a drop in hematocrit from ~45% to 28 ± 10% 2 days after injury. The following antibody treatments were initiated 2 days after injury and were administered at 5 mg/kg, twice weekly for 4 weeks: B20-4 targeting murine VEGF-A, and YW107.4.87 blocking the VEGF165 binding site on Nrp1. The CXCR4 antagonist, AMD3100 (300 µg/day by subcutaneous osmotic pump) was included as positive control as it corrects hypervascularity induced by hemophilic joint bleeding (Wyseure et al . ISTH 2017).Four weeks after injury blood flow in the joint, measured by ultrasound-Power Doppler (PD), was increased 2.8-fold in injured vs uninjured FVIII-/- mice (p<0.001; n=13). Anti-VEGF treatment resulted in a similar 3.2-fold increase in PD signal (n=8), indicating that total inhibition of VEGF had no effect on the aberrant blood flow. Inhibition of Nrp1 had a partial effect (1.9-fold increase over baseline; p=0.16 vs no treatment; n=7), whereas inhibition of CXCL12-mediated vascular cell recruitment by the CXCR4 antagonist significantly blunted aberrant PD signals (p<0.05 vs no treatment; n=10). On histology, the total vessel count after anti-Nrp1 treatment was similar to no treatment and significantly greater than baseline (86 anti-Nrp1 vs 80 no treatment vs 42 baseline; p<0.01). Similarly, anti-Nrp1 treatment had no effect on the number of abnormally enlarged vessels (with a diameter ≥ 20 µm) compared to no treatment (15 anti-Nrp1 vs 13 no treatment vs 3 baseline; p<0.01 vs baseline). In contrast, with CXCR4 antagonist treatment both the total vessel count (64; p=0.3 vs baseline) and the number of abnormally enlarged vessels (7; p=0.1 vs baseline) remained low. However, anti-Nrp1 treatment did prevent the 2.5-fold increased perivascular expression of smooth muscle cell actin (αSMA; p<0.01) that typically accompanies the abnormally enlarged vessels in injured FVIII-/- mice. Thus, inhibition of Nrp1 lowered αSMA expression after hemophilic bleeding, similar to baseline and CXCR4 antagonist treatment, although it had no effects on vessel number and enlargement. This suggests that anti-Nrp1 treatment prevents the maturation during vascular remodeling in HA, potentially leaving the vessels destabilized and prone to vascular permeability. Towards that end, staining with Prussian Blue demonstrated increased hemosiderin deposits in anti-Nrp1 treated mice, similar to untreated injured FVIII-/- mice, whereas no signs of macroscopic joint bleeding or hemosiderin deposits were observed after treatment with the CXCR4 antagonist.Conclusions: Abrogating the VEGF165-Nrp1 interaction was not sufficient to prevent neo-angiogenesis and vessel lumen expansion in a murine hemophilic joint injury model. However, inhibition of Nrp1 did reduce perivascular remodeling that may allow regression of the aberrant vasculature over time, but also may promote further vessel instability and additional hemorrhaging. Thus, inhibition of the CXCL12/CXCR4 pathway affects neo-angiogenesis, whereas inhibition of the VEGF165/Nrp1 pathway predominantly affects perivascular maturation, but not neo-angiogenesis. These findings provide novel insights on the potential benefits and pitfalls of anti-angiogenic treatments in HA. Disclosuresvon Drygalski:Hematherix LLC: Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria; Novo Nordisk: Honoraria; CSL Behring: Honoraria; Bioverativ: Honoraria; Bayer: Honoraria; Shire: Honoraria. Mosnier:Hematherix LLC: Membership on an entity's Board of Directors or advisory committees.

Whole blood transfusion improves vascular integrity and increases survival in artemether-treated experimental cerebral malaria

Pathological features observed in both human and experimental cerebral malaria (ECM) are endothelial dysfunction and changes in blood components. Blood transfusion has been routinely used in patients with severe malarial anemia and can also benefit comatose and acidotic malaria patients. In the present study Plasmodium berghei-infected mice were transfused intraperitoneally with 200 μL of whole blood along with 20 mg/kg of artemether. ECM mice showed severe thrombocytopenia and decreases in hematocrit. Artemether treatment markedly aggravated anemia within 24 h. Whole blood administration significantly prevented further drop in hematocrit and partially restored the platelet count. Increased levels of plasma angiopoietin-2 (Ang-2) remained high 24 h after artemether treatment but returned to normal levels 24 h after blood transfusion, indicating reversal to quiescence. Ang-1 was depleted in ECM mice and levels were not restored by any treatment. Blood transfusion prevented the aggravation of the breakdown of blood brain barrier after artemether treatment and decreased spleen congestion without affecting splenic lymphocyte populations. Critically, blood transfusion resulted in markedly improved survival of mice with ECM (75.9% compared to 50.9% receiving artemether only). These findings indicate that whole blood transfusion can be an effective adjuvant therapy for cerebral malaria.

Can the application of a temporary uterine tourniquet during an abdominal myomectomy reduce bleeding?

Uterine fibroids are common, benign uterine tumours. The three most common surgical treatment approaches for uterine fibroids are laparoscopic, robotic and abdominal myomectomies. Bleeding is a risk with all three approaches. The present study compared post-operative and pregnancy outcomes in patients with bilateral uterine artery occlusion who underwent an abdominal myomectomy, with or without a temporary uterine tourniquet. This retrospective study included patients with intra-mural fibroids (≥5 cm) who underwent an abdominal myomectomy. The patients were divided into two groups according to the use or non-use of a temporary uterine tourniquet. Post-operative and pregnancy outcomes in the tourniquet use and non-use groups were compared. The association of the number of uterine fibroids removed (≤3 vs >3) with laboratory parameters was also evaluated. A total of 84 patients were included, divided into use (n=36) and non-use (n=48) of the temporary tourniquet. There was a statistically significant difference between the groups with >3 myomas removed and with a uterine tourniquet applied and not applied in terms of reduction in hemoglobin and hematocrit, transfusion amounts, operation times and lengths of hospitalization in favour of the uterine tourniquet use group (p=0.019, p=0.023, p=0.012, p=0.044 and p=0.036, respectively). Bilateral uterine arterial occlusion using a temporary uterine tourniquet had no negative effects on pregnancy outcomes. A temporary uterine tourniquet may be an effective method for reducing the amount of perioperative bleeding in patients with multiple, large-sized myomas located close to vascular structures.

Misoprostol Versus Manual Vacuum Aspiration in Treatment of Missed Miscarriage in First Trimester

Abstract Background: Manual vacuum aspiration (MVA) is a safe and effective technology for the treatment of missed miscar-riage but it is not widely available and affordable in rural areas particularly in low resource countries. Misoprostol is an alternative to manual vacuum aspiration for the treatment of missed miscarriage. Aim of Study: The purpose of this study was to compare the effectiveness, patient satisfaction and hematocrit drop of misoprostol versus MVA to understand the potential role of misoprostol as a first line for treatment of first trimester missed miscarriage. Patients and Methods: A Randomized Controlled Trial was conducted from January 2020 to January 2021 at Mansoura University Maternity Hospital. Included 70 participants were randomized to treatment with either MVA or 800µg vaginal misoprostol. The main outcome measures assessed at 1 week follow up were complete uterine evacuation, patient's accept-ability and satisfaction. Results: There is no statistically significant difference between studied groups regarding success rate and mean patient satisfaction score immediately and after one week, 82.9% of misoprostol group and 94.3% of MVA group suc-cesses. The mean hemoglobin and hematocrit after treatment illustrated statistically significant lower mean value among misoprostol group than MVA group (10.07 & 10.91, respec-tively for Hb) and (30.75 & 33, respectively for hematocrit value). Hemoglobin drop for both groups illustrated no statis-tically significant difference between studied groups. There is statistically significant negative correlation between en-dometrial thickness/mm and satisfaction after one week among both group. Conclusion: Both misoprostol and MVA had high rates of satisfaction and complete uterine evacuation, which could ultimately reduce maternal complications from abortion. Medical treatment is as effective as surgical treatment of first trimester missed miscarriages. Recommendations: Although misoprostol is a very effec-tive drug, the health care professional should have thorough knowledge of the dose, side effects, complications and contraindications before prescribing it. More studies with larger sample size are needed to elucidate the optimal method for missed miscarriage management and patient satisfaction.

Cangrelor vs. glycoprotein IIb/IIIa inhibitors during percutaneous coronary intervention

To date, there are no real-world studies comparing cangrelor to glycoprotein IIb/IIIa inhibitors (GPI) during percutaneous coronary intervention (PCI). Thus, we performed this study to evaluate the safety and effectiveness of cangrelor compared to GPI during PCI. We identified patients who underwent PCI at our institution who received either cangrelor or GPI during PCI. Patients already on GPI or cangrelor prior to PCI or who received both cangrelor and GPI were excluded. Baseline demographics and clinical outcomes were extracted. Major bleeding is defined as a composite of major hematoma >4 cm, hematocrit drop >15, and gastrointestinal bleeding. A total of 2072 patients received adjunctive antiplatelet therapy during PCI (cangrelor [n=478]; GPI [n=1594]). Patients' mean age was 61±12 years. Most (66%) presented with acute coronary syndrome. Patients who received cangrelor were older and had a higher percentage of acute coronary syndrome and lower baseline hematocrit in comparison with patients who received GPI. Procedural success was achieved in 94% of patients, with no difference between groups. Major bleeding events (1.7% vs. 5.1%, P=.001), any vascular complication rates, and hospital length of stay were significantly lower in the cangrelor group. In-hospital ischemic events did not differ between groups. On regression analysis, patients on cangrelor were noted to have significantly lower major bleeding events (OR 0.23; 95% CI, 0.09-0.59). Balancing ischemic and bleeding risks with adjunctive antiplatelet drugs is of prime importance during PCI. Our real-world analysis shows that cangrelor is safe and effective when compared to GPI during PCI.

Efficacy and safety of tranexamic acid in the prevention of postpartum haemorrhage after vaginal delivery

Introduction: Postpartum haemorrhage is one of the leading causes of death in women who deliver after 20 weeks of gestation. The prevalence of PPH in India is 23%. Delayed diagnosis and poor management of PPH are associated with increased morbidity and mortality. Material and Methods: This prospective randomised controlled study was conducted on one thousand women at period of gestation ≥37 weeks for vaginal delivery. Aim and Objectives: To evaluate the role of tranexamic acid in decreasing blood loss after normal vaginal delivery. Results: Majority of women belonged to 21-25 years age group in both the group. Blood loss at 3rd stage of labour in TXA group was 376.12±63.82 ml and in control group it was 654.08±86.61 ml. The mean haemoglobin reduction (pre-post) suggested that tranexamic acid group (0.44±4.3) had a significantly less haemoglobin drop as compared to control group (1.850±0.58). There was significant less fall in mean haemoglobin percentage (3.86% versus 16.15%) and mean haematocrit percentage (3.80% versus 12.72%) in TXA group as compared to control group. Forty four (8.8%) women in TXA group and seventy eight women (15.6%) in control group had postpartum haemorrhage. Twenty one (4.2%) women received blood transfusion in TXA group and forty four (8.8%) women in control group. Forty four women had PPH and out of which, 33 (6.6%) were managed medically and in 11 (2.2%) women, balloon tamponade was used along with additional uterotonics for control of PPH. In control group, a total of 78 (15.6%) women had PPH and 55 (11%) were managed by medically and 23(4.6%) by balloon tamponade along with additional uterotonics for control of PPH. The most common side effect was nausea/vomiting observed in both the groups. Conclusion: Tranexamic acid was found to be safe and effective in reducing blood loss after normal vaginal delivery. There was less drop in haemoglobin and haematocrit in tranexamic acid group which reduced the risk of blood transfusion and additional uterotonics.

English

BACKGROUND The primary objective in the management of splenic injury earlier was to achieve early haemostasis which resulted in splenectomy as the treatment of choice. But after recognising the role of spleen in immune and haematopoietic functions, nonoperative management (NOM) was started. In order to practice non-operative management safely a better way to assess the severity of splenic injury was necessary. Eventually it became possible with the advent of computed tomography. Along with clinical assessment, it enabled us in the selection of appropriate patients for non-operative management. Now this modality is considered as the gold standard for patients who are hemodynamically stable or readily stabilisable. It decreases the duration of hospital stay and prevents postoperative morbidity. We wanted to find out the proportion of cases and predictors for failure of non-operative management among splenic injury patients in VIMSAR, Burla. METHODS This cross-sectional study was done among 35 patients with splenic injury who were hemodynamically stable from November 2018 to October 2020. RESULTS Age, sex, systolic blood pressure, diastolic blood pressure, mechanism of injury, Glasgow Coma Score (GCS), associated injury (if hemodynamically stable) were not found to be significant predictors in deciding the failure of non-operative management. CONCLUSIONS Most important predictor for failure of non-operative management was development of haemodynamic instability. Tachycardia, low mean arterial pressure (MAP), drop in haemoglobin (Hb) and haematocrit were significant parameters in our study and all these parameters ultimately point towards hemodynamic instability. KEYWORDS Non-Operative Management (Successful), Non-Operative Management (Failure), Hemodynamically Stable, Blunt Trauma Abdomen

Impact of tranexamic acid on blood loss and transfusion rate in children with cerebral palsy undergoing hip reconstruction with two or more osteotomies.

Tranexamic acid (TXA), a synthetic lysine analogue, has been used in orthopedic procedures to limit blood loss and prevent allogeneic blood transfusions. However, data are scarce on its use in hip reconstruction of patients with cerebral palsy (CP). This study examines the effect of TXA on patients with CP undergoing hip reconstruction with at least two osteotomies. This is a single-center, retrospective study of patients with CP who underwent hip reconstruction with two or more osteotomies from January 2013 to April 2019. There were 43 patients, with a mean age of 9.9years. Age, procedure, preoperative and postoperative hemoglobin/hematocrit, estimated blood loss (EBL), transfusions and length of stay were recorded. The patients were split into the following two groups: 24 patients who had received intraoperative TXA and 19 who had not. Age, EBL, mean preoperative and postoperative hemoglobin or hematocrit, preoperative to postoperative hematocrit drop, and length of stay were similar for the two groups (p > 0.05). The risk for intraoperative transfusion (21 vs. 17%), postoperative transfusion (26 vs. 8%), and any transfusion (42 vs. 21%) appeared to be greater in the group that did not receive TXA, but this difference did not achieve statistical significance. This pilot study shows patients with CP undergoing hip reconstruction with two or more osteotomies; the use of TXA, while not statistically significant, shows a trend toward a decreased need for allogeneic blood transfusion.

Quantification of Blood Loss Improves Detection of Postpartum Hemorrhage and Accuracy of Postpartum Hemorrhage Rates: A Retrospective Cohort Study.

ObjectiveTo evaluate the ability of estimated blood loss (EBL) and quantitative blood loss (QBL) to predict the need for blood transfusion in postpartum patients.MethodsThis is a retrospective observational study involving all deliveries one year before and after the change from EBL to QBL assessment in June 2017. Blood loss, need for blood transfusion, admission hematocrit, and postpartum nadir hematocrit were collected. Descriptive and bivariable analyses were performed. Receiver operator curves were compared.ResultsOverall, the baseline characteristics between the EBL (n=2743) and QBL (n=2,712) groups were similar. Although there was a higher rate of blood loss ≥ 1,000 mL in QBL vs EBL (6.5% vs 2.1%, P<0.001), there was no difference in the rate of blood transfusions (2.0% vs 2.0%, P=1). Among cesarean deliveries, QBL outperformed EBL for predicting blood transfusion and/or ≥10 point drop in hematocrit (AUC 0.75 vs 0.66, P=0.02). QBL also outperformed EBL for predicting transfusion after vaginal delivery (AUC 0.93 vs 0.81, P=0.03). ConclusionQBL is a more sensitive test for detecting clinically significant blood loss, which could lead to earlier recognition of hemorrhage and interventions.

Differential effects of chronic immunosuppression on behavioral, epigenetic, and Alzheimer\u2019s disease-associated markers in 3xTg-AD mice

BackgroundCirculating autoantibodies and sex-dependent discrepancy in prevalence are unexplained phenomena of Alzheimer’s disease (AD). Using the 3xTg-AD mouse model, we reported that adult males show early manifestations of systemic autoimmunity, increased emotional reactivity, enhanced expression of the histone variant macroH2A1 in the cerebral cortex, and loss of plaque/tangle pathology. Conversely, adult females display less severe autoimmunity and retain their AD-like phenotype. This study examines the link between immunity and other traits of the current 3xTg-AD model.MethodsYoung 3xTg-AD and wild-type mice drank a sucrose-laced 0.4 mg/ml solution of the immunosuppressant cyclophosphamide on weekends for 5 months. After behavioral phenotyping at 2 and 6 months of age, we assessed organ mass, serologic markers of autoimmunity, molecular markers of early AD pathology, and expression of genes associated with neurodegeneration.ResultsChronic immunosuppression prevented hematocrit drop and reduced soluble Aβ in 3xTg-AD males while normalizing the expression of histone variant macroH2A1 in 3xTg-AD females. This treatment also reduced hepatosplenomegaly, lowered autoantibody levels, and increased the effector T cell population while decreasing the proportion of regulatory T cells in both sexes. Exposure to cyclophosphamide, however, neither prevented reduced brain mass and BDNF expression nor normalized increased tau and anxiety-related behaviors.ConclusionThe results suggest that systemic autoimmunity increases soluble Aβ production and affects transcriptional regulation of macroH2A1 in a sex-related manner. Despite the complexity of multisystem interactions, 3xTg-AD mice can be a useful in vivo model for exploring the regulatory role of autoimmunity in the etiology of AD-like neurodegenerative disorders.

Fibrin clot susceptibility to lysis is impaired after on-pump coronary artery by-pass grafting with tranexamic acid: clinical implications.

Coronary artery bypass grafting (CABG) done on-pump may cause a significant blood loss. Low fibrinogen is associated with perioperative bleeding. The influence of cardiopulmonary bypass on fibrin clot properties is poorly investigated. We studied 55 patients with isolated coronary artery disease on aspirin undergoing on-pump CABG with tranexamic acid. Fibrinogen levels, fibrinolytic capacity expressed as clot lysis time (CLT), thrombin generation potential and platelet count were assessed before and after the surgery (prior to admission to the intensive care unit). A postoperative drop in haemoglobin (-30% from baseline), haematocrit (-31% from baseline) and platelet count (-42% from baseline) was observed (all, P < 0.0001). Postoperative fibrinogen level was lower by 57%, compared with preoperative value (1.5 [1.3-1.8] vs. 3.5 [2.8-3.9] g/l, P < 0.0001). Postoperative CLT was longer by 48 min, compared with preoperative (182 [170-218] vs. 134 [122-165] min, P < 0.0001). Thrombin generation was impaired postoperatively: both lag time and time to peak thrombin were prolonged by 44 and 45%, respectively, whereas endogenous thrombin potential and peak thrombin generation decreased by 45 and 78%, respectively (all P < 0.0001). Median postoperative drainage at 12 h was 400 [290-570] ml. Predictors of blood loss at 12 h identified in multivariable linear regression model adjusted for sex and preoperative fibrinogen level were: BMI (b = -23.4, P = 0.048) and postoperative CLT (b = -2.4, P = 0.042). Despite decreased fibrinogen levels after on-pump CABG with tranexamic acid, fibrin clot susceptibility to lysis is impaired, as reflected by prolonged CLT. Postoperative CLT is associated with mediastinal drainage at 12 h.

Effectiveness of preoperative tranexamic acid in reducing blood loss during caesarean section at Aminu Kano Teaching Hospital, Kano: a randomized controlled trial.

Introductionbleeding during and after caesarean section is one of the contributors to maternal mortality and morbidity. Tranexamic acid can be given before surgery to significantly reduce the amount of blood loss during caesarean section. The objective was to evaluate the effectiveness of preoperative tranexamic acid in reducing blood loss during caesarean section at Aminu Kano Teaching Hospital, Kano.Methodsthis was a randomized double blind placebo controlled study that was carried out among 244 women who were to have emergency caesarean section between December 2017 and June 2018 and were randomly assigned to the study group or control group. Women in the study group received lg (10mls) of tranexamic acid intravenously while women in the control group received 10ml of normal saline. Oxytocin was administered in the two groups according to protocol. Measurement of blood loss was done immediately after surgery. Postoperative drop in haemoglobin and haematocrit were also determined. Statistical analysis was done using SPSS Version 22.Resultsthe average intra operative blood loss was 414.0 ml in the study group and 773.8 ml in the control group (t = - 16.18, p ≤ 0.01). Average postoperative haemoglobin was 10.1 g/dl in the study group and 9.5 g/dl in the control group (t = 4.99, p ≤ 0.01). Average postoperative haematocrit was 31.5% in the study group and 29.9% in the control group (t = 4.70, p ≤ 0.01).Conclusionthere was a significant reduction in the blood loss when preoperative tranexamic acid was given to patients who were to undergo emergency caesarean section.

Combined treatment of intraoperative cell-salvage and tranexamic acid for primary unilateral total hip arthroplasty: Are there added benefits?

BackgroundBlood management strategies in total hip arthroplasty (THA) are essential in reducing intraoperative blood loss, blood transfusion and associated complications. This study investigates whether using intraoperative cell-salvage (ICS) with tranexamic acid (TXA) has additional effects on blood loss and allogeneic transfusion in primary THA. Additionally, we evaluated the financial impact of using ICS on our institution. MethodsUsing an institutional database, 1171 cases of primary unilateral THA performed between May 2015 and January 2016 were identified. Subjects were separated into those who received only TXA (n = 323) and those who received TXA and ICS (n = 848). Calculated blood loss and post-operative blood transfusions were assessed using logistic regression. Drop in hematocrit was assessed using linear regression. Multivariable models adjusted for intraoperative blood transfusions, pre-operative autologous blood donation, anticoagulation medications, sex, and body mass index. Pricing data was used to calculate the costs associated with these interventions. ResultsThe likelihood of post-operative allogeneic blood transfusion was similar for the combined group relative to the TXA group (OR = 0.63; 95% CI: 0.26, 1.54), as was the likelihood of any post-operative blood transfusion (OR = 1.13; 95% CI: 0.63, 2.01). There was no correlative relationship between use of ICS and hematocrit drop when accounting for baseline hematocrit (R2 = 0.118). Factoring in rental, service fees, and disposable equipment, the utilization of ICS added $146 to each case, resulting in a gross expenditure of over $123,000 during the study period. ConclusionsThe combination of ICS with TXA for primary unilateral THA did not improve blood loss or transfusion outcomes compared to TXA alone. As there was no observed clinical benefit to combined treatment, additional costs associated with routine usage of ICS may not be justifiable. Our institution would have reduced expenditures for blood loss management products by 85% during the study period if all patients had only received TXA.

Implementation of a Prescriptive Extracorporeal Circuit and Its Effect on Hemodilution and Blood Product Usage during Cardiac Surgery.

The use of cardiopulmonary bypass (CPB) contributes significantly to intraoperative anemia. The use of a prescriptive circuit that is tailored to the patient size could significantly reduce priming volumes, resulting in less hemodilution. The purpose of this study was to determine whether a prescriptive circuit resulted in decreased hemodilution, reduced blood product usage, and improved outcomes. In total, 204 patients prospectively received the prescriptive protocol between March 2019 and November 2019. This protocol was composed of three circuit sizes: small [body surface area (BSA) ≤ 1.85 m2], medium (BSA 1.86-2.30 m2), and large (BSA ≥ 2.31 m2). Data for CPB and post-bypass transfusions were collected, along with postoperative outcomes. These patients were then 1:2 propensity score matched to 401 patients who were retrospectively reviewed who had undergone cardiac surgery using a one-sized CPB circuit. The prescriptive protocol cohort had more patients with renal disease, whereas the conventional cohort had more history of hypertension. Intraoperative results show the prescriptive circuit had lower mean prime volume and total prime volume after reverse autologous prime (1,084 mL vs. 1,798 mL, p < .0001; 725 mL vs. 1,181 mL, p < .0001). Ultrafiltration was higher in the prescriptive group (872 vs. 645 mL, p < .0001), which likely balanced the increased use of del Nido cardioplegia in the prescriptive group (1,295 vs. 377 mL, p < .0001). The drop in hematocrit (HCT) from baseline was less in the prescriptive group (15.1 ± 4.91 vs. 16.2 ± 4.88, p = .0149), whereas the postoperative HCT was higher (32.79 ± 4.88 vs. 31.68 ± 4.99, p = .0069). Transfusion of packed red cells did not change between the two groups. Implementation of a prescriptive circuit did not reduce on-bypass or intraoperative blood product usage. However, there was a significant reduction in on-bypass hemodilution and increased postoperative HCT.

Implementation of a Prescriptive Extracorporeal Circuit and Its Effect on Hemodilution and Blood Product Usage during Cardiac Surgery

The use of cardiopulmonary bypass (CPB) contributes significantly to intraoperative anemia. The use of a prescriptive circuit that is tailored to the patient size could significantly reduce priming volumes, resulting in less hemodilution. The purpose of this study was to determine whether a prescriptive circuit resulted in decreased hemodilution, reduced blood product usage, and improved outcomes. In total, 204 patients prospectively received the prescriptive protocol between March 2019 and November 2019. This protocol was composed of three circuit sizes: small [body surface area (BSA) ≤ 1.85 m2], medium (BSA 1.86–2.30 m2), and large (BSA ≥ 2.31 m2). Data for CPB and post-bypass transfusions were collected, along with postoperative outcomes. These patients were then 1:2 propensity score matched to 401 patients who were retrospectively reviewed who had undergone cardiac surgery using a one-sized CPB circuit. The prescriptive protocol cohort had more patients with renal disease, whereas the conventional cohort had more history of hypertension. Intraoperative results show the prescriptive circuit had lower mean prime volume and total prime volume after reverse autologous prime (1,084 mL vs. 1,798 mL, p &lt; .0001; 725 mL vs. 1,181 mL, p &lt; .0001). Ultrafiltration was higher in the prescriptive group (872 vs. 645 mL, p &lt; .0001), which likely balanced the increased use of del Nido cardioplegia in the prescriptive group (1,295 vs. 377 mL, p &lt; .0001). The drop in hematocrit (HCT) from baseline was less in the prescriptive group (15.1 ± 4.91 vs. 16.2 ± 4.88, p = .0149), whereas the postoperative HCT was higher (32.79 ± 4.88 vs. 31.68 ± 4.99, p = .0069). Transfusion of packed red cells did not change between the two groups. Implementation of a prescriptive circuit did not reduce on-bypass or intraoperative blood product usage. However, there was a significant reduction in on-bypass hemodilution and increased postoperative HCT.

Surgical management of obstructing clot at the jejunojejunostomy after gastric bypass: a single center experience and literature review.

Roux-en-Y gastric bypass is a proven treatment for morbid obesity and its sequelae. Gastric bypass has a safe risk profile, but postoperative complications can be seen. We report on 10 cases of postoperative bleeding causing an obstructing clot at the jejunojejunostomy (JJ) occurring over a 9-year period. The aim was to document presenting symptoms of obstructing clots at the JJ and to suggest a treatment approach to minimize complications. University Hospital, United States METHODS: The local Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database was queried for all patients undergoing reoperation after Roux-en-Y gastric bypass, from July 2009 until December 2019. All patients who were found to have postoperative bleeding causing an obstructing clot at the JJ were selected for retrospective medical-record review. The most common presenting symptoms were Hematocrit drop (10 of 10), nausea (9 of 10), abdominal pain (7 of 10), and hematemesis (4 of 10). There were 12 reoperations in the 10 patients, 10 of which were completed laparoscopically. Infectious complications were the most frequent morbidity in our patients; 4 patients developed abscesses. In all of these, the operative notes described gross spillage into the peritoneal cavity. In later cases, the remnant stomach was decompressed before reoperation, reducing spillage. Despite the low rate of obstructing clots at the JJ, without rapid recognition and reoperation, there is a risk for serious complications. Typical presenting symptoms include nausea and abdominal pain, which help differentiate it from other causes of decreased hematocrit. Diagnosis is commonly made with computerized tomographic (CT) scan. Decompression of a dilated remnant stomach before addressing the clot can prevent intraperitoneal spillage and subsequent abscess formation. Enterotomy creation and removal of clot is recommended, without fear of continued bleeding.

The New Zealand white rabbit animal model of acute radiation syndrome: hematopoietic and coagulation-based parameters by radiation dose following supportive care

Purpose Animal models that accurately reflect human responses to radiation injury are needed for advanced mechanistic investigation and development of effective therapeutics. The rabbit is an established animal model accepted by the FDA for studies of cardiovascular disease, lipid metabolism, the development of anticoagulants, testing of bone implants, and the development of treatments for infectious diseases such as HIV. The purpose of this study was to investigate the New Zealand White (NZW) Rabbit model as a model of acute radiation exposure because of its established similarity to human vascular, immune, and coagulation responses. Materials and methods Two sequential studies were performed in a total of 81 male NZW rabbits, 16–20 weeks of age. All animals underwent clinical observations and peripheral blood analyses following a single dose of 0, 6, 7, 8, 8.5, 9, or 10 Gy of total body irradiation via a 6 MV Linear accelerator photon source on day 0. Animals were treated with timed release fentanyl patch (days 0–30), subcutaneous hydration (day 1, Study 2 only), and oral sulfamethoxazole/trimethoprim 30 mg/kg once daily (days 3–30) and were followed for 30 days or to time of mortality. Results Study 1 revealed the estimated LD30, −50, −70, and −90 with 95% confidence intervals (CI) at 30 days to be 6.7 (CI: 5.9–7.4), 7.3 (CI: 6.7–7.8), 7.9 (CI: 7.3–8.4), and 8.8 (CI: 7.9–9.7) Gy, respectively. In study 2, a survey of blood coagulation and biochemical parameters were performed over time and necropsy. Complete blood counts taken from animals exposed to 7, 8, or 10 Gy, demonstrated dose-dependent depletion of lymphocytes, neutrophils, and platelets. Platelet counts recovered to baseline levels in survivors by day 30, whereas lymphocyte and neutrophil counts did not. Decedent animals demonstrated grade 3 or 4 neutropenia and lymphopenia at time of death; 64% of the decedents experienced a 30% or greater drop in hematocrit. Decedent animals demonstrated more than 100% increases from serum baseline levels of blood urea nitrogen, creatinine, aspartate aminotransferase, and triglyceride levels at the time of death whereas survivors on average demonstrated modest or no elevation. Conclusion This NZW rabbit model demonstrates dose-dependent depletion of hematopoietic parameters. The LD50/30 of 7.8 Gy (95% CI: 6.6–8.4) with supportive care appears to be close to the ranges reported for rhesus macaques (5.25–7.44 Gy) and humans (6–8 Gy) with supportive care. These findings support the utility of the NZW rabbit model for further mechanistic investigation of acute radiation exposure and medical countermeasure testing.