Doses Of Heparin Research Articles

Abstract P431: Heparin-Warfarin Administered for Pulmonary Vein Thrombi Partially Dissolves Thrombi and Ameliorates Mild to Moderate Type 2 Diabetes Mellitus

Background: Pulmonary infection generates arterial thrombi, an important component of which are neutrophil extracellular traps, to defend the host. Pulmonary vein thrombi (PVTs) are underrated compared to arterial thrombi. In 2014, we reported that at least 61% (35 of 57) of elderly patients with chest pain had PVTs, as estimated using cardiac computed tomography (CT), and in 2022, we reported that 98.6% (215 of 218) of senior patients with age-related diseases such as hypertension, dyslipidemia, and type 2 diabetes mellitus (T2DM) had PVTs, as evaluated using cardiac CT and transesophageal echocardiography. T2DM is a common disease that can cause atherosclerosis, leading to ischemic stroke and acute myocardial infarction. It is important to better understand the mechanisms of T2DM and how to treat T2DM patients. The relationships between PVTs and T2DM are still unclear. Additionally, the relationships between heparin-warfarin therapy and T2DM are unknown. Methods: We identified PVTs in 15 T2DM patients (73.5 ± 9.9 y.o., range 50 y.o. to 88 y.o.; 10 males and 5 females) using both cardiac CT and transesophageal echocardiography. Among the 15 patients, two did not take DM medications; one took one DM medication; one took two DM medications; five took three DM medications; four took 4 DM medications; one took 5 DM medications; and one was treated with insulin. Results: The PVTs were partially dissolved by standard doses of heparin and warfarin given at the same time for one month. During the treatment, blood glucose levels were examined 30 minutes before breakfast, lunch, dinner and sleep. Between one and two weeks, the blood glucose levels of 10 patients decreased, especially before lunch, and some patients showed symptoms of hypoglycemia; therefore, the number of administered DM medications was decreased to zero for 6 patients and to one for 4 patients. After one month, the patients’ HbA1c levels had decreased slightly. We treated 10 patients with warfarin for the next several months, none of whom needed to resume DM medications, although their blood glucose tended to increase slightly. Three patients with comparatively severe T2DM showed no change in blood glucose following therapy. Conclusions: Heparin-warfarin therapy partially dissolved PVTs and decreased DM medications in patients with mild to moderate T2DM.

Normalizing Anti-Thrombin III for heparin management during routine cardiopulmonary bypass for congenital cardiothoracic surgery: A single institution practice review.

Over the past decade, there has been an increase in the use of recombinant Anti-Thrombin III (AT-III) administration during neonatal and pediatric short- and long-term mechanical support for the replacement of acquired deficiencies. Recombinant AT-III (Thrombate) administration is an FDA licensed drug indicated primarily for patients with hereditary deficiency to treat and prevent thromboembolism and secondarily to prevent peri-operative and peri-partum thromboembolism. Herein we propose further use of Thrombate for primary AT-III deficiency of the newborn as well as for acquired dilution and consumption secondary to cardiopulmonary bypass (CPB). All patients undergoing CPB obtain a preoperative AT-III level. Patients with identified deficiencies are normalized in the OR using recombinant AT-III as a patient load, in the CPB prime, or both. Patient baseline Heparin Dose Response (HDR) is assessed using the Heparin Management System (HMS) before being exposed to AT-III. If a patient load of AT-III is given, a second HDR is obtained and this AT-III Corrected HDR is used as the primary goal during CPB. Once CPB is initiated, an AT-III level is obtained with the first patient blood analysis. A subtherapeutic level results in an additional dose of AT-III. During the rewarm period, a final AT-III level is obtained and AT-III treated once again if subtherapeutic. A retrospective, matched analysis review of practice analyzing two groups, a Study Group (Repeat HDR, May 2022 onward) and Matched Group (Without Repeat HDR, July 2019 to April 2022), for age (D), weight (Kg) and operation was conducted. The focus of the study was to determine any change in heparin sensitivity identified post AT-III patient bolus load in the HDR (U/mL), Slope (U/mL/s), ACT (s), and total amount of heparin on CPB (U) and protamine (mg) used in each group. No significance was seen in Baseline AT-III (%), post heparin load HDR (U/mL), first CPB ACT (s), first CPB HDR (U/mL), or total CPB heparin (u/Kg) between the two groups. Statistical significance was seen in Baseline ACT (s), Baseline HDR (U/mL), Baseline Slope (U/mL/s), Post Heparin Load ACT (s), first CPB AT-III (%), and Protamine (mg/Kg) (p < .05). No statistical significance was seen in the Study Intragroup between pre versus post AT-III patient load baseline sample in ACT (s), however significance was seen in HDR (U/mL) and Slope (U/mL/s) (p < .05). Implementation of AT-III monitoring and therapy before and during CPB in conjunction with the HMS allows patients to maintain a steady state of anticoagulation with overall less need for excessive heparin replacement and potentially thrombin activation. The result is obtaining a steady state of anticoagulation, a reduced fluctuation in the heparin and ACT levels and a potential for lower co-morbidities associated with prolonged CPB times.

Diagnosis and treatment of venous thromboembolism during pregnancy relate to genetic polymorphism.

Previous research had shown that age, a positive family history, comorbidities, major surgical operations, gestation, and use of several medications could increase the incidence of venous thromboembolism (VTE). With the development of medical and clinical individualized treatment, many people exposed to above risk factors did not develop VTE, suggested that genetic factors are also involved in the development of VTE. In this review, we aim to summarize VTE diagnosis and treatment in pregnancy women related to gene polymorphism. A comprehensive electronic search using PubMed, MEDLINE, EMBASE and Web of Science was conducted to find relevant journal articles with key search terms including: "pregnancy OR pregnant," "venous thromboembolism OR VTE," "deep vein thrombosis OR DVT," "pulmonary embolism OR PE," and "genetic OR gene." Prominent publications from establishment of database till present were analysed to achieve a deeper understanding of VTE during pregnancy relate to genetic polymorphism, and the information was then collated to form this review. The literature review revealed that inherited thrombophilia significantly associated with the development of VTE, especially the factor V Leiden (FVL) and prothrombin gene mutation (PGM). Furthermore, the role of methylenetetrahydrofolate reductase (MTHFR) gene mutation in the development of pregnancy-related VTE remains controversial, further study is required. In the present study, Marburg I polymorphism (G511E), c.1538G>A and c.1601G>A in Factor V (FV), JAK2V617F mutation were reported as an independent risk factor for VTE, there is no sufficient evidence to confirm the gene mutation is related to VTE during pregnancy, these factors appearing as another promising potential diagnostic marker of VTE during pregnancy. Besides, the dosages of heparin in the treatment of VTE during pregnancy need be adjusted according to gene polymorphism of these population, particularly FVL or PGM carriers, and this area is not studied deeply, it is worth further study. Inherited thrombophilia significantly associated with the development of VTE, especially the FVL and PGM, however the relation between MTHFR gene mutation and pregnancy-related VTE remains controversial, further study is needed. In addition, the dosages of heparin in the treatment of VTE during pregnancy suggested to adjusted based on gene polymorphism in FVL and PGM, and establish better prediction models is a direction of future research.

Heparin Dosing During Percutaneous Coronary Intervention and Obesity.

Unfractionated heparin is the most common anticoagulant used during percutaneous coronary intervention. Practice guidelines recommend an initial weight-based heparin bolus dose between 70 and 100 U/kg to achieve target activated clotting time (ACT) of 250-300 seconds. The impact of severe obesity on weight-based heparin dosing is not well studied. We performed a retrospective analysis of 424 patients undergoing percutaneous coronary intervention who received heparin for anticoagulation. We collected detailed data on cumulative heparin administration and measured ACT values in this cohort. We performed separate analyses to identify clinical predictors that may affect dose-response curves. There was significant variability in dosing with mean dose of 103.9 ± 32-U/kg heparin administered to achieve target ACT ≥ 250 seconds. Women received higher initial heparin doses when adjusted for weight than men (97.6 ± 31 vs. 89 ± 28 U/kg, P = 0.004), and only 49% of patients achieved ACT ≥ 250 s with the initial recommended heparin bolus dose (70-100 U/kg). Lower heparin dose (U/kg) was required in obese patients to achieve target ACT. In multivariate linear regression analysis with ACT as dependent variable, after inclusion of weight-based dosing for heparin, body mass index was the only significant covariate. In conclusion, there is significant variability in the therapeutic effect of heparin, with a lower weight-adjusted heparin dose required in obese patients.

Effects of Extracorporeal Membrane Oxygenation on the Coagulation System.

This study aimed to investigate the effects of long-term awake extracorporeal membrane oxygenation (ECMO) on the coagulation system in a sheep model. A total of ten healthy sheep were included in the study, with 5 sheep in each group. In the veno-arterial ECMO (V-A ECMO) group, cannulation was performed in the right carotid artery and the right external jugular vein. In the veno-venous ECMO (V-V ECMO) group, a dual-lumen catheter was utilized to insert into the right external jugular vein. After initiating ECMO, the sheep were recovered from anesthesia and remained awake for 7 days. The target activated clotting time (ACT) goal was set at 220-250 s. In both groups, the actual ACT fluctuated around 250 s with the dose of heparin gradually increasing, reaching almost 60 IU/kg/min at the end of the experiments. Moreover, the activated partial thromboplastin time (APTT) and thrombin time (TT) values were significantly higher in the V-A ECMO group compared to the V-V ECMO group, despite receiving the same doses of heparin. Although laboratory test results fluctuated within a normal and reasonable range, infarct foci in the kidneys were observed in both groups at the end of the study.

Contributing factors to heparin resistance during cardiopulmonary bypass.

Since the risk factors for heparin resistance (HR) before cardiopulmonary bypass (CPB) have not been fully clarified, this study investigated the contributing factors for HR after the initial unfractionated heparin (UFH) dose of 500IU/kg. We retrospectively analyzed the data of 371 patients who underwent CPB surgery, with the initial UFH dose of 500IU/kg, between May 2017 and December 2021. We defined HR as the failure to achieve activated clotting time (ACT) of > 480s after the initial UFH dose of 500IU/kg. HR was observed in 36 patients (9.7%) (HR group), while HR was not observed in 335 patients (control group). The HR group included significantly more patients with preoperative use of UFH, with significantly higher white blood cell counts, fibrinogen, fibrinogen degradation products, D-dimer, and C-reactive protein, and lower hemoglobin and albumin. The multivariable logistic regression analysis identified albumin (OR: 3.09, 95% CI 1.3504-7.0845, p = 0.0075) and fibrinogen (OR: 0.99, 95% CI 0.9869-0.9963, p = 0.0003) as independent predictors for HR. Using the Youden index, the cutoffs of albumin and fibrinogen were calculated as 3.8g/dL and 303mg/dL, respectively. The receiver operating characteristic curves showed the predictive performance of albumin (area under the curve (AUC): 0.78, sensitivity: 65%, specificity: 81%) and fibrinogen (AUC: 0.77, sensitivity: 56%, specificity: 88%). The incidence of HR after the initial UFH dose of 500IU/kg was 9.7%. The preoperative albumin < 3.8g/dL and fibrinogen > 303mg/dL were independent predictors for HR.

Comparison of Blood Concentration and Weight-Based Heparin and Protamine Dosing Strategies for Cardiopulmonary Bypass: A Systematic Review and Meta-Analysis.

The conventional method of heparin and protamine management during cardiopulmonary bypass (CPB) is based on total body weightwhich fails to account for the heterogeneous response to heparinin each patient. On the other hand, the literature is inconclusive on whether individualized anticoagulation management based on real-time blood heparin concentration improves post-CBP outcomes. We searched databases of Medline, Excerpta Medica dataBASE (EMBASE), PubMed, Cumulative Index to Nursing and Allied Health Literature (CINHL), and Google Scholar, recruiting randomized controlled trials (RCTs) and prospective studies comparing the outcomes of dosing heparinand/or protamine based on measured heparin concentration versus patient'stotal body weightfor CPB.Random effects meta-analyses and meta-regression were conducted to compare the outcome profiles. Primary endpoints include postoperative blood loss and the correlation with heparin and protamine doses, the reversal protamine and loading heparin dose ratio; secondary endpoints included postoperative platelet counts, antithrombin III, fibrinogen levels, activated prothrombin time (aPTT), incidences of heparin rebound, and re-exploration of chest wound for bleeding. Twenty-six studies, including 22 RCTs and four prospective cohort studies involving 3,810 patients, were included.Compared to body weight-based dosing, patients of individualized, heparin concentration-based group had significantly lower postoperative blood loss (mean difference (MD)=49.51mL, 95% confidence interval (CI): 5.33-93.71), lower protamine-to-heparin dosing ratio (MD=-0.20, 95% CI: -0.32~ -0.12), and higher early postoperative platelet counts (MD=8.83, 95% CI: 2.07-15.59). The total heparin doses and protamine reversal were identified as predictors of postoperative blood loss by meta-regression. There was a significant correlation between the doses of heparin and protamine with postoperative blood loss; therefore, précised dosing of both could be critical for reducingbleeding and transfusion requirements. Data from the enrolled studies indicated that compared to conventional weight-based dosing, individualized, blood concentration-based heparin and protamine dosing may have outcome benefits reducing postoperative blood loss.The dosing calculation of heparin based on the assumption of a one-compartment pharmacokinetic/pharmacodynamic (PK/PD) model and linear relationship between the calculated dose and blood heparin concentration may be inaccurate.With the recent advancement of the technologies of machine learning, individualized, precision management of anticoagulation for CPB may be possible in the near future.

Impact of anticoagulation intensity on blood transfusion for venoarterial extracorporeal membrane oxygenation during lung transplantation

Venoarterial ECMO is increasingly used for mechanical circulatory support during lung transplant. Optimal intensity of intraoperative anticoagulation would be expected to mitigate thromboembolism without increasing bleeding and blood product transfusions. Yet, the optimal intensity of intraoperative anticoagulation is unknown. We performed a retrospective cohort study of 163 patients who received a bilateral lung transplant at a single center. We categorized intensity of anticoagulation into four groups (very low to high) based on the bolus dose of unfractionated heparin given during lung transplant and compared the rates of intraoperative blood transfusions and the occurrence of thromboembolism between groups. When compared to the very low intensity group, each higher intensity group was associated with higher red blood cell, fresh frozen plasma, and platelet transfusions. The occurrence of thromboembolism was similar across groups. These preliminary data suggest that lower intensity anticoagulation may reduce the rate of intraoperative blood transfusions although further study is needed.

Evaluation of anticoagulant effect and predicted dose of low molecular weight heparin in hemodialysis by anti-Ⅹa factor activity

The purpose of this study was to explore the reasonable dose of low molecular weight heparin (LMWH) in hemodialysis (HD) and the strategy of preventing extracorporeal circuit coagulation (ECC). A retrospective case-control study included patients who used LMWH for anticoagulation during maintenance hemodialysis (MHD) in the Hemodialysis Center of Beijing Hospital from December 2020 to January 2021. Basic data such as weight, height, basic kidney disease, dialysis age and anti-Ⅹa factor activity before, during and after dialysis were collected. A total of 46 patients were enrolled in this study, including 5 patients in coagulation group (10.9%) and 41 patients in non-coagulation group (89.1%). The anti-Ⅹa factor activity reached its peak at 0.5 h after the start of HD. The level of anti-Ⅹa factor was incorporated into the receiver operating characteristic curve (ROC curve). The results showed that the area under the ROC curve (AUC) was 0.802 (95% confidence interval: 0.651-0.54, P=0.029), and the cutoff was 0.31 IU/ml (sensitivity 1, specificity 0.683). It is suggested that the body surface area should be used as the basis to estimate the anticoagulant dose of LMWH in HD, and the activity of HD 4 h anti-Ⅹa factor ≤0.31 IU/ml, which is of diagnostic value for ECC. In addition, the results of binary logistic regression analysis showed that dialysis age was an independent risk factor for ECC (OR value 1.319, 95%CI 1.052-1.654, P=0.017). In summary, this study reveals that dialysis age may be a risk factor for ECC and that the activity of HD 4 h anti-Ⅹa factor ≤0.31 IU/ml can be used as a potential diagnostic cut-off point for ECC in HD patients, which provides a scientific basis for monitoring strategies to prevent blood coagulation in HD filters.

Antithrombin Levels and Heparin Responsiveness during Venoarterial Extracorporeal Membrane Oxygenation: A Prospective Single-center Cohort Study.

Unfractionated heparin, administered during venoarterial extracorporeal membrane oxygenation to prevent thromboembolic events, largely depends on plasma antithrombin for its antithrombotic effects. Decreased heparin responsiveness seems frequent on extracorporeal membrane oxygenation; however, its association with acquired antithrombin deficiency is poorly understood. The objective of this study was to describe longitudinal changes in plasma antithrombin levels during extracorporeal membrane oxygenation support and evaluate the association between antithrombin levels and heparin responsiveness. The hypothesis was that extracorporeal membrane oxygenation support would be associated with acquired antithrombin deficiency and related decreased heparin responsiveness. Adults receiving venoarterial extracorporeal membrane oxygenation were prospectively included. All patients received continuous intravenous unfractionated heparin using a standardized protocol (target anti-Xa 0.3 to 0.5 IU/ml). For each patient, arterial blood was withdrawn into citrate-containing tubes at 11 time points (from hour 0 up to day 7). Anti-Xa (without dextran or antithrombin added) and antithrombin levels were measured. The primary outcome was the antithrombin plasma level. In the absence of consensus, antithrombin deficiency was defined as a time-weighted average of antithrombin less than or equal to 70%. Data regarding clinical management and heparin dosage were collected. Fifty patients, including 42% postcardiotomy, were included between April 2020 and May 2021, with a total of 447 samples. Median extracorporeal membrane oxygenation duration was 7 (interquartile range, 4 to 12) days. Median antithrombin level was 48% (37 to 60%) at baseline. Antithrombin levels significantly increased throughout the follow-up. Time-weighted average of antithrombin levels was 63% (57 to 73%) and was less than or equal to 70% in 32 (64%) of patients. Overall, 45 (90%) patients had at least one antithrombin value less than 70%, and 35 (70%) had at least one antithrombin value less than 50%. Antithrombin levels were not significantly associated with heparin responsiveness evaluated by anti-Xa assay or heparin dosage. Venoarterial extracorporeal membrane oxygenation support was associated with a moderate acquired antithrombin deficiency, mainly during the first 72 h, that did not correlate with heparin responsiveness.

Non-Thyroidal Illness in Chronic Renal Failure: Triiodothyronine Levels and Modulation of Extra-Cellular Superoxide Dismutase (ec-SOD).

Oxidative stress (OS) is implicated in several chronic diseases. Extra-cellular superoxide dismutase (ec-SOD) catalyses the dismutation of superoxide anions with a protective role in endothelial cells. In chronic kidney disease (CKD), OS and thyroid dysfunction (low fT3 syndrome) are frequently present, but their relationship has not yet been investigated. This cohort study evaluated ec-SOD activity in CKD patients during haemodialysis, divided into "acute haemodialytic patients" (AH, 1-3 months of treatment) and "chronic haemodialytic patients" (CH, treated for a longer period). We also evaluated plasmatic total antioxidant capacity (TAC) and its relationships with thyroid hormones. Two basal samples ("basal 1", obtained 3 days after the last dialysis; and "basal 2", obtained 2 days after the last dialysis) were collected. On the same day of basal 2, a sample was collected 5 and 10 min after the standard heparin dose and at the end of the procedure. The ec-SOD values were significantly higher in CH vs. AH in all determinations. Moreover, the same patients had lower TAC values. When the CH patients were divided into two subgroups according to fT3 levels (normal or low), we found significantly lower ec-SOD values in the group with low fT3 in the basal, 5, and 10 min samples. A significant correlation was also observed between fT3 and ec-SOD in the basal 1 samples. These data, confirming OS and low fT3 syndrome in patients with CKD, suggest that low fT3 concentrations can influence ec-SOD activity and could therefore potentially contribute to endothelial oxidative damage in these patients.

Splenic Infarction and Myocardial Infarction in A Patient with COVID-19 on Anticoagulant Therapy with Normal D-Dimer Levels

Many studies have shown that COVID-19 can progress with coagulopathy and multisystem thrombotic pathologies. This article presents the case of a patient who, 9 days after laboratory-confirmed coronavirus pneumonia against the background of anticoagulant therapy, was diagnosed with splenic infarction in combination with acute myocardial infarction during subsequent hospitalization. Prevention of thrombosis with prophylactic doses of low molecular weight heparin in hospitalized patients with COVID-19 may not be sufficient to prevent the development of coagulopathy. Abdominal visceral thromboembolism should be suspected in a COVID-19 positive patient with abdominal pain despite anticoagulant therapy and normal D-dimer levels.

P-11 Case report of Primary Hyperparathyroidism and Pulmonary Embolism

Abstract Introduction Primary hyperparathyroidism (PHPT) is a disorder characterized by excessive parathyroid hormone secretion, resulting in hypercalcaemia. Patients with PHPT are believed to be in a hypercoagulable state due to the role of calcium in the platelet function and the coagulation pathway. Clinical Case An 82-year-old male with a background history of deep vein thrombosis twelve years ago, was admitted with left leg pain following a fall, he was found to have an intra-capsular left neck of femur fracture for which he underwent left hip hemiarthroplasty at a later stage during his admission. He was also found to have adjusted calcium of 2.9 mmol/L at admission, parathyroid hormone of 15.2 pmol/L, raised urine calcium-creatinine ratio of 0.39 and he was vitamin D replete (vitamin D 50.3 nmol/L). He was treated for delirium and a urinary tract infection and his inflammatory markers continued to worsen, this triggered performing a CT scan of the chest, abdomen and pelvis, which revealed a right parathyroid nodule and an acute pulmonary embolism (PE). He was commenced on prophylactic dose of low molecular weight heparin at admission, it was changed to a therapeutic dose of low molecular weight heparin after the PE diagnosis and then to Apixaban for three months. The patient was assessed to not be suitable for parathyroidectomy, the decision was made to manage the PHPT medically and he is going to be followed up locally at the Endocrinology Clinic. Conclusion There have been few case reports suggesting a correlation between the hypercalcaemic PHPT and the risk of venous thromboembolism. Ionised calcium is necessary for thrombin formation, platelet activation and aggregation, as well as activation of various clotting factors, such as factor VII and factor X. Studies have also shown that these patients have increased protein S activity and fibrinogen levels. This case, among other cases that we have observed in our hospital, highlights that the hypercalcaemia could pose an additional hypercoagulability risk in the presence of other risk factors.

Evidence-Based Approaches to Anticoagulation in Reconstructive Microsurgery-A Systematic Literature Review.

This systematic review addresses the crucial role of anticoagulation in microsurgical procedures, focusing on free flap reconstruction and replantation surgeries. The objective was to balance the prevention of thrombotic complications commonly leading to flap failure, with the risk of increased bleeding complications associated with anticoagulant use. A meticulous PubMed literature search following Evidence-Based-Practice principles yielded 79 relevant articles, including both clinical and animal studies. The full-texts were carefully reviewed and evaluated by the modified Coleman methodology score. Clinical studies revealed diverse perioperative regimens, primarily based on aspirin, heparin, and dextran. Meta-analyses demonstrated similar flap loss rates with heparin or aspirin. High doses of dalteparin or heparin, however, correlated with higher flap loss rates than low dose administration. Use of dextran is not recommended due to severe systemic complications. In animal studies, systemic heparin administration showed predominantly favorable results, while topical application and intraluminal irrigation consistently exhibited significant benefits in flap survival. The insights from this conducted systematic review serve as a foundational pillar towards the establishment of evidence-based guidelines for anticoagulation in microsurgery. An average Coleman score of 55 (maximum 103), indicating low overall study quality, however, emphasizes the need for large multi-institutional, randomized-clinical trials as the next vital step.

Factors Affecting Heparin Induced Thrombocytopenia: A Case Series Study

Heparin-induced thrombocytopenia (HIT) is a condition that can affect patients who are exposed to heparin across a variety of disease states. A case series study was conducted to evaluate the effect of patient age, unfractionated heparin dose and nadir platelet count on the 4T score in a multiple regression analysis. The number of cases selected was ten. The regression analysis showed that patient age and nadir platelet count were statistically significant (P&lt;.05) and the R-squared value was 0.7. A Pearson correlation coefficient analysis also revealed a low positive correlation between heparin dose and platelet count (r = 0.3). These findings add to the body of knowledge encompassing unfractionated heparin which remains a widely used anticoagulant for patients with thrombotic disease and other conditions and procedures. Future studies should continue to evaluate factors that affect HIT including outcomes between Type I and Type II HIT.

Once daily vs twice daily dose of low molecular weight heparin in treatment of severe acute pancreatitis: A randomized, controlled, open-label, pilot study

Once daily vs twice daily dose of low molecular weight heparin in treatment of severe acute pancreatitis: A randomized, controlled, open-label, pilot study

An animal study to evaluate the safety and efficacy of a novel superelastic sizing device

Aim: Atrial septal defect measurement can be performed by stretching balloon diameter, two- and 3-dimensional transesophageal echocardiography (TEE). We evaluated a new superelastic sizing device (SSD) for deliniation of atrial septal defect margins and exact measurement without changing anatomy of the defect. Material and Methods: An artificial ASD was created in 8 swines and defect sizing was done by TEE and SSSD in fluoroscopy and autopsy. Correlation analysis was done between 3 methods in defect size measurement. Any adverse events, such as mortality or heart perforation were assessed. Results: There was a cardiac tamponade case in one animal because of the limited animal experience of the operator. Thrombus formation was observed in some animals due to prolongation of procedure time and low heparin dosage. SSD and TEE correlation (r=0.97, p&lt;0.0001); TEE and autopsy correlation (r=0.973, p&lt;0.0001); SSD and autopsy correlation (r=0.993; p&lt;0.0001) all were statistically significant. Conclusion: In our animal study superelastic sizing device precisely delineated atrial septal defect margins on TEE and fluoroscopy. SSD measurements showed good correlation with TEE and autopsy measurements. The right and left portions of the device were well formed and central indentation allowed exact sizing of the atrial septal defect margins.

Heparin dosing in patients with Impella-supported cardiogenic shock

BackgroundImpella™ is increasingly used in cardiogenic shock. However, thromboembolic and bleeding events are frequent during percutaneous mechanical circulatory support (pMCS). ObjectiveTherefore, we aimed to explore the optimal anticoagulation regime for pMCS to prevent thromboembolism and bleedings. MethodsThis hypothesis-generating multi-center cohort study investigated 170 patients with left-Impella™ support. We (A) compared bleeding/thrombotic events in two centers with therapeutic range (TR-aPTT) activated partial thromboplastin time (60–80s) and (B) compared events of these centers with one center with intermediate range aPTT (40–60s). ResultsAfter matching, there were no differences in patients' characteristics. In centers aiming at TR-aPTT, major bleeding was numerically lower with aPTT <60s within 48 h of left-Impella™ support, versus patients that achieved the aimed aPTT of ≥60s [aPTT ≥60s: 22 (37.3%) vs. aPTT<60s 14 (23.7%); Hazard ratio [HR], 0.62 (95%) CI, 0.28–1.38; p = 0.234]. Major cardiovascular and cerebrovascular adverse events (MACCE) did not differ between groups. In comparison of centers, TR-aPTT strategy showed higher major bleeding rates [TR: 8 (47.1%) vs. intermediate range: 1 (5.9%); HR, 0.06 (95%) CI, 0.01–0.45; p = 0.006]. MACCE were lower in the intermediate range aPTT group as well [TR 12 (70.6%) vs. intermediate range 5 (29.4%) HR, 0.32 (95%) CI, 0.11–0.92; p = 0.034]. ConclusionThis pilot analysis showed that lowering UFH-targets in left-Impella™ supported CS patients seems to be a safe and promising strategy for reducing major bleedings without increasing MACCE. This needs to be validated in larger, randomized clinical trials.

Effect of acute heparin administration on glycocalyx thickness and endothelial function in healthy younger adults.

The endothelial glycocalyx is a dynamic, gel-like layer that is critical to normal vascular endothelial function. Heparin impairs the endothelial glycocalyx and reduces vascular endothelial function in a murine model; however, this has yet to be tested in healthy humans. We hypothesized that a single bolus dose of heparin would increase circulating glycocalyx components and decrease endothelial glycocalyx thickness resulting in blunted brachial artery vasodilation in healthy younger adults. Healthy adults (n = 19, aged 18-39 yr, 53% female) underwent measurements of the endothelial glycocalyx and vascular endothelial function at baseline and after a single bolus 5,000 U dose of heparin. The glycocalyx components syndecan-1 and heparan sulfate were measured from plasma samples using enzyme-linked immunosorbent assays. Glycocalyx thickness was determined as perfused boundary region (PBR) in sublingual microvessels using the GlycoCheck. Endothelial function was measured via ultrasonography and quantified as brachial artery flow-mediated dilation (FMD). Following acute heparin administration, there was no increase in syndecan-1 or heparan sulfate (P = 0.90 and P = 0.49, respectively). In addition, there was no change in PBR 4-7 µm (P = 0.55), PBR 10-25 µm (P = 0.63), or 4-25 µm (P = 0.49) after heparin treatment. Furthermore, we did not observe a change in FMDmm (P = 0.23), FMD% (P = 0.35), or plasma nitrite concentrations (P = 0.10) in response to heparin. Finally, time to peak dilation and peak FMD normalized to shear stress were unchanged following heparin (P = 0.59 and P = 0.21, respectively). Our pilot study suggests that a single bolus intravenous dose of heparin does not result in endothelial glycocalyx degradation or vascular endothelial dysfunction in healthy younger adults.NEW & NOTEWORTHY The endothelial glycocalyx's role in modulating vascular endothelial dysfunction with aging and disease is becoming increasingly recognized. This study presents novel findings that acute heparin administration is not a feasible method to experimentally degrade the endothelial glycocalyx and measure concurrent changes in vascular endothelial function in healthy humans. Alternative approaches will be needed to translate findings from preclinical studies and test the effects of acute endothelial glycocalyx degradation on vascular endothelial function in humans.

Unpredictable Blood Product Usage in Orthotropic Liver Transplantation: A Foregone Conclusion or A Problem Solved by Artificial Intelligence?

Abstract Introduction/Objective Orthotropic liver transplantation (OLT) is a complex procedure requiring coordination between operative and transfusion medicine staff. Unanticipated blood product demands during these surgeries strain blood bank inventory, especially when units are needed for patients with significant alloantibodies. Currently, transfusion medicine services issue set numbers of crossmatched red blood cell (RBC) units for these procedures. At our institution, 10 units are issued for each OLT. This project categorized OLT patients into three groups by RBC unit requirements: &amp;lt;5 units, 5-9 units and &amp;gt;10 units. Furthermore, we identified pre-operative clinical and lab factors predicting placement into each category. From this data, we developed an artificial intelligence platform (CCBBAI-1). Methods/Case Report We collected data from 474 adults (&amp;gt;18 years old) that underwent OLT from Jan. 1, 2021, to Dec. 31, 2022. Demographic, anticoagulant, and lab testing data generated within 24 hours of admission were obtained. Data analysis was performed in R-studio. CCBBAI-1 was built using machine intelligence learning optimizer platform (MILO). Results (if a Case Study enter NA) Based on univariate regression analysis (p-value&amp;lt;0.05, 95% confidence interval (CI)), the following lab variables were predictive of &amp;gt;10 RBC units issued: high INR (OR 3.48 [CI 2.35-5.26]), admission heparin dosage (2.61 [1.56-4.31]), total bilirubin (1.06 [1.04-1.08]), conjugated bilirubin (1.08 [1.04-1.11]), PTT (1.04 [1.03-1.06]), BUN (1.03 [1.02-1.04]), and creatinine (1.55 [1.33-1.83]). Low albumin (1.50 [1.13-2.22]) and MCV (1.04 [1.02-1.07]) also projected a 10 RBC unit procedural requirement. The univariate regression analysis variables predictive in categorizing patients requiring 5-9 units vs &amp;lt; 5 units were as follows: decreased albumin (2.17 [1.42-3.33]), decreased serum calcium level (1.72 [1.13-2.63]) and elevated INR (2.14 [1.36-3.40]). The mean number of units issued for each patient group including those requiring &amp;gt;10, 5-9, and &amp;lt;5 units were 22, 7, and 2 units, respectively. CCBBAI-1 achieved a sensitivity of 87.0% and specificity of 70.0% in classifying patients requiring &amp;gt;10 RBC units. Patients needing &amp;lt;10 units were analyzed in a second module to determine if they needed 5-9 units, achieving a sensitivity of 64.7% and a specificity of 62.4%. Conclusion Our study divided OLT patients into three categories and identified predictive laboratory values characterizing each group, a step towards improving transfusion medicine efficacy in this context.