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Journal of Clinical Pharmacology Jul 2024Extracorporeal membrane oxygenation (ECMO) support of critically ill pediatric patients is associated with increased risk of thromboembolic events, and unfractionated...
Extracorporeal membrane oxygenation (ECMO) support of critically ill pediatric patients is associated with increased risk of thromboembolic events, and unfractionated heparin is used commonly for anticoagulation. Given reports of acquired antithrombin (AT) deficiency in this patient population and associated concern for heparin resistance, AT activity measurement and off-label AT replacement have become common in pediatric ECMO centers despite limited optimal dosing regimens. We conducted a retrospective cohort study of pediatric ECMO patients (0 to <18 years) at a single academic center to characterize the pharmacokinetics (PK) of human plasma-derived AT. We demonstrated that a two-compartment turnover model appropriately described the PK of AT, and the parameter estimates for clearance, central volume, intercompartmental clearance, peripheral volume, and basal AT input under non-ECMO conditions were 0.338 dL/h/70 kg, 38.5 dL/70 kg, 1.16 dL/h/70 kg, 40.0 dL/70 kg, and 30.4 units/h/70 kg, respectively. Also, ECMO could reduce bioavailable AT by 50% resulting in 2-fold increase of clearance and volume of distribution. To prevent AT activity from falling below predetermined thresholds of 50% activity in neonates and 80% activity in older infants and children, we proposed potential replacement regimens for each age group, accompanied by therapeutic drug monitoring.
PubMed: 38953605
DOI: 10.1002/jcph.2493 -
Research and Practice in Thrombosis and... May 2024Implantation of a left ventricular assist device (LVAD) is a crucial therapeutic option for selected end-stage heart failure patients. However, major bleeding (MB)...
BACKGROUND
Implantation of a left ventricular assist device (LVAD) is a crucial therapeutic option for selected end-stage heart failure patients. However, major bleeding (MB) complications postimplantation are a significant concern.
OBJECTIVES
We evaluated current risk scores' predictive accuracy for MB in LVAD recipients.
METHODS
We conducted an observational, single-center study of LVAD recipients (HeartWare or HeartMate-3, November 2010-December 2022) in the Netherlands. The primary outcome was the first post-LVAD MB (according to the International Society on Thrombosis and Haemostasis [ISTH] and Interagency Registry for Mechanically Assisted Circulatory Support [INTERMACS], and INTERMACS combined with intracranial bleeding [INTERMACS+] criteria). Mortality prior to MB was considered a competing event. Discrimination (C-statistic) and calibration were evaluated for the Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly score, Hepatic or Renal Disease, Ethanol Abuse, Malignancy, Older Age, Reduced Platelet Count or Function, Re-Bleeding, Hypertension, Anemia, Genetic Factors, Excessive Fall Risk and Stroke score, Anticoagulation and Risk Factors in Atrial Fibrillation score, Outpatient Bleeding Risk Index, venous thromboembolism score, atrial fibrillation score, and Utah Bleeding Risk Score (UBRS).
RESULTS
One hundred four patients were included (median age, 64 years; female, 20.2%; HeartWare, 90.4%; HeartMate-3, 9.6%). The cumulative MB incidence was 75.7% (95% CI 65.5%-85.9%) by ISTH and INTERMACS+ criteria and 67.0% (95% CI 56.0%-78.0%) per INTERMACS criteria over a median event-free follow-up time of 1916 days (range, 59-4521). All scores had poor discriminative ability on their intended prediction timeframe. Cumulative area under the receiving operator characteristic curve ranged from 0.49 (95% CI 0.35-0.63, venous thromboembolism-BLEED) to 0.56 (95% CI 0.47-0.65, UBRS) according to ISTH and INTERMACS+ criteria and from 0.48 (95% CI 0.40-0.56, Anticoagulation and Risk Factors in Atrial Fibrillation) to 0.56 (95% CI 0.47-0.65, UBRS) per INTERMACS criteria. All models showed poor calibration, largely underestimating MB risk.
CONCLUSION
Current bleeding risk scores exhibit inadequate predictive accuracy for LVAD recipients. There is a need for an accurate risk score to identify LVAD patients at high risk of MB who may benefit from patient-tailored antithrombotic therapy.
PubMed: 38953051
DOI: 10.1016/j.rpth.2024.102437 -
Frontiers in Immunology 2024Hereditary angioedema (HAE) is a rare disease characterized by localized and self-limited angioedema (AE) attacks. A local increase of bradykinin (BK) mediates AE...
BACKGROUND
Hereditary angioedema (HAE) is a rare disease characterized by localized and self-limited angioedema (AE) attacks. A local increase of bradykinin (BK) mediates AE attacks in HAE, however the role of inflammation in HAE has been poorly explored We aim to analyze the role of inflammatory mediators in HAE patients during AE attacks.
METHODS
Patients with a confirmed HAE diagnosis due to C1 inhibitor deficiency (HAE-C1INH) or patients gene mutations (HAE-FXII) attending to our outpatient clinic between November-2019 and May-2022 were included. Demographic and clinical characteristics were analyzed. Blood samples were collected both during symptom-free periods (baseline) and during HAE attacks, and acute phase reactants (APR), such as serum amyloid A (SAA), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), D-Dimer and white blood cells were measured.
RESULTS
Seventy-eight patients were enrolled in the study, with a predominant representation of women (76%, n=59), and a mean age of 47.8 years (range 6-88). Among them, 67% (n=52) of patients had HAE-C1INH (46 classified as type 1 and 6 as type 2) while 33% (n=26) had HAE-FXII. During attack-free periods, the majority of patients exhibited normal levels of SAA, ESR, D-dimer, ACE and WCC. However, in a subset of patients (16% for SAA, 18% for ESR, and 14.5% for D-dimer), elevations were noted at baseline. Importantly, during HAE attacks, significant increases were observed in SAA in 88% of patients (p< 0.0001 vs. baseline), in ESR in 65% (p= 0.003 baseline) and D-dimer in 71% (p=0.001 . baseline) of the patients. A comparison between baseline and acute attack levels in 17 patients revealed significant differences in SAA AA (p<0. 0001), ESR (p<0.0001) and D-dimer (p= 0.004). No significant differences were observed in CRP (p=0.7), ACE (p=0.67) and WCC (p=0.54). These findings remained consistent regardless of HAE type, disease activity or location of angioedema.
CONCLUSION
The systemic increase in APR observed during HAE attacks suggests that inflammation extends beyond the localized edematous area. This finding underscores the potential involvement of inflammatory pathways in HAE and highlights the need for further investigation into their role in the pathophysiology of HAE.
Topics: Humans; Female; Male; Adult; Angioedemas, Hereditary; Middle Aged; Biomarkers; Aged; Inflammation; Adolescent; Child; Young Adult; Aged, 80 and over; Complement C1 Inhibitor Protein; Serum Amyloid A Protein; Factor XII; Blood Sedimentation; Inflammation Mediators; Fibrin Fibrinogen Degradation Products
PubMed: 38953032
DOI: 10.3389/fimmu.2024.1400526 -
RSC Advances Jun 2024Endowing implanted biomaterials with better hemocompatibility, anticoagulation, antioxidant and antiplatelet adhesion is necessary because of their potential to trigger...
Endowing implanted biomaterials with better hemocompatibility, anticoagulation, antioxidant and antiplatelet adhesion is necessary because of their potential to trigger activation of multiple reactive mechanisms including coagulation cascade and potentially causing serious adverse clinical events like late thrombosis. Active ingredients from natural sources including , , and have the ability to inhibit the coagulation cascade and thrombus formation around biomedical implants. These properties are of interest for the development of a novel drug for biomedical implants to potentially solve the current blood clotting and coagulation problems which lead to stent thrombosis. The objective of this study was to incorporate different anticoagulants from natural sources into a degradable matrix of chitosan with varying concentrations ranging from 5% to 15% and a composite containing all three drugs. The presence of anticoagulant constituents was identified using GC-MS. Subsequently, all the compositions were characterized principally by using Fourier transform infrared spectroscopy and scanning electron microscopy while the drug release profile was determined using UV-spectrometry for a 30 days immersion period. The results indicated an initial burst release which was subsequently followed by the sustained release pattern. Compared to heparin loaded chitosan, DPPH and hemolysis tests revealed better blood compatibility of natural drug loaded films. Moreover, the anticoagulation activity of natural drugs was equivalent to the heparin loaded film; however, through docking, the mechanism of inhibition of the coagulation cascade of the novel drug was found to be through blocking the extrinsic pathway. The study suggested that the proposed drug composite expresses an optimum composition which may be a practicable and appropriate candidate for biomedical implant coatings.
PubMed: 38952927
DOI: 10.1039/d4ra00796d -
Pakistan Journal of Medical Sciences Jul 2024Oure review aimed to examine evidence on the safety and efficacy of direct oral anticoagulants (DOAC) vs Vitamin K antagonists (VKA) in patients with solid organ... (Review)
Review
OBJECTIVE
Oure review aimed to examine evidence on the safety and efficacy of direct oral anticoagulants (DOAC) vs Vitamin K antagonists (VKA) in patients with solid organ transplants.
METHODS
PubMed, Embase, and Web of Science libraries were searched from inception to 25 November 2023 for all studies comparing DOAC with VKA in solid organ recipients.
RESULTS
Nine studies were included with patients who had undergone kidney, heart, or liver transplants. Meta-analysis showed that patients receiving DOAC had a significantly reduced risk of composite bleeding as compared to those with VKA (RR: 0.45 95% CI: 0.30, 0.68 I=25%). However, the risk of major bleeding was not significantly different between the two groups (RR: 0.76 95% CI: 0.40, 1.42 I=37%). Pooled analysis showed that the risk of VTE (RR: 0.90 95% CI: 0.72, 1.13 I=0%) and ischemic stroke (RR: 0.87 95% CI: 0.39, 1.94 I=12%) was not significantly different between DOAC and VKA groups.
CONCLUSION
Limited data shows that DOAC are safe and effective in patients with solid organ transplants. The overall risk of bleeding may be reduced with the use of DOAC. There is a need for randomized controlled trials comparing DOAC and VKA in such patients to obtain high-quality evidence.
PubMed: 38952515
DOI: 10.12669/pjms.40.6.9305 -
Clinical Case Reports Jul 2024Portal vein thrombosis (PVT) is a rare condition, particularly in non-cirrhotic patients. Anticoagulation remains the mainstay of the treatment. Extensive PVT can lead...
Portal vein thrombosis (PVT) is a rare condition, particularly in non-cirrhotic patients. Anticoagulation remains the mainstay of the treatment. Extensive PVT can lead to variceal bleeding, ascites, bowel ischemia, and hypersplenism. The role of thrombolysis and thrombectomy in these patients remains unclear. However, there is evidence that local thrombolysis and thrombectomy should be considered in those who remain symptomatic on anticoagulation and are at risk of complications with acute PVT.
PubMed: 38952464
DOI: 10.1002/ccr3.8920 -
Clinical Transplantation Jul 2024We aimed to evaluate the characteristics, clinical outcomes, and blood product transfusion (BPT) rates of patients undergoing cardiac transplant (CT) while receiving... (Observational Study)
Observational Study
BACKGROUND
We aimed to evaluate the characteristics, clinical outcomes, and blood product transfusion (BPT) rates of patients undergoing cardiac transplant (CT) while receiving uninterrupted anticoagulation and antiplatelet therapy.
METHODS
A retrospective, single-center, and observational study of adult patients who underwent CT was performed. Patients were classified into four groups: (1) patients without anticoagulation or antiplatelet therapy (control), (2) patients on antiplatelet therapy (AP), (3) patients on vitamin K antagonists (AVKs), and (4) patients on dabigatran (dabigatran). The primary endpoints were reoperation due to bleeding and perioperative BPT rates (packed red blood cells (PRBC), fresh frozen plasma, platelets). Secondary outcomes assessed included morbidity and mortality-related events.
RESULTS
Of the 55 patients included, 6 (11%) received no therapy (control), 8 (15%) received antiplatelet therapy, 15 (27%) were on AVKs, and 26 (47%) were on dabigatran. There were no significant differences in the need for reoperation or other secondary morbidity-associated events. During surgery patients on dabigatran showed lower transfusion rates of PRBC (control 100%, AP 100%, AVKs 73%, dabigatran 50%, p = 0.011) and platelets (control 100%, AP 100%, AVKs 100%, dabigatran 69%, p = 0.019). The total intraoperative number of BPT was also the lowest in the dabigatran group (control 5.5 units, AP 5 units, AVKs 6 units, dabigatran 3 units; p = 0.038); receiving significantly less PRBC (control 2.5 units, AP 3 units, AVKs 2 units, dabigatran 0.5 units; p = 0.011). A Poisson multivariate analysis showed that only treatment on dabigatran reduces PRBC requirements during surgery, with an expected reduction of 64.5% (95% CI: 32.4%-81.4%).
CONCLUSIONS
In patients listed for CT requiring anticoagulation due to nonvalvular atrial fibrillation, the use of dabigatran and its reversal with idarucizumab significantly reduces intraoperative BPT demand.
Topics: Humans; Female; Male; Retrospective Studies; Middle Aged; Platelet Aggregation Inhibitors; Anticoagulants; Follow-Up Studies; Heart Transplantation; Prognosis; Blood Transfusion; Risk Factors; Aged; Adult; Dabigatran; Postoperative Complications
PubMed: 38952201
DOI: 10.1111/ctr.15380 -
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi =... Jun 2024Objective To observe the expression of anti-β2 glycoprotein I (β2GPI) autoantibody in connective tissue diseases and its relationship with the degree of inflammation...
Objective To observe the expression of anti-β2 glycoprotein I (β2GPI) autoantibody in connective tissue diseases and its relationship with the degree of inflammation and immune function. Methods Patients with broad connective tissue diseases including connective tissue disease (CTD), rheumatoid arthritis (RA), Sjogren's syndrome (SS), and systemic lupus erythematosus (SLE) were observed. β2GPI was quantified by chemiluminescence, ESR was measured by Weil's method, and C-reactive protein (CRP), rheumatoid factor (RF), anti-cyclic citrullinated polypeptide (CCP) antibody were measured by automatic biochemical analyzer. Results β2GPI and their subtypes were significantly higher in RA patients compared with CTD, SS, and SLE patients. CRP was positively associated with anti-β2GPI antibody and anti-β2GPI antibody IgM in patients with connective tissue disease. ESR was positively associated with anti-β2GPI antibody. Anti-β2GPI antibody and anti-β2GPI antibody IgM were elevated in the abnormal CRP group compared with the normal CRP group. Compared with the ESR normal group, anti-β2GPI antibody and anti-β2GPI antibody IgG were elevated in the ESR abnormal group. Anti-β2GPI antibody was positively correlated with ESR and anti-CCP antibody in RA patients. Anti-β2GPI antibody IgG was positively correlated with RF. Conclusion β2GPI can be used as a predictor of the degree of inflammation and assessment of immune disorders in CTD.
Topics: Humans; Autoantibodies; beta 2-Glycoprotein I; Connective Tissue Diseases; Female; Male; Middle Aged; Adult; Inflammation; C-Reactive Protein; Rheumatoid Factor; Aged; Sjogren's Syndrome; Young Adult; Arthritis, Rheumatoid
PubMed: 38952093
DOI: No ID Found -
Alimentary Pharmacology & Therapeutics Jul 2024The incidence of major gastrointestinal bleeding (GIB) in patients on low-dose direct-acting oral anticoagulants (DOACs) is relatively unknown. Estimates from randomised...
Incidence and predictors of major gastrointestinal bleeding in patients on aspirin, low-dose rivaroxaban, or the combination: Secondary analysis of the COMPASS randomised controlled trial.
BACKGROUND
The incidence of major gastrointestinal bleeding (GIB) in patients on low-dose direct-acting oral anticoagulants (DOACs) is relatively unknown. Estimates from randomised controlled trials (RCTs) are lacking.
AIMS
To assess GIB incidence and predictors from RCT data of patients on aspirin, low-dose rivaroxaban, or both.
METHODS
This was a secondary analysis of RCT data wherein patients received aspirin 100 mg daily and rivaroxaban 2.5 mg b.d., aspirin alone, or rivaroxaban 5 mg b.d. Patients were followed from 2013 to 2016 at 602 centres. Outcomes included overall, upper, and lower GIB. We employed multivariable logistic regression to yield odds ratios (ORs) and 95% confidence intervals for potential exposures.
RESULTS
Among 27,395 patients, the annual incidence of GIB on rivaroxaban 2.5 mg b.d. with aspirin was 801.7 per 100,000 compared with 372.3 in 100,000 for aspirin. Age (OR 4.16, 2.53-6.82 for ≥75 vs. 55-64), peptic ulcer disease (PUD, OR 1.57, 1.01-2.44), liver disease (OR 2.09, 1.01-4.33), hypertension (OR 1.42, 1.04-1.94), and smoking (OR 1.85, 1.26-2.73) were associated with overall GIB. Kidney disease (OR 1.68, 1.12-2.51) was significantly associated with upper GIB, whereas diverticular disease (OR 3.75, 1.88-7.49) was associated with lower GIB. Addition of rivaroxaban to aspirin was associated more with lower GIB (OR 2.82, 1.64-4.84) than upper GIB (OR 1.86, 1.18-2.92).
CONCLUSIONS
We established incidences and identified risk factors for GIB in users of low-dose DOACs. Novel risk factors included current or former smoking and diverticulosis. Future studies should aim to validate these risk factors.
PubMed: 38952045
DOI: 10.1111/apt.18139 -
Orthopaedic Surgery Jul 2024Total hip arthroplasty (THA) remains the primary treatment option for femoral neck fractures in elderly patients. This study aims to explore the risk factors associated...
Development and Validation of a Machine Learning Algorithm to Predict the Risk of Blood Transfusion after Total Hip Replacement in Patients with Femoral Neck Fractures: A Multicenter Retrospective Cohort Study.
OBJECTIVE
Total hip arthroplasty (THA) remains the primary treatment option for femoral neck fractures in elderly patients. This study aims to explore the risk factors associated with allogeneic blood transfusion after surgery and to develop a dynamic prediction model to predict post-operative blood transfusion requirements. This will provide more accurate guidance for perioperative humoral management and rational allocation of medical resources.
METHODS
We retrospectively analyzed data from 829 patients who underwent total hip arthroplasty for femoral neck fractures at three third-class hospitals between January 2017 and August 2023. Patient data from one hospital were used for model development, whereas data from the other two hospitals were used for external validation. Logistic regression analysis was used to screen the characteristic subsets related to blood transfusion. Various machine learning algorithms, including logistic regression, SVA (support vector machine), K-NN (k-nearest neighbors), MLP (multilayer perceptron), naive Bayes, decision tree, random forest, and gradient boosting, were used to process the data and construct prediction models. A 10-fold cross-validation algorithm facilitated the comparison of the predictive performance of the models, resulting in the selection of the best-performing model for the development of an open-source computing program.
RESULTS
BMI (body mass index), surgical duration, IBL (intraoperative blood loss), anticoagulant history, utilization rate of tranexamic acid, Pre-Hb, and Pre-ALB were included in the model as well as independent risk factors. The average area under curve (AUC) values for each model were as follows: logistic regression (0.98); SVA (0.91); k-NN (0.87) MLP, (0.96); naive Bayes (0.97); decision tree (0.87); random forest (0.96); and gradient boosting (0.97). A web calculator based on the best model is available at: (https://nomo99.shinyapps.io/dynnomapp/).
CONCLUSION
Utilizing a computer algorithm, a prediction model with a high discrimination accuracy (AUC > 0.5) was developed. The logistic regression model demonstrated superior differentiation and reliability, thereby successfully passing external validation. The model's strong generalizability and applicability have significant implications for clinicians, aiding in the identification of patients at high risk for postoperative blood transfusion.
PubMed: 38951965
DOI: 10.1111/os.14160