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Clinical Chemistry and Laboratory... Jun 2024Monoclonal gammopathies frequently associate with hemostatic alterations. Thrombotic events occur with high incidence particularly upon treatment, while in rarer cases...
OBJECTIVES
Monoclonal gammopathies frequently associate with hemostatic alterations. Thrombotic events occur with high incidence particularly upon treatment, while in rarer cases hemorrhagic diathesis can be observed. The pathology of these tendencies could be caused by thrombocytopenia or hyperviscosity burden of circulating monoclonal antibodies. Studies also suggest interference of monoclonal antibodies with primary hemostasis. We isolated monoclonal whole IgG paraproteins from two myeloma patients to observe their effect on thrombin formation and fibrin polymerization.
METHODS
Monoclonal whole IgG was prepared from sera of two newly diagnosed untreated multiple myeloma patients and control normal plasma samples. Fibrin formation was measured using thrombin time and dilute prothrombin time tests and thrombin formation was detected with a fluorimetric thrombin generation assay. In addition, molecular interactions were investigated by surface plasmon resonance (SPR).
RESULTS
Thrombin time was prolonged upon addition of monoclonal IgG even at 30 g/L by 12 %, increasing up to 36 % at 60 g/L concentration. Dilute prothrombin time was prolonged by 20 % even at 30 g/L. Thrombin generation assay indicated an impairment in thrombin formation at the presence of monoclonal IgG compared to polyclonal at equivalent concentration. By an SPR assay we determined that both clonality IgG preparations interacted with fibrinogen, however interaction with human thrombin was only detected with monoclonal immunoglobulins (K=1.03 × 10 M).
CONCLUSIONS
Here we provide evidence that isolated monoclonal whole IgG from myeloma patients can impair both fibrin and thrombin formation and we demonstrate by SPR assay that it interacts with components of the final phase of the coagulation system.
PubMed: 38912717
DOI: 10.1515/cclm-2024-0252 -
Frontiers in Immunology 2024The intimal hyperplasia (IH) and vascular remodelling that follows endovascular injury, for instance after post-angioplasty re-stenosis, results in downstream ischaemia...
Neointimal hyperplasia after endoluminal injury in mice is dependent on tissue factor- and angiopoietin-2 dependent interferon gamma production by fibrocytes and macrophages.
BACKGROUND
The intimal hyperplasia (IH) and vascular remodelling that follows endovascular injury, for instance after post-angioplasty re-stenosis, results in downstream ischaemia and progressive end organ damage. Interferon gamma (IFNγ) is known to play a critical role in this process. In mouse models we have previously shown that fibrocytes expressing tissue factor (TF) are recruited early to the site of injury. Through thrombin generation and protease activated receptor-1 (PAR-1) activation, fibrocytes secrete angiopoietin-2, stimulate neointimal cell proliferation, inhibit apoptosis and induce CXCL-12 production, all of which contribute to the progressive IH that then develops. In this study we investigated the relationship between TF, angiopoietin-2 and IFNγ.
METHODS AND RESULTS
IH developing in carotid arteries of wild-type mice 4 weeks after endoluminal injury contained a significant proportion of IFNγ+ fibrocytes and macrophages, which we show, using a previously defined adoptive transfer model, were derived from circulating CD34+ cells. IH did not develop after injury in IFNγ-deficient mice, except after transplantation of WT bone marrow or adoptive transfer of WT CD34+ cells. , CD34+ cells isolated from post-injury mice did not express IFNγ, but this was induced when provided with FVIIa and FX, and enhanced when prothrombin was also provided: In both cases IFNγ secretion was TF-dependent and mediated mainly through protease activated PAR-1. IFNγ was predominantly expressed by fibrocytes. , all IFNγ+ neointimal cells in WT mice co-expressed angiopoietin-2, as did the small numbers of neointimal cells recruited in IFNγ-/- mice. Adoptively transferred WT CD34+ cells treated with either an anti-TIE-2 antibody, or with siRNA against angiopoetin-2 inhibited the expression of IFNγ and the development of IH.
CONCLUSION
TF-dependent angiopoietin-2 production by newly recruited fibrocytes, and to a lesser extent macrophages, switches on IFNγ expression, and this is necessary for the IH to develop. These novel findings enhance our understanding of the pathophysiology of IH and expose potential targets for therapeutic intervention.
Topics: Animals; Mice; Interferon-gamma; Angiopoietin-2; Neointima; Macrophages; Hyperplasia; Thromboplastin; Mice, Knockout; Mice, Inbred C57BL; Disease Models, Animal; Male; Fibroblasts; Carotid Artery Injuries
PubMed: 38911855
DOI: 10.3389/fimmu.2024.1345199 -
Annals of Indian Academy of Neurology May 2024Pharmacogenomics plays an important role in drug metabolism. A stable anticoagulation is important for primary and secondary prevention of cardioembolic stroke and...
OBJECTIVE
Pharmacogenomics plays an important role in drug metabolism. A stable anticoagulation is important for primary and secondary prevention of cardioembolic stroke and cerebral venous sinus thrombosis (CVST). We report the role of cytochrome P450 ( CYP2C9*2/*3 ) and vitamin K epoxide reductase subunit 1 ( VKORC1 ) genotypes and acquired causes in maintaining stability of anticoagulation following acenocoumarin in cardioembolic stroke and CVST.
METHODS
The study comprised 157 individuals with cardioembolic stroke and CVST who were on acenocoumarin. Their comorbidities, comedication, and dietary habits were noted. Prothrombin time and international normalized ratio (INR) were measured during follow-up, and the coagulation status was categorized as stable (>50% occasions in therapeutic range) and unstable (>50% below and above therapeutic range). Genotyping of VKORC1 , CYP2C9*2 , and CYP2C9*3 was done by polymerase chain reaction-restriction fragment length polymorphism. Bleeding and embolic complications were noted. The predictors of unstable INR were evaluated using multivariate analysis.
RESULTS
INR was stable in 47.8% and unstable in 52.2% of patients. Patients with mutant genotypes required low dose of acenocoumarin. The predictors of unstable INR were metallic valve (odds ratio [OR] 4.07, 95% confidence interval [CI] 1.23-13.49, P = 0.02), use of digoxin (OR 0.031, 95% CI 0.13-0.74, P = 0.09), proton pump inhibitor (OR 0.23, 95% CI 0.06-0.91, P = 0.037), sodium valproate (OR 0.22, 95% CI 0.05-0.85, P = 0.029), and CYP2C9*2 genotype (OR 5.57, 95% CI 1.19-26.06, P = 0.02).
CONCLUSIONS
Variant genotypes of VKORC1 , CYP2C9*2 , and CYP2C9*3 required lower dose of acenocoumarin, and CYP2C9*2 was associated with unstable INR. Comedication is a modifiable risk factor that needs attention.
PubMed: 38907686
DOI: 10.4103/aian.aian_886_23 -
World Journal of Clinical Cases Jun 2024Transarterial chemoembolization (TACE) is a standard treatment for intermediate-stage hepatocellular carcinoma (HCC). The complications of TACE include biliary tract...
BACKGROUND
Transarterial chemoembolization (TACE) is a standard treatment for intermediate-stage hepatocellular carcinoma (HCC). The complications of TACE include biliary tract infection, liver dysfunction, tumor lysis syndrome, biloma, partial intestinal obstruction, cerebral lipiodol embolism, . There are few reports about tracheal fistula induced by TACE.
CASE SUMMARY
A 42-year-old man came to our hospital with cough and expectoration for 1 month after TACE for HCC. Laboratory test results showed abnormalities of albumin, hemoglobin, prothrombin time, C-reactive protein, D-dimer, and prothrombin. Culture of both phlegm and liver pus revealed growth of . Computed tomography showed infection in the inferior lobe of the right lung and a low-density lesion with gas in the right liver. Liver ultrasound showed that there was a big hypoechoic liquid lesion without blood flow signal. Drainage for liver abscess by needle puncture under ultrasonic guidance was performed. After 1 month of drainage and anti-infection therapy, the abscess in the liver and the infection in the lung were reduced obviously, and the symptom of expectoration was relieved.
CONCLUSION
Clinicians should be alert to the possibility of complications of liver abscess and tracheal fistula after TACE for HCC. Drainage for liver abscess by needle puncture under ultrasonic guidance could relieve the liver abscess and tracheal fistula.
PubMed: 38899298
DOI: 10.12998/wjcc.v12.i16.2911 -
Journal of Clinical Medicine Jun 2024We aimed to assess the effectiveness and safety of transcatheter arterial embolization (TAE) in the management of spontaneous or traumatic psoas and/or retroperitoneal...
We aimed to assess the effectiveness and safety of transcatheter arterial embolization (TAE) in the management of spontaneous or traumatic psoas and/or retroperitoneal hemorrhage. This single-center retrospective study enrolled 36 patients who underwent TAE for the treatment of psoas and/or retroperitoneal hemorrhage between May 2016 and February 2024. The patients' mean age was 61.3 years. The spontaneous group (SG, 47.1%) showed higher rates of anticoagulation therapy use compared with the trauma group (TG, 15.8%) ( = 0.042). The TG (94.7%) demonstrated higher survival rates compared with the SG (64.7%; = 0.023). Clinical failure was significantly associated with the liver cirrhosis ( = 0.001), prothrombin time ( = 0.004), and international normalized ratio ( = 0.007) in SG and pRBC transfusion ( = 0.008) in TG. Liver cirrhosis (OR (95% CI): 55.055 (2.439-1242.650), = 0.012) was the only identified independent risk factor for primary clinical failure in the multivariate logistic regression analysis. TAE was a safe and effective treatment for psoas and/or retroperitoneal hemorrhage, regardless of the cause of bleeding. However, liver cirrhosis or the need for massive transfusion due to hemorrhage increased the risk of clinical failure and mortality, necessitating aggressive monitoring and treatment.
PubMed: 38893030
DOI: 10.3390/jcm13113317 -
American Journal of Translational... 2024To explore the prevention and management of venous thromboembolism (VTE) following major orthopaedic surgery (MOS) by fostering doctor-to-patient cultivation of...
Prevention and control of venous thromboembolism after major orthopedic surgery through doctor-to-patient cultivation of musculoskeletal ability based on King's theory of goal attainment.
OBJECTIVES
To explore the prevention and management of venous thromboembolism (VTE) following major orthopaedic surgery (MOS) by fostering doctor-to-patient cultivation of musculoskeletal ability, guided by King's theory of goal attainment.
METHODS
A cohort of patients (n = 116) undergoing MOS was selected for the study, and were divided into two groups: the regular group and the observation group, with patients in the regular group experiencing routine nursing care and management and those in the observation group undergoing musculoskeletal ability cultivation based on King's theory of goal attainment. Baseline data, limb vascular ultrasonography, coagulation function, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, VTE prevention efficacy, Exercise of Self-care Ability Scale (ESCA) score, and nursing satisfaction were analysed comparatively.
RESULTS
There was no significant within-group difference in baseline data (P > 0.05). Following the interventions, the observation group demonstrated statistically significant reductions in the Musculoskeletal-Integrated Imaging Score, various dimensions of WOMAC scores, and D-dimer (D-D) levels (P < 0.05) both in comparison to their levels before interventions and to those observed in the regular group (P < 0.05). Additionally, the observation group exhibited increases in prothrombin time levels and various dimensions of ESCA scores (P < 0.05) post-intervention, surpassing the pre-intervention levels and those obtained in the regular group (P < 0.05). Furthermore, the observation group exhibited a significantly lower incidence of VTE (P < 0.05) and higher nursing satisfaction (P < 0.05) compared to the regular group.
CONCLUSIONS
Nursing intervention measures, utilizing doctor-to-patient cultivation of musculoskeletal ability based on King's theory of goal attainment, have demonstrated a significant clinical benefit for VTE prevention and control in post-MOS patients. This approach not only effectively prevented VTE in post MOS patients but also enhanced their satisfaction towards nursing care.
PubMed: 38883378
DOI: 10.62347/HEQE4868 -
Scientific Reports Jun 2024Data on the pathophysiological mechanisms of hemostatic alterations in the thrombotic events that occur during Ramadan intermittent fasting (RIF), particularly in the...
Data on the pathophysiological mechanisms of hemostatic alterations in the thrombotic events that occur during Ramadan intermittent fasting (RIF), particularly in the natural coagulation inhibitors, are very limited. Thus, our objective was to evaluate the effect of RIF on the natural anticoagulants level, antithrombin, protein C, and total and free protein S (PS) in healthy participants. Participants were divided into two groups. Group I consisted of 29 healthy fasting participants whose blood samples were taken after 20 days of fasting. Group II included 40 healthy non-fasting participants whose blood samples were taken 2-4 weeks before the month of Ramadan. Coagulation screening tests including prothrombin time (PT), activated partial thromboplastin time (APTT) and plasma fibrinogen level, natural anticoagulants; antithrombin, protein C, free and total PS and C4 binding protein (C4BP) levels were evaluated in the two groups. High levels of total and free PS without change in antithrombin, protein C, and C4BP levels were noted in the fasting group as compared with non-fasting ones (p < 0.05). PT and APTT showed no difference between the two groups. However, the fibrinogen level was higher in the fasting group. In conclusion, RIF was found to be associated with improved anticoagulant activity in healthy participants, which may provide temporal physiological protection against the development of thrombosis in healthy fasting people.
Topics: Humans; Fasting; Male; Adult; Female; Case-Control Studies; Blood Coagulation; Anticoagulants; Islam; Protein C; Protein S; Blood Coagulation Tests; Healthy Volunteers; Fibrinogen; Middle Aged; Young Adult; Prothrombin Time; Antithrombins; Partial Thromboplastin Time; Intermittent Fasting
PubMed: 38879576
DOI: 10.1038/s41598-024-64582-8 -
Medicine Jun 2024The aim of this study is to describe the general information, disease and treatment of venous thromboembolism (VTE) in critically ill patients, to explore the... (Observational Study)
Observational Study
The aim of this study is to describe the general information, disease and treatment of venous thromboembolism (VTE) in critically ill patients, to explore the characteristics of severe patients with deep venous VTE and provide clinical reference data for the prevention and treatment of VTE in critically ill patients. This study carried out a retrospective study on the medical records of patients who were treated in the intensive care unit of Affiliated Hospital of Jining Medical College from 2020 to 2022. The general data, general conditions, drug use, past history, VTE prevention measures, post-VTE conditions, and Padua risk score of 297 patients with VTE during the period of hospitalization in intensive care unit (ICU) were classified and statistically analyzed. A total of 297 including 171 male and 126 male patient medical records were included in the analysis, we compared multiple clinical indicators between male and female patients. Compared to women, male patients have a higher acute physiology and chronic health evaluation II score(APACHE-II score) (P = .027), a higher state of consciousness (P = .003), a higher rate of smoking and drinking history (P < .001), a lower rate of heart failure (P = .003) and chronic depression (P = .013), and a higher rate of recommended operations for male patients after VTE (P = .031). The prothrombin time (PT) (P = .041) and activated partial thromboplastin time (APTT) (P = .040) of male patients were significantly higher than those of female patients, while triglyceride (P = .009) and total cholesterol (TC) (P = .001) were significantly lower than those of female patients. The difference in D-dimer (P = .739) was not significant. This study shows that male and female patients with VTE in the ICU have significant differences in general characteristics, general clinical conditions, history of past illness, thrombosis character, and examination items, this may be the reason for the different rates of VTE between male and female patients in the ICU.
Topics: Humans; Male; Female; Retrospective Studies; Venous Thromboembolism; Middle Aged; Critical Illness; Sex Factors; Aged; Adult; Risk Factors; Intensive Care Units; APACHE
PubMed: 38875425
DOI: 10.1097/MD.0000000000038423 -
Cureus May 2024Laparoscopic cholecystectomy (LC) is universally accepted as the gold standard treatment for symptomatic gallstones. However, it has some drawbacks. Some of the major...
Comparative Study of Levels of Serum Bilirubin, Serum Transaminase, Serum Alkaline Phosphatase, and Prothrombin Time After Laparoscopic Cholecystectomy and Open Cholecystectomy.
Laparoscopic cholecystectomy (LC) is universally accepted as the gold standard treatment for symptomatic gallstones. However, it has some drawbacks. Some of the major drawbacks of LC include increased bile duct injuries and longer operation time. Furthermore, it may cause changes in the body systems, such as alterations in acid-base, pulmonary status, cardiovascular system, and liver function. Thus far, no causes for these changes have been identified. This study aimed to evaluate the effect of laparoscopic and open cholecystectomy on liver enzymes, prothrombin time (PT), and serum bilirubin. In the current study, we found significant increases in aspartate transferase (AST), alanine transaminase (ALT), and total bilirubin, on day 1 and day 3 after LC but no significant change in alkaline phosphatase (ALKP) and PT. It is important for surgeons to know about these transient changes in the immediate postoperative period to avoid misdiagnosis and adopt proper treatment and management.
PubMed: 38872670
DOI: 10.7759/cureus.60296 -
Frontiers in Immunology 2024This study aimed to develop a prognostic nomogram for predicting the recurrence-free survival (RFS) of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC)...
Machine learning-based model for predicting tumor recurrence after interventional therapy in HBV-related hepatocellular carcinoma patients with low preoperative platelet-albumin-bilirubin score.
INTRODUCTION
This study aimed to develop a prognostic nomogram for predicting the recurrence-free survival (RFS) of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients with low preoperative platelet-albumin-bilirubin (PALBI) scores after transarterial chemoembolization (TACE) combined with local ablation treatment.
METHODS
We gathered clinical data from 632 HBV-related HCC patients who received the combination treatment at Beijing You'an Hospital, affiliated with Capital Medical University, from January 2014 to January 2020. The patients were divided into two groups based on their PALBI scores: low PALBI group (n=247) and high PALBI group (n=385). The low PALBI group was then divided into two cohorts: training cohort (n=172) and validation cohort (n=75). We utilized eXtreme Gradient Boosting (XGBoost), random survival forest (RSF), and multivariate Cox analysis to pinpoint the risk factors for RFS. Then, we developed a nomogram based on the screened factors and assessed its risk stratification capabilities and predictive performance.
RESULTS
The study finally identified age, aspartate aminotransferase (AST), and prothrombin time activity (PTA) as key predictors. The three variables were included to develop the nomogram for predicting the 1-, 3-, and 5-year RFS of HCC patients. We confirmed the nomogram's ability to effectively discern high and low risk patients, as evidenced by Kaplan-Meier curves. We further corroborated the excellent discrimination, consistency, and clinical utility of the nomogram through assessments using the C-index, area under the curve (AUC), calibration curve, and decision curve analysis (DCA).
CONCLUSION
Our study successfully constructed a robust nomogram, effectively predicting 1-, 3-, and 5-year RFS for HBV-related HCC patients with low preoperative PALBI scores after TACE combined with local ablation therapy.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Male; Female; Middle Aged; Machine Learning; Bilirubin; Neoplasm Recurrence, Local; Nomograms; Hepatitis B virus; Chemoembolization, Therapeutic; Prognosis; Blood Platelets; Hepatitis B; Adult; Serum Albumin; Retrospective Studies; Platelet Count
PubMed: 38863693
DOI: 10.3389/fimmu.2024.1409443