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Journal of Clinical Medicine Sep 2023Knowledge of the natural history and management of hepatic hemangiomas is lacking. The aim of this study was to investigate the natural history of hemangiomas and to...
BACKGROUND
Knowledge of the natural history and management of hepatic hemangiomas is lacking. The aim of this study was to investigate the natural history of hemangiomas and to elucidate the factors that determine tumor growth and optimal management.
METHODS
A total of 211 adult patients were enrolled, with follow-up for more than three years. Follow-up was performed with repeated ultrasonography (US) and laboratory tests for liver function and coagulation factors (platelets, prothrombin time (PT), fibrinogen, thrombin-antithrombin III complex (TAT), D-dimer, and fibrin and fibrinogen degradation products (FDP)).
RESULTS
Tumor size decreased in 38.9% of patients, showed no change in 31.3%, and increased in 29.8%. The incidence of a size increase was very high in patients under 40 years of age and decreased gradually with age, whereas the incidence of a size decrease increased with age and increased markedly over 60 years of age. The incidence of an increase in size decreased gradually with size enlargement, whereas the incidence of a decrease in size increased markedly with tumor size and further increased rapidly when hemangiomas became larger than 60 mm. Values of TAT, D-dimer, FDP, and Mac-2 binding protein glycosylation isomer (M2BPGi) were closely related to the change in size of hemangiomas.
CONCLUSIONS
Hemangiomas in older patients (>60 years of age) and larger tumors (>60 mm in size) had a tendency to decrease in size, resulting from the reduction in coagulation disorders and the progression of liver fibrosis. Therefore, the majority of patients with hemangiomas can be safely managed by clinical observation.
PubMed: 37685768
DOI: 10.3390/jcm12175703 -
British Journal of Clinical Pharmacology May 2020Antithrombin III (AT-III) concentrates have been used to prevent critical thrombosis in the immediate post-liver transplantation period without clear evidence regarding...
AIMS
Antithrombin III (AT-III) concentrates have been used to prevent critical thrombosis in the immediate post-liver transplantation period without clear evidence regarding the optimal dose or administration scheme. The relationship between the AT-III dosage and the plasma activity levels during the period was evaluated in this study.
METHODS
The plasma AT-III activity levels and clinical data obtained from patients who received liver transplantation from January 2017 to September 2018 were retrospectively analysed. A population pharmacokinetic (PK) model was developed using nonlinear mixed-effects method and externally validated thereafter. Several dosing scenarios were simulated to maintain the plasma AT-III activity level within the normal range using the developed PK model to search for an optimal AT-III dosing regimen.
RESULTS
The plasma AT-III activity levels were best described by a single compartment model with first order elimination kinetics. The recovery of endogenous AT-III level during the postoperative days was modelled using an E model. The typical values (95% confidence interval) of volume of distribution and clearance were 3.86 (3.40-4.32) L, and 0.129 (0.111-0.147) L h , respectively. Serum albumin and body weight had significant effect on clearance and were included in the model. External validation of the proposed model demonstrated adequate prediction performance. Furthermore, simulation of previously suggested or modified dosing scenarios showed successful maintenance of AT-III activity level within the normal range.
CONCLUSION
A population PK model of AT-III concentrate was developed using data from liver recipients. Dosing scenarios simulated in our study may help establish a practical guide for AT-III concentrate titration after liver transplantation.
Topics: Antithrombin III; Female; Humans; Liver Transplantation; Male; Models, Biological; Postoperative Period; Retrospective Studies; Treatment Outcome
PubMed: 31840271
DOI: 10.1111/bcp.14200 -
Biomolecules Jul 2023Adsorbing toxins from the blood to augment membrane-based hemodialysis is an active area of research. Films composed of β-cyclodextrin-co-(methacryloyloxy)ethyl...
Adsorbing toxins from the blood to augment membrane-based hemodialysis is an active area of research. Films composed of β-cyclodextrin-co-(methacryloyloxy)ethyl phosphorylcholine (p(PMβCD-co-MPC)) with various monomer ratios were formed on magnetic nanoparticles and characterized. Surface chemistry effects on protein denaturation were evaluated and indicated that unmodified magnetic nanoparticles greatly perturbed the structure of proteins compared to coated particles. Plasma clotting assays were conducted to investigate the stability of plasma in the presence of particles, where a 2:2 monomer ratio yielded the best results for a given total surface area of particles. Total protein adsorption results revealed that modified surfaces exhibited reduced protein adsorption compared to bare particles, and pure MPC showed the lowest adsorption. Immunoblot results showed that fibrinogen, α1-antitrypsin, vitronectin, prekallikrein, antithrombin, albumin, and C3 correlated with film composition. Hemocompatibility testing with whole blood illustrated that the 1:3 ratio of CD to MPC had a negative impact on platelets, as evidenced by the increased activation, reduced response to an agonist, and reduced platelet count. Other formulations had statistically significant effects on platelet activation, but no formulation yielded apparent adverse effects on hemostasis. For the first time, p(PMβCD-co-MPC)-coated MNP were synthesized and their general hemocompatibility assessed.
Topics: Phosphorylcholine; Magnetite Nanoparticles; Adsorption; Antithrombin III; Blood Coagulation
PubMed: 37627230
DOI: 10.3390/biom13081165 -
Medicines (Basel, Switzerland) Jul 2019The polyanionic nature and the ability to interact with proteins with different affinities are properties of sulfated glycosaminoglycans (GAGs) that determine their... (Review)
Review
The polyanionic nature and the ability to interact with proteins with different affinities are properties of sulfated glycosaminoglycans (GAGs) that determine their biological function. In designing drugs affecting the interaction of proteins with GAGs the challenge has been to generate agents with high binding specificity. The example to emulated has been a heparin-derived pentasaccharide that binds to antithrombin-III with high affinity. However, the portability of this model to other biological situations is questioned on several accounts. Because of their structural flexibility, oligosaccharides with different sulfation and uronic acid conformation can display the same binding proficiency to different proteins and produce comparable biological effects. This circumstance represents a formidable obstacle to the design of drugs based on the heparin scaffold. The conceptual framework discussed in this article is that through a direct intervention on the heparin-binding functionality of proteins is possible to achieve a high degree of action specificity. This objective is currently pursued through two strategies. The first makes use of small molecules for which in the text we provide examples from past and present literature concerning angiogenic factors and enzymes. The second approach entails the mutagenesis of the GAG-binding site of proteins as a means to generate a new class of biologics of therapeutic interest.
PubMed: 31362364
DOI: 10.3390/medicines6030080 -
Frontiers in Psychiatry 2021The evaluation of treatment response to antidepressant therapy commonly depends on neuropsychologic assessments, as there are currently no suitable biomarkers. Previous...
The evaluation of treatment response to antidepressant therapy commonly depends on neuropsychologic assessments, as there are currently no suitable biomarkers. Previous research has identified a panel of increased proteins in patients with major depressive disorder (MDD), including antithrombin III (ATIII), as potential biomarkers of depression. A total of 90 MDD patients were recruited. Of these, 74 patients received occipital repetitive transcranial magnetic stimulation (rTMS) as individualized, standard, or sham treatment for 5 days, and underwent the complete procedure, including clinical assessments, blood collection, and protein measurement. After treatment, ATIII was significantly decreased in both the individualized and standard groups (both < 0.001) relative to the sham group. In the individualized group, reduction in ATIII was associated with improvements in several neuropsychological assessments. Furthermore, ATIII at baseline in the standard group and after individualized rTMS showed good performance for evaluating or predicting the response to five-day treatment (AUC = 0.771, 95% CI, 0.571-0.971; AUC = 0.875, 95% CI, 0.714-1.000, respectively) and remission at follow-up (AUC = 0.736, 95% CI, 0.529-0.943; AUC = 0.828, 95% CI, 0.656-1.000, respectively). Lastly, both baseline ATIII and change in ATIII showed good predictive value for the 24-item Hamilton Depression Rating Scale at follow-up ( = 0.024 and 0.023, respectively). Our study revealed a reduction in ATIII after occipital rTMS in MDD patients and a relationship between change in ATIII and therapeutic response. Taken together, these findings provide evidence for the potential of ATIII as a biomarker for the evaluation and prediction of antidepressive effects.
PubMed: 34777034
DOI: 10.3389/fpsyt.2021.678384 -
International Journal of Molecular... Jul 2022The vascular endothelium has several important functions, including hemostasis. The homeostasis of hemostasis is based on a fine balance between procoagulant and... (Review)
Review
The vascular endothelium has several important functions, including hemostasis. The homeostasis of hemostasis is based on a fine balance between procoagulant and anticoagulant proteins and between fibrinolytic and antifibrinolytic ones. Coagulopathies are characterized by a mutation-induced alteration of the function of certain coagulation factors or by a disturbed balance between the mechanisms responsible for regulating coagulation. Homeostatic therapies consist in replacement and nonreplacement treatments or in the administration of antifibrinolytic agents. Rebalancing products reestablish hemostasis by inhibiting natural anticoagulant pathways. These agents include monoclonal antibodies, such as concizumab and marstacimab, which target the tissue factor pathway inhibitor; interfering RNA therapies, such as fitusiran, which targets antithrombin III; and protease inhibitors, such as serpinPC, which targets active protein C. In cases of thrombophilia (deficiency of protein C, protein S, or factor V Leiden), treatment may consist in direct oral anticoagulants, replacement therapy (plasma or recombinant ADAMTS13) in cases of a congenital deficiency of ADAMTS13, or immunomodulators (prednisone) if the thrombophilia is autoimmune. Monoclonal-antibody-based anti-vWF immunotherapy (caplacizumab) is used in the context of severe thrombophilia, regardless of the cause of the disorder. In cases of disseminated intravascular coagulation, the treatment of choice consists in administration of antifibrinolytics, all-trans-retinoic acid, and recombinant soluble human thrombomodulin.
Topics: Anticoagulants; Endothelium, Vascular; Factor V; Factor VIII; Homeostasis; Humans; Protein C; Thrombophilia; von Willebrand Factor
PubMed: 35955419
DOI: 10.3390/ijms23158283 -
Annals of Translational Medicine Jan 2022To determine the prevalence of detectable serum hepatitis B virus (HBV) DNA in patients who are hepatitis B surface antigen (HBsAg)-negative and hepatitis B core...
BACKGROUND
To determine the prevalence of detectable serum hepatitis B virus (HBV) DNA in patients who are hepatitis B surface antigen (HBsAg)-negative and hepatitis B core antibody (HBcAb)-positive. The correlation between HBV DNA viral load and serological markers, as well as liver and coagulation function indicators were investigated. Furthermore, the effects of immunosuppressive therapy on DNA replication were assessed.
METHODS
A total of 2,013 HBsAg-negative/HBcAb-positive patients admitted to our hospital between January and December 2019 were enrolled in this study. Patient clinical characteristics including serological markers, HBV DNA viral load, liver function and coagulation function indicators, and immune function status were analyzed.
RESULTS
In the Hunan province in China, the prevalence of detectable HBV DNA was 5.4% in HBsAg-negative/HBcAb-positive patients. However, the prevalence of detectable HBV DNA in HBsAg-negative/HBcAb-positive patients may vary because of different HBV serological markers. In patients with detectable serum HBV DNA, the log10 HBV DNA value was positively correlated with alanine transaminase (ALT) and aspartate transaminase (AST) levels, and negatively correlated with antithrombin III (AT III) concentrations. Moreover, in patients receiving immunosuppressive therapy, ALT and AST levels were higher than those of patients who did not receive immunosuppressive therapy. The ALT and AST levels in hepatitis B e antibody (HBeAb)-positive patients were significantly higher than that observed in HBeAb-negative patients.
CONCLUSIONS
For HBsAg-negative/HBcAb-positive patients, clinicians should pay attention to the patient's immune function status. In situations where HBV DNA cannot be detected, changes in serum ALT, AST, and AT III concentrations can be used to speculate on viral replication status to reduce the risk of HBV infection and transmission.
PubMed: 35242870
DOI: 10.21037/atm-21-6272 -
Clinical and Translational Science Jul 2023Antithrombin-III (AT-III) concentrates have been used in the immediate postoperative period after liver transplantation to prevent critical thrombosis. We aimed to... (Randomized Controlled Trial)
Randomized Controlled Trial
Antithrombin-III (AT-III) concentrates have been used in the immediate postoperative period after liver transplantation to prevent critical thrombosis. We aimed to investigate a more appropriate method for AT-III concentrate administration to maintain plasma AT-III activity level within the target range. In this randomized controlled trial, 130 adult patients undergoing living-donor liver transplantation were randomized to either the intermittent group or continuous group. In the intermittent group, 500 international units (IU) of AT-III concentrate were administered after liver transplantation and repeated every 6 h for 72 h. In the continuous group, 3000 IU of AT-III were continuously infused for 71 h after a loading dose of 2000 IU over 1 h. Plasma AT-III activity level was measured at 12, 24, 48, 72, and 84 h from the first AT-III administration. The primary outcome was the target (80%-120%) attainment rate at 72 h. Target attainment rates at other timepoints and associated complications were collected as secondary outcomes. A total of 107 patients were included in the analysis. The target attainment rates at 72 h post-dose were 30% and 62% in the intermittent group and continuous group, respectively (p = 0.003). Compared to the intermittent group, patients in the continuous group reached the target level more rapidly (12 vs. 24 h, median time, p < 0.001) and were more likely to remain in the target range until 84 h. For maintaining the target plasma AT-III activity level after living-donor liver transplantation, continuous infusion of AT-III seemed to be more appropriate compared to the conventional intermittent infusion regimen.
Topics: Adult; Humans; Antithrombin III; Liver Transplantation; Living Donors; Anticoagulants; Thrombosis
PubMed: 37038357
DOI: 10.1111/cts.13521 -
Clinical Epidemiology 2019Apolipoproteins C-I, C-II, C-III and E have been associated with risk of arterial thrombotic diseases. We investigated whether these apolipoproteins have prothrombotic...
PURPOSE
Apolipoproteins C-I, C-II, C-III and E have been associated with risk of arterial thrombotic diseases. We investigated whether these apolipoproteins have prothrombotic properties and are associated with risk of venous thromboembolism (VTE).
PATIENTS AND METHODS
A total of 127 VTE patients and 299 controls were randomly selected from the Multiple Environmental and Genetic Assessment of Risk Factors for Venous Thrombosis study (1999-2004), in the Netherlands. The apolipoproteins were quantified using mass spectrometry (LC/MS/MS), and their levels were analyzed as continuous variable (per SD increase).
RESULTS
In controls, increases in levels of apolipoproteins were associated with increases in levels of vitamin K-dependent factors, factor XI, antithrombin and clot lysis time. Additionally, increasing apolipoproteins C-III and E levels were associated with higher factor VIII and von Willebrand factor levels. Levels of C-reactive protein were not associated with any apolipoprotein. The age- and sex-adjusted odds ratios of apolipoproteins E, C-III, CII and CI to the risk of venous thrombosis were 1.21 (95% CI, 0.98-1.49), 1.19 (95% CI, 0.99-1.44), 1.24 (95% CI, 0.95-1.61) and 1.06 (95% CI, 0.87-1.30) per SD increase, respectively. These odds ratios did not attenuate after adjustments for statin use, estrogen use, BMI, alcohol use, and self-reported diabetes.
CONCLUSIONS
Levels of apolipoproteins C-I, C-II, C-III and E are associated with those of several coagulation factors. However, whether these apolipoproteins are also associated with an increased risk of VTE remains to be established.
PubMed: 31413640
DOI: 10.2147/CLEP.S196266 -
Journal of Cancer Research and... Nov 2021To preliminarily evaluate the effect of microwave ablation (MWA) alone on platelet (PLT) and coagulation function in patients with BCLC-A hepatocellular carcinoma...
AIM
To preliminarily evaluate the effect of microwave ablation (MWA) alone on platelet (PLT) and coagulation function in patients with BCLC-A hepatocellular carcinoma (B-A-HCC) using a retrospective method.
MATERIALS AND METHODS
A total of 36 patients with 48 B-A-HCCs were radically treated with MWA alone under the guidance of ultrasound between April and October 2018. PLT coagulation indexes were measured before and after MWA at 1 day, 3 days, 1 week, and 2 weeks, and blood samples (after morning fasting) were collected from cubital veins. Coagulation indexes included prothrombin time (PT), prothrombin activity (PTA), thrombin time (TT), Activated Partial Thromboplastin Time (APTT), international standardized ratio (INR), plasma fibrinogen (FIB), plasma antithrombin III (AT-III), and D dimer (DD). Overall survival (OS), recurrence-free survival (RFS), local tumor progression (LTP), and adverse reactions were also recorded.
RESULTS
All patients were radically treated with MWA alone. The median size of the lesion was 2.6 (1.5-7.0) cm. On the first day after MWA, the level of PLT decreased significantly compared with the values before MWA and gradually returned to preoperative levels one week after MWA. One day after MWA, the levels of PT, INR, and AT-III increased markedly and the level of PTA decreased significantly, all of them gradually returned to baseline after 3 days to a week of time. 1, 3, and 7 days after MWA, the levels of FIB, and DD increased significantly, and the level of TT decreased significantly; all of them gradually returned to baseline at 2 weeks. At 6 months posttreatment, the OS and RFS rates were 100% and 91.7%, the LTP rates was 5.6%, no significant adverse reactions.
CONCLUSION
PLT and coagulation indexes were abnormal in patients with B-A-HCC who were radically treated with MWA alone after treatment; without specific treatment, they all gradually returned to baseline within a week or two.
Topics: Adult; Aged; Blood Coagulation; Blood Coagulation Tests; Blood Platelets; Carcinoma, Hepatocellular; Female; Fibrin Fibrinogen Degradation Products; Follow-Up Studies; Humans; Liver Neoplasms; Male; Microwaves; Middle Aged; Partial Thromboplastin Time; Prognosis; Radiofrequency Ablation; Retrospective Studies
PubMed: 34850778
DOI: 10.4103/jcrt.JCRT_448_19