Patterns of comorbidities in patients with atrial fibrillation and impact on management and long-term prognosis: an analysis from the Prospective Global GLORIA-AF Registry.

BACKGROUND: Clinical complexity, as the interaction between ageing, frailty, multimorbidity and polypharmacy, is an increasing concern in patients with AF. There remains uncertainty regarding how combinations of comorbidities influence management and prognosis of patients with atrial fibrillation (AF). We aimed to identify phenotypes of AF patients according to comorbidities and to assess associations between comorbidity patterns, drug use and risk of major outcomes. METHODS: From the prospective GLORIA-AF Registry, we performed a latent class analysis based on 18 diseases, encompassing cardiovascular, metabolic, respiratory and other conditions; we then analysed the association between phenotypes of patients and (i) treatments received and (ii) the risk of major outcomes. Primary outcome was the composite of all-cause death and major adverse cardiovascular events (MACE). Secondary exploratory outcomes were also analysed. RESULTS: 32,560 AF patients (mean age 70.0 ± 10.5 years, 45.4% females) were included. We identified 6 phenotypes: (i) low complexity (39.2% of patients); (ii) cardiovascular (CV) risk factors (28.2%); (iii) atherosclerotic (10.2%); (iv) thromboembolic (8.1%); (v) cardiometabolic (7.6%) and (vi) high complexity (6.6%). Higher use of oral anticoagulants was found in more complex groups, with highest magnitude observed for the cardiometabolic and high complexity phenotypes (odds ratio and 95% confidence interval CI): 1.76 [1.49-2.09] and 1.57 [1.35-1.81], respectively); similar results were observed for beta-blockers and verapamil or diltiazem. We found higher risk of the primary outcome in all phenotypes, except the CV risk factor one, with highest risk observed for the cardiometabolic and high complexity groups (hazard ratio and 95%CI: 1.37 [1.13-1.67] and 1.47 [1.24-1.75], respectively). CONCLUSIONS: Comorbidities influence management and long-term prognosis of patients with AF. Patients with complex phenotypes may require comprehensive and holistic approaches to improve their prognosis.

Effect of Enoxaparin and Daikenchuto Coadministration on Hepatic Disorder Markers in Gynecological Cancer Patients after Abdominal Surgery.

Enoxaparin and daikenchuto are commonly administered to prevent venous thromboembolism and intestinal obstruction after gynecological malignancy surgery. However, the effects of their combined use on hepatic function are not well studied. This study aimed to clarify the effects of the coadministration of enoxaparin and daikenchuto on hepatic function. First, Japanese Adverse Drug Event Report (JADER) data were analyzed to identify signals of hepatic disorders. Second, a retrospective observational study of patients who underwent surgery for gynecological malignancies was conducted. This study defined hepatic disorders as an increase in aspartate aminotransferase (AST) or alanine aminotransaminase (ALT) levels above the reference values, using 1-h postoperative values as the baseline. The analysis of JADER data revealed an increased risk for hepatic disorders with the coadministration of enoxaparin and daikenchuto. An observational study also showed higher odds ratios (95% confidence intervals) for the occurrence of hepatic disorders in the coadministration group (4.27; 2.11-8.64) and enoxaparin alone group (2.48; 1.31-4.69) than in the daikenchuto alone group. The median increase in the ALT level was also higher in the coadministration group (34; 15-59) than in the enoxaparin alone (19; 6-38) and daikenchuto alone groups (8; 3-33). In conclusion, our study suggests that compared with the use of enoxaparin or daikenchuto alone, enoxaparin and daikenchuto coadministration increases the risk of hepatic disorders, with more significant increases in AST and ALT levels. Healthcare workers need to be aware of these potential side effects when combining these drugs after surgery for gynecological malignancies.

Toward Genetic Testing of Rivaroxaban? Insights from a Systematic Review on the Role of Genetic Polymorphism in Rivaroxaban Therapy.

BACKGROUND: Investigations into the rivaroxaban response from the perspective of genetic variation have been relatively recent and wide in scope, whereas there is no consensus on the necessity of genetic testing of rivaroxaban. Thus, this systematic review aims to thoroughly evaluate the relationship between genetic polymorphisms and rivaroxaban outcomes. METHODS: The PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Chinese databases were searched to 23 October 2022. We included cohort studies reporting the pharmacogenetic correlation of rivaroxaban. Outcomes measured included efficacy (all-cause mortality, thromboembolic events and coagulation-related tests), safety (major bleeding, clinically relevant non-major bleeding [CRNMB] and any hemorrhage), and pharmacokinetic outcomes. A narrative synthesis was performed to summarize findings from individual studies according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and the reporting guideline for Synthesis Without Meta-Analysis. RESULTS: A total of 12 studies published between 2019 and 2022 involving 1364 patients were included. Ten, one, and six studies focused on the ABCB1, ABCG2, and CYP gene polymorphisms, respectively. Pharmacokinetic outcomes accounted for the majority of the outcomes reported (n = 11), followed by efficacy (n = 5) [including prothrombin time (PT) or international normalized ratio (n = 3), platelet inhibition rate (PIR) or platelet reactivity units (PRUs; n = 1), thromboembolic events (n = 1)], and safety (n = 5) [including major bleeding (n = 2), CRNMB (n = 2), any hemorrhage (n = 1)]. For ABCB1 gene polymorphism, the relationship between PT and ABCB1 rs1045642 was inconsistent across studies, however there was no pharmacogenetic relationship with other efficacy outcomes. Safety associations were found in ABCB1 rs4148738 and major bleeding, ABCB1 rs4148738 and CRNMB, ABCB1 rs1045642 and CRNMB, and ABCB1 rs2032582 and hemorrhage. Pharmacokinetic results were inconsistent among studies. For ABCG2 gene polymorphism, no correlation was observed between ABCG2 rs2231142 and dose-adjusted trough concentration (Cmin/D). For CYP gene polymorphisms, PIR or PRUs have a relationship with CYP2C19 rs12248560, however bleeding or pharmacokinetic effects did not show similar results. CONCLUSIONS: Currently available data are insufficient to confirm the relationship between clinical or pharmacokinetic outcomes of rivaroxaban and gene polymorphisms. Proactive strategies are advised as a priority in clinical practice rather than detection of SNP genotyping. CLINICAL TRIALS REGISTRATION: PROSPERO registration number CRD42022347907.

Safety of dry needling in stroke patients: a scoping review.

INTRODUCTION: Spasticity is a common problem in stroke patients. Treatments of spasticity often have side effects or are insufficiently effective. Dry needling (DN) has been proposed as a potential additional option to consider in the multimodal treatment of post-stroke spasticity, although questions about its safety remain. The goal of this study is to assess the safety of DN in stroke patients. EVIDENCE ACQUISITION: A systematic search in Medline, Embase, The Cochrane Library, Web of Science, CIHNAL and PEDro was conducted in June 2023. Two reviewers independently screened abstracts according to the eligibility criteria. EVIDENCE SYNTHESIS: Twenty-five articles were included in this review. Only six studies reported adverse events, all of which were considered minor. None of the included studies reported any serious adverse events. In four of the included studies anticoagulants were regarded as contra-indicative for DN. Anticoagulants were not mentioned in the other included studies. CONCLUSIONS: There is a paucity of literature concerning the safety of DN in stroke patients. This review is the first to investigate the safety of DN in stroke patients and based on the results there is insufficient evidence regarding the safety of DN in stroke patients. CLINICAL REHABILITATION IMPACT: Although DN could be a promising treatment in post-stroke spasticity, further research is indicated to investigate its mechanism of action and its effect on outcome. However, before conducting large clinical trials to assess outcome parameters, the safety of DN in stroke patients must be further investigated.

Magnetic nanoparticles immobilized thrombin ligand fishing to screen thrombin inhibitors in natural products.

In this study, thrombin was immobilized with magnetic particles modified by glutaraldehyde. The changes in secondary structures of immobilized enzyme revealed an increment in conformational rigidity and stability, which can be reflected in temperature and pH stability as well as the tolerance of organic reagents. The optimal reutilization times of magnetic particle immobilized thrombin were 7 times, and the half-life of enzyme activity preserved at room temperature was 5 days, which was 2.5 times higher than that of free enzyme. Ligusticum chuanxiong and Anemarrhenae Rhizoma with high enzyme inhibitory activity were selected for primary screening, and six potential inhibitors of thrombin were identified by HPLC/MS. The results showed that three compounds in Anemarrhenae Rhizoma had better predictive thrombin inhibitory activity. Through the in vitro thrombin activity inhibition experiment, it was also verified that mangiferin and neo-mangiferin had an ideal thrombin activity inhibition effect, which was consistent with the results of molecular docking.

Validation of the IMPEDE VTE score for prediction of venous thromboembolism in Chinese patients with multiple myeloma: A single-center retrospective cohort study.

Multiple myeloma (MM) significantly increases the risk of venous thromboembolism (VTE) within 6 months of treatment initiation. The IMPEDE VTE score is a VTE risk prediction model which is recently incorporated into the National Comprehensive Cancer Network (NCCN) guidelines, but it lacks validation among Asians, including Chinese MM patients. We performed a retrospective chart review of 405 Chinese with newly diagnosed MM who started therapy at Beijing Jishuitan Hospital between April 2013 to October 2022. The 6-month cumulative incidence of VTE was 3.8 % (95 % CI:1.6-7.6), 8.6 % (95 % CI: 5.3-21.9) and 40.5 % (95 % CI: 24.9-55.7) in the low-, intermediate- and high-risk groups (P < 0.001), respectively. The C-statistic of the IMPEDE VTE scores for predicting VTE within 6 months of treatment initiation was 0.74 (95 % CI: 0.65-0.83). Of note, in this single-center cohort study, we propose that the anticoagulant LMWH may be more effective than the antiplatelet aspirin in potentially preventing VTE in newly diagnosed MM patients. Our findings suggest that the IMPEDE VTE score is a valid evidence-based risk stratification tool in Chinese patients with newly diagnosed MM.

Warfarin-A natural anticoagulant: A review of research trends for precision medication.

BACKGROUND: Warfarin is a widely prescribed anticoagulant in the clinic. It has a more considerable individual variability, and many factors affect its variability. Mathematical models can quantify the quantitative impact of these factors on individual variability. PURPOSE: The aim is to comprehensively analyze the advanced warfarin dosing algorithm based on pharmacometrics and machine learning models of personalized warfarin dosage. METHODS: A bibliometric analysis of the literature retrieved from PubMed and Scopus was performed using VOSviewer. The relevant literature that reported the precise dosage of warfarin calculation was retrieved from the database. The multiple linear regression (MLR) algorithm was excluded because a recent systematic review that mainly reviewed this algorithm has been reported. The following terms of quantitative systems pharmacology, mechanistic model, physiologically based pharmacokinetic model, artificial intelligence, machine learning, pharmacokinetic, pharmacodynamic, pharmacokinetics, pharmacodynamics, and warfarin were added as MeSH Terms or appearing in Title/Abstract into query box of PubMed, then humans and English as filter were added to retrieve the literature. RESULTS: Bibliometric analysis revealed important co-occuring MeShH and index keywords. Further, the United States, China, and the United Kingdom were among the top countries contributing in this domain. Some studies have established personalized warfarin dosage models using pharmacometrics and machine learning-based algorithms. There were 54 related studies, including 14 pharmacometric models, 31 artificial intelligence models, and 9 model evaluations. Each model has its advantages and disadvantages. The pharmacometric model contains biological or pharmacological mechanisms in structure. The process of pharmacometric model development is very time- and labor-intensive. Machine learning is a purely data-driven approach; its parameters are more mathematical and have less biological interpretation. However, it is faster, more efficient, and less time-consuming. Most published models of machine learning algorithms were established based on cross-sectional data sourced from the database. CONCLUSION: Future research on personalized warfarin medication should focus on combining the advantages of machine learning and pharmacometrics algorithms to establish a more robust warfarin dosage algorithm. Randomized controlled trials should be performed to evaluate the established algorithm of warfarin dosage. Moreover, a more user-friendly and accessible warfarin precision medicine platform should be developed.

Conventional extraction of fucoidan from Irish brown seaweed Fucus vesiculosus followed by ultrasound-assisted depolymerization.

Fucoidan has attracted considerable attention from scientists and pharmaceutical companies due to its antioxidant, anticoagulant, anti-inflammatory, anti-tumor, and health-enhancing properties. However, the extraction of fucoidan from seaweeds often involves the use of harsh chemicals, which necessitates the search for alternative solvents. Additionally, the high viscosity and low cell permeability of high molecular weight (Mw) fucoidan can limit its effectiveness in drug action, while lower Mw fractions exhibit increased biological activity and are also utilized as dietary supplements. The study aimed to (1) extract fucoidan from the seaweed Fucus vesiculosus (FV) using an environmentally friendly solvent and compare it with the most commonly used extraction solvent, hydrochloric acid, and (2) assess the impact of ultrasound-assisted depolymerization on reducing the molecular weight of the fucoidan extracts and examine the cytotoxic effect of different molecular weight fractions. The findings indicated that the green depolymerization solvent, in conjunction with a brief ultrasound treatment, effectively reduced the molecular weight. Moreover, a significant decrease in cell viability was observed in selected samples, indicating potential anticancer properties. As a result, ultrasound was determined to be an effective method for depolymerizing crude fucoidan from Fucus Vesiculosus seaweed.

Effectiveness of Taohong Siwu decoction in the prevention of deep vein thrombosis in hip surgery patients: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: This systematic review and meta-analysis aimed to evaluate the effects of Taohong Siwu Decoction (THSWD) combined with low molecular weight heparin (LMWH), as well as THSWD alone, on the incidence of Deep vein thrombosis (DVT), D-dimer levels, prothrombin time (PT), activated partial thromboplastin time (APTT), visual analogue scale (VAS) pain score, and calf swelling in patients undergoing hip fracture or replacement surgery, compared to LMWH. METHODS: According to the predefined inclusion criteria, we conducted a comprehensive search for randomized controlled trials (RCTs) examining the efficacy of THSWD combined with LMWH or THSWD compared to LMWH in patients with hip fractures or undergoing replacement surgery. The search was performed across multiple databases including China National Knowledge Internet, WanFang, Sinomed, Duxiu, PubMed, Embase, Google Scholar, Cochrane, and Web of Science from their inception until December 2023. Additionally, relevant literature references were retrieved and hand searching of pertinent journals was conducted. The methodological quality assessment of the included trials was carried out following the guidelines outlined in the Cochrane Handbook. Review Manager 5.4 was applied in analyzing and synthesizing. RESULTS: A total of 18 RCTs with 1353 patients were included. The results of meta-analysis showed that compared with the control group, the combined group had a better effect on the incidence of DVT [RR = 0.32, 95% CI(0.17, 0.58; P = .0002], D-dimer [SMD = -5.88, 95% CI(-7.66, -4.11); P < .00001], VAS [MD = -1.16, 95% CI(-1.81, -0.50); P = .0005], Calf circumference difference [MD = -0.56, 95% CI(-1.05, -0.08); P = .02]. There was no significant difference in PT and APTT between the combined group and the control group. Meta-analysis results show that the D-dimer, incidence of DVT, PT, and APTT did not significantly differ between the THSWD and the LMWH groups. CONCLUSION: This meta-analysis shows that compared with LMWH, THSWD combined with LMWH has a better efficacy in the treatment of DVT after hip surgery, without a significant increase in the incidence of adverse events. Additionally, the combined therapy can also reduce D-dimer, VAS, and swelling. However, due to the limitations of the included studies (such as small sample size and low-quality evidence), the results need to be further verified in more rigorous multicenter clinical trials with a large sample size.

Perioperative Treatment with Rivaroxaban and Dabigatran on Changes of Coagulation and Platelet Activation Biomarkers following Left Atrial Appendage Closure.

Insufficient data exist regarding the investigation of the impact of novel oral anticoagulants (NOACs) on coagulation activation biomarkers in the context of left atrial appendage closure (LAAC) and device-related thrombosis (DRT). The study was designed to investigate the changes and presence of coagulation activation biomarkers between different antithrombotic strategies following LAAC. A total of 120 nonvalvular atrial fibrillation patients intolerant of long-term anticoagulants, who underwent successful WATCHMAN closure implantation, were enrolled (rivaroxaban, n = 82; dabigatran, n = 38). Blood samples were obtained from left atrium (LA) and left atrial appendage (LAA) during the operation and fasting blood samples on the same day of LAAC and 45 days after discharge. The biochemical indicators, thrombin-antithrombin complex (TAT), soluble P-selectin (sP-selectin), von Willebrand factor (vWF), and CD40 ligand (CD40L), were measured by enzyme-linked immunosorbent assay. The primary endpoints of this study were the efficacy and safety characteristics of different antithrombotic strategies, including DRT incidence, stroke or transient ischemic attack, systemic embolism, and clinical major and nonmajor bleeding complications during the follow-up of 180 days. The results revealed that TAT, vWF, sP-selectin, and CD40L levels in vein were significantly reduced by 2.4% (p = 0.043), 5.0% (p < 0.001), 8.7% (p < 0.001), and 2.5% (p = 0.043) from their baseline levels after rivaroxaban treatment. Conversely, no significant changes were detected in the dabigatran group. Furthermore, the plasma levels of platelet activation biomarkers (CD40L and sP-selectin) in both LA and LAA groups were significantly lower after anticoagulation with rivaroxaban, as compared to dabigatran treatment (CD40L: 554.62 ± 155.54 vs. 445.02 ± 130.04 for LA p = 0.0013, 578.51 ± 156.28 vs. 480.13 ± 164.37 for LAA p = 0.0052; sP-selectin: 2849.07 ± 846.69 vs. 2225.54 ± 799.96 for LA p = 0.0105, 2915.52 ± 1402.40 vs. 2203.41 ± 1061.67 for LAA p = 0.0022). Notably, the present study suggests that rivaroxaban may be more effective in the prevention of DRT for patients undergoing LAAC.

Pulse modulation in En-Bloc HoLEP: does it really matter? A propensity score matched analysis.

INTRODUCTION: Holmium laser enucleation of the prostate (HoLEP) is an established option in the surgical treatment of benign prostatic hyperplasia. Pulse modulation, such as MOSES® technology, has recently been introduced and may offer potential advantages in HoLEP. METHODS: Perioperative data from 117 patients who underwent MOSES® laser enucleation of the prostate (MoLEP) were collected. Propensity score matching using prostate volume, age, body mass index (BMI), and anticoagulant intake was performed using a database of 237 patients treated with HoLEP. In total, 234 patients were included in the analysis. RESULTS: Prostate volume (104 vs. 102 ml), age (70 vs. 71 years), BMI (27 vs. 27), and anticoagulant intake (34 vs. 35%) did not differ significantly between the groups. There were no significant differences in operation time (61.5 vs. 58.1 min, p = 0.42), enucleation efficiency (2.5 vs. 2.6 g/min, p = 0.74), hemostasis time (7.8 vs. 8 min, p = 0.75) and hemoglobin drop (0.9 vs. 0.7 mg/dl, p = 0.48). The complication rates were low in both groups (16.2% for HoLEP and 17.1% for MoLEP). No differences were noted in the Clavien-Dindo Classification (p = 0.63) and the Comprehensive Complication Index (p = 0.24). The rate of complications > CDC IIIa was 0.9% for HoLEP (endoscopic coagulation) and 1.7% for MoLEP (2 cases of endoscopic coagulation). No transfusions were administered. CONCLUSION: Overall, the enucleation efficiency was high in both groups and the procedure time was short. HoLEP is an efficient and safe treatment option in experienced hands, regardless of the use of pulse modulation technology.

Clot time ratio (CTR) and treatment outcomes in Apixaban-treated atrial fibrillation patients.

There are clinical situations where information about the anticoagulant effects of Apixaban could be useful. Specialised methods for measuring Apixaban concentrations are not available at all medical laboratories while methods for measuring the functional effects of Apixaban, using clot time ratio (CTR), can be performed in most medical laboratories around the clock using well-established measurement procedures. The aim of this study was to investigate CTR in trough and peak samples during Apixaban treatment of atrial fibrillation and to correlate the findings to bleeds and thrombotic events. Three trough- and three peak samples from 61 patients (31 on Apixaban 5 mg twice daily and 30 on Apixaban 2.5 mg twice daily) were analysed with MRX PT DOAC. Patients were followed for 30 + /-15 months, and bleeds and thrombotic events were documented. The effect of Apixaban could be measured with MRX PT DOAC and there was a statistically significant difference between CTR in trough samples compared to peak samples (p < 0.001). A total of 21 patients suffered bleeds during follow-up; two patients suffered major bleeds, and 19 suffered minor bleeds. Patients with major bleeds had both mean peak- and mean trough CTR above the respective first to third quartile (Q1-Q3) range. Four patients suffered thromboembolic events. Generally, the peak CTRs were below or in the lower end of the peak Q1-Q3 for these patients. The new test MRX PT DOAC can be used to measure the effect of Apixaban during the treatment of atrial fibrillation. High mean peak- and mean trough CTR were seen in 2 patients with major bleeds, and low peak CTR was seen in 4 patients with thromboembolic events.

A decade of experience in over 300 surgically treated spine patients with long-term oral anticoagulation: a propensity score matched cohort study.

PURPOSE: The aim of this study was to investigate the risks and outcomes of patients with long-term oral anticoagulation (OAC) undergoing spine surgery. METHODS: All patients on long-term OAC who underwent spine surgery between 01/2005 and 06/2015 were included. Data were prospectively collected within our in-house Spine Surgery registry and retrospectively supplemented with patient chart and administrative database information. A 1:1 propensity score-matched group of patients without OAC from the same time interval served as control. Primary outcomes were post-operative bleeding, wound complications and thromboembolic events up to 90 days post-surgery. Secondary outcomes included intraoperative blood loss, length of hospital stay, death and 3-month post-operative patient-rated outcomes. RESULTS: In comparison with the control group, patients with OAC (n = 332) had a 3.4-fold (95%CI 1.3-9.0) higher risk for post-operative bleeding, whereas the risks for wound complications and thromboembolic events were comparable between groups. The higher bleeding risk was driven by a higher rate of extraspinal haematomas (3.3% vs. 0.6%; p = 0.001), while there was no difference in epidural haematomas and haematoma evacuations. Risk factors for adverse events among patients with OAC were mechanical heart valves, posterior neck surgery, blood loss > 1000 mL, age, female sex, BMI > 30 kg/m2 and post-operative PTT levels. At 3-month follow-up, most patients reported favourable outcomes with no difference between groups. CONCLUSION: Although OAC patients have a higher risk for complications after spine surgery, the risk for major events is low and patients benefit similarly from surgery.

Effects of sodium ferulate for injection on anticoagulation of warfarin in rats in vivo.

BACKGROUND: Herb-drug interactions may result in increased adverse drug reactions or diminished drug efficacy, especially for drugs with a narrow therapeutic index such as warfarin. The current study investigates the effects of sodium ferulate for injection (SFI) on anticoagulation of warfarin from aspects of pharmacodynamics and pharmacokinetics in rats and predicts the risk of the combination use. METHODS: Rats were randomly divided into different groups and administered single- or multiple-dose of warfarin (0.2 mg/kg) with or without SFI of low dose (8.93 mg/kg) or high dose (26.79 mg/kg). Prothrombin time (PT) and activated partial thromboplastin time (APTT) were detected by a blood coagulation analyzer, and international normalized ratio (INR) values were calculated. UPLC-MS/MS was conducted to measure concentrations of warfarin enantiomers and pharmacokinetic parameters were calculated by DAS2.0 software. RESULTS: The single-dose study demonstrated that SFI alone had no effect on coagulation indices, but significantly decreased PT and INR values of warfarin when the two drugs were co-administered (P < 0.05 or P < 0.01), while APTT values unaffected (P > 0.05). Cmax and AUC of R/S-warfarin decreased but CL increased significantly in presence of SFI (P < 0.01). The multiple-dose study showed that PT, APTT, INR, and concentrations of R/S-warfarin decreased significantly when SFI was co-administered with warfarin (P < 0.01). Warfarin plasma protein binding rate was not significantly changed by SFI (P > 0.05). CONCLUSIONS: The present study implied that SFI could accelerate warfarin metabolism and weaken its anticoagulation intensity in rats.

Anticoagulant therapy likely increases risk of bleeding in Gynura segetum-induced hepatic sinus obstruction syndrome.

This study aimed to analyze the clinical characteristics of Gynura segetum (Tusanqi)-induced hepatic sinusoidal obstruction syndrome (HSOS) and the benefits and risks of anticoagulant therapy for Tusanqi-induced HSOS. This was a retrospective analysis of 49 patients with Tusanqi-induced HSOS who were treated with anticoagulation or standard therapy between July 2006 and December 2022. Clinical manifestations included abdominal pain (n = 47) and peritoneal or pleural effusion (n = 46); 2 patients died. Nineteen patients requested standard medical treatment, while 30 were treated with anticoagulants. HSOS resolved within 6 months in 22 patients but did not resolve in 27 patients. The resolution rate was higher in the anticoagulant than standard treatment group (P = .037). Logistic regression analysis revealed that a history of chronic liver disease or treatment increased the risk of poor outcomes. Bleeding complications occurred in 6 patients in the anticoagulant treatment group. Early diagnosis and anticoagulant treatment are beneficial for rapid recovery after Tusanqi-induced HSOS. However, anticoagulant treatment is associated with the risk of multisite bleeding.

Fingerprint analysis of dang-gui-Si-Ni decoction and its anticoagulant activity in vivo-in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Dang-Gui-Si-Ni (DGSN) decoction is a classic prescription in the clinical practice of traditional Chinese Medicine (TCM). DGSN decoction is often used to relieve symptoms of cold coagulation and blood stasis recorded by Treatise on Febrile Diseases (Shang Han Lun) and treat Raynaud's disease, dysmenorrhea, arthritis, migraine in TCM clinic. Accumulated evidences have suggested that this diseases are related to microcirculation disturbance. However, the anticoagulant activity and underlying mechanisms of DGSN decoction responsible for the therapeutic not well understood. AIM OF THE STUDY: The fingerprint and anticoagulant activity in vivo-in vitro of DGSN decoction were evaluated to strengthen the quality control and activity study of formulas. MATERIALS AND METHODS: The chemical components of DGSN decoction were analyzed by HPLC and its fingerprint similarity were evaluated by "Chinese Medicine Chromatographic Fingerprint Similarity Evaluation Software (2012 Edition)". The anticoagulant activity of DGSN decoction was assessed by measuring four coagulation factors (PT, TT, APTT, FIB) in vitro. Zebrafish thrombosis model induced by punatinib was established to evaluate the activity of improving microvascular hemodynamics in vivo. Quantitative real-time polymerase chain reaction (q-PCR) were adopted to compare the changes in the RNA expression levels of coagulation factor II (FII), VII (FVII), IX (FIX) and X (FX) in zebrafish thrombosis model. RESULTS: The fingerprint similarity evaluation method of DGSN decoction was established. The results showed that 18 samples had higher similarity (S1-S18 > 0.878). Pharmacodynamic results showed that DGSN decoction could extend PT, TT and APTT, and reduce FIB content in vitro. Meanwhile, it markedly enhanced the cardiac output and blood flow velocity at low dosage (500 µg mL-1) in vivo. q-PCR data demonstrated that DGSN decoction (500 µg mL-1) could downregulate the RNA expression of FII, FVII, FIX and FX. Interestingly, there were a bidirectional regulation of FII, FIX and FX in a certain concentration range. In general, DGSN decoction can significantly improve hemodynamics and downregulate coagulation factors, and the results were consistent both in vitro - in vivo. CONCLUSION: The fingerprint study provide a new perspective for improving the quality control of DGSN decoction. DGSN decoction possess anticoagulant activity by regulating multiple coagulation factors simultaneously. Thus, it has the potential to develop into the novel raw material of anticoagulant drugs.

Structural and biofunctional diversity of sulfated polysaccharides from the genus Codium (Bryopsidales, Chlorophyta): A review.

It is believed that polysaccharides will become a focal point for future production of food, pharmaceuticals, and materials due to their ubiquitous and renewable nature, as well as their exceptional properties that have been extensively validated in the fields of nutrition, healthcare, and materials. Sulfated polysaccharides derived from seaweed sources have attracted considerable attention owing to their distinctive structures and properties. The genus Codium, represented by the species C. fragile, holds significance as a vital economic green seaweed and serves as a traditional Chinese medicinal herb. To date, the cell walls of the genus Codium have been found to contain at least four types of sulfated polysaccharides, specifically pyruvylated ß-d-galactan sulfates, sulfated arabinogalactans, sulfated ß-l-arabinans, and sulfated ß-d-mannans. These sulfated polysaccharides exhibit diverse biofunctions, including anticoagulant, immune-enhancing, anticancer, antioxidant activities, and drug-carrying capacity. This review explores the structural and biofunctional diversity of sulfated polysaccharides derived from the genus Codium. Additionally, in addressing the impending challenges within the industrialization of these polysaccharides, encompassing concerns regarding scale-up production and quality control, we outline potential strategies to address these challenges from the perspectives of raw materials, extraction processes, purification technologies, and methods for quality control.

[Anticoagulant rodenticide poisoning in dogs: Retrospective analysis of clinical and laboratory diagnostic data]. / Vergiftung mit Cumarinderivaten beim Hund: Retrospektive Analyse klinischer und labordiagnostischer Daten.

OBJECTIVE: In this retrospective study, patient records of dogs suffering from poisoning with coumarin derivatives were evaluated to characterize the clinical appearance more precisely. MATERIAL UND METHODS: Retrospective data analysis included 52 dogs with hemostaseologically proven anticoagulant rodenticide poisoning which were treated as inpatients at the Clinic for Small Animals between September 2011 and October 2018. RESULTS: In only 2 dogs (4%) the intake of poison could be observed with certainty. The most common clinical signs observed were reduced general behavior (79%), pallor of the mucosa (79%), anorexia (60%), and dyspnea/tachypnea (60%). In contrast, macroscopically visible internal and external bleedings occurred less frequently. Initially, all cases showed a highly altered prothrombin time and most patients a considerably prolonged activated partial thromboplastin time. Anemia was present in 75% of patients. All dogs included in the study received initially an intravenous treatment with 10 mg/kg vitamin K1. Pretreatment with 1 mg/kg prednisolone was given for prophylaxis of possible incompatibility reactions. No patient showed signs of anaphylactic reaction. Transfusions of whole blood or concentrated red cells were given to only 10 of the 52 animals; only one received 2 transfusions of erythrocytes. 94% of the animals could be discharged home for outpatient therapy after a median length of hospitalization of 3 days (1-9 days) with physiological or almost physiological coagulation test results. CONCLUSION: Anticoagulant rodenticide poisoning is often associated with non-specific symptoms and good prognosis if treated adequately. CLINICAL RELEVANCE: Coagulation diagnostics is always indicated in cases with unclear disorders. In life-threatening emergencies, immediate intravenous infusion of high-dose vitamin K1 is a very effective treatment and results in a rapid increase in coagulation factor activity.

Real-world evidence of heparin and citrate use in extracorporeal photopheresis: A hypothesis-generating data review of device settings and performance.

Extracorporeal photopheresis (ECP) is widely used for the treatment of cutaneous T-cell lymphoma, graft-vs-host disease, and other immune-related conditions. To avoid clotting during treatment, the ECP system used must be effectively primed with an anticoagulant. Heparin is the recommended anticoagulant for the THERAKOS CELLEX System, but acid citrate dextrose-A (ACDA) is often used. We compared system performance between these two anticoagulants for this ECP system. Deidentified data for ECP device performance were obtained at each treatment session, from automatically logged Smart Cards or labels completed by device operators. We compared the effects of ACDA or heparin on overall treatment duration, buffy coat (leukocyte) collection time, photoactivation time and the number of alarms and warnings. The variability in these parameters was also assessed. Data from 23 334 treat sessions were analyzed; ACDA was used in 34.4% and heparin in 65.6%. Overall, the ECP procedure duration, buffy coat collection time and photoactivation time were numerically similar regardless of whether ACDA or heparin was used, and regardless of needle mode. Photoactivation time variability was lower with ACDA compared with heparin in all needle modes. Among treatments that were completed automatically without any operator intervention, total treatment duration and photoactivation time were significantly reduced with ACDA use in both the double- and single-needle modes. The data presented indicate that, in both double- and single-needle modes, the THERAKOS® CELLEX® integrated ECP system performed similarly with ACDA compared to heparin, although ACDA demonstrated potential benefits in reducing variability in photoactivation time.

New anticoagulant protein from medicinal leech.

The saliva of the medicinal leech contains various anticoagulants. Some of them, such as hirudin, are well known. However, it is reasonable to believe that not all anticoagulant proteins from medicinal leech saliva have been identified. We previously performed a comprehensive study of the transcriptome, genome, and proteome of leech salivary gland cells, which led to the discovery of several previously unknown hypothetical proteins that may have anticoagulant properties. Subsequently, we obtained a series of recombinant proteins and investigated their impact on coagulation in in vitro assays. We identified a previously undescribed protein that exhibited a high ability to suppress coagulation. The His-tagged recombinant protein was expressed in Escherichia coli and purified using metal chelate chromatography. To determine its activity, commonly used coagulation methods were used: activated partial thromboplastin time, prothrombin time, and thrombin inhibition clotting assay. Clotting and chromogenic assays for factor Xa inhibition were performed to evaluate anti-Xa activity. We used recombinant hirudin as a control anticoagulant protein in all experiments. The new protein showed significantly greater inhibition of coagulation than hirudin at the same molar concentrations in the activated partial thrombin time assay. However, hirudin demonstrated better results in the direct thrombin inhibition test, although the tested protein also exhibited the ability to inhibit thrombin. The chromogenic analysis of factor Xa inhibition revealed no activity, whereas the clotting test for factor Xa showed the opposite result. Thus, a new powerful anticoagulant protein has been discovered in the medicinal leech. This protein is homologous to antistatin, with 28 % identical amino acid residues. The recombinant protein was expressed in E. coli. This protein is capable of directly inhibiting thrombin, and based on indirect evidence, other proteases of the blood coagulation cascade have been identified.