A pyruvylated and sulfated galactan from the green alga Dictyosphaeria cavernosa: Structure, anticoagulant property and inhibitory effect on zebrafish thrombosis.

A pyruvylated and sulfated galactan from the green alga Dictyosphaeria cavernosa, designated PSG, was obtained by dilute alkali extraction, ion-exchange and gel filtration chromatography. The backbone of PSG was composed of 3-linked ß-d-Galp units with partial sulfation on C-4 and C-6. Pyruvate ketals were linked to O-3 and O-4 of nonreducing terminal ß-d-Galp, as well as O-4 and O-6 of 3-linked ß-d-Galp. The branches consisting of 6-linked ß-d-Galp(4SO4) and ß-d-Galp(3,4-Pyr)-(1→ units were located at C-6 of 3-linked ß-d-Galp unit. PSG possessed obvious anticoagulant effect in vitro as assessed by the tests of activated partial thromboplastin time and thrombin time. The assay of anticoagulant mechanism showed that PSG promoted thrombin inactivation mediated by heparin cofactor-II and antithrombin-III (ATIII), and could effectively potentiate factor Xa inactivation by ATIII. The antithrombotic activity of PSG in vivo was assessed by phenylhydrazine (PHZ)-induced zebrafish thrombotic model. The results indicated that PSG obviously reduced peripheral erythrocytes aggregation, enhanced cardiac blood flow and improved peripheral platelet circulation, and PSG possessed a marked inhibitory effect on the PHZ-induced zebrafish thrombosis. Thus, PSG is a hopeful anticoagulant and antithrombotic polysaccharide.

Balancing anticoagulation and hemostasis in an infant with severe hemophilia A during cardiac transplantation: Review of the literature and development of a surgical protocol.

Hemophilia A is a disorder resulting in a deficiency of clotting factor VIII that can lead to life-threatening bleeding. Evidence-based guidelines for surgical interventions like cardiac surgery are limited. Anticoagulation is necessary for cardiac bypass, thus risk of bleeding in a patient with hemophilia is increased and requires careful attention to maintain hemostasis. We report the first infant with severe hemophilia A and dilated cardiomyopathy who underwent successful cardiac transplantation, and review the literature on previous cardiac transplant cases in congenital hemophilia. To ensure safe and effective management, a multidisciplinary approach was used to develop the surgical protocol for transplant.

Design, expression and biological evaluation of DX-88mut as a novel selective factor XIa inhibitor for antithrombosis.

Thrombotic diseases, such as myocardial infarction, stroke, and deep vein thrombosis, severely threaten human health, and anticoagulation is an effective way to prevent such illnesses. However, most anticoagulant drugs in the clinic have different bleeding risks. Previous studies have shown that coagulation factor XI is an ideal target for safe anticoagulant drug development. Here, we designed the FXIa inhibitory peptide DX-88mut by replacing Loop1 (DGPCRAAHPR) and Loop2 (IYGGC) in DX-88, which is a clinical drug targeting PKa for the treatment of hereditary angioedema, using Loop1 (TGPCRAMISR) and Loop2 (FYGGC) in the FXIa inhibitory peptide PN2KPI, respectively. DX-88mut selectively inhibited FXIa against a panel of serine proteases with an IC50 value of 14.840 ± 0.453 nM, dose-dependently prolonged APTT in mouse, rat and human plasma, and potently inhibited FeCl3-induced carotid artery thrombosis in mice at a dose of 1 µmol/kg. Additionally, DX-88mut did not show a significant bleeding risk at a dose of 5 µmol/kg. Taken together, these results show that DX-88mut is a potential candidate for the development of a novel antithrombotic agent.

Bleeding Complications in a Patient After the Unexpected Interaction between Valproic Acid and Phenprocoumon.

BACKGROUND: Phenprocoumon is a vitamin K antagonist that is widely prescribed in Europe and Latin America for the prophylaxis and treatment of thromboembolic events. CASE PRESENTATION: A 90-year-old female was admitted to our hospital with tonic-clonic seizures, possibly due to dementia syndrome. Valproic acid (VPA) was prescribed for the treatment of seizures. VPA is an inhibitor of cytochrome P450 (CYP) 2C9 enzymes. A pharmacokinetic interaction with phenprocoumon occurred, which is a substrate for CYP2C9 enzymes. The interaction resulted in a strong INR increase and subsequent clinically relevant bleeding in our patient. Valproic acid is not specifically mentioned in the phenprocoumon drug label as a CYP2C9 inhibitor, and in the Dutch medication surveillance database, no medication alert is shown when prescribing this combination, and no interaction with phenprocoumon has been reported so far. CONCLUSION: When prescribing this combination, the prescriber should be warned and advised to intensify INR monitoring if the combination is to be continued.

A facile fluorescence microplate immunoassay based on an in situ fluorogenic reaction for the detection of two highly toxic anticoagulant rodenticides in food and biological matrix.

Bromadiolone and brodifacoum, the most frequently used anticoagulant rodenticides, are highly toxic and pose a threat to public health by causing food poisoning incidents. Here, we developed a fluorescence microplate immunoassay for facile and sensitive detection of bromadiolone and brodifacoum by introducing three commercial chemicals (p-phenylenediamine, polyethyleneimine, H2O2) as a new substrate of horseradish peroxidase and then generating fluorescence signals based on an in situ fluorogenic reaction (detection time within 75 min). This assay exhibited higher efficiency in generating fluorescence signals, thereby exhibiting a 6-fold improvement in sensitivity compared with colorimetric ELISA. The limit of detection was 0.23-0.28 ng/mL (ng/g) for bromadiolone and 0.34-0.61 ng/mL (ng/g) for brodifacoum in corn and human serum, with recovery ratios higher than 82.3 %. These satisfactory results illustrated our proposed assay was a potential tool for food analysis and poisoning diagnosis caused by bromadiolone and brodifacoum.

Pediatric arterial thrombosis: A single-institution cohort study of patient characteristics and thrombosis outcomes.

BACKGROUND: Arterial thrombosis (AT) is an increasingly recognized complication in pediatrics. Consensus clinical practice guidelines suggest immediate removal of the indwelling arterial catheter and a short course (5-7 days) of anticoagulation. The optimal duration and modality of antithrombotic therapy in children are yet to be determined. AIMS: Describe treatment patterns and outcomes in pediatric patients with AT and explore predictors for complete thrombus resolution or long-term complications. METHODS: Single-institution retrospective study. Patients were identified by ICD-9 and ICD-10 codes for the diagnosis of AT or reports of AT on ultrasound from January 1, 2012, to October 1, 2022. Descriptive and logistic regression analyses were used. RESULTS: 101 patients were included. The median age was 2.2 months. The most common underlying diagnoses were congenital heart disease (39.6%) and infection (22.8%). A majority of patients had symptomatic thrombosis in an extremity, and 78% were catheter-associated. 81% of patients received anticoagulation with a median duration of 35 days. Out of the 70 patients who were treated with anticoagulation alone and had a follow-up imaging, 70% had complete resolution after 90 days of anticoagulation. No clear predictors of complete resolution were identified. Eighteen patients had long-term sequelae secondary to arterial insufficiency. Those with infection-associated AT were more likely to have long-term complications. The major and clinically relevant non-major bleeding rate was 11%. CONCLUSION: Duration of anticoagulation was widely variable, and 70% of patients achieved complete resolution by 90 days of anticoagulation. A significant proportion of patients developed long-term sequelae secondary to arterial insufficiency. Sepsis/infection at the time of diagnosis with AT was more likely to be associated with long-term complications.

Controversies in Stoppage of Antiplatelet and Anticoagulant Medications Prior to Oral Surgery.

Dental procedures can pose a risk of bleeding, and it is not uncommon for dentists to consult prescribing physicians regarding a mutual patient's antiplatelet and anticoagulant medication to prevent excessive bleeding during or after an upcoming procedure. However, there has been a growing controversy in the dental community surrounding the stoppage of these medications prior to dental procedures. Some believe that stopping these medications prior to dental procedures is necessary to reduce the risk of bleeding complications, while others argue that stopping them can increase the risk of stroke or other thromboembolic events. The debate has left many dentists and specialists unsure about the best course of action when it comes to managing bleeding risk during dental procedures.In this article, we will review the antithrombotic medications, indications, mechanism of action, and its effects on the coagulation pathway, laboratory testing and reversal agents. Also, we will explore the controversy surrounding the stoppage of novel anitplatelets (eg,: prasurgrel and ticagrelor), dual-antiplatelets, triple-antiplatelet, vitamin K antagonists (eg,: wafarin, coumadin), and direct oral anticoagulants (eg,: dabigatran, rivaroxaban, xarelto and endoxaban) in dentistry and examine the current evidence and guidelines for managing dental patients undergoing oral surgery.

Failure-to-Salvage After Femoropopliteal Bypass Surgery is Associated With Nonmodifiable Risk Factors.

INTRODUCTION: Bypass graft failure and major amputation are among the worst complications after femoropopliteal bypass surgery. In this large multicenter analysis, we examined our incidence and risk factors for failure-to-salvage (FTS) following either bypass surgery or bypass graft failure. METHODS: A regional multicenter database was retrospectively queried for all femoropopliteal bypass procedures performed between 2002 and 2021. Re-do bypasses were excluded. The primary outcome was FTS, defined as major ipsilateral limb amputation within 90 d following index bypass surgery or bypass graft failure. Bypass graft failure was defined as critical stenosis or occlusion of the bypass graft requiring reintervention. Graft rescue was defined as bypass graft failure without subsequent major ipsilateral limb amputation within 90 d. Multivariable logistic regression analysis was utilized to identify factors associated with bypass graft failure and FTS. RESULTS: Over the study period, 1315 femoropopliteal bypass procedures were performed across five hospitals. There were 25 major amputations within 90 d of initial bypass. Bypass graft failure was diagnosed in an additional 503 (38.3%) patients. Mean time to graft failure was 619 d. On multivariable analysis, bypass for tissue loss (adjusted odds ratio [aOR] 1.38 [95% confidence interval (CI) 1.03-1.83], P = 0.03) was associated with graft failure. Of patients with graft failure, 33 had major amputation, leading to an overall FTS incidence of 4.4% (n = 58) over a mean follow-up period of 3.4 y. Patient demographics, medical comorbidities, and bypass conduits were similar between the FTS and graft rescue groups (n = NS each). The FTS group more frequently underwent bypass for tissue loss (51.7% versus 29.8%, P = 0.002), and an infrageniculate bypass target was more frequently utilized in FTS compared to graft rescue patients (81.0% versus 60.4%, P = 0.002). Anticoagulation (34.5% in FTS versus 37.7% in rescue) and dual antiplatelet therapy (15.5% versus 22.1%, respectively) were similar between groups (P = NS each). On multivariable analysis, factors associated with FTS included infrageniculate target (aOR 2.42 [95% CI 1.22-4.08], P = 0.01), black race (aOR 2.47 [95% CI 1.04-5.84], P = 0.04), and bypass for tissue loss (aOR 4.75 [95% CI 1.41-16.0], P = 0.01). Anticoagulation and dual antiplatelet therapy were not associated with loss of graft patency or FTS. CONCLUSIONS: Failure-to-salvage after femoropopliteal bypass surgery is associated with nonmodifiable factors, and may represent progression of underlying disease. These data may help inform vascular surgeons in counseling patients with failing bypass grafts. Further investigation of care delivery factors improving likelihood of graft salvage may be warranted.

Greater predisposition to second generation anticoagulant rodenticide exposure in red foxes (Vulpes vulpes) weakened by suspected infectious disease.

Anticoagulant rodenticide (AR) exposure in wild carnivores is a current and global concern due to continuous and widespread use worldwide. We studied the prevalence of ARs in liver samples of 25 red foxes (Vulpes vulpes), 3 European badgers (Meles meles) and 2 genets (Genneta genneta) from Alicante (Spanish Levante region) obtained in 2021 and 2022. In addition to trauma, poisoning by pesticides is the most frequent cause of death in wild carnivores in this region. The present research aims to explain a possible association between the fact of suffering from an infectious disease and the increase in ARs concentrations in the affected animals. Both first- and second-generation ARs were analysed by HPLC/MS/TOF in liver samples. Apart from the cause of death, the influence of other variables such as age, sex and body weight were also assessed on AR liver concentrations. Potential health risks for individuals and populations in the study area have also been studied. Our research detected higher AR concentrations in the group of red foxes clinically diagnosed with infectious disease compared to the group of apparently healthy red foxes, mostly killed by trauma. Furthermore, our results lead us to suggest that red fox could be considered a good sentinel species for the risk of exposure to ARs in other wild mammals. All the livers analysed contained ARs and the most detected compounds in red fox were difenacoum, bromadiolone, brodifacoum, present in all the samples analysed, and flocoumafen (in 96 %). Additionally, 53 % of the animals had at least one second generation anticoagulant rodenticide (SGAR) above the threshold value reported as triggering adverse health effects (200 ng/g). Regarding this, the level of risk in red fox in this area might be classified as high and worrying. Moreover, we suggest that individuals and populations with weakened health due to other diseases (for example, infectious or parasitic diseases) might be more prone to high exposure to anticoagulant rodenticides and, very probably, would be more sensitive to suffering serious effects at lower doses of ARs.

First evidence of widespread anticoagulant rodenticide exposure of the Eurasian otter (Lutra lutra) in Germany.

Exposure of wildlife to anticoagulant rodenticides (ARs) has been extensively documented for species directly or indirectly linked to pest rodents via the terrestrial food web. Recently, the scientific focus extended to a former blind spot, namely AR emissions to the aquatic environment, and provided clear evidence of AR residues in freshwater fish. As second-generation ARs are likely to be transferred along the aquatic food chain, a total of 122 Eurasian otter (Lutra lutra) individuals found dead in Germany between 2005 and 2021 were investigated to shed more light on resultant environmental risks. Target analytes comprised one pharmaceutical and eight biocidal anticoagulants, as well as one suspected bait impurity. Notably, all target compounds were detected in the analyzed livers of otters, a primarily piscivorous top predator and indicator species for the aquatic environment, strictly protected by conservation laws. In regions with pronounced rodent control measures, otters were frequently exposed to biocidal ARs. The elevated AR levels measured in multiple otters, compared to freshwater fish, hinted at biomagnification of second-generation ARs within the aquatic food web. The results indicated that risk mitigation measures implemented in Germany within the biocidal product authorization may not be sufficient to protect aquatic non-target wildlife from AR exposure, challenging the effectiveness of current regulatory measures.

Effects of Deep Venous Thrombosis Treatments on Early and Long-term Quality of Life: Medical Therapy vs. Systemic Thrombolysis vs. Pharmacomechanical Thrombolysis.

OBJECTIVES: The present study aimed to compare the effects of medical therapy (MT), systemic thrombolysis (ST), and pharmacomechanical thrombolysis (PMT) methods used in our clinic for the treatment of deep venous thrombosis (DVT) on symptom reduction, the incidence of post-thrombotic syndrome (PTS) development, and quality of life. METHODS: Data from160 patients diagnosed with acute DVT between January 2012 and May 2021 and treated and followed up in our clinic were retrospectively analyzed. The patients were divided into three groups according to treatment method. The patients who received MT treatment were defined as Group 1, anticoagulant treatment after ST as Group 2, and anticoagulant treatment after PMT as Group 3. The patients were called to the outpatient clinic, informed consent was obtained, EuroQol-5D-3 L (EQ-5D-3 L) scoring and Villalta scoring were performed, and anamnesis was taken. RESULTS: A total of 160 patients were included, with 71 (44.4%) patients in Group 1, 45 (28.1%) in Group 2, and 44 (27.5%) in Group 3. The mean age was 48.9 ± 14.9 years for Group 1, 42.2 ± 10.8 for Group 2, and 29.0 ± 7.2 for Group 3. When the time to return to normal life and the EQ-5D-3 L score index were compared, the differences between Groups 1 and 2 and between Groups 1 and 3 were statistically significant (P = .000 and P = .000, respectively). However, the differences between Groups 2 and 3 were statistically insignificant (P = .213 andp = .074, respectively). When Villalta scores and EQ Visual Analogue Scale (EQ-VAS) scores were compared between groups, the difference between all groups was statistically significant (P = .000). CONCLUSIONS: The medical treatment alone was observed to be insufficient in terms of symptomatic improvement, development of PTS, quality of life, and long-term complications. When the ST and PMT groups were compared, it was determined that PMT treatment was more advantageous in terms of EQ-VAS score and PTS development, although there was no statistical difference regarding complications, such as return to normal life and long-term quality of life, the incidence of recurrent DVT development, and pulmonary thromboembolism incidence.

A metabolomics discrimination-based strategy for screening the antithrombin active markers of perilla seeds: A natural oil crop.

Natural crops oil with high nutritional value has gradually attracted attention. Perilla seeds are regarded as a source of functional edible oil in America, Asia and European countries due to its abundant nutrients. In this research, samples were extracted by different polarity solvents and evaluated their thrombin inhibition activities in vitro. Metabolomics combined with chemometrics revealed the antithrombin active markers of perilla seeds. The enzyme kinetics and molecular docking results were useful in clarifying their inhibition of thrombin. The orthogonal experimental design was applied to optimize the extraction process of six antithrombin active markers from perilla seeds. The results showed that rosmarinic acid, luteolin, luteolin-7-O-glucoside, α-linolenic acid, linoleic acid, and oleic acid were screened out as functional and active markers. Besides, perilla seeds as a natural oil crop had the potential of antithrombin. It can also be applied in the food field because of its nutraceutical functions. Metabolomics combined with chemometrics will facilitate the discovery of functional, active markers in perilla seeds, which is conducive to accurate quality control.

Research Progress on Antiviral Activity of Heparin.

Heparin, as a glycosaminoglycan, is known for its anticoagulant and antithrombotic properties for several decades. Heparin is a life-saving drug and is widely used for anticoagulation in medical practice. In recent years, there have been extensive studies that heparin plays an important role in non-anticoagulant diseases, such as anti-inflammatory, anti-viral, anti-angiogenesis, anti-neoplastic, anti-metastatic effects, and so on. Clinical observation and in vitro experiments indicate that heparin displays a potential multitarget effect. In this brief review, we will summarize heparin and its derivative's recently studied progress for the treatment of various viral infections. The aim is to maximize the benefits of drugs through medically targeted development, to meet the unmet clinical needs of serious viral diseases.

Using tungsten oxide quantum-dot enhanced electrochemiluminescence to measure thrombin activity and screen its inhibitors.

A thrombin-activity-based electrochemiluminescence (ECL) biosensor was successfully constructed using tungsten oxide quantum dots (WO3-x QDS) as the co-reactant and thrombin-cleavable peptides as the recognizer. Specifically, Ru(bpy)32+ were doped on silica nanoparticles (Ru@SiO2), which greatly enhanced the ECL potential. AuNPs@WO3-x QDs composite was then prepared to accelerate electron transfer and improve the ECL signal by 219 times. Under ideal conditions, the limit of detection for thrombin in serum was determined to be 0.28 µU/mL with a linear range from 1 µU/mL to 1 U/mL. In addition, the developed ECL biosensor was used to screen for thrombin inhibitors from 12 compounds in Artemisiae Argyi Folium. Among the compounds tested, it was observed that 100 µmol/L luteolin exhibited a significantly higher inhibition rate (exceeding 80%) compared to apigenin, isorhamnetin, naringin, or eriodictyol. In an in-vitro anticoagulation experiment, luteolin (100 µmol/L) prolonged APTT by 49%, and the molecular docking assay indicated that luteolin had binding sites of Gly219 and Asp189 in the active pockets of thrombin. This may have been the main reason underpinning luteolin's anticoagulation effects. Overall, the Ru@WO3-x QDS ECL biosensor provided a reliable strategy for thrombin activity assay and screening of anticoagulant agents.

Efecto de la técnica de la tos durante la inyección subcutánea de heparina sobre la severidad del dolor y la satisfacción individual / Effect of the coughing technique during subcutaneous heparin injection on pain severity and individual satisfaction / Efeito da técnica de tosse durante injeção subcutânea de heparina na intensidade da dor e satisfação individual

Objetivo: examinar el efecto de la técnica de tos de mediana intensidad durante la inyección subcutánea de heparina de bajo peso molecular sobre la severidad del dolor y la satisfacción individual en pacientes de cirugía general. Método: estudio prospectivo, cuasi experimental, que incluyó a 100 pacientes a los que se les prescribió una inyección subcutánea de heparina de bajo peso molecular una vez cada 24 horas. Cada paciente recibió dos inyecciones por el mismo investigador utilizando técnica de inyección estándar con técnica de tos de intensidad media y solo técnica de inyección estándar. Resultados: hubo una diferencia estadísticamente significativa entre las puntuaciones medias de los pacientes sobre la intensidad del dolor y los niveles de satisfacción después de las inyecciones administradas por las dos técnicas (p= 0,000). Además, se encontró que el género afectó la severidad del dolor relacionado con la inyección, pero no afectó el nivel de satisfacción individual. Conclusión: se encontró que la técnica de tos de intensidad media reduce la severidad del dolor y aumenta la satisfacción del paciente de cirugía general que reciben inyecciones subcutáneas de heparina de bajo peso molecular. Registro del ensayo: NCT05681338.

Objective: to examine the effect of the medium intensity coughing technique during subcutaneous low molecular weight heparin injection on pain severity and individual satisfaction in general surgery patients. Method: the prospective, quasi-experimental study included 100 patients who had been prescribed a subcutaneous low molecular weight heparin injection once in 24 hours. Each patient received two injections by the same researcher, one using the standard injection technique with medium intensity coughing technique and the other only the standard injection technique. Results: there was a statistically significant difference between patients' mean scores on pain severity and satisfaction levels after injections administered by the two techniques (p= 0.000). Also, it was found that gender affected pain severity relating to the injection but did not affect the level of individual satisfaction. Conclusion: the medium intensity coughing technique was found to reduce pain severity and increase patient satisfaction in general surgery patients receiving subcutaneous low molecular weight heparin injections. Trial registration: NCT05681338.

Objetivo: examinar o efeito da técnica de tosse de média intensidade durante injeção subcutânea de heparina de baixo peso molecular na intensidade da dor e satisfação individual em pacientes submetidos à cirurgia geral. Método: estudo prospetivo, quasi experimental que incluiu 100 pacientes que haviam recebido uma injeção subcutânea de heparina de baixo peso molecular em 24 horas. Cada paciente recebeu duas injeções pelo mesmo pesquisador usando a técnica de injeção padrão com técnica de tosse de média intensidade e apenas técnica de injeção padrão. Resultados: houve diferença estatisticamente significativa entre as pontuações médias dos pacientes quanto à gravidade da dor e níveis de satisfação após as injeções administradas pelas duas técnicas (p = 0,000). Além disso, verificou-se que o sexo do paciente afetou a intensidade da dor relacionada à injeção, mas não afetou o nível de satisfação individual. Conclusão: a técnica de tosse de média intensidade reduz a intensidade da dor e aumenta a satisfação de pacientes submetidos à cirurgia geral recebendo injeções subcutâneas de heparina de baixo peso molecular. Registro do ensaio clínico: NCT05681338.

Regulation of the innate immune system by fragmented heparin-conjugated lipids on lipid bilayered membranes in vitro.

Surface modification with heparin is a powerful biomaterial coating strategy that protects against innate immunity activation since heparin is a part of the proteoglycan heparan sulfate on cell surfaces in the body. We studied the heparinization of cellular and material surfaces via lipid conjugation to a heparin-binding peptide. In the present study, we synthesized fragmented heparin (fHep)-conjugated phospholipids and studied their regulation of the innate immune system on a lipid bilayered surface using liposomes. Liposomes have versatile applications, such as drug-delivery systems, due to their ability to carry a wide range of molecules. Owing to their morphological similarity to cell membranes, they can also be used to mimic a simple cell-membrane to study protein-lipid interactions. We investigated the interaction of complement-regulators, factor H and C4b-binding protein (C4BP), as well as the coagulation inhibitor antithrombin (AT), with fHep-lipids on the liposomal surface. Herein, we studied the ability of fHep-lipids to recruit factor H, C4BP, and AT using a quartz crystal microbalance with dissipation monitoring. With dynamic light scattering, we demonstrated that liposomes could be modified with fHep-lipids and were stable up to 60 days at 4 °C. Using a capillary western blot-based method (Wes), we showed that fHep-liposomes could recruit factor H in a model system using purified proteins and assist in the degradation of the active complement protein C3b to iC3b. Furthermore, we found that fHep-liposomes could recruit factor H and AT from human plasma. Therefore, the use of fHep-lipids could be a potential coating for liposomes and cell surfaces to regulate the immune system on the lipid surface.

Hematologists' awareness of venous thromboembolism in multiple myeloma: a national survey in China.

BACKGROUND: Venous thromboembolism (VTE) is one of the most common and severe complications of multiple myeloma (MM). The aim of this study was to learn about the current awareness regarding MM-associated VTE among Chinese hematologists. METHODS: A nationwide, online, questionnaire-based survey was sent to the specialized hematologists in mainland China. The questionnaire investigated respondents' demographic and occupational characteristics, their ability to identify VTE risk factors, and their thromboprophylaxis decisions for different anti-MM regimens. Six clinical vignettes were used to evaluate hematologists' awareness of stratified thromboprophylaxis. The data were analyzed using SPSS software. RESULTS: A total of 518 valid questionnaires were received. Of the 518 hematologists investigated, only 23.7% of them could identify VTE-related risk factors correctly. Most hematologists could select appropriate thromboprophylaxis for common anti-MM regimens such as VCd (bortezomib, cyclophosphamide, and dexamethasone) and VRd (bortezomib, lenalidomide, and dexamethasone), but not for uncommon ones such as VTD-PACE (bortezomib, thalidomide, dexamethasone, cisplatin, doxorubicin, cyclophosphamide, and etoposide) and KRd (carfilzomib, lenalidomide, and dexamethasone). The results from the vignettes suggested that only 19.5% of the hematologists could be defined as the 'stratified thromboprophylaxis' group, and the awareness of stratified thromboprophylaxis depended significantly on physicians' age and working seniority. CONCLUSION: The results of our study showed that a large proportion of Chinese hematologists failed to recognize the VTE risk factors, most of them cannot select appropriate thromboprophylaxis for different MM therapeutic regimens and lack awareness of stratified thromboprophylaxis for MM-associated VTE. A standard VTE prevention guideline is urgently needed for the Chinese myeloma group. Continuous education for new professionals should be encouraged. A VTE collaborative group is supposed to be established in each hospital to enhance the overall medical care for VTE patients.

The substantial myeloma patient population and extensive use of immunomodulatory drugs indicate that MM-associated VTE deserves more attention in China.The results from our cross-sectional study showed that a significant proportion of Chinese hematologists failed to identify the VTE risk factors, most of them cannot select appropriate thromboprophylaxis for different MM therapeutic regimens and lack awareness of stratified thromboprophylaxis for MM-associated VTE.

Thrombotic events and prophylactic anticoagulation in pediatric patients with COVID-19: a systematic review and meta-analysis.

BACKGROUND: Venous thromboembolism (VTE) can occur in children with COVID-19, and the efficacy and safety of prophylactic anticoagulant therapy are uncertain. This study aimed to assess the incidence of VTE in pediatric patients with COVID-19, the association of D-dimer with thrombus formation, and the effectiveness and safety of prophylactic anticoagulation treatment. METHODS: We systematically searched databases from January 2020 to February 2023. A systematic review and meta-analysis were conducted to determine the incidence of VTE in children and evaluate the efficacy and safety of prophylactic anticoagulant therapy. RESULTS: Thirteen cohort studies and one clinical trial were included. The pooled incidence rate of VTE in affected children was 1.5% (95% CI 0.4-2.9%). Children with D-dimer levels five times higher than normal had a higher risk of VTE (OR 4.92, 95% CI 1.60-15.11). Prophylactic anticoagulant therapy did not significantly reduce the risk of VTE (OR 1.35, 95% CI 0.74-2.49). The safety of prophylactic anticoagulant therapy was relatively high, with major bleeding and all-cause mortality rates below 0.1% (95% CI 0.0-0.2%). CONCLUSIONS: The incidence of VTE in children with COVID-19 is low, and prophylaxis based on ISTH standards is reasonable. Low-molecular-weight heparin (LMWH) for VTE prevention has a high level of safety. However, more high-quality studies are needed to understand the impact of anticoagulant therapy on VTE incidence in pediatric patients with COVID-19.

[Development and implementation of common data sets for venous thromboembolism: current situation and application prospects].

Venous thromboembolism (VTE) is a formidable disease that poses a serious threat to the health and well-being of hospitalized patients. Owing to its high incidence, debilitating morbidity, and alarming mortality rates, VTE has gained increasing attention from the clinical medicine community worldwide. Unfortunately, the current state of clinical prevention and treatment of VTE is not very optimistic, necessitating the establishment of large disease-specific databases and real-world studies, which can accumulate effective evidence-based medical evidence to gradually standardize the clinical prevention and treatment and quality control of VTE. The construction and development of large medical databases depend greatly on standardized datasets, which establish the conceptual data models of VTE through data standardization routes, set the object classes according to the model, define the attributes of the classes, standardize the data types and property values, and organize the standardized data elements. This article focuses on providing an in-depth overview of the unique characteristics of various domestic and foreign VTE datasets, describing their application and research progress in VTE, as well as the role of datasets in standardizing clinical and research practices to strengthen quality control and artificial intelligence. Through this comprehensive discussion, we hope to promote the establishment of VTE datasets and enable their use in high-quality large real-world studies.

Short- and long-term outcomes of patients with minor stroke and nonvalvular atrial fibrillation.

BACKGROUND AND PURPOSE: Nonvalvular atrial fibrillation (NVAF) is a risk factor for stroke. This study was undertaken to determine the influence of NVAF on the mortality and recurrent stroke after a minor stroke event. METHODS: Data were derived from the Third China National Stroke Registry (CNSR-III) which enrolled 15,166 subjects during August 2015 through March 2018 in China. Patients with minor stroke (NIHSS ≤ 5) within 24 h after onset were included. Clinical outcomes including all-cause mortality, cardiovascular death, recurrent ischemic stroke, and recurrent hemorrhagic stroke were collected. The Cox proportional hazards models were used to determine the association between NVAF and clinical outcomes. RESULTS: A total of 4,753 patients were included in our study. Of them, 222 patients had NVAF (4.7%) (mean age, 71.1 years) and 4,531 patients were without AF (95.3%) (mean age, 61.4 years). NVAF was associated with 12-month cardiovascular mortality in both univariate (hazards ratio [HR], 4.13; 95% confidence interval [CI], 1.84 to 9.31; P < 0.001) and multivariate analyses (HR, 4.66; 95% CI, 1.79 to 12.15; P = 0.001). There was no difference in the in-hospital ischemic stroke recurrence rate between the two groups (HR, 0.45 [95% CI, 0.19 to 1.05] P = 0.07 at discharge). However, patients with NVAF had a lower rate of recurrent ischemic stroke at medium- (3 months and 6 months) and long-term (12 months) follow-up (HR, 0.33 [95% CI, 0.16 to 0.68] P = 0.003 at 3 months; 0.49 [95% CI, 0.27 to 0.89] P = 0.02 at 6 months; 0.55 [95% CI, 0.32 to 0.94] P = 0.03 at 12 months, respectively) compared with those without. There was no difference in all-cause mortality and hemorrhagic stroke between the two groups during follow-up. CONCLUSIONS: Minor stroke patients with NVAF were at higher risk of cardiovascular death but had a lower rate of recurrent ischemic stroke compared to those without during the subsequent year after stroke event. A more accurate stroke risk prediction model for NVAF is warranted for optimal patient care strategies.