OBJECTIVE: Raising awareness of acquired hemophilia A (AHA) and early diagnosis is critical to reduce the associated mortality rate. We aimed to characterize acquired hemophilia in Chinese patients and evaluate the effectiveness of immunotherapy.
METHODS: The clinical characteristics, laboratory test data, therapeutic approaches, and outcomes of 20 patients with AHA who were admitted to Xi\'an Central Hospital between January 2012 and December 2020 were retrospectively studied.
RESULTS: Nine of the patients (45%) were treated by single glucocorticoid administration; three (15%) with cyclophosphamide (CP) in combination with a glucocorticoid; four individuals (20%) received a combination therapy of rituximab with CP and glucocorticoid or rituximab with CP, vincristine, and a glucocorticoid; three (15%) by injection of human immunoglobulin in combination with a glucocorticoid; and one (5%) with CP alone. Six patients (30%) achieved total remission and 11 (55%) partial remission (PR), but three (15%) did not enter remission, indicating an objective response rate of 85%.
CONCLUSIONS: Combination therapy with rituximab or intravenous human immunoglobulin achieves superior results in some patients with AHA. Immunosuppression and the administration of coagulation factors can rapidly control the disease and are efficacious, but >50% of patients only achieved PR. These findings suggest that the complete elimination of inhibitors requires prolonged immunosuppression therapy.

Thromboembolic diseases pose a serious risk to human health worldwide. Fucosylated chondroitin sulfate (FCS) is reported to have good anticoagulant activity with a low bleeding risk. Molecular weight plays a significant role in the anticoagulant activity of FCS, and FCS smaller than octasaccharide in size has no anticoagulant activity. Therefore, identifying the best candidate for developing novel anticoagulant FCS drugs is crucial. Herein, native FCS was isolated from sea cucumber Cucumaria frondosa (FCScf) and depolymerized into a series of lower molecular weights (FCScfs). A comprehensive assessment of the in vitro anticoagulant activity and in vivo bleeding risk of FCScfs with different molecule weights demonstrated that 10 kDa FCScf (FCScf-10 K) had a greater intrinsic anticoagulant activity than low molecular weight heparin (LMWH) without any bleeding risk. Using molecular modeling combined with experimental validation, we revealed that FCScf-10 K can specifically inhibit the formation of the Xase complex by binding the negatively charged sulfate group of FCScf-10 K to the positively charged side chain of arginine residues on the specific surface of factor IXa. Thus, these data demonstrate that the intermediate molecular weight FCScf-10 K is a promising candidate for the development of novel anticoagulant drugs.

Increased cortisol levels in the preovulatory follicular fluid suggests a role of glucocorticoid in human ovulation. However, the mechanisms through which cortisol regulates the ovulatory process remain poorly understood. In this study, we examined the upregulation of f5 mRNA by glucocorticoid and its receptor (Gr) in the preovulatory follicles of zebrafish. Our findings demonstrate a significant increase in 11β-hydroxysteroid dehydrogenase type 2 (hsd11b2), a cortisol response gene, in preovulatory follicles. Additionally, hydrocortisone exerts a dose- and time-dependent upregulation of f5 mRNA in these follicles. Importantly, this stimulatory effect is Gr-dependent, as it was completely abolished in gr-/- mutants. Furthermore, site-directed mutagenesis identified a glucocorticoid response element (GRE) in the promoter of zebrafish f5. Interestingly, successive incubation of hydrocortisone and the native ovulation-inducing steroid, progestin (17α,20β-dihydroxy-4-pregnen-3-one, DHP), further enhanced f5 expression in preovulatory follicles. Overall, our results indicate that the dramatic increase of f5 expression in preovulatory follicles is partially attributable to the regulation of glucocorticoid and Gr.

BACKGROUND: 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.
OBJECTIVE: The fingerprint and anticoagulant activity in vivo-in vitro of DGSN decoction were evaluated to strengthen the quality control and activity study of formulas.
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.
CONCLUSIONS: 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.

BACKGROUND: Trauma-induced coagulopathy (TIC) is a common and potentially life-threatening coagulopathy as a result of traumatic injury, characterized by abnormal blood clotting and bleeding. Although several treatments have been proposed for TIC, their effectiveness and safety remain unclear. Further, numerous systematic reviews and meta-analyses on trauma have been conducted; however, to our knowledge, there is no systematic review and meta-analysis that specifically focuses on TIC management. Therefore, a comprehensive synthesis of the available evidence on interventions for TIC is needed.
OBJECTIVE: This systematic review and meta-analysis aim to evaluate the effectiveness and safety of interventions for the management of TIC.
METHODS: We will conduct a systematic review and meta-analysis of randomized and nonrandomized controlled trials as well as observational studies regarding severe trauma in patients with TIC. The interventions will include administration of coagulation factor concentrates, tranexamic acid, and blood component products. The control group will be managed with an ordinal transfusion or administered placebo. The primary outcome will be in-hospital mortality. We will search the electronic databases of MEDLINE (PubMed), Web of Science, and the Cochrane Central Register of Controlled Trials. Two reviewers will independently screen the titles and abstracts, retrieve the full text of the selected articles, and extract essential data. We will apply uniform criteria for evaluating the risk of bias associated with individual randomized controlled trials and nonrandomized trials based on the Cochrane risk-of-bias tool. Risk ratio values will be expressed as point estimates with 95% CIs. Continuous variables will be expressed as the mean difference along with their 95% CIs and P values. We will assess the strength of evidence using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. This review will be the first systematic review and meta-analysis providing information on the effectiveness and safety of interventions for the management of TIC, including the administration of coagulation factor concentrates, tranexamic acid, and blood component products. Ethics approval and patient consent were not required for this study protocol, as we conducted a systematic review and meta-analysis of publicly available data, without any direct involvement of human participants.
RESULTS: We will summarize the selection of the eligible studies using a PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flowchart. The results will be presented in a table summarizing the evidence. The results of the meta-analysis will be depicted using figures and forest plots.
CONCLUSIONS: This systematic review will provide updated information on the efficacy and safety of using coagulation factor concentrates, tranexamic acid, and blood component products for patients with TIC. To our knowledge, there is no systematic review and meta-analysis that specifically focuses on treatments for TIC.
BACKGROUND: UMIN registry UMIN000050170; https://tinyurl.com/yr8pcrj6.
UNASSIGNED: DERR1-10.2196/49582.

Introduction: This study on lung adenocarcinoma (LUAD), a common lung cancer subtype with high mortality. Aims: This study focuses on how tumor cell interactions affect immunotherapy responsiveness. Methods: Using public databases, we used non-negative matrix factorization clustering method, ssGSEA, CIBERSORT algorithm, immunophenotype score, survival analysis, protein-protein interaction network method to analyze gene expression data and coagulation-related genes. Results: We divided LUAD patients into three coagulation-related subgroups with varying immune characteristics and survival rates. A cluster of three patients, having the highest immune infiltration and survival rate, also showed the most potential for immunotherapy. We identified five key genes influencing patient survival using a protein-protein interaction network. Conclusion: This research offers valuable insights for forecasting prognosis and immunotherapy responsiveness in LUAD patients, helping to inform clinical treatment strategies.

Cerebral venous sinus thrombosis (CVST) has become a rare but potentially life-threatening condition in perinatal women. Early and rapid identification of CVST in pregnant women is a challenge for frontline clinical workers. In this study, 40 perinatal patients with CVST in our hospital were included in the five-year period, and 120 normal perinatal pregnant women in the obstetrics and gynecology department of our hospital were randomly enrolled in the five-year period as the control group, including 60 cases in pregnancy and puerperium. 5 mL of fasting venous blood was collected from puerperal CVST patients in the acute phase of onset (within 72 h of onset) and the recovery phase (fourth week of treatment). In the control group, 5 mL of fasting venous blood was collected. Coagulation factors X, XI, and XII, plasma D-Dimer were analyzed and compared. Coagulation factors X, XI, and XII in plasma of CVST patients were significantly increased compared with controls. Plasma coagulation factors X, XI, and XII and their combined detection (Union Model = 0.056 * FX: C + 0.046 * FXI: C + 0.081 * FXII: C) have diagnostic values for perinatal CVST. Plasma coagulation factors X, XI, and XII were significantly positively correlated with plasma D-dimer levels in perinatal CVST patients. Plasma coagulation factors X, XI, and XII have diagnostic values for perinatal CVST.

Hepatocellular carcinoma (HCC) is a life-threatening complication of hemophilia. Reports of patients with hemophilia undergoing hepatectomy for HCC are scarce. We report the cases of patients with hemophilia A and B who underwent laparoscopic hepatectomy for HCC. Perioperative hemophilia management was supervised by the hematology team. The patients received coagulation factor bolus injections immediately preoperatively, then continuous intravenous infusions intra- and postoperatively. A laparoscopic segment II partial hepatectomy was performed in case 1. Due to severe adhesions, intermittent pedicle clamping could not be used during parenchymal transection. The surgical duration was 235 min, and the estimated blood loss was 13 mL. The patient was discharged 11 days postoperatively without any complications. In case 2, laparoscopic partial hepatectomy for segments V/VI was performed. An intermittent pedicle clamp (Pringle method) was used during parenchymal transection. The surgical duration and estimated blood loss were 219 min and 18 mL, respectively. The patient was discharged 8 days postoperatively without complications. In both cases, intraoperative bleeding was minimal, and the patients were discharged without postoperative hemorrhage with appropriate perioperative coagulation factor management. Laparoscopic hepatectomy can be safely performed and appears to be a feasible treatment option for HCC in patients with hemophilia.

OBJECTIVE: Children with lupus anticoagulant hypoprothrombinemia syndrome (LAHPS) are characterized by prolonged activated partial thromboplastin time (APTT) and prothrombin time (PT), lupus anticoagulant positivity and low prothrombin (factor II, FII) levels. Bleeding or thrombosis tendencies related to LAHPS in children can occur due to the development of anti-prothrombin antibodies that are usually linked to autoimmune or infectious diseases.
METHODS: We report three pediatric cases of LAHPS and describe details on their clinical symptoms, laboratory characteristics, treatment. PubMed, Medline, and Web of Science searches were conducted on LAHPS in children between 1960 and 2023; articles in English were included.
RESULTS: The coagulation profile revealed prolonged PT and APTT, with low prothrombin levels (19.4%, 21.0% and 12.9%, respectively) and positive lupus anticoagulant in 3 pediatric cases. Fifty-nine relevant articles reported 93 pediatric LAHPS cases (mean age: 9 years (0.8-17 years)); 63 females and 30 males, 87 patients presented with minor to severe bleeding diathesis, and 3 patients presented with thrombosis events. Among 48 patients ≥9 years old, 36 had SLE; among 45 patients <9 years, 29 had viral infection. When all patients were divided into two groups based on age, associated disease, and factor II level, Pearson\'s χ2 tests were performed, p =.00, and there was clinical significance between autoimmune and infectious disease in patients ≥9 years old and <9 years old, and in patients FII level ≤10% and >10%. LAHPS patients with autoimmune disease had a protracted course and needed prolonged treatment with immune-modulating therapy, while those patients with infectious disease resolved spontaneously or needed short-term immune-modulating therapy.
CONCLUSIONS: LAHPS caused by autoimmune disease are common in patients ≥9 years old, especially SLE, and FII level ≤10% is often reported in patients caused by autoimmune disease, suggesting that children ≥9 years old diagnosed with LAHPS-related autoimmune disease should pay special attention to the FII level. While LAHPS caused by infectious disease is more frequently observed in patients <9 years, especially viral infection. Early diagnostic investigations are critical to differentiating LAHPS caused by autoimmune or infectious disease, as the prognosis, treatment and outcome are distinct.

Macrophages (Mø) are widely considered fundamental in the development of kidney fibrosis since Mø accumulation commonly aggravates kidney fibrosis, while Mø depletion mitigates it. Although many studies have aimed to elucidate Mø-dependent mechanisms linked to kidney fibrosis and have suggested various mechanisms, the proposed roles have been mostly passive, indirect, and non-unique to Mø. Therefore, the molecular mechanism of how Mø directly promote kidney fibrosis is not fully understood. Recent evidence suggests that Mø produce coagulation factors under diverse pathologic conditions. Notably, coagulation factors mediate fibrinogenesis and contribute to fibrosis. Thus, we hypothesized that kidney Mø express coagulation factors that contribute to the provisional matrix formation during acute kidney injury (AKI). To test our hypothesis, we probed for Mø-derived coagulation factors after kidney injury and uncovered that both infiltrating and kidney-resident Mø produce non-redundant coagulation factors in AKI and chronic kidney disease (CKD). We also identified F13a1, which catalyzes the final step of the coagulation cascade, as the most strongly upregulated coagulation factor in murine and human kidney Mø during AKI and CKD. Our in vitro experiments revealed that the upregulation of coagulation factors in Mø occurs in a Ca2 + -dependent manner. Taken together, our study demonstrates that kidney Mø populations express key coagulation factors following local injury, suggesting a novel effector mechanism of Mø contributing to kidney fibrosis.