Deficiency Of Factor Research Articles

Autoantibodies in Autoimmune Coagulation Factor Deficiencies: A Review of Inhibitory and Clearance-Accelerating Mechanisms from Japanese Practice.

Autoimmune acquired coagulation factor deficiency (AiCFD) represents a rare coagulation disorder that primarily affects older people and sometimes causes fatal bleeding; therefore, clinicians need to consider this when encountering patients with unexplained bleeding. AiCFD is caused by the production of autoantibodies against one's own coagulation factor, which markedly inhibit its function, or accelerate its clearance from plasma, resulting in hemostatic failure. The plasma of affected patients shows various abnormal findings, because anti-coagulation factor autoantibodies are polyclonal, and each clone has different properties. First, inhibitor type autoantibodies target the functional sites of coagulation factors, thereby considerably reducing their activity. Second, clearance-accelerating autoantibodies bind to non-functional sites and cause rapid removal of coagulation factors from the blood, thereby reducing their levels (and their activity in parallel). Third, mixed type autoantibodies (inhibitory clearance-accelerating) substantially reduce coagulation factor activity and level to various degrees. Most anti-coagulation factor autoantibodies are inhibitory clearance-accelerating types, although pure inhibitor types remain clinically significant; however, the pure clearance-accelerating type appears to be rare, possibly because the autoantibody is not detected unless it exceeds the level of the target coagulation factor (pseudo-autoantibody negative). Moreover, anti-factor XIII autoantibodies are particularly complex, as they interfere with the A subunit (Aa type), its activated form (Ab type), and/or the B subunit (B type). Of the three types, Aa type anti-factor XIII autoantibodies contain a mixture of different inhibitor type autoantibodies in various ratios in plasma, resulting in an extremely diverse range of test findings. Therefore, care must be taken when diagnosing and assessing the efficacy of treatment.

Thrombotic complications in hemophilia: an intricate conundrum.

Hemophilia A and hemophilia B are rare genetic disorders characterized by low plasma levels of coagulation factor VIII of factor IX, resulting in a bleeding tendency with a clinical severity proportional to the degree of the clotting factor deficiency. Although rarely, hemophilia patients can paradoxically experience thrombotic events that complicate the clinical picture and the management by physicians operating at hemophilia treatment centers. Such thromboembolic complications, which can involve either the arterial or the venous districts, recognize various causes, including aging (due to the progress of care during the last three decades) and inherited and acquired (treatment-related) risk factors. These determinants often interact with each other to increase patients' susceptibility to thrombosis. In this narrative review we summarize the current knowledge on the mechanisms, clinical presentation, and management of thrombotic complications in hemophilia patients.

Quantra analyzer with the QStat® Cartridge compared with conventional laboratory tests during postpartum hemorrhage: a retrospective cohort study (2021-2023).

Point-of-care viscoelastic testing devices are of interest for rapid detection of obstetric coagulopathy in postpartum hemorrhage (PPH). However, there is a lack of data on the assessment of coagulation during PPH with the new Quantra device based on sonic estimation of elasticity via resonance. We conducted a retrospective observational cohort study of 130 obstetric patients with PPH with Quantra QStat assessment. Quantra QStat measurements of clotting time (CT), fibrinogen contribution to clot stiffness (FCS) and platelet contribution to clot stiffness (PCS) were compared with the following paired laboratory tests: aPTT, Clauss fibrinogen (CF), and platelet count. The primary aim was to assess correlations between Quantra-QStat measurements and standard laboratory test during PPH. Secondary aims were to investigate the ability of Quantra QStat to diagnose hypofibrinogenemia, thrombocytopenia or coagulation factor deficiencies. We analyzed 160 paired Quantra QStat and standard laboratory tests. Quantra-QStat tests correlated with laboratory tests as follows: CT with aPTT ratio (rs=0.61; P<0.001), PCS with platelet count (rs=0.75; P<0.001), and FCS with CF (rs=0.84; P<0.001). FCS predicted a CF≤2 g/L with an AUC of 0.96 (P<0.0001). The optimal cut-off value was 2hPa. PCS predicted a platelet count<80,000/μL with an AUC of 0.94 (P<0.0001). The optimal cut-off value was 11.5hPa, with a sensitivity of 0.89 and a specificity of 0.88. CT predicted an aPTT ratio>1.2 or>1.5 with an AUC of 0.94 (P<0.001) and 0.92 (P<0.0001). The optimal cut-off values were 127 and 133seconds. Quantra parameters during PPH provide rapid and reliable detection of blood clotting disorders.

A rare case of type 2A von Willebrand disease with compound heterozygous mutation.

von Willebrand disease (VWD) is defined by a quantitative or qualitative deficiency of von Willebrand factor, which impairs platelet adhesion and aggregation. Here we describe a rare case of type 2A VWD with compound heterozygous mutation. A 27-year-old girl presented with oral bleeding for two days after dental surgery. A systemic physical examination turned up unremarkable. Type 2 von Willebrand disease was confirmed by laboratory tests. Further genetic investigation revealed the existence of compound mutations of VWF (von Willebrand factor) gene, inherited separately from her parents. Interestingly, her mother presented decreased VWF antigen and activity, but that was not found in her father.

Discussion on the Mechanism of Traditional Chinese Medicine in Treating Myasthenia Gravis Based on the Theory of “Atrophy Syndrome” and Its Syndrome Differentiation and Treatment

Myasthenia Gravis (MG) is an autoimmune disease caused by transmission disorders at the neuromuscular junction. Among them, ocular myasthenia (OMG) is the most common type, mainly manifested as ptosis of the upper eyelid, diplopia, and ocular movement disorders. Traditional Chinese Medicine (TCM) treatment for MG has unique advantages. Through overall regulation and syndrome differentiation and treatment, it can improve symptoms and reduce the side effects of Western medicine. This article systematically reviews the understanding and treatment progress of MG in TCM: MG belongs to the category of “flaccidity syndrome”, and the causes involve deficiency of the spleen and stomach, insufficiency of liver and kidney, dampness, heat, and blood stasis. The pathogenesis is related to deficiency of yang qi, obstruction of dampness by pathogenic factors, failure of closure of yangming meridian, and deficiency and stasis of collaterals and pathogenic factors. It explains the main TCM syndrome differentiation types and prescriptions and medications for treating MG. It introduces the research on single herb drugs with distinctive features in treatment, aiming to deepen the mechanism exploration by combining modern technologies in the future, carry out high-quality clinical research, optimize the integrated treatment plan of TCM and Western medicine, and provide more effective strategies for the diagnosis and treatment of MG.

Accelerated Fibrinolysis: A Tendency to Bleed?

Hyperfibrinolysis is rarely investigated as an underlying mechanism in patients with mild-to-moderate bleeding disorders (MBDs) and bleeding disorders of unknown cause (BDUC). Hereditary hyperfibrinolytic disorders, including α2-antiplasmin (α2-AP) deficiency, plasminogen activator inhibitor type 1 (PAI-1) deficiency, Quebec platelet disorder, and tissue plasminogen activator (tPA) excess, present with mild-to-moderate bleeding symptoms that are common in patients with MBD or BDUC, but may also manifest as life-threatening bleeding. This review summarizes the available data on hyperfibrinolysis in MBD and BDUC patients, and its assessment by various methods such as measurement of fibrinolytic factors, global hemostatic assays (e.g., viscoelastic testing, turbidity-based plasma clot lysis), and fluorogenic plasmin generation (PG). However, evidence on the relationship between hyperfibrinolytic profiles and bleeding severity is inconsistent, and, although found in some coagulation factor deficiencies, has not been universally observed. In BDUC, increased tPA activity and paradoxical increases in thrombin-activatable fibrinolysis inhibitor and α2-AP have been reported. Some studies reported no change in PAI-1 levels, while others observed reduced PAI-1 levels in a significant subset of patients. The tPA-ROTEM (tPA-rotational thromboelastometry) assay identified a hyperfibrinolytic profile in up to 20% of BDUC patients. PG analysis revealed a paradoxically reduced peak plasmin, but showed strong predictive power in differentiating BDUC patients from healthy controls. Although global fibrinolytic assays may help identify hyperfibrinolytic profiles as a potential cause of increased bleeding in some MBD or BDUC patients, the utility of measuring fibrinolytic factors requires further investigation. Tranexamic acid is commonly used to treat hereditary hyperfibrinolysis and is also recommended in MBD/BDUC patients prior to hemostatic challenges.

Predicting Inhibitor Development in Hemophilia 'A' using Machine Learning: A Comprehensive Approach to Data Preprocessing, Balancing, and Biomarker Identification Using AI on the CHAMP Dataset.

Hemophilia 'A' (HA) is a genetic blood disorder characterized by a deficiency of Factor VIII (FVIII), with treatment often triggering the development of neutralizing antibodies (inhibitors) to FVIII. Predicting the development of these inhibitors is crucial for clinical applications but presents significant computational challenges due to data imbalance, skewed data, and inadequate data sanitization. This study aimed to develop a machine-learning/AI approach to find biomarkers and predict the development of inhibitors to Factor VIII in patients with Hemophilia 'A,' addressing the challenges associated with data imbalance and enhancing prediction accuracy. The data were sanitized and encoded for prediction, and the Random Over-sampling (ROS) technique was employed to resolve data imbalance in the CHAMP dataset. Several machine- learning classification models, including Random Forest, XG Boost, Cat Boost, Logistic Regression, Gradient Boosting, and Light GBM, were utilized. Hyperparameters were tuned using GridSearchCV optimization with a stratified k-fold approach. The performance of the models was evaluated based on accuracy, precision, recall, and F1 scores. The Random Forest model was further analyzed using an explainable AI (XAI) tool known as SHAP (SHapley Additive exPlanations) to identify the variables influencing model performance. The Random Forest model outperformed other classifiers, achieving a mean accuracy of 97.37%, along with closely aligned precision, recall, and F1 scores. The XAI tool SHAP facilitated the ranking of variables Clinical Severity, Variant Type, Exon, HGVS cDNA, hg19 Coordinates, and others according to their impact on the model's predictions. Additionally, the study identified biomarkers associated with FVIII inhibition. This study presents a breakthrough in the early prediction of inhibitor development in Hemophilia 'A' patients, paving the way for personalized and effective treatment programs. The integration of the preprocessing pipeline, Random Forest model, and SHAP analysis offers a novel solution for guiding treatment strategies for HA patients, which could significantly enhance the development of targeted and effective therapies.

Abstract 4103: MLL4/COMPASS dysfunction in cancer and treatment

Epigenetic status-altering mutations in chromatin-modifying enzymes are a feature of human diseases, including many cancers. We investigated cellular dependencies, or vulnerabilities, that arise when enhancer function is compromised by loss of the frequently mutated COMPASS family members MLL3 (KMT2C) and MLL4 (KMT2D). We performed a CRISPR dropout screen that revealed a targetable metabolic dependency arising from epigenetic factor deficiency, identifying potential therapies for cancers with epigenetic alterations secondary to MLL3/4-COMPASS dysfunction. We identified strong evidence that there is an internal balance between promoter and enhancer usage dictated by MLL1- versus MLL4-COMPASS, and this equilibrium is subject to disruption during cancer. Using an autochthonous carcinogen model of bladder cancer, we demonstrate that truncated, cytoplasmic MLL4 predicts response to targeted metabolic inhibition therapy for bladder cancer and could be developed as a biomarker for KMT2D-mutated cancers. We also highlight the broader potential for prognosis, patient stratification and treatment decision-making based on KMT2D mutation status in MLL4 truncation-relevant diseases, including human cancers and Kabuki Syndrome. Due to the high prevalence of loss-of-function mutations affecting MLL4 or its COMPASS partner UTX (KDM6A) in bladder cancer, we hypothesized that KMT2D mutation status may predict responsiveness to purine-targeting therapy, including methotrexate and pemetrexed. Our study found that KMT2D mutant bladder cancer cells were selectively dependent on TYMS and showed heightened sensitivity to pemetrexed, a drug that inhibits TYMS, DHFR, and GART. This suggests that targeting multiple enzymes within the one-carbon metabolism and de novo purine synthesis pathway could be promising for the treatment of MLL4/UTX-COMPASS mutant bladder cancer. Based on our previous and current findings, a clinical trial using pemetrexed in MLL4/UTX-COMPASS mutant solid tumors is being launched at Northwestern Medicine. Citation Format: Zibo Zhao, Sarah Gold, Yuki Aoi, Khyati A. Meghani, Luke St John, Rukkia Liaqat, Carolyn Moloney, Yanni Yu, Jun Qian, Issam Ben-Sahra, Rintaro Hashizume, Devalingam Mahalingam, Joshua Meeks, Ali Shilatifard. MLL4/COMPASS dysfunction in cancer and treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4103.

A Rare Co-occurrence: Von Willebrand Disease in a Patient with Schizophrenia

Schizophrenia is a severe neuropsychiatric disorder that affects cognitive and emotional functioning, while von Willebrand Disease (vWD) is the most common inherited bleeding disorder caused by a deficiency or dysfunction of von Willebrand Factor (vWF). Although both conditions are well-studied individually, their co-occurrence is exceedingly rare, posing unique diagnostic and therapeutic challenges. This case report describes a patient diagnosed with schizophrenia who also presented with vWD, highlighting the complexities in management due to overlapping clinical manifestations, medication interactions, and the need for a multidisciplinary approach. Potential shared genetic and inflammatory mechanisms are discussed, along with the importance of integrated care to optimize patient outcomes. This case underscores the necessity for heightened awareness and collaboration between psychiatry and hematology to manage such rare coexisting conditions effectively.

Deficiency of fibroblast growth factor 2 promotes contractile phenotype of pericytes in ascending thoracic aortic aneurysm.

Pericytes exhibit progenitor cell-like qualities and associate with the vasa vasorum-vital microvessels nourishing larger arteries and veins. How pericytes change in human ascending thoracic aortic aneurysm (ATAA) remains unknown. Here, we used the public single-nuclei sequencing data to reveal a contractile phenotype transition of pericytes in human ATAA specimens. In addition, we found that a protective factor, fibroblast growth factor 2 (FGF2), is decreased in the aortic adventitia of both male and female patients with ATAA and impacts pericytes. We demonstrated that FGF2 maintained pericytes in a less contractile and high angiogenic phenotype via MAPK and PI3K-AKT signaling pathways. These findings suggested the latent engagement of pericytes in ATAA, providing insights that could guide the development of new therapies against aortic disease.NEW & NOTEWORTHY Here, we revealed that pericytes transition into a contractile phenotype in human ATAA. We demonstrated that FGF2 maintained pericytes in a less contractile and high angiogenic stage via MAPK and PI3K-AKT signaling pathway, whereas we found FGF2 is decreased in the aortic adventitia of patients with ATAA. Our findings suggest how growth factor deficiency in the microenvironment affects pericytes during ATAA, offering leads for potential new therapies for aortic diseases.

Patient anti-FVIII drug antibodies bind preferentially to a subset of FVIII covalent states.

Haemophilia A is a chronic life-threatening condition caused by deficiency or dysfunction of plasma coagulation factor VIII (FVIII) and commonly managed by prophylaxis with regular infusion of FVIII protein. A major obstacle to FVIII replacement therapy is the generation of alloantibodies that diminish efficacy. Disulfide bonds link pairs of cysteine residues in proteins and in several proteins have been found to be only partially formed in the mature proteins. FVIII contains 8 disulfide bonds and their redox state in human blood and recombinant FVIII was determined using differential cysteine alkylation and mass spectrometry. All 8 disulfide bonds were found to be unformed in ~10% to ~70% of molecules of FVIII populations, which suggested a conformational flexibility that could favour binding of certain ligands to subsets of FVIII with more or less formed disulfide bonds. To test this hypothesis, the binding of a panel of five patient-derived anti-FVIII antibodies to the population of FVIII disulfide-bonded states was evaluated. All five antibodies bound preferentially to FVIII states where 2 or 3 of the 8 disulfides are significantly more unformed; C1918-C1922 in the A3 domain, C2040-C2188 in the C1 domain and C2193-C2345 in the C2 domain. Disulfide bond mutagenesis experiments and molecular dynamics simulations indicate that this subset of FVIII states have long-range conformational dynamism that favours anti-drug antibody binding. These findings will assist efforts to engineer a FVIII molecule that is less prone to neutralization by anti-drug antibodies and has general implications for autoimmune conditions and antibody drug efficacy.

Flow Mode‐Dependent Regulation of von Willebrand Factor Degradation in Mechanical Circulatory Support

ABSTRACTBackgroundAmong patients reliant on continuous‐flow (CF) mechanical circulatory support devices, bleeding is primarily caused by an acquired von Willebrand factor (vWF) deficiency, precipitated by the high shear stress and diminished pulsatility inherent to these systems. However, despite its clinical significance, the relationship between these devices' flow modes and the development of vWF defects remains poorly investigated. Herein, we conducted molecular dynamic (MD) simulations and in vivo validation to investigate this relationship.MethodsThis study involved the analysis of a novel flow sensory mechanism of the vWF molecule, elucidating the inherent relationship through an integrated approach including simulations, an in vitro flow platform, and experiments involving rats undergoing venoarterial extracorporeal membrane oxygenation (V‐A ECMO).ResultsMD simulations demonstrated that the vWF‐A dimer underwent significant retraction under pulsatile‐flow (PF) conditions, indicating an autoinhibitory effect on enzymatic cleavage. Conversely, under CF conditions, we observed a pronounced reduction in circulating vWF levels and a decrease in endothelial cell vWF secretion compared with both the PF and sham groups of rats undergoing V‐A ECMO.ConclusionThese findings underscore the critical importance of pulsatility in the design of next‐generation blood pumps and highlight the potential of our novel rat model in future investigations of the physiological and molecular responses to different blood flow patterns during V‐A ECMO.

Gene therapy as an innovative approach to the treatment of hemophilia B-a review.

Hemophilia B is a disease that affects the human coagulation system, causing the absence or deficiency of coagulation factor IX, which may manifest itself in uncontrolled bleeding that is life-threatening to patients. Due to its inheritance, the disease more often affects men, and the severity of symptoms directly correlates with the concentration of the missing factor IX; hence, the aim of therapy is to maintain it at a level that allows for sufficient hemostasis. The basic model of treatment offered to patients is based on primary prevention with coagulation factor IX with a prolonged half-life, which, however, does not solve the numerous problems faced by patients. An innovative proposal that, despite initial concerns, is becoming more and more popular every day is the recently approved genetic therapy in Europe, which uses viral vectors to transfer the correct gene that encodes coagulation factor IX. The introduction of a recombinant gene in place of its defective counterpart seems to be a promising solution and the beginning of a new era in which genetic therapies have a chance to develop their full potential and replace existing therapeutic regimens.

Gut microbiota and metabolites are linked to disease progression in multiple sclerosis.

Gut microbiota and metabolites are linked to disease progression in multiple sclerosis.

Revolutionizing Treatment Strategies through Inhibition of Tissue Factor Pathway Inhibitor: A Promising Therapeutic Approach for Hemophilia Management.

Hemophilia, an X-linked genetic bleeding disorder, is caused by the deficiency of coagulation factors VIII (hemophilia A) or IX (hemophilia B). Regular replacement therapy with the missing clotting factor is an effective standard-of-care treatment. However, it comes with a significant fallout of frequent intravenous dosing with poor compliance, the risk of inhibitor development, and a substantial treatment burden. Research has progressed from missing clotting factors and factor VIII mimetics to the most recent rebalancing therapy that suppresses tissue factor pathway inhibitor (TFPI). Thrombin generation is restricted by TFPI, which inhibits the tissue factor-mediated activation of factor VII. This promising therapeutic approach rebalances hemostasis by inhibiting TFPI, a critical regulator of the extrinsic coagulation pathway, thereby increasing thrombin generation. Novel monoclonal antibodies (concizumab and marstacimab) enhance thrombin generation by blocking TFPI to restore hemostasis. Clinical trials have demonstrated good clinical efficacy and safety of these anti-TFPI, besides their convenient subcutaneous administration using pen devices. These innovative therapies have the potential to enhance the quality of life (QoL) of people with hemophilia. This review provides a comprehensive overview of the clinical development, therapeutic potential, challenges, and prospects of anti-TFPI in the management of hemophilia.

Annualized bleeding rate in hemophilia A patients in Brazil: a systematic review.

Annualized bleeding rate in hemophilia A patients in Brazil: a systematic review.

Applying artificial intelligence to uncover the genetic landscape of coagulation factors.

Applying artificial intelligence to uncover the genetic landscape of coagulation factors.

Dual Delivery of Cells and Bioactive Molecules for Wound Healing Applications.

Chronic wounds not only cause significant patient morbidity but also impose a substantial economic burden on the healthcare system. The primary barriers to wound healing include a deficiency of key modulatory factors needed to progress beyond the stalled inflammatory phase and an increased susceptibility to infections. While antimicrobial agents have traditionally been used to treat infections, stem cells have recently emerged as a promising therapy due to their regenerative properties, including the secretion of cytokines and immunomodulators that support wound healing. This study aims to develop an advanced dual-delivery system integrating stem cells and antibiotics. Stem cells have previously been delivered by encapsulation in gelatin methacrylate (GelMA) hydrogels. To explore a more effective delivery method, GelMA was processed into microparticles (MP). Compared to a bulk GelMA hydrogel (HG) encapsulation, GelMA MP supported greater cell growth and enhanced in vitro wound healing activity of human mesenchymal stem cells (hMSCs), likely due to a larger surface area for cell attachment and improved nutrient exchange. To incorporate antimicrobial properties, the broad-spectrum antibiotics penicillin/streptomycin (PS) were loaded into a bulk GelMA hydrogel, which was then cryo-milled into MPs to serve as carriers for hMSCs. To achieve a more sustained antibiotic release, gelatin nanoparticles (NP) were used as carriers for PS. PS was either incorporated during NP synthesis (NP+PS(S)) or absorbed into NP after synthesis (NP+PS(A)). MPs containing PS, NP+PS(S), or NP+PS(A) were tested for their cell carrier functions and antibacterial activities. The incorporation of PS did not compromise the cell-carrying function of MP configurations. The anti-S. aureus activity was detected in conditioned media from MPs for up to eight days-four days longer than from bulk HG containing PS. Notably, the presence of hMSCs prolonged the antimicrobial activity of MPs, suggesting a synergistic effect between stem cells and antibiotics. PS loaded via synthesis (NP+PS(S)) exhibited a delayed initial release, whereas PS loaded via absorption (NP+PS(A)) provided a more immediate release, with potential for sustained delivery. This study demonstrates the feasibility of a dual-delivery system integrating thera.

Prothrombin Complex Concentrate vs Frozen Plasma for Coagulopathic Bleeding in Cardiac Surgery

Excessive bleeding is a common and prognostically important complication of cardiac surgery. For bleeding related to coagulation factor deficiency, frozen plasma is the most used therapy. Preliminary trials indicate that 4-factor prothrombin complex concentrate (PCC) may be a suitable alternative. To compare the efficacy and safety of PCC with frozen plasma in patients undergoing cardiac surgery with coagulopathic bleeding. Unblinded randomized noninferiority controlled clinical trial at 12 hospitals in Canada and the US involving adults (≥18 years) who had developed bleeding related to coagulation factor deficiency after termination of cardiopulmonary bypass during surgery (November 30, 2022, to May 28, 2024). Final 30-day follow-up visit was completed on June 28, 2024. A total of 265 patients were randomized to receive PCC (1500 IU ≤60 kg; 2000 IU >60 kg) and 263, frozen plasma (3 U ≤60 kg; 4 U >60 kg) in the operating room. A second dose was allowed over the next 24 hours if indicated; thereafter, only frozen plasma could be used. The primary outcome was hemostatic response (effective if no hemostatic interventions occurred from 60 minutes to 24 hours after treatment initiation). The noninferiority of PCC vs frozen plasma was assessed using a 10% margin and a 1-sided α of .025, with subsequent testing for superiority if noninferiority was demonstrated. Secondary outcomes included allogeneic blood transfusions and adverse events. Patients were followed up until postoperative day 30. Of 538 enrolled patients, 420 patients (median age, 66 years [IQR, 57-73 years]; 74%, male; 10%, Asian; 1%, Black; and 65%, White) were included in the primary analysis; of those, 296 (70%) underwent complex surgeries. Compared with the 207 patients in the frozen plasma group, the 213 patients in the PCC group had higher hemostatic effectiveness (166 [77.9%] vs 125 [60.4%]; difference, 17.6%; 95% CI, 8.7%-26.4%; P < .001 for noninferiority and superiority) and had received fewer transfusions including red blood cells, platelets, and noninvestigational frozen plasma units (mean, 6.6 units; 95% CI, 5.7-7.7 vs 9.3 units; 95% CI, 8.0-10.8; difference, 2.7; 95% CI, 1.0-4.4; P = .002). Seventy-seven patients (36.2%) in the PCC group vs 98 (47.3%) in the frozen plasma group experienced serious adverse events (relative risk [RR], 0.76; 95% CI, 0.61-0.96; P = .02). Twenty-two patients (10.3%) in the PCC group and 39 (18.8%) in the frozen plasma group had acute kidney injury (RR, 0.55; 95% CI, 0.34-0.89; P = .02). In this unblinded randomized clinical trial, PCC had superior hemostatic efficacy and safety advantages to frozen plasma among patients requiring coagulation factor replacement for bleeding during cardiac surgery. ClinicalTrials.gov Identifier: NCT05523297.

Exploring Hemophilia: Understanding the Underlying Mechanisms, Diagnostic Strategies, and Therapeutic Advances

Hemophilia is an inherited blood disorder resulting in impaired blood clotting upon vascular damage due to defective or deficient coagulation factors. The three types of hemophilia are hemophilia A, hemophilia B, and hemophilia C, which result from the defect or deficiency of factor VIII, factor IX, and factor XI respectively. Hemophilia affects hundreds of millions of people worldwide, with the highest incidence in Asian countries including India, Bangladesh, and Indonesia. This review encompasses the epidemiology, etiology, pathophysiology, diagnosis, and treatment for hemophilia, and the literature sources were collected from other publications, including journal articles and books.