Sean M McNary, Madalyn Kuhlenberg, Lucia F Basilio, Nathan P Clark, Rita L Hui, Fang Niu, Thomas Delate
{"title":"Impact of cytochrome P-450 3A4 enzyme/P-glycoprotein inducing antiseizure medications on direct oral anticoagulant therapy.","authors":"Sean M McNary, Madalyn Kuhlenberg, Lucia F Basilio, Nathan P Clark, Rita L Hui, Fang Niu, Thomas Delate","doi":"10.1097/MBC.0000000000001342","DOIUrl":"10.1097/MBC.0000000000001342","url":null,"abstract":"<p><strong>Objectives: </strong>Concomitant use of cytochrome P-450 and P-glycoprotein (CYP 3A4/P-gp) inducing antiseizure medications and direct oral anticoagulants (DOAC) may result in reduced DOAC effectiveness, but study results are inconsistent and of variable quality. The purpose of this study was to assess the safety of concomitant CYP 3A4/P-gp inducing antiseizure medications and DOAC use.</p><p><strong>Methods: </strong>This was a retrospective cohort study of adult patients who were newly, concomitantly receiving a DOAC (apixaban, dabigatran, or rivaroxaban) and either a CYP 3A4/P-gp inducer (carbamazepine, phenytoin, phenobarbital, or primidone) or noninducer (gabapentin). The primary outcome was the occurrence of a thromboembolic complication, defined as the composite of ischemic stroke and systemic embolism (S/SE) and venous thromboembolism (VTE). Secondary outcomes included the components of the primary composite as well as all-cause mortality and clinically relevant bleeding. Adjusted multivariate proportional hazards modeling was used to compare outcomes for each DOAC individually in the inducer and noninducer groups.</p><p><strong>Results: </strong>There were 1843 and 14 647 patients who received a DOAC plus a CYP3A4/P-gp inducer and noninducer, respectively. Overall, patients were primarily older, white, had atrial fibrillation, and were dispensed dabigatran. After adjustment, there were no statistically significant differences in the primary outcome between the groups ( P > 0.05); however, concomitant inducer and DOAC use was associated with an increased risk of all-cause mortality ( P < 0.05).</p><p><strong>Conclusions: </strong>No excess risk of thrombosis during concomitant use of DOACs with CYP3A4/P-gp inducing antiseizure medications compared to use with gabapentin was identified. Further research is needed to confirm an association with excess all-cause mortality.</p>","PeriodicalId":8992,"journal":{"name":"Blood Coagulation & Fibrinolysis","volume":" ","pages":"71-77"},"PeriodicalIF":1.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Venous thromboembolism secondary prophylaxis in elderly people (over 75 years old) with low-dose direct oral anticoagulants.","authors":"Hinpetch Daungsupawong, Viroj Wiwanitkit","doi":"10.1097/MBC.0000000000001350","DOIUrl":"https://doi.org/10.1097/MBC.0000000000001350","url":null,"abstract":"","PeriodicalId":8992,"journal":{"name":"Blood Coagulation & Fibrinolysis","volume":"36 3","pages":"117"},"PeriodicalIF":1.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Coincidental occurrence of severe factor XII deficiency in a case of mild hemophilia A: a unique coagulation laboratory diagnostic conundrum.","authors":"Bipin P Kulkarni, Chandrakala Shanmukhaiah, Kirti Ghargi, Puloma Pandey, Shruti Kharat, Prachi Pawar, Sayali Shinde, Nikesh Kawankar, Sharda Shanbhag","doi":"10.1097/MBC.0000000000001346","DOIUrl":"10.1097/MBC.0000000000001346","url":null,"abstract":"<p><p>We present a unique case of severe factor XII (FXII) deficiency in a mild hemophilia A patient. The co-occurrence of these two inherited coagulation disorders poses laboratory diagnostic challenges. We discuss the clinical presentation, laboratory findings, and molecular characterization of this unique case.</p>","PeriodicalId":8992,"journal":{"name":"Blood Coagulation & Fibrinolysis","volume":" ","pages":"99-100"},"PeriodicalIF":1.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kush Wangoo, Vinh Dat David Nguyen, Karen Byth, Rajesh Malik, Andrew Coggins
{"title":"Massive transfusion protocol prediction decision aids in an Australian trauma setting.","authors":"Kush Wangoo, Vinh Dat David Nguyen, Karen Byth, Rajesh Malik, Andrew Coggins","doi":"10.1097/MBC.0000000000001338","DOIUrl":"10.1097/MBC.0000000000001338","url":null,"abstract":"<p><strong>Background: </strong>Trauma patients may require activation of an emergent massive transfusion protocol (MTP). Several decision aids are designed to predict massive transfusion requirements but have not been widely studied in the Australasian setting.</p><p><strong>Methods: </strong>Commonly used MTP decision aids were assessed for accuracy in injured patients at an urban Level 1 trauma centre. Consecutive cases were prospectively enrolled to a complete registry of thromboelastogram assays in trauma patients. Analysis was undertaken using receiver operating characteristic (ROC) curves, sensitivity and specificity.</p><p><strong>Results: </strong>A total of 114 patients met inclusion criteria (56 received MTP). More detailed and military derived scores including McLaughlin and Larson demonstrated >90% specificity. Area under ROC curve results were similar to prior reports, but the ABC score performed less accurately than expected.</p><p><strong>Conclusion: </strong>In the setting of traumatic haemorrhage, the available MTP prediction decision aids should be applied cautiously and used only in combination with on-going clinical judgement.</p>","PeriodicalId":8992,"journal":{"name":"Blood Coagulation & Fibrinolysis","volume":"36 2","pages":"58-61"},"PeriodicalIF":1.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alyssa Qian, Armita Zandi, Regan Bucciol, Maha Othman
{"title":"The role of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as venous thromboembolism predictors in breast cancer patients pre- and post-therapy.","authors":"Alyssa Qian, Armita Zandi, Regan Bucciol, Maha Othman","doi":"10.1097/MBC.0000000000001341","DOIUrl":"10.1097/MBC.0000000000001341","url":null,"abstract":"<p><strong>Objectives: </strong>Breast cancer (BC) accounts for 12.3% of all cancer-associated venous thromboembolism (VTE). Platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) are recognized inflammatory biomarkers but have not been incorporated into thrombosis risk stratification models. We evaluated NLR and PLR as predictive biomarkers for VTE in BC patients to determine their optimal predictive cutoffs and net predictive value before and after treatment.</p><p><strong>Methods: </strong>We conducted a prospective pilot study that involved 56 women with BC, recruited prior to treatment (chemotherapy and immunotherapy) initiation with at least 6-month monitoring for VTE. NLR and PLR were assessed pre and posttreatment.</p><p><strong>Results: </strong>Five patients (8.9%) developed VTE. NLR and PLR increased significantly posttreatment (P = 0.001). Post, not pretreatment, NLR (P = 0.029) and PLR (P = 0.033) were significantly associated with VTE occurrence. Receiver Operating curve analysis indicated enhanced predictive capacity for VTE postimmunotherapy. Optimal posttreatment cutoffs were 3.6 for NLR and 280 for PLR, aligning with existing literature, with slightly elevated NLR.</p><p><strong>Conclusions: </strong>Posttreatment NLR and PLR have higher predictability for VTE in patients receiving immunotherapy compared to chemotherapy. NLR outperforms PLR, particularly postimmunotherapy. This data holds promise for thrombosis risk stratification in the context of immunotherapy but requires evaluation in larger studies.</p>","PeriodicalId":8992,"journal":{"name":"Blood Coagulation & Fibrinolysis","volume":"36 2","pages":"62-67"},"PeriodicalIF":1.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Two patients with protein S deficiency and cerebral venous sinus thrombosis: nonsense mutations of the PROS1 gene may account for these deficiencies.","authors":"Lingling Hou, Xiaoli Chen, Haixiao Xie, Ke Zhang, Yanhui Jin, Minshan Wang, Lihong Yang, Fei Xu","doi":"10.1097/MBC.0000000000001343","DOIUrl":"10.1097/MBC.0000000000001343","url":null,"abstract":"<p><p>Cerebral venous sinus thrombosis (CVST) is a rare and atypical thrombotic condition, particularly prevalent among young adults, with a complex cause. In July and October 2023, two patients were diagnosed with hereditary protein S deficiency (PSD) presenting with CVST at the Department of Neurology, the first affiliated hospital of Wenzhou Medical University. This study analysed the phenotypes and gene mutations in two hereditary PSD pedigrees to investigate the link between hereditary PSD and CVST. A total of 11 individuals from these two pedigrees were involved. We measured protein S activity (PS:A) and total protein S antigen (TPS:Ag), and free protein S antigen (FPS:Ag) for all participants, screened them for mutations in the protein S1 (PROS1) gene. Both probands with CVST were diagnosed at a young to middle age. The concurrent reductions in PS:A, TPS:Ag, and FPS:Ag levels observed in the probands and their family members (A-I2, A-II1, A-II2, A-II3, A-III1, A-III2, B-I2) indicate type I PSD. Gene analysis unveiled two heterozygous nonsense mutations, c.1687C>T (p. Gln563∗) and c.1680T>A (p. Tyr560∗), in exon 14 of the PROS1 gene for pedigrees A and B, respectively. The reduced protein S levels in the probands and their relatives, along with CVST in both probands, are all linked to nonsense mutations p. Gln563∗ and p. Tyr560∗ in the PROS1 gene.</p>","PeriodicalId":8992,"journal":{"name":"Blood Coagulation & Fibrinolysis","volume":"36 2","pages":"51-57"},"PeriodicalIF":1.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Rare coagulation factor deficiencies: a five-year experience from a single tertiary care center in South India.","authors":"Nivedita Suresh, Bitty Kurian, Reshma Jeladharan, Amrita Sao, Neeraj Sidharthan, Reema Miria Abraham","doi":"10.1097/MBC.0000000000001339","DOIUrl":"10.1097/MBC.0000000000001339","url":null,"abstract":"<p><strong>Objective: </strong>Rare coagulation factor deficiencies (RCFD) comprise a heterogeneous class of coagulation disorders due to deficiencies/abnormalities in coagulation factors other than factors VIII, IX and von Willebrand factor (VWF). Due to its rarity and varying geographic prevalence, bleeding characteristics and behaviour pattern are not known. Our aim was to study the frequency and clinical profile of RCFD, assess the severity of deficiency, evaluate blood component requirements and surgical outcomes.</p><p><strong>Methods: </strong>This is a retrospective cohort study done at Advanced Coagulation Laboratory, Amrita Hospital, Kerala from September 2018 to October 2023. Clinical characteristics including bleeding phenotype were noted. The patients were diagnosed based on their complete coagulation workup.</p><p><strong>Results: </strong>Total of 1019 patients were evaluated, 93 (9.1%) patients had RCFD. Males and females were 60 (64.5%) and 33 (35.5%), respectively (M : F ratio 2 : 1). Median age at diagnosis was 26 years (range: 2 months-74 years). Half the patients (47) had bleeding episodes, 23 (25%) patients were detected incidentally and 23 (25%) patients as a part of preoperative evaluation. Mucocutaneous bleeding was the commonest symptom. The most common RCFD was factor VII deficiency (40%). Transfusion/hemostatic support was required for 29 (31.2%) patients during their life time. No adverse outcome was noted in 27 (29%) patients who underwent surgeries.</p><p><strong>Conclusion: </strong>Factor VII deficiency was the commonest RCFD. Only half of the patients with RCFD were symptomatic. RCFDs generally have a favorable surgical/ pregnancy outcome. Data from resource limited settings are lacking; more studies are required to formulate management guidelines.</p>","PeriodicalId":8992,"journal":{"name":"Blood Coagulation & Fibrinolysis","volume":"36 2","pages":"37-43"},"PeriodicalIF":1.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bingqing Luo, Xia Wu, Jing Zhu, Shu Chen, Shifeng Lou, Xiaoyan Tan
{"title":"Compound heterozygous mutations (p.L68R∗37 and p.T241N) lead to abnormal protein levels and structures in hereditary FVII deficiency.","authors":"Bingqing Luo, Xia Wu, Jing Zhu, Shu Chen, Shifeng Lou, Xiaoyan Tan","doi":"10.1097/MBC.0000000000001340","DOIUrl":"10.1097/MBC.0000000000001340","url":null,"abstract":"<p><strong>Background: </strong>Congenital factor VII (FVII) deficiency is a genetic disorder characterized by decreased FVII activity, which sometimes leads to fatal bleeding. Numerous variants have been found in FVII deficiency, but mutations vary among patients. Each mutation deserves further exploration for each patient at risk of bleeding. We previously reported a Chinese patient with p.L68R∗37 and p.T241N compound heterozygous mutations. In this study, we further investigated the impact of these two mutations on the FVII expression through in vitro expression experiments.</p><p><strong>Methods: </strong>Mutations were introduced into the FVII coding region using site-directed mutagenesis, and recombinant FVII was combined with two different plasmids, and then quantitative PCR and western blot analyses were performed subsequently.</p><p><strong>Results: </strong>The p.L68R∗37 mutation had no effect on mRNA levels but caused a significant decrease in protein levels. In the p.T241N mutant vector, mRNA levels did not show a noticeable decrease, but protein levels exhibited a slight decrease. Structural analysis revealed that the p.T241N mutation resulted in an altered secondary structure and protein instability, indicating impaired functional properties.</p><p><strong>Conclusion: </strong>Our study demonstrated that the p.L68R∗37 and p.T241N mutations impacted the protein levels and function of FVII, ultimately leading to a severe reduction in FVII activity. This study may contribute to further understanding of the molecular pathogenesis of FVII deficiency and offer insights for genetic counseling.</p>","PeriodicalId":8992,"journal":{"name":"Blood Coagulation & Fibrinolysis","volume":" ","pages":"44-50"},"PeriodicalIF":1.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11789605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142999595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Who is currently dying from pulmonary embolism? Analysis of the US National Vital Statistics System.","authors":"Camilla Mattiuzzi, Giuseppe Lippi","doi":"10.1097/MBC.0000000000001344","DOIUrl":"https://doi.org/10.1097/MBC.0000000000001344","url":null,"abstract":"","PeriodicalId":8992,"journal":{"name":"Blood Coagulation & Fibrinolysis","volume":"36 2","pages":"68-69"},"PeriodicalIF":1.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sanchi Dhinoja, Jabila Mary, Ayah Al Qaryoute, Anthony De Maria, Pudur Jagadeeswaran
{"title":"Generation and characterization of zebrafish f9l mutant confirmed that f9l is f10 like gene.","authors":"Sanchi Dhinoja, Jabila Mary, Ayah Al Qaryoute, Anthony De Maria, Pudur Jagadeeswaran","doi":"10.1097/MBC.0000000000001337","DOIUrl":"10.1097/MBC.0000000000001337","url":null,"abstract":"<p><strong>Aim: </strong>This study aimed to create an f9l mutant zebrafish using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) and characterize its coagulation properties to investigate its functional similarity to human FX and explore the potential synergy between f9l and f10 .</p><p><strong>Methods: </strong>Three gRNAs targeting exon 8 encoded by the catalytic domain of the f9l gene were injected into 300 single-cell zebrafish embryos using CRISPR/Cas9 technology. DNA from the resulting adults was extracted from tail tips, and PCR was used to detect indels. The identified founder mutant was bred to homozygosity, and functional assays, kinetic Russel viper venom time, bleeding assay in adults, and venous laser injury on larvae were conducted to assess its hemostatic function. Additionally, f10 was knocked down in f9l homozygous embryos using f10 antisense morpholinos to study their interaction by monitoring its survival.</p><p><strong>Results: </strong>DNA from 60 adults was screened for indels, resulting in a fish with a heritable complex mutation involving one insertion and two deletions in exon 8. The f9l homozygous mutants exhibited impaired F10 activity, mild bleeding after mechanical injury, and developmental deformities in early larval stages. The caudal vein thrombosis assay showed variable occlusion times, indicating a bleeding phenotype with incomplete penetrance. Knocking down f10 in f9l homozygous embryos resulted in 50% mortality within five dpf, compared to f9l homozygous embryos injected with control morpholinos.</p><p><strong>Conclusion: </strong>In summary, we generated f9l knockout and showed it is a paralog to f10. We also found a synergy between f9l and f10 genes, highlighting its importance in hemostasis.</p>","PeriodicalId":8992,"journal":{"name":"Blood Coagulation & Fibrinolysis","volume":" ","pages":"26-33"},"PeriodicalIF":1.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11759647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}