Seminars in thrombosis and hemostasis最新文献

{"title":"Recurrent Thromboembolism in Pediatric Congenital Heart Disease: Cumulative Incidence and Prognostic Factors.","authors":"Amy L Kiskaddon, Therese M Giglia, Marisol Betensky, Nhue L Do, Daniel M Witt, Arabela C Stock, Ernest K Amankwah, Jamie L Fierstein, Dina Ashour, Vera Ignjatovic, James A Quintessenza, Neil A Goldenberg","doi":"10.1055/s-0044-1800967","DOIUrl":"https://doi.org/10.1055/s-0044-1800967","url":null,"abstract":"<p><p>Congenital heart disease (CHD) is a risk factor for thromboembolism (TE). Data describing the rate of, and risk factors associated with, recurrent TE in children with CHD are limited. We prospectively evaluated TE recurrence risk in children with CHD and acute TE and investigated clinical risk factors associated with recurrent TE. Patients < 21 years of age with CHD and acute TE were enrolled in a single-institutional prospective inception cohort study (July 2013-April 2024). Descriptive statistics summarized variables including CHD and thrombus characteristics, antithrombotic regimens, bleeding, and recurrent TE. Multivariable logistic regression determined risk factors for recurrent TE. Among 40 children with CHD and acute TE, 13 (33%) developed ≥ 1 recurrent TE (arterial <i>n</i> = 1 [6%], venous <i>n</i> = 15 [83%], venous + arterial <i>n</i> = 2 [11%]) at a median time of 86 (interquartile range, 45-112) days postdiagnosis of the index TE. One-year cumulative incidence of recurrent TE was 38%. Twelve (67%) recurrent TE events were central venous catheter (CVC)-related. In univariable analyses, immobility (46% vs. 7%, <i>p</i> = 0.01), the presence of a CVC (69% vs. 30%, <i>p</i> = 0.02), and lower extremity index venous TE (89% vs. 41%, <i>p</i> = 0.04) were associated with TE recurrence. After adjustment for other potential risk factors via multivariable logistic regression, immobility (adjusted odds ratio [OR] 13.2, 95% confidence interval [CI] 1.16-151.3, <i>p</i> = 0.04) and the presence of a CVC (adjusted OR 5.28, 95% CI 1.03-27.1, <i>p</i> = 0.05) remained as independent risk factors for recurrent TE. The 1-year risk of TE recurrence was high among pediatric patients with CHD and acute TE. Immobility and the presence of CVC were independent risk factors for recurrent TE. Multicenter prospective cohort studies are warranted to substantiate and expand upon these important findings.</p>","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive Mendelian Randomization Analysis of Smoking and Its Effects on Venous Thromboembolism.","authors":"Yuhong Li, Ling Tong, Youqian Zhang, Birun Huang, Liping Zhu","doi":"10.1055/s-0044-1800980","DOIUrl":"https://doi.org/10.1055/s-0044-1800980","url":null,"abstract":"<p><p>An increasing number of Mendelian randomization (MR) studies have evaluated the causal link between smoking and venous thromboembolism (VTE). However, previous studies often rely on single genetic variants related to smoking quantity and exhibit various other shortcomings, making them prone to pleiotropy and potentially leading to imprecise causal estimates. Thus, the deeper causal mechanisms remain largely unexplored. This MR study reassessed the causal relationship between smoking and VTE, including its subtypes-deep vein thrombosis (DVT) and pulmonary embolism (PE). Data on VTE were sourced from the FinnGen consortium with nonoverlapping sample sizes. The smoking phenotypes analyzed included smoking initiation, lifetime smoking, the number of cigarettes smoked per day by both current and former smokers (CigDay), and total pack-years of smoking in adulthood. The primary analytical method was inverse-variance-weighted (IVW), supplemented by multiple verification methods to ensure robust results. Statistical rigor was ensured through LDtrait pruning and Steiger filtering for reverse causation, with comprehensive sensitivity analyses including RadialMR confirming the findings' robustness. After Bonferroni correction, this study demonstrates significant causal evidence linking lifetime smoking with the incidence of VTE (odds ratio [OR]_IVW = 1.50, 95% confidence interval [CI] 1.21-1.85, <i>p</i> = 1.75 × 10^-4) and PE (OR_IVW = 1.69, 95% CI 1.25-2.28, <i>p</i> = 6.55 × 10^-4), and suggestive evidence with DVT, consistent in direction with previous studies but showing considerable differences in effect sizes and significance. Additionally, CigDay (past and current) increases the risks of VTE and DVT, while no causal link was found between smoking initiation and VTE or its subtypes (<i>p</i> < 0.05), both directly contradicting previous conclusions. Furthermore, our study is the first to suggest a causal link between pack-years and an increased risk of VTE. This MR study employed rigorous statistical pruning of its instrumental variables, using the most comprehensive smoking phenotype to date. It successfully mitigated biases such as winner's curse, yielding causal effect results distinct from previous studies.</p>","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Overlooked Risk of Venous Thromboembolism in Psychiatric Patients: Epidemiology, Pathophysiology, and Implications for Clinical Care.","authors":"Giris Jacob, Yoab Ocytil, Benjamin Brenner","doi":"10.1055/s-0044-1800968","DOIUrl":"https://doi.org/10.1055/s-0044-1800968","url":null,"abstract":"<p><p>Psychiatric patients face a significantly shorter life expectancy than the general population due to a complex interplay of medical, behavioral, and social factors. Venous thromboembolism (VTE), encompassing both pulmonary embolism and deep vein thrombosis, is an underrecognized yet critical contributor to morbidity and mortality in this population. Evidence suggests a two to three times higher prevalence of VTE in psychiatric patients compared to the general population, with incidence rates up to 4.5 per 1,000 person-years. This elevated risk is attributed to a hypercoagulable-hypofibrinolytic state. It is influenced by metabolic abnormalities, pro-inflammatory pathways, antipsychotic medications, and genetic factors. Health care biases and reduced treatment compliance further exacerbate the burden. This review explores the epidemiology, pathophysiology, and mechanistic underpinnings of VTE in psychiatric populations, emphasizing the role of metabolic syndrome and antipsychotic therapy. To mitigate mortality and enhance outcomes for these high-risk individuals, it is imperative to address this issue through improved risk stratification and preventive strategies.</p>","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlation between Phenotype and Coagulation Factor Activity Level in Rare Bleeding Disorders: A Systematic Review.","authors":"Behnaz Tavasoli, Alireza Zangooie, Seyed Mehrab Safdari, Taraneh Hoseinnezhad, Ashkan Shabannezhad, Amirreza Alikhani, Zahra Salehi, Akbar Dorgalaleh","doi":"10.1055/s-0044-1800832","DOIUrl":"https://doi.org/10.1055/s-0044-1800832","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Rare bleeding disorders (RBDs) represent 3 to 5% of congenital bleeding disorders and are primarily inherited in an autosomal recessive manner, with increased prevalence in consanguineous populations. Clinically, RBDs can be accompanied by mild to severe bleeding episodes, often assessed using bleeding assessment tools (BATs) such as the International Society on Thrombosis and Hemostasis (ISTH)-BAT. However, the correlation between bleeding severity and coagulation factor activity levels remains inconsistent. This systematic review investigates this relationship to enhance understanding and improve management strategies for patients with RBD. This review adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was registered with the International Prospective Register for Systematic Reviews (PROSPERO) (CRD42024504537). Using the PICO (Population, Intervention, Comparator, and Outcomes) framework, the study focused on RBD patients to explore the correlation between coagulation factor activity levels and bleeding severity. A comprehensive search was conducted across PubMed, Scopus, and Web of Science until April 1, 2024, with data extracted on bleeding severity, phenotype, and coagulation factor activity levels. The analysis highlights complex and often inconsistent relationships between coagulation factor levels and the severity of bleeding. In cases of fibrinogen deficiency, three out of four studies (&lt;i&gt;n&lt;/i&gt; = 73 of 111 cases, 66%) demonstrated a moderate to strong correlation between fibrinogen levels and bleeding severity. In prothrombin deficiency, one of two studies (&lt;i&gt;n&lt;/i&gt; = 16 of 29 cases, 55%) found a strong correlation between FII levels and bleeding severity. Four of six studies (&lt;i&gt;n&lt;/i&gt; = 106 of 139 cases, 76%) in FV deficiency found a weak or no correlation between factor activity and bleeding severity. In combined FV and FVIII deficiency, two of three studies (&lt;i&gt;n&lt;/i&gt; = 26 of 60 cases, 43%) found a significant correlation between factor activity and bleeding severity. In FVII deficiency, four (of nine) studies with a study population of 325 patients (65%) found a weak correlation between factor activity and severity of bleeding. Almost all studies (five of six studies, &lt;i&gt;n&lt;/i&gt; = 114 of 118 patients, 97%) in FX deficiency revealed a strong correlation between FX levels and bleeding severity. In FXI deficiency, most studies (five of seven studies, &lt;i&gt;n&lt;/i&gt; = 254 patients, 93%) found a weak or no correlation between factor activity and bleeding severity or symptoms. For FXIII deficiency, there was a moderate to strong correlation between FXIII activity and bleeding severity in all three studies (&lt;i&gt;n&lt;/i&gt; = 61 patients). In conclusion, despite current controversies, this review highlights a moderate or strong correlation between factor activity and bleeding severity in fibrinogen, FX, and FXIII deficiencies, but no correlation or weak correlation for FV, FVII, and FXI deficiencies.","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142787020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Precision Medicine in Rare Bleeding Disorders.","authors":"Akbar Dorgalaleh, Maha Othman","doi":"10.1055/s-0044-1800833","DOIUrl":"https://doi.org/10.1055/s-0044-1800833","url":null,"abstract":"","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142787028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factor XIII Deficiency: Laboratory, Molecular, and Clinical Aspects.","authors":"Akbar Dorgalaleh, Sina Jozdani, Masoumeh Kiani Zadeh","doi":"10.1055/s-0044-1796673","DOIUrl":"https://doi.org/10.1055/s-0044-1796673","url":null,"abstract":"<p><p>Factor XIII-A (FXIII-A) deficiency is an ultra-rare bleeding disorder characterized by high rates of morbidity and mortality, primarily resulting from intracranial hemorrhage, umbilical cord bleeding, and miscarriage, whereas patients with severe FXIII-B deficiency present with a milder phenotype. Although the estimated incidence of severe FXIII-A deficiency is one per 2 million, a high prevalence ranging from 0.8 to 3.5% has been observed for heterozygous FXIII-A deficiency. Unlike most bleeding disorders, individuals with heterozygous FXIII-A deficiency, particularly women, are more likely to experience hemorrhagic complications during hemostatic challenges. About 200 Mutations have been observed in <i>F13A</i> and <i>F13B</i> genes, with most being missense mutations, while large deletions are the rarest. There is no correlation between genotype and phenotype, but a moderate to strong correlation between factor activity and clinical severity in FXIII-A deficiency difficult. Primary prophylaxis is mandatory for all patients with severe FXIII-A deficiency, while those with heterozygous deficiency are generally asymptomatic and may require on-demand therapy during hemostatic challenges, most commonly in women. On the other hand, patients with severe FXIII-B deficiency may only require on-demand therapy, while heterozygotes are generally asymptomatic. Although there are general recommended therapeutic regimens for prophylaxis or on-demand therapy in different situations, personalized pharmacokinetic-based replacement therapy represents the optimal approach that can optimize intervention efficacy. In such an approach, several factors may affect the effectiveness of treatment and determine the dose and type of intervention, including the classification of FXIII deficiency, residual plasma levels of FXIII, clinical situation requiring intervention, age, weight, and also gender.</p>","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulatory Effect of PDGF/PDGFR on Hematopoiesis.","authors":"Yong Liu, Junbin Huang, Lindi Li, Yifei Duan, Beng H Chong, Liang Li, Mo Yang","doi":"10.1055/s-0044-1796630","DOIUrl":"https://doi.org/10.1055/s-0044-1796630","url":null,"abstract":"<p><p>Platelet-derived growth factor (PDGF) is a critical cytokine with substantial regulatory effects on hematopoiesis. Recent research highlights the essential role of PDGF in the modulation of hematopoietic stem/progenitor cells (HSPCs), megakaryocytes/platelets, and thrombopoietin (TPO) synthesis within the bone marrow microenvironment. PDGF directly stimulates the proliferation and differentiation of HSPCs while also inhibiting apoptosis. In addition, PDGF indirectly enhances the production of other growth factors, including granulocyte-macrophage colony-stimulating factors. Further, PDGF regulates TPO production and influences the bone marrow milieu, thus impacting hematopoiesis and platelet formation. Mechanistically, PDGF binds to its receptor, PDGF receptor (PDGFR), thus activating the PDGF/PDGFR signaling pathway. This pathway subsequently activates phosphoinositide 3-kinase/protein kinase B, leading to the activation of downstream cytokines, including c-Fos and NF-E2, while inhibiting caspase-3 activation. Collectively, these actions have prodifferentiation and antiapoptotic effects on megakaryocytes, thereby regulating platelet production. This review provides a comprehensive analysis of the regulatory role of the PDGF/PDGFR axis in hematopoiesis, with a particular focus on platelet production, by summarizing all studies on PDGF/PDGFR from our group and globally.</p>","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Platelets in Atherosclerosis: A Historical Review.","authors":"Stefania Momi, Paolo Gresele","doi":"10.1055/s-0044-1795097","DOIUrl":"https://doi.org/10.1055/s-0044-1795097","url":null,"abstract":"<p><p>Atherosclerosis is a chronic, multifactorial inflammatory disorder of large and medium-size arteries, which is the leading cause of cardiovascular mortality and morbidity worldwide. Although platelets in cardiovascular disease have mainly been studied for their crucial role in the thrombotic event triggered by atherosclerotic plaque rupture, over the last two decades it has become clear that platelets participate also in the development of atherosclerosis, owing to their ability to interact with the damaged arterial wall and with leukocytes. Platelets participate in all phases of atherogenesis, from the initial functional damage to endothelial cells to plaque unstabilization. Platelets deposit at atherosclerosis predilection sites before the appearance of manifest lesions to the endothelium and contribute to induce endothelial dysfunction, thus supporting leukocyte adhesion to the vessel wall. In particular, platelets release matrix metalloproteinases, which interact with protease-activated receptor 1 on endothelial cells triggering adhesion molecule expression. Moreover, P-selectin and glycoprotein Ibα expressed on the surface of vessel wall-adhering platelets bind PSGL-1 and β2 integrins on leukocytes, favoring their arrest and transendothelial migration. Platelet-leukocyte interactions promote the formation of radical oxygen species which are strongly involved in the lipid peroxidation associated with atherosclerosis. Platelets themselves actively migrate through the endothelium toward the plaque core where they release chemokines that modify the microenvironment by modulating the function of other inflammatory cells, such as macrophages. While current antiplatelet agents seem unable to prevent the contribution of platelets to atherogenesis, the inhibition of platelet secretion, of the release of MMPs, and of some specific pathways of platelet adhesion to the vessel wall may represent promising future strategies for the prevention of atheroprogression.</p>","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acquired Hemophilia A after Tislelizumab Treatment in a Patient with Right Lung Squamous Cell Carcinoma.","authors":"Fengfei Liu, Ying Wang, Naiqi Pang, Juan Xie, Peizhang Li","doi":"10.1055/s-0044-1792106","DOIUrl":"https://doi.org/10.1055/s-0044-1792106","url":null,"abstract":"","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Laboratory and Molecular Diagnosis of Factor XI Deficiency.","authors":"Simon Davidson, Keith Gomez","doi":"10.1055/s-0044-1792033","DOIUrl":"https://doi.org/10.1055/s-0044-1792033","url":null,"abstract":"<p><p>The prevalence of factor XI (FXI) deficiency is 1 per 10 to 20,000 in the general population, much higher than that reported in most texts. The prevalence is higher in Ashkenazi Jews where it is about 1:20. Clinically, FXI deficiency presents as a mild bleeding disorder mostly associated with posttraumatic or postsurgical hemorrhages or unexplained minor bleeding. It is often discovered due to incidental finding of a prolonged activated partial thromboplastin time (aPTT) on routine laboratory screening. FXI deficiency is an autosomal recessive bleeding disorder with many causative <i>F11</i> gene defects. Diagnosis is based on FXI activity, antigen levels, and molecular diagnostics. As FXI levels do not correlate with bleeding symptoms, identification of pathogenic genetic variants may be a more accurate predictor of bleeding risk and therefore aid in the clinical management of the patient. Two variants in the <i>F11</i> gene account for most cases found in the Jewish and Arab populations. Patients with FXI deficiency can develop inhibitors to FXI although spontaneously acquired inhibitors are extremely rare. We will discuss laboratory and molecular assays used to diagnose FXI deficiency as well as interferences that can complicate diagnosis including new anticoagulants and acquired FXI inhibitors.</p>","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}