Pub Date : 2024-08-14DOI: 10.1016/j.thromres.2024.109115
Introduction
Hemophilia A is an inherited bleeding disorder caused by pathogenic variants in the factor VIII gene (F8), which leads to factor VIII (FVIII) deficiency. Immune tolerance induction (ITI) is a therapeutic approach to eradicate alloantibodies (inhibitors) against exogenous FVIII in people with inherited hemophilia A. Few studies have evaluated the role of F8 variants on ITI outcome.
Material and methods
We included people with severe hemophilia A (FVIII ˂ 1 international units/dL) and high-responding inhibitors (≥ 5 Bethesda units/mL lifelong) who underwent a first course of ITI. Socio-demographic, clinical and laboratory data were collected. ITI outcomes were defined as total, partial successes, and failure. Detection of intron 1 and 22 inversions was performed by polymerase-chain reaction, followed by F8 sequencing.
Results
We included 168 people with inherited hemophilia A and high-responding inhibitors, median age 6 years at ITI start. Intron 22 inversion was the most prevalent variant (53.6 %), followed by nonsense (16.1 %), small insertion/deletion (11.3 %), and large deletion (10.7 %). In comparison with intron 22 inversion, the odds of ITI failure were 15.5 times higher (odds ratio [OR] 15.50; 95 % confidence interval [95 % CI] 4.59–71.30) and 4.25 times higher (95 % CI, 1.53–12.3) among carriers of F8 large deletions and small insertions and deletions, respectively.
Conclusion
F8 large deletions and small insertions/deletions predicted ITI failure after a first course of ITI in patients with severe hemophilia A and high-responding inhibitors. This is the first study to show F8 large deletions and small insertions/deletions as predictors of ITI failure.
{"title":"Large deletions and small insertions and deletions in the factor VIII gene predict unfavorable immune tolerance induction outcome in people with severe hemophilia A and high-responding inhibitors","authors":"","doi":"10.1016/j.thromres.2024.109115","DOIUrl":"10.1016/j.thromres.2024.109115","url":null,"abstract":"<div><h3>Introduction</h3><p>Hemophilia A is an inherited bleeding disorder caused by pathogenic variants in the factor VIII gene (<em>F8</em>), which leads to factor VIII (FVIII) deficiency. Immune tolerance induction (ITI) is a therapeutic approach to eradicate alloantibodies (inhibitors) against exogenous FVIII in people with inherited hemophilia A. Few studies have evaluated the role of <em>F8</em> variants on ITI outcome.</p></div><div><h3>Material and methods</h3><p>We included people with severe hemophilia A (FVIII ˂ 1 international units/dL) and high-responding inhibitors (≥ 5 Bethesda units/mL lifelong) who underwent a first course of ITI. Socio-demographic, clinical and laboratory data were collected. ITI outcomes were defined as total, partial successes, and failure. Detection of intron 1 and 22 inversions was performed by polymerase-chain reaction, followed by <em>F8</em> sequencing.</p></div><div><h3>Results</h3><p>We included 168 people with inherited hemophilia A and high-responding inhibitors, median age 6 years at ITI start. Intron 22 inversion was the most prevalent variant (53.6 %), followed by nonsense (16.1 %), small insertion/deletion (11.3 %), and large deletion (10.7 %). In comparison with intron 22 inversion, the odds of ITI failure were 15.5 times higher (odds ratio [OR] 15.50; 95 % confidence interval [95 % CI] 4.59–71.30) and 4.25 times higher (95 % CI, 1.53–12.3) among carriers of <em>F8</em> large deletions and small insertions and deletions, respectively.</p></div><div><h3>Conclusion</h3><p><em>F8</em> large deletions and small insertions/deletions predicted ITI failure after a first course of ITI in patients with severe hemophilia A and high-responding inhibitors. This is the first study to show <em>F8</em> large deletions and small insertions/deletions as predictors of ITI failure.</p></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142058232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-12DOI: 10.1016/j.thromres.2024.109117
Introduction
Hereditary Hemorrhagic Telangiectasia (HHT) is charactered by telangiectasia and arteriovenous malformations (AVMs). Recurrent visceral and mucocutaneous bleeding is frequently reported among HHT patients, while data on the prevalence of thrombosis remains limited. This study aims to describe the clinical manifestations and molecular biological characteristics of HHT patients.
Methods
We conducted a retrospective study at Ruijin Hospital, affiliated with Shanghai Jiao Tong University School of Medicine. A total of 24 HHT patients, observed between January 2019 and December 2023, were included. We recorded the biological, clinical, and therapeutic events, with particular attention to bleeding and thrombotic events. Gene mutation analysis and blood constituent measurements were performed.
Results
The prevalence of bleeding among all HHT patients was 100 %, while thrombotic events were noted in 41.70 % of cases. Hepatic arteriovenous malformations (HAVMs) were identified in six patients, pulmonary arteriovenous malformations (PAVMs) in five patients, and cerebral arteriovenous malformations (CAVMs) in one patient. For patients with thrombosis, the discontinuation rates were 23.08 % for antiplatelet therapy and 33.33 % for anticoagulant therapy due to the increased risk of bleeding. Genetic mutations related to HHT were present in 16 patients, with ACVRL1 (activin A receptor-like type 1) mutations being the most frequent at 41.67 %, followed by ENG (endoglin) mutations at 20.83 %, and GDF2 (growth differentiation factor 2) mutations at 4.17 %. The incidence of PAVMs was 75.00 % in HHT1 patients with ENG mutations and 20 % in HHT2 patients with ACVRL1 mutations, while HAVMs occurred in 0 % and 40.00 % of these groups, respectively. Patients were divided into non-AVMs and AVMs groups. Compared to normal controls, von Willebrand factor (vWF) activity was significantly increased in all HHT patients (149.10 % vs. 90.65 %, P < 0.001). In the non-AVMs group, the median level of stromal cell-derived factor-1 (SDF-1) was significantly elevated (124.31 pg/mL vs. 2413.57 pg/mL, P < 0.05), while vWF antigen levels were markedly higher in the AVMs group (165.30 % vs. 130.60 %, P = 0.021). Further grouping of HHT patients based on bleeding and thrombosis phenotypes revealed that those with thrombosis had significantly higher median percentages of schistocytes (3.50 % vs. 0 %, P = 0.002), ferritin concentrations (318.50 μg/L vs. 115.50 μg/L, P = 0.001), and lactate dehydrogenase (LDH) levels (437 U/L vs. 105 U/L, P < 0.001). There were no significant differences in the activity of vWF, protein C (PC), protein S (PS), and factor VIII (FVIII) between the two groups.
Conclusion
This study highlighted the complex relationship between arteriovenous malformations
{"title":"Molecular mechanisms and clinical manifestations of hereditary hemorrhagic telangiectasia","authors":"","doi":"10.1016/j.thromres.2024.109117","DOIUrl":"10.1016/j.thromres.2024.109117","url":null,"abstract":"<div><h3>Introduction</h3><p>Hereditary Hemorrhagic Telangiectasia (HHT) is charactered by telangiectasia and arteriovenous malformations (AVMs). Recurrent visceral and mucocutaneous bleeding is frequently reported among HHT patients, while data on the prevalence of thrombosis remains limited. This study aims to describe the clinical manifestations and molecular biological characteristics of HHT patients.</p></div><div><h3>Methods</h3><p>We conducted a retrospective study at Ruijin Hospital, affiliated with Shanghai Jiao Tong University School of Medicine. A total of 24 HHT patients, observed between January 2019 and December 2023, were included. We recorded the biological, clinical, and therapeutic events, with particular attention to bleeding and thrombotic events. Gene mutation analysis and blood constituent measurements were performed.</p></div><div><h3>Results</h3><p>The prevalence of bleeding among all HHT patients was 100 %, while thrombotic events were noted in 41.70 % of cases. Hepatic arteriovenous malformations (HAVMs) were identified in six patients, pulmonary arteriovenous malformations (PAVMs) in five patients, and cerebral arteriovenous malformations (CAVMs) in one patient. For patients with thrombosis, the discontinuation rates were 23.08 % for antiplatelet therapy and 33.33 % for anticoagulant therapy due to the increased risk of bleeding. Genetic mutations related to HHT were present in 16 patients, with <em>ACVRL1</em> (activin A receptor-like type 1) mutations being the most frequent at 41.67 %, followed by <em>ENG</em> (endoglin) mutations at 20.83 %, and <em>GDF2</em> (growth differentiation factor 2) mutations at 4.17 %. The incidence of PAVMs was 75.00 % in HHT1 patients with <em>ENG</em> mutations and 20 % in HHT2 patients with <em>ACVRL1</em> mutations, while HAVMs occurred in 0 % and 40.00 % of these groups, respectively. Patients were divided into non-AVMs and AVMs groups. Compared to normal controls, von Willebrand factor (vWF) activity was significantly increased in all HHT patients (149.10 % vs. 90.65 %, <em>P</em> < 0.001). In the non-AVMs group, the median level of stromal cell-derived factor-1 (SDF-1) was significantly elevated (124.31 pg/mL vs. 2413.57 pg/mL, <em>P</em> < 0.05), while vWF antigen levels were markedly higher in the AVMs group (165.30 % vs. 130.60 %, <em>P</em> = 0.021). Further grouping of HHT patients based on bleeding and thrombosis phenotypes revealed that those with thrombosis had significantly higher median percentages of schistocytes (3.50 % vs. 0 %, <em>P</em> = 0.002), ferritin concentrations (318.50 μg/L vs. 115.50 μg/L, <em>P</em> = 0.001), and lactate dehydrogenase (LDH) levels (437 U/L vs. 105 U/L, <em>P</em> < 0.001). There were no significant differences in the activity of vWF, protein C (PC), protein S (PS), and factor VIII (FVIII) between the two groups.</p></div><div><h3>Conclusion</h3><p>This study highlighted the complex relationship between arteriovenous malformations","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141990496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-09DOI: 10.1016/j.thromres.2024.109112
Background
Computed tomography pulmonary angiography (CTPA) simplifies the diagnosis of pulmonary embolism (PE) but is not suitable for all patients. Transthoracic lung ultrasound (LUS) is a potential alternative; this meta-analysis evaluates its accuracy for diagnosing PE.
Methods
We systematically searched PubMed, Embase and Cochrane Library from the inception of each database up to April 2024 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Diagnostic Test Accuracy Studies guidelines. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool, and a bivariate random effects model was used to pool sensitivity and specificity.
Results
A total of 18 studies with 2158 patients were analyzed. Lung ultrasound showed a sensitivity of 0.80 (95 %, confidence interval (CI): 0.71–0.86; I2 = 85.2 %) and specificity of 0.87 (95 %, CI: 0.81–0.92; I2 = 87.3 %). The diagnostic score was 3.27 (95 %, CI: 2.75–3.78; I2 = 61.9 %), and the diagnostic odds ratio was 26 (95 %, CI: 16–44; I2 = 100.0 %). The pooled positive likelihood ratio was 6.2 (95 %, CI: 4.2–9.1; I2 = 79.2 %), and the negative likelihood ratio was 0.24 (95 %, CI: 0.16–0.34; I2 = 83.7 %). The summary area under the curve was 0.91 (95 %, CI: 0.88–0.93). Significant heterogeneity was observed, which may impact the generalisability of the results, and no publication bias was detected.
Conclusion
Transthoracic LUS shows potential as an alternative to CTPA for PE diagnosis, but further research is needed to improve its accuracy and establish standardised diagnostic criteria. The observed heterogeneity highlights the need for a cautious interpretation of the results.
{"title":"Accuracy of transthoracic lung ultrasound for diagnosing pulmonary embolism: An updated systematic review and meta-analysis","authors":"","doi":"10.1016/j.thromres.2024.109112","DOIUrl":"10.1016/j.thromres.2024.109112","url":null,"abstract":"<div><h3>Background</h3><p>Computed tomography pulmonary angiography (CTPA) simplifies the diagnosis of pulmonary embolism (PE) but is not suitable for all patients. Transthoracic lung ultrasound (LUS) is a potential alternative; this meta-analysis evaluates its accuracy for diagnosing PE.</p></div><div><h3>Methods</h3><p>We systematically searched PubMed, Embase and Cochrane Library from the inception of each database up to April 2024 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Diagnostic Test Accuracy Studies guidelines. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool, and a bivariate random effects model was used to pool sensitivity and specificity.</p></div><div><h3>Results</h3><p>A total of 18 studies with 2158 patients were analyzed. Lung ultrasound showed a sensitivity of 0.80 (95 %, confidence interval (CI): 0.71–0.86; I<sup>2</sup> = 85.2 %) and specificity of 0.87 (95 %, CI: 0.81–0.92; I<sup>2</sup> = 87.3 %). The diagnostic score was 3.27 (95 %, CI: 2.75–3.78; I<sup>2</sup> = 61.9 %), and the diagnostic odds ratio was 26 (95 %, CI: 16–44; I<sup>2</sup> = 100.0 %). The pooled positive likelihood ratio was 6.2 (95 %, CI: 4.2–9.1; I<sup>2</sup> = 79.2 %), and the negative likelihood ratio was 0.24 (95 %, CI: 0.16–0.34; I<sup>2</sup> = 83.7 %). The summary area under the curve was 0.91 (95 %, CI: 0.88–0.93). Significant heterogeneity was observed, which may impact the generalisability of the results, and no publication bias was detected.</p></div><div><h3>Conclusion</h3><p>Transthoracic LUS shows potential as an alternative to CTPA for PE diagnosis, but further research is needed to improve its accuracy and establish standardised diagnostic criteria. The observed heterogeneity highlights the need for a cautious interpretation of the results.</p></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-08DOI: 10.1016/j.thromres.2024.109114
{"title":"Mechanical thrombectomy vs catheter directed thrombolysis vs anticoagulation alone: A tertiary center PERT Registry Cohort Analysis","authors":"","doi":"10.1016/j.thromres.2024.109114","DOIUrl":"10.1016/j.thromres.2024.109114","url":null,"abstract":"","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-07DOI: 10.1016/j.thromres.2024.109110
Background
The Chinese Haemophilia Individualized Prophylaxis Study (CHIPS), which was launched in 2016, reported a significant reduction in haemarthrosis over a one-year study. However, its long-term efficacy requires verification. This paper summarizes the clinical outcomes of 18 severe haemophilia A (SHA) patients who completed one year on the CHIPS and 3 more years of follow-up.
Methods
Clinical follow-up was based on the CHIPS protocol (from July 2018 to July 2021). Escalation was based on index joint bleeding, and serial ultrasound (greyscale and colour Doppler) examinations of the index joints (both sides of the ankles, knees and elbows) were conducted every 6 months via a scoring system.
Results
A total of 18 SHA patients completed the 3-year study. Fifteen patients dropped out due to the financial crisis during the COVID-19 pandemic in China. The median age was 5.4 (range 4.3–6.9) years. A significant reduction in haemarthrosis was achieved, with mean annual bleeding rates reduced from 18.9 ± 2.8 to 1.7 ± 0.4 (p < 0.001), annual joint bleeding rates from 3.1 ± 0.7 to1.2 ± 0.3 (p < 0.028). 5 out of 8 target joint resolved. Sixteen doses were escalated. At study exit, the heterogeneous treatment outcomes of the SHA boys were 5 at step 4 (20–25 lU/kg, every other day), 10 at step 3 (15–20 IU/kg, 3×/week), 2 at step 2 (10–15 lU/kg, 3×/week) and 1 at step 1 (10–15 lU/kg, 2×/week). The mean FVIII consumption was 2964 IU/kg/year, with savings. The quality of life improved, with Canadian Haemophilia Outcomes-Kids Life Assessment Tool (CHO-KLAT, Chinese Version 2.0) scores ranging from 68.8 to 78.8. There was no change in the ultrasound score.
Conclusion
Our follow-up data on the 18 SHA boys after completing one year on the CHIPS verify the long-term efficacy of the CHIPS for haemarthrosis reduction, joint health preservation, improvement in the quality of life of the boys and cost savings.
{"title":"A long term outcomes analysis of severe haemophilia A boys receiving 4 years prophylaxis on the Chinese Haemophilia Individualized escalating low dose Prophylaxis (CHIPS)","authors":"","doi":"10.1016/j.thromres.2024.109110","DOIUrl":"10.1016/j.thromres.2024.109110","url":null,"abstract":"<div><h3>Background</h3><p>The Chinese Haemophilia Individualized Prophylaxis Study (CHIPS), which was launched in 2016, reported a significant reduction in haemarthrosis over a one-year study. However, its long-term efficacy requires verification. This paper summarizes the clinical outcomes of 18 severe haemophilia A (SHA) patients who completed one year on the CHIPS and 3 more years of follow-up.</p></div><div><h3>Methods</h3><p>Clinical follow-up was based on the CHIPS protocol (from July 2018 to July 2021). Escalation was based on index joint bleeding, and serial ultrasound (greyscale and colour Doppler) examinations of the index joints (both sides of the ankles, knees and elbows) were conducted every 6 months via a scoring system.</p></div><div><h3>Results</h3><p>A total of 18 SHA patients completed the 3-year study. Fifteen patients dropped out due to the financial crisis during the COVID-19 pandemic in China. The median age was 5.4 (range 4.3–6.9) years. A significant reduction in haemarthrosis was achieved, with mean annual bleeding rates reduced from 18.9 ± 2.8 to 1.7 ± 0.4 (<em>p</em> < 0.001), annual joint bleeding rates from 3.1 ± 0.7 to1.2 ± 0.3 (<em>p</em> < 0.028). 5 out of 8 target joint resolved. Sixteen doses were escalated. At study exit, the heterogeneous treatment outcomes of the SHA boys were 5 at step 4 (20–25 lU/kg, every other day), 10 at step 3 (15–20 IU/kg, 3×/week), 2 at step 2 (10–15 lU/kg, 3×/week) and 1 at step 1 (10–15 lU/kg, 2×/week). The mean FVIII consumption was 2964 IU/kg/year, with savings. The quality of life improved, with Canadian Haemophilia Outcomes-Kids Life Assessment Tool (CHO-KLAT, Chinese Version 2.0) scores ranging from 68.8 to 78.8. There was no change in the ultrasound score.</p></div><div><h3>Conclusion</h3><p>Our follow-up data on the 18 SHA boys after completing one year on the CHIPS verify the long-term efficacy of the CHIPS for haemarthrosis reduction, joint health preservation, improvement in the quality of life of the boys and cost savings.</p></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141907774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-03DOI: 10.1016/j.thromres.2024.109113
Background
The risk of venous thromboembolism (VTE) is 15 to 35-fold higher in the postpartum period compared to non-pregnant individuals. Clinical practice guidelines recommend the use of postpartum thromboprophylaxis with low molecular weight heparin (LMWH) for 6 weeks in individuals at high risk of developing VTE. However, a marked reduction in the risk of VTE risk occurs beyond the third week of the postpartum period.
Objective
We sought to characterize practice patterns of clinicians who manage postpartum individuals at high risk of VTE.
Methods
We conducted a cross-sectional study using a self-administered electronic questionnaire. The survey explored the use of postpartum thromboprophylaxis in high-risk individuals. Descriptive statistics were used to summarize survey responses.
Results
Of the 113 participants that responded to the initial invitation, 78 completed the survey (Europe (53.9 %); North America (23.2 %); Australia and New Zealand (19.0 %)). For individuals with a prior unprovoked or provoked deep venous thrombosis or pulmonary embolism, cerebral vein thrombosis and splanchnic vein thrombosis, 97.4 %, 93.5 %, 91.0 % and 88.5 % of the respondents recommended six weeks of postpartum thromboprophylaxis using LMWH, respectively. The recommendation for 6 weeks of thromboprophylaxis in patients with sickle cell disease and obstetric APS was comparatively lower (70.5 and 78.2 % respectively). Respondents with higher practice volumes and more years of experience in clinical practice were more likely to recommend a shorter duration of thromboprophylaxis.
Conclusion
Our study highlights the variability in clinician recommendations and the acceptability of treatment durations for postpartum thromboprophylaxis in high-risk conditions. Prospective studies are needed to determine optimal duration and establish evidence-based management.
{"title":"Examining postpartum anticoagulation practices: An international survey of healthcare providers","authors":"","doi":"10.1016/j.thromres.2024.109113","DOIUrl":"10.1016/j.thromres.2024.109113","url":null,"abstract":"<div><h3>Background</h3><p>The risk of venous thromboembolism (VTE) is 15 to 35-fold higher in the postpartum period compared to non-pregnant individuals. Clinical practice guidelines recommend the use of postpartum thromboprophylaxis with low molecular weight heparin (LMWH) for 6 weeks in individuals at high risk of developing VTE. However, a marked reduction in the risk of VTE risk occurs beyond the third week of the postpartum period.</p></div><div><h3>Objective</h3><p>We sought to characterize practice patterns of clinicians who manage postpartum individuals at high risk of VTE.</p></div><div><h3>Methods</h3><p>We conducted a cross-sectional study using a self-administered electronic questionnaire. The survey explored the use of postpartum thromboprophylaxis in high-risk individuals. Descriptive statistics were used to summarize survey responses.</p></div><div><h3>Results</h3><p>Of the 113 participants that responded to the initial invitation, 78 completed the survey (Europe (53.9 %); North America (23.2 %); Australia and New Zealand (19.0 %)). For individuals with a prior unprovoked or provoked deep venous thrombosis or pulmonary embolism, cerebral vein thrombosis and splanchnic vein thrombosis, 97.4 %, 93.5 %, 91.0 % and 88.5 % of the respondents recommended six weeks of postpartum thromboprophylaxis using LMWH, respectively. The recommendation for 6 weeks of thromboprophylaxis in patients with sickle cell disease and obstetric APS was comparatively lower (70.5 and 78.2 % respectively). Respondents with higher practice volumes and more years of experience in clinical practice were more likely to recommend a shorter duration of thromboprophylaxis.</p></div><div><h3>Conclusion</h3><p>Our study highlights the variability in clinician recommendations and the acceptability of treatment durations for postpartum thromboprophylaxis in high-risk conditions. Prospective studies are needed to determine optimal duration and establish evidence-based management.</p></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0049384824002457/pdfft?md5=29d62180228501f11f189f306580d109&pid=1-s2.0-S0049384824002457-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-02DOI: 10.1016/j.thromres.2024.109111
Thrombosis is the primary cause of death in patients with cancer. Resveratrol inhibits platelet activation, a crucial pathophysiological basis of thrombosis, in healthy individuals. However, its effects and mechanisms of action in patients with colon cancer remain unknown. Here, we investigated the effect of resveratrol on platelet adhesion and aggregation in patients with colon cancer. Through numerous in vitro and in vivo analyses, including flow cytometry, western blotting, ELISA, and immunofluorescence and colon cancer rat models, we demonstrated that resveratrol reduced thrombosis in patients with colon cancer by inhibiting the phosphorylation of the MAPK and activating the cyclic-GMP/vasodilator-stimulated phosphoprotein pathway. These findings demonstrate the potential of resveratrol in reducing thrombosis in patients with colon cancer and could be used to develop novel therapeutic strategies for this condition.
{"title":"Inhibitory effects of resveratrol on platelet activation and thrombosis in colon cancer through regulation of the MAPK and cGMP/VASP pathways","authors":"","doi":"10.1016/j.thromres.2024.109111","DOIUrl":"10.1016/j.thromres.2024.109111","url":null,"abstract":"<div><p>Thrombosis is the primary cause of death in patients with cancer. Resveratrol inhibits platelet activation, a crucial pathophysiological basis of thrombosis, in healthy individuals. However, its effects and mechanisms of action in patients with colon cancer remain unknown. Here, we investigated the effect of resveratrol on platelet adhesion and aggregation in patients with colon cancer. Through numerous in vitro and in vivo analyses, including flow cytometry, western blotting, ELISA, and immunofluorescence and colon cancer rat models, we demonstrated that resveratrol reduced thrombosis in patients with colon cancer by inhibiting the phosphorylation of the MAPK and activating the cyclic-GMP/vasodilator-stimulated phosphoprotein pathway. These findings demonstrate the potential of resveratrol in reducing thrombosis in patients with colon cancer and could be used to develop novel therapeutic strategies for this condition.</p></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141890139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-31DOI: 10.1016/j.thromres.2024.109109
Despite the predisposition to bleeding, patients with immune thrombocytopenia (ITP) may also have an increased risk of arterial and venous thrombosis, which can contribute to significant morbidity. The risk of thrombosis increases with age and the presence of cardiovascular risk factors. This narrative review explores the multifactorial nature of thrombosis in ITP, focusing on new pathological mechanisms, emerging evidence on the association between established treatments and thrombotic risk, the role of novel treatment approaches, and the challenges in assessing the balance between bleeding and thrombosis in ITP. The review also explores the challenges in managing acute thrombotic events in ITP, since the platelet count does not always reliably predict either the risk of bleeding or thrombosis and antithrombotic strategies lack specific guidelines for ITP. Notably, second-line therapeutic options, such as splenectomy and thrombopoietin receptor agonists (TPO-RAs), exhibit an increased risk of thrombosis especially in older individuals or those with multiple thrombotic risk factors or previous thrombosis, emphasizing the importance of careful risk assessment before treatment selection. In this context, it is important to consider second-line therapies such as rituximab and other immunosuppressive agents, dapsone and fostamatinib, which are not associated with increased thrombotic risk. In particular, fostamatinib, an oral spleen tyrosine kinase inhibitor, has promisingly low thrombotic risk. During the current era of the emergence of several novel ITP therapies that do not pose additional risks for thrombosis, it is critical to outline evidence-based strategies for the prevention and treatment of thrombosis in ITP patients.
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Pub Date : 2024-07-31DOI: 10.1016/j.thromres.2024.109108
Introduction
Despite thromboprophylaxis, women with antiphospholipid syndrome (APS) face high-risk pregnancies due to proinflammatory and prothrombotic states. This highlights the need for new monitoring and prognostic tools. Recent insights into the pathophysiological role of neutrophil activation and extracellular trap (NET) formation in this syndrome led to the exploration of plasma cell-free DNA (cfDNA), a derivative of NETosis, as a promising biomarker.
Materials and methods
cfDNA was isolated and quantified from plasma samples of healthy pregnant women (control group, HC) and women with APS (APS group). We assessed the physiological variability of cfDNA across the three trimesters in HC. Levels of cfDNA were compared between APS and HC by gestational trimester. ROC curve analysis was performed to evaluate the efficacy of cfDNA levels for classifying APS patients. Furthermore, cfDNA levels in pregnant women with APS with obstetric complications were compared to those from uncomplicated pregnancies.
Results
Among HC, cfDNA significantly increased in the third trimester compared to the first and second. Elevated cfDNA levels in APS compared to HC were observed in the first and second trimesters. First-trimester cfDNA levels demonstrated the highest classification ability to discriminate between APS and HC patients (AUC: 0.906). Among APS, those with complicated pregnancies (fetal growth restriction, preeclampsia, placenta accreta) exhibited significantly elevated cfDNA levels in the second trimester.
Conclusions
Elevated levels of cfDNA in pregnant women with APS, particularly among those with obstetric complications, supports further investigation into the potential of cfDNA as a valuable tool in the obstetric management of women with APS.
导言：尽管采取了血栓预防措施，但患有抗磷脂综合征（APS）的妇女仍会因促炎和促血栓形成状态而面临高风险妊娠。这凸显了对新的监测和预后工具的需求。材料和方法：从健康孕妇（对照组，HC）和 APS 孕妇（APS 组）的血浆样本中分离并量化了 cfDNA。我们评估了 HC 三个孕期 cfDNA 的生理变化。比较了 APS 和 HC 在妊娠三个月中的 cfDNA 水平。我们进行了 ROC 曲线分析，以评估 cfDNA 水平对 APS 患者分类的有效性。此外，还将有产科并发症的APS孕妇的cfDNA水平与无并发症孕妇的cfDNA水平进行了比较：结果：在 HC 孕妇中，cfDNA 在妊娠期的第三个月明显高于妊娠期的第一个月和第二个月。与 HC 相比，APS 孕妇在妊娠头三个月和后三个月的 cfDNA 水平升高。妊娠头三个月的 cfDNA 水平显示了区分 APS 和 HC 患者的最高分类能力（AUC：0.906）。在APS患者中，复杂妊娠（胎儿生长受限、子痫前期、胎盘早剥）患者的cfDNA水平在妊娠后三个月显著升高：APS孕妇的cfDNA水平升高，尤其是在那些有产科并发症的孕妇中，这支持进一步研究cfDNA作为APS孕妇产科管理的一种有价值的工具的潜力。
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Pub Date : 2024-07-31DOI: 10.1016/j.thromres.2024.109107
Background
Although anticoagulants may potentially increase the risk of post-colonoscopy bleeding events, temporary discontinuation of medications could elevate the risk of thromboembolism (TE). There is a paucity of data regarding the incidence of bleeding and TE events in patients undergoing colonoscopy while on uninterrupted or interrupted anticoagulant therapy. Therefore, we aimed to ascertain the risks of post-colonoscopy TE and bleeding in patients with continuous or interrupted use of anticoagulant agents.
Methods
The electronic databases of PubMed, Embase, and the Cochrane library were comprehensively searched from inception to March 15, 2024. We identified studies reporting the incidence of bleeding and TE events in patients undergoing colonoscopy with uninterrupted or interrupted anticoagulant therapy. The pooled incidence rate of bleeding and TE events was estimated using a random-effects model.
Results
This study included a total of 15 studies involving 63, 017 patients. Overall, the incidence of post-procedural bleeding for uninterrupted and interrupted direct oral anticoagulants (DOACs) was found to be 3.60 % (95 % CI: 1.60 %–5.60 %), and 0.90 % (95 % CI: 0.10 %–10.30 %), respectively. Subgroup analysis revealed that older age patients (≥65 years) had a significantly higher rate of bleeding with uninterrupted DOACs therapy compared to younger age patients (< 65 years) (7.20 % vs. 2.00 %). The highest rate of bleeding was observed in Asia (7.20 %, 95 % CI: 2.20 %–12.10 %). Similarly, the risk of bleeding was significantly increased among patients interrupting DOACs therapy in Asia compared to North America (1.40 % vs. 0.26 %). For patients on uninterrupted and interrupted warfarin, a higher rate of bleeding events was observed in older age patients than younger age patients (4.90 % vs. 0.80 %, and 2.20 % vs. 1.70 %, respectively). Uninterrupted warfarin showed a more significant risk of bleeding in Asia (4.20 %, 95%CI: 1.90 %–6.60 %) compared to North America (1.00 %, 95%CI: 0.50 %–1.50 %). Among those who did not interrupt DOACs therapy, the incidence of TE was the lowest (0.08 %, 95%CI: 0.04 %–0.11 %).
Conclusion
This study provides a comprehensive assessment of bleeding and TE risks in patients undergoing colonoscopy while receiving uninterrupted or interrupted anticoagulant therapy in the real-world setting. The overall incidence of post-colonoscopy bleeding and TE events is relatively low. However, the uninterrupted DOACs and warfarin are associated with an elevated risk of bleeding, particularly among elderly patients and the Asian population.
{"title":"Risks of bleeding and thromboembolic events in patients undergoing colonoscopy on uninterrupted and interrupted anticoagulant therapy in real-world setting","authors":"","doi":"10.1016/j.thromres.2024.109107","DOIUrl":"10.1016/j.thromres.2024.109107","url":null,"abstract":"<div><h3>Background</h3><p>Although anticoagulants may potentially increase the risk of post-colonoscopy bleeding events, temporary discontinuation of medications could elevate the risk of thromboembolism (TE). There is a paucity of data regarding the incidence of bleeding and TE events in patients undergoing colonoscopy while on uninterrupted or interrupted anticoagulant therapy. Therefore, we aimed to ascertain the risks of post-colonoscopy TE and bleeding in patients with continuous or interrupted use of anticoagulant agents.</p></div><div><h3>Methods</h3><p>The electronic databases of PubMed, Embase, and the Cochrane library were comprehensively searched from inception to March 15, 2024. We identified studies reporting the incidence of bleeding and TE events in patients undergoing colonoscopy with uninterrupted or interrupted anticoagulant therapy. The pooled incidence rate of bleeding and TE events was estimated using a random-effects model.</p></div><div><h3>Results</h3><p>This study included a total of 15 studies involving 63, 017 patients. Overall, the incidence of post-procedural bleeding for uninterrupted and interrupted direct oral anticoagulants (DOACs) was found to be 3.60 % (95 % CI: 1.60 %–5.60 %), and 0.90 % (95 % CI: 0.10 %–10.30 %), respectively. Subgroup analysis revealed that older age patients (≥65 years) had a significantly higher rate of bleeding with uninterrupted DOACs therapy compared to younger age patients (< 65 years) (7.20 % <em>vs.</em> 2.00 %). The highest rate of bleeding was observed in Asia (7.20 %, 95 % CI: 2.20 %–12.10 %). Similarly, the risk of bleeding was significantly increased among patients interrupting DOACs therapy in Asia compared to North America (1.40 % <em>vs.</em> 0.26 %). For patients on uninterrupted and interrupted warfarin, a higher rate of bleeding events was observed in older age patients than younger age patients (4.90 % <em>vs.</em> 0.80 %, and 2.20 % <em>vs.</em> 1.70 %, respectively). Uninterrupted warfarin showed a more significant risk of bleeding in Asia (4.20 %, 95%CI: 1.90 %–6.60 %) compared to North America (1.00 %, 95%CI: 0.50 %–1.50 %). Among those who did not interrupt DOACs therapy, the incidence of TE was the lowest (0.08 %, 95%CI: 0.04 %–0.11 %).</p></div><div><h3>Conclusion</h3><p>This study provides a comprehensive assessment of bleeding and TE risks in patients undergoing colonoscopy while receiving uninterrupted or interrupted anticoagulant therapy in the real-world setting. The overall incidence of post-colonoscopy bleeding and TE events is relatively low. However, the uninterrupted DOACs and warfarin are associated with an elevated risk of bleeding, particularly among elderly patients and the Asian population.</p></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141890142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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