Pub Date : 2024-11-26DOI: 10.1016/j.thromres.2024.109225
Federica De Pascali , Yulia Aleksandrovna Filippova , Marco P. Donadini , Vittorio Pengo , Alessandro Squizzato
Background
Anti-Phospholipid Antibodies (aPL) are autoantibodies predisposing to an increased risk of thrombotic events. The net clinical benefit of antithrombotic prophylaxis in aPL carriers is still unclear. We performed a systematic review to assess the efficacy and safety of antiplatelet drugs for the primary prevention of thrombotic events in aPL carriers.
Methods
Studies were identified by electronic search of MEDLINE and EMBASE database until May 2023. The differences in the outcomes among groups were estimated as pooled odds ratio (OR) and corresponding 95 % confidence interval (CI). Statistical heterogeneity was evaluated using the I2 statistic.
Results
1056 participants were included in 10 studies, 2 RCTs and 8 cohorts. Low-dose acetylsalicylic acid (LDA) was the antiplatelet drug in treated patients. Thrombotic events were significantly reduced in the LDA group compared to the control group [OR 0.46 (95 % CI 0.30–0.71), I2 27%, fixed-effects model]. Arterial thrombotic events were significantly reduced in the LDA group compared to the control group [OR 0.47 (95 % CI 0.26–0.86), I2 0%, fixed-effects model]. Venous thrombotic events were significantly reduced in the LDA group compared to the control group [OR 0.44 (95 % CI 0.21–0.89, I2 1%, fixed-effects model]. No major bleedings occurred in the five studies reporting them.
Conclusions
aPL carriers receiving long-term LDA had a significant reduction of thrombotic events, without a significant increase of the risk of major bleeding. It remains unclear if LDA has the same benefit/risk profile in all aPL profile, i.e. single, double, or triple positivity.
{"title":"Efficacy and safety of low-dose acetylsalicylic acid for the prevention of thromboembolic events in individuals positive for antiphospholipid antibodies: A systematic review and meta-analysis","authors":"Federica De Pascali , Yulia Aleksandrovna Filippova , Marco P. Donadini , Vittorio Pengo , Alessandro Squizzato","doi":"10.1016/j.thromres.2024.109225","DOIUrl":"10.1016/j.thromres.2024.109225","url":null,"abstract":"<div><h3>Background</h3><div>Anti-Phospholipid Antibodies (aPL) are autoantibodies predisposing to an increased risk of thrombotic events. The net clinical benefit of antithrombotic prophylaxis in aPL carriers is still unclear. We performed a systematic review to assess the efficacy and safety of antiplatelet drugs for the primary prevention of thrombotic events in aPL carriers.</div></div><div><h3>Methods</h3><div>Studies were identified by electronic search of MEDLINE and EMBASE database until May 2023. The differences in the outcomes among groups were estimated as pooled odds ratio (OR) and corresponding 95 % confidence interval (CI). Statistical heterogeneity was evaluated using the I2 statistic.</div></div><div><h3>Results</h3><div>1056 participants were included in 10 studies, 2 RCTs and 8 cohorts. Low-dose acetylsalicylic acid (LDA) was the antiplatelet drug in treated patients. Thrombotic events were significantly reduced in the LDA group compared to the control group [OR 0.46 (95 % CI 0.30–0.71), I2 27%, fixed-effects model]. Arterial thrombotic events were significantly reduced in the LDA group compared to the control group [OR 0.47 (95 % CI 0.26–0.86), I2 0%, fixed-effects model]. Venous thrombotic events were significantly reduced in the LDA group compared to the control group [OR 0.44 (95 % CI 0.21–0.89, I2 1%, fixed-effects model]. No major bleedings occurred in the five studies reporting them.</div></div><div><h3>Conclusions</h3><div>aPL carriers receiving long-term LDA had a significant reduction of thrombotic events, without a significant increase of the risk of major bleeding. It remains unclear if LDA has the same benefit/risk profile in all aPL profile, i.e. single, double, or triple positivity.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"245 ","pages":"Article 109225"},"PeriodicalIF":3.7,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142702847","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 : 2024-11-24DOI: 10.1016/j.thromres.2024.109231
Zighed Hanna , Huguenin Yoann , Blanc Laurence , Valentin Jean-Baptiste , Babuty Antoine , Cussac Vincent , Heritier Sebastien , Biron-Andreani Christine , Jeziorski Eric , Moulis Lionel , Harroche Annie , Theron Alexandre
Introduction
Lupus-anticoagulant hypoprothrombinemia syndrome (LAHS) is a rare but potentially serious condition. LAHS can be of post-infectious (PI) or autoimmune (AI) origin. However, there is currently no clear data available on the differences between these two forms.
Method
A retrospective multicenter study of cases in France was performed, followed by a review of cases in the literature.
Result
A total of 84 patients were included in the study. Seventeen patients were selected from the French cohort, and 67 were selected from a systematic review of the literature. 95 % of patients presented with hemorrhagic symptoms, with nearly half of these cases being severe. PI or AI context was identified in 33 % and 53 % of cases. 54 % of patients were treated with corticosteroids, and 30 % received immunomodulatory therapy. Thrombopenia and lower factor V were associated with a higher risk of bleeding. The AI group consisted of older children and exhibited significantly more severe bleeding (p < 0.001). The treatment was more frequent and intensive, and the relapse rate was higher in the AI group (p < 0.001).
Conclusion
Post-infectious forms are transient and associated with a low risk of serious hemorrhage. The treatment must be adapted according to the clinical and biological context.
导言狼疮抗凝血功能减退综合征（LAHS）是一种罕见但潜在的严重疾病。LAHS可由感染后（PI）或自身免疫（AI）引起。方法 对法国的病例进行了回顾性多中心研究，随后对文献中的病例进行了回顾。研究共纳入了 84 名患者，其中 17 名患者来自法国队列，67 名患者来自文献系统回顾。95%的患者出现出血性症状，其中近一半病情严重。33%和53%的病例确定有 PI 或 AI 背景。54%的患者接受了皮质类固醇治疗，30%接受了免疫调节治疗。血栓减少症和V因子降低与出血风险升高有关。免疫调节剂组的患儿年龄较大，出血情况明显更严重（p <0.001）。治疗更频繁、更密集，AI 组的复发率更高（p < 0.001）。治疗必须根据临床和生物学背景进行调整。
{"title":"Lupus-associated hypoprothrombinemia syndrome in children: Differences between post-infectious and autoimmune forms","authors":"Zighed Hanna , Huguenin Yoann , Blanc Laurence , Valentin Jean-Baptiste , Babuty Antoine , Cussac Vincent , Heritier Sebastien , Biron-Andreani Christine , Jeziorski Eric , Moulis Lionel , Harroche Annie , Theron Alexandre","doi":"10.1016/j.thromres.2024.109231","DOIUrl":"10.1016/j.thromres.2024.109231","url":null,"abstract":"<div><h3>Introduction</h3><div>Lupus-anticoagulant hypoprothrombinemia syndrome (LAHS) is a rare but potentially serious condition. LAHS can be of post-infectious (PI) or autoimmune (AI) origin. However, there is currently no clear data available on the differences between these two forms.</div></div><div><h3>Method</h3><div>A retrospective multicenter study of cases in France was performed, followed by a review of cases in the literature.</div></div><div><h3>Result</h3><div>A total of 84 patients were included in the study. Seventeen patients were selected from the French cohort, and 67 were selected from a systematic review of the literature. 95 % of patients presented with hemorrhagic symptoms, with nearly half of these cases being severe. PI or AI context was identified in 33 % and 53 % of cases. 54 % of patients were treated with corticosteroids, and 30 % received immunomodulatory therapy. Thrombopenia and lower factor V were associated with a higher risk of bleeding. The AI group consisted of older children and exhibited significantly more severe bleeding (<em>p</em> < 0.001). The treatment was more frequent and intensive, and the relapse rate was higher in the AI group (p < 0.001).</div></div><div><h3>Conclusion</h3><div>Post-infectious forms are transient and associated with a low risk of serious hemorrhage. The treatment must be adapted according to the clinical and biological context.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"245 ","pages":"Article 109231"},"PeriodicalIF":3.7,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142702848","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 : 2024-11-19DOI: 10.1016/j.thromres.2024.109213
Spencer Keene , Hoda Abbasizanjani , Fatemeh Torabi , Rochelle Knight , Venexia Walker , Elena Raffetti , Genevieve Cezard , Samantha Ip , Alexia Sampri , Thomas Bolton , Rachel Denholm , Kamlesh Khunti , Ashley Akbari , Jennifer Quint , Spiros Denaxas , Cathie Sudlow , Emanuele Di Angelantonio , Jonathan A.C. Sterne , Angela Wood , William N. Whiteley
<div><h3>Objective</h3><div>Pneumonia, influenza, COVID-19, and other common infections might increase the risk of thrombotic events acutely through an interaction between inflammation and the thrombotic system. The long-term risks of arterial and venous thrombotic events following hospitalisation for COVID-19 and hospitalisation for pneumonia or influenza are unclear.</div></div><div><h3>Materials and methods</h3><div>In a population-wide cohort of linked Welsh health data of adults, we calculated the incidence of arterial and venous thrombosis after hospitalisation for COVID-19 (2020−2021). We then compared this post-hospitalisation incidence with the incidence prior to COVID-19 hospitalisation in the same individuals, and with the incidence in individuals who were never hospitalised for COVID-19. We then repeated this analysis for hospitalisation for pneumonia or influenza in a separate cohort (2016–2019). We estimated adjusted hazard ratios (aHRs) in separate time periods starting from the date of the first infection that resulted in hospitalisation (day 0, 1 to 7 days, 2 to 4 weeks, 5 to 16 weeks, and 17 to 75 weeks) using time-varying Cox regression. Confounders included age, sex, smoking status, obesity, deprivation (fifths of Welsh Index of Multiple Deprivation), rural or urban setting, care home attendance, Elixhauser comorbidity index, surgery in the last year, medications (e.g. lipid-lowering and antiplatelet/anticoagulant use), hypertension and/or hypertensive medication use, and past medical history of chronic kidney disease, diabetes, chronic obstructive pulmonary disease, dementia, cancer, or any CVD.</div></div><div><h3>Results</h3><div>For the first arterial thrombosis, the aHRs were 3.80 (95 % CI: 2.50–5.77) between days 1–7, 5.24 (4.21–6.51) between weeks 2–4, 2.12 (1.72–2.60) between weeks 5–16, and 1.60 (1.38–1.86) between weeks 17–75 after hospitalisation for COVID-19. The corresponding aHRs after hospitalisation for pneumonia/influenza were: 5.42 (4.35–6.75), 3.87 (3.32–4.49), 1.96 (1.74–2.21), and 1.41 (1.30–1.53).</div><div>For first venous thrombosis, aHRs were 7.47 (3.56–15.7) between days 1–7, 22.6 (17.5–29.1) between weeks 2–4, 6.58 (4.98–8.68) between weeks 5–16, and 2.25 (1.67–3.02) between weeks 17–75 after hospitalisation for COVID-19. The corresponding aHRs after hospitalisation for pneumonia/influenza were: 15.1 (10.3–22.0), 11.8 (9.23–15.1), 5.80 (4.75–7.08), and 1.89 (1.57–2.29).</div><div>Excess risk was highest in individuals aged ≥60 years, in whom we estimated 2,700 and 2,320 additional arterial and 1,270 and 840 additional venous events after 100,000 hospitalisations for COVID-19 and pneumonia/influenza, respectively.</div></div><div><h3>Conclusions</h3><div>Both hospitalisation for COVID-19 and pneumonia/influenza increase the risk of arterial and venous thrombosis. Preventative healthcare policies are needed for cardiovascular risk factor management, vaccination, and anticoagulation in high-risk patient
{"title":"Risks of major arterial and venous thrombotic diseases after hospitalisation for influenza, pneumonia, and COVID-19: A population-wide cohort in 2.6 million people in Wales","authors":"Spencer Keene , Hoda Abbasizanjani , Fatemeh Torabi , Rochelle Knight , Venexia Walker , Elena Raffetti , Genevieve Cezard , Samantha Ip , Alexia Sampri , Thomas Bolton , Rachel Denholm , Kamlesh Khunti , Ashley Akbari , Jennifer Quint , Spiros Denaxas , Cathie Sudlow , Emanuele Di Angelantonio , Jonathan A.C. Sterne , Angela Wood , William N. Whiteley","doi":"10.1016/j.thromres.2024.109213","DOIUrl":"10.1016/j.thromres.2024.109213","url":null,"abstract":"<div><h3>Objective</h3><div>Pneumonia, influenza, COVID-19, and other common infections might increase the risk of thrombotic events acutely through an interaction between inflammation and the thrombotic system. The long-term risks of arterial and venous thrombotic events following hospitalisation for COVID-19 and hospitalisation for pneumonia or influenza are unclear.</div></div><div><h3>Materials and methods</h3><div>In a population-wide cohort of linked Welsh health data of adults, we calculated the incidence of arterial and venous thrombosis after hospitalisation for COVID-19 (2020−2021). We then compared this post-hospitalisation incidence with the incidence prior to COVID-19 hospitalisation in the same individuals, and with the incidence in individuals who were never hospitalised for COVID-19. We then repeated this analysis for hospitalisation for pneumonia or influenza in a separate cohort (2016–2019). We estimated adjusted hazard ratios (aHRs) in separate time periods starting from the date of the first infection that resulted in hospitalisation (day 0, 1 to 7 days, 2 to 4 weeks, 5 to 16 weeks, and 17 to 75 weeks) using time-varying Cox regression. Confounders included age, sex, smoking status, obesity, deprivation (fifths of Welsh Index of Multiple Deprivation), rural or urban setting, care home attendance, Elixhauser comorbidity index, surgery in the last year, medications (e.g. lipid-lowering and antiplatelet/anticoagulant use), hypertension and/or hypertensive medication use, and past medical history of chronic kidney disease, diabetes, chronic obstructive pulmonary disease, dementia, cancer, or any CVD.</div></div><div><h3>Results</h3><div>For the first arterial thrombosis, the aHRs were 3.80 (95 % CI: 2.50–5.77) between days 1–7, 5.24 (4.21–6.51) between weeks 2–4, 2.12 (1.72–2.60) between weeks 5–16, and 1.60 (1.38–1.86) between weeks 17–75 after hospitalisation for COVID-19. The corresponding aHRs after hospitalisation for pneumonia/influenza were: 5.42 (4.35–6.75), 3.87 (3.32–4.49), 1.96 (1.74–2.21), and 1.41 (1.30–1.53).</div><div>For first venous thrombosis, aHRs were 7.47 (3.56–15.7) between days 1–7, 22.6 (17.5–29.1) between weeks 2–4, 6.58 (4.98–8.68) between weeks 5–16, and 2.25 (1.67–3.02) between weeks 17–75 after hospitalisation for COVID-19. The corresponding aHRs after hospitalisation for pneumonia/influenza were: 15.1 (10.3–22.0), 11.8 (9.23–15.1), 5.80 (4.75–7.08), and 1.89 (1.57–2.29).</div><div>Excess risk was highest in individuals aged ≥60 years, in whom we estimated 2,700 and 2,320 additional arterial and 1,270 and 840 additional venous events after 100,000 hospitalisations for COVID-19 and pneumonia/influenza, respectively.</div></div><div><h3>Conclusions</h3><div>Both hospitalisation for COVID-19 and pneumonia/influenza increase the risk of arterial and venous thrombosis. Preventative healthcare policies are needed for cardiovascular risk factor management, vaccination, and anticoagulation in high-risk patient","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"245 ","pages":"Article 109213"},"PeriodicalIF":3.7,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142720729","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 : 2024-11-19DOI: 10.1016/j.thromres.2024.109226
Paolo Prandoni , Franca Bilora , Raffaele Pesavento , José María Pedrajas , José Luis Fernández-Reyes , Covadonga Gómez-Cuervo , Aurora Villalobos , Alicia Alda-Lozano , Paolo Simioni , Manuel Monreal , RIETE Investigators
{"title":"DOAC Score for prediction of major bleeding in patients with venous thromboembolism: Findings from the RIETE registry","authors":"Paolo Prandoni , Franca Bilora , Raffaele Pesavento , José María Pedrajas , José Luis Fernández-Reyes , Covadonga Gómez-Cuervo , Aurora Villalobos , Alicia Alda-Lozano , Paolo Simioni , Manuel Monreal , RIETE Investigators","doi":"10.1016/j.thromres.2024.109226","DOIUrl":"10.1016/j.thromres.2024.109226","url":null,"abstract":"","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"245 ","pages":"Article 109226"},"PeriodicalIF":3.7,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693612","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 : 2024-11-19DOI: 10.1016/j.thromres.2024.109229
Yaseelan Palarasah , Rikke Borg , Else-Marie Bladbjerg , Stephanie Thuy Duong Pham , Anna Mejldal , Christian Nielsen , Erik Bo Pedersen , Per Bruno Jensen , Helle Charlotte Thiesson , Katrine Pilely
Background and hypothesis
The contact system (CAS) is a part of both the immune system and the coagulation system. The involvement of the CAS in chronic kidney disease (CKD) and hemodialysis (HD) has been documented, yet conflicting findings have hindered a comprehensive understanding. This study aimed to investigate whether CAS activation occurs in patients with chronic kidney failure undergoing HD compared with those undergoing peritoneal dialysis (PD), patients with CKD not receiving replacement therapy, or healthy controls and to assess the impact of HD on CAS from pre- to post-dialysis during a single session of HD.
Methods
In this cross-sectional study, blood samples from HD patients (n = 106), PD patients (n = 40), CKD patients (n = 60), and healthy control subjects (n = 80) were analyzed. The levels of CAS components, including factor XII, prekallikrein, high-molecular-weight kininogen (HK), cleaved HK (cHK), and C1-inhibitor, and functional kallikrein generation were determined. Among HD patients, CAS measures were evaluated both pre- and post-dialysis. Linear regression models and linear mixed models were employed to analyze associations and changes.
Results
HD patients had altered levels of prekallikrein, factor XII, and cHK compared with PD patients, CKD patients, and the healthy control group. Moreover, HD patients demonstrated increased levels of C1-inhibitor and reduced functional kallikrein generation, a pattern also observed in PD patients and, to a lesser degree, in CKD patients when compared with healthy controls. Notably, no CAS activation was detected during HD.
Conclusions
Impaired kidney function, especially in patients undergoing HD or PD, was associated with reduced functional kallikrein generation and altered levels of CAS components, implying continuous CAS activation in CKD. There was no indication of significant activation of factor XII-mediated CAS during HD. The role of CAS in CKD, independently of dialysis, should be addressed in future research.
背景与假设：接触系统（CAS）是免疫系统和凝血系统的一部分。接触系统参与慢性肾脏病（CKD）和血液透析（HD）的研究已有记载，但相互矛盾的研究结果阻碍了对其的全面了解。本研究旨在调查接受血液透析的慢性肾衰竭患者与接受腹膜透析（PD）的患者、未接受替代疗法的慢性肾衰竭患者或健康对照组相比，CAS 是否被激活，并评估在一次血液透析过程中，从透析前到透析后血液透析对 CAS 的影响：在这项横断面研究中，分析了血液透析患者（106 人）、血液透析患者（40 人）、慢性肾脏病患者（60 人）和健康对照组（80 人）的血液样本。测定了CAS成分的水平，包括因子XII、前激肽原、高分子量激肽原（HK）、裂解HK（cHK）和C1-抑制剂，以及功能性激肽原的生成。在血液透析患者中，透析前和透析后都对 CAS 测量进行了评估。采用线性回归模型和线性混合模型分析相关性和变化：结果：与帕金森病患者、慢性肾脏病患者和健康对照组相比，HD 患者的前胰高血糖素、XII因子和 cHK 水平发生了变化。此外，与健康对照组相比，HD 患者的 C1 抑制剂水平升高，功能性allikrein 生成减少，这一模式在 PD 患者中也有观察到，在 CKD 患者中程度较轻。值得注意的是，在血液透析过程中未检测到CAS活化：结论：肾功能受损，尤其是在接受 HD 或 PD 的患者中，与功能性降钙素生成减少和 CAS 成分水平改变有关，这意味着 CAS 在 CKD 中持续活化。在血液透析过程中，没有迹象表明 XII 因子介导的 CAS 被明显激活。未来的研究应关注 CAS 在 CKD 中的作用，而非透析。
{"title":"The contact system in chronic kidney disease and hemodialysis – A cross-sectional study","authors":"Yaseelan Palarasah , Rikke Borg , Else-Marie Bladbjerg , Stephanie Thuy Duong Pham , Anna Mejldal , Christian Nielsen , Erik Bo Pedersen , Per Bruno Jensen , Helle Charlotte Thiesson , Katrine Pilely","doi":"10.1016/j.thromres.2024.109229","DOIUrl":"10.1016/j.thromres.2024.109229","url":null,"abstract":"<div><h3>Background and hypothesis</h3><div>The contact system (CAS) is a part of both the immune system and the coagulation system. The involvement of the CAS in chronic kidney disease (CKD) and hemodialysis (HD) has been documented, yet conflicting findings have hindered a comprehensive understanding. This study aimed to investigate whether CAS activation occurs in patients with chronic kidney failure undergoing HD compared with those undergoing peritoneal dialysis (PD), patients with CKD not receiving replacement therapy, or healthy controls and to assess the impact of HD on CAS from pre- to post-dialysis during a single session of HD.</div></div><div><h3>Methods</h3><div>In this cross-sectional study, blood samples from HD patients (<em>n</em> = 106), PD patients (<em>n</em> = 40), CKD patients (<em>n</em> = 60), and healthy control subjects (<em>n</em> = 80) were analyzed. The levels of CAS components, including factor XII, prekallikrein, high-molecular-weight kininogen (HK), cleaved HK (cHK), and C1-inhibitor, and functional kallikrein generation were determined. Among HD patients, CAS measures were evaluated both pre- and post-dialysis. Linear regression models and linear mixed models were employed to analyze associations and changes.</div></div><div><h3>Results</h3><div>HD patients had altered levels of prekallikrein, factor XII, and cHK compared with PD patients, CKD patients, and the healthy control group. Moreover, HD patients demonstrated increased levels of C1-inhibitor and reduced functional kallikrein generation, a pattern also observed in PD patients and, to a lesser degree, in CKD patients when compared with healthy controls. Notably, no CAS activation was detected during HD.</div></div><div><h3>Conclusions</h3><div>Impaired kidney function, especially in patients undergoing HD or PD, was associated with reduced functional kallikrein generation and altered levels of CAS components, implying continuous CAS activation in CKD. There was no indication of significant activation of factor XII-mediated CAS during HD. The role of CAS in CKD, independently of dialysis, should be addressed in future research.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"245 ","pages":"Article 109229"},"PeriodicalIF":3.7,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693615","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 : 2024-11-19DOI: 10.1016/j.thromres.2024.109227
Melina Verso , Giorgio Maraziti , Alessandra Vinci , Danilo Castellani , Gabrio Bassotti , Olivia Morelli
{"title":"Clinical and endoscopic findings in patients with acute gastrointestinal bleeding associated with direct oral anticoagulants: Results from a single-center prospective cohort study","authors":"Melina Verso , Giorgio Maraziti , Alessandra Vinci , Danilo Castellani , Gabrio Bassotti , Olivia Morelli","doi":"10.1016/j.thromres.2024.109227","DOIUrl":"10.1016/j.thromres.2024.109227","url":null,"abstract":"","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"245 ","pages":"Article 109227"},"PeriodicalIF":3.7,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142703150","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 : 2024-11-18DOI: 10.1016/j.thromres.2024.109216
Hailey L. Vandenhazel , Aaron S. Wilson , Xiangyang Ye , Sara R. Vazquez , Daniel M. Witt
Background
Anticoagulants, including warfarin and direct oral anticoagulants (DOACs), are used to prevent and treat venous thromboembolism (VTE) which is common in patients with obesity. Guidance statements regarding use of DOACs for VTE treatment in this patient population have been updated.
Objective
Examine DOAC prescribing trends in patients with obesity and VTE.
Methods
We performed a retrospective, single-site cross-sequential study of DOAC prescribing trends in adult patients with obesity (BMI ≥30) and objectively confirmed VTE diagnosis between 2014 and 2022. The primary outcome of interest was the proportion of patients with obesity prescribed DOACs.
Results
A total of 1826 patients were included in our analysis. Most patients were of White race (85.8 %) and approximately half were female. Pulmonary embolism was the most common VTE type (62.2 %). A total of 1018 patients were prescribed DOAC therapy (55.8 %), 524 warfarin therapy (28.7 %), and 284 enoxaparin (15.6 %). Logistic regression analysis revealed that the utilization of DOACs exhibited a significant upward trend from 2017 to 2022 (odds ratio [OR] 1.85 to 14.08 compared to 2014), but not from 2015 to 2016 (OR 1.30 to 1.52). Patients with BMI ≥ 40 and ≥ 50 were twice and 4-times as likely to be prescribed warfarin than DOACs, respectively.
Conclusion
Between 2017 and 2022, the proportion of patients with obesity prescribed DOACs for the treatment of VTE increased significantly. This suggests an increasing likelihood to prescribe DOACs in this patient population despite the lack of safety and efficacy data from randomized controlled trials except for very heavy patients.
{"title":"Direct oral anticoagulant prescribing trends for venous thromboembolism among adult patients with obesity at University of Utah Health","authors":"Hailey L. Vandenhazel , Aaron S. Wilson , Xiangyang Ye , Sara R. Vazquez , Daniel M. Witt","doi":"10.1016/j.thromres.2024.109216","DOIUrl":"10.1016/j.thromres.2024.109216","url":null,"abstract":"<div><h3>Background</h3><div>Anticoagulants, including warfarin and direct oral anticoagulants (DOACs), are used to prevent and treat venous thromboembolism (VTE) which is common in patients with obesity. Guidance statements regarding use of DOACs for VTE treatment in this patient population have been updated.</div></div><div><h3>Objective</h3><div>Examine DOAC prescribing trends in patients with obesity and VTE.</div></div><div><h3>Methods</h3><div>We performed a retrospective, single-site cross-sequential study of DOAC prescribing trends in adult patients with obesity (BMI <em>≥</em>30) and objectively confirmed VTE diagnosis between 2014 and 2022. The primary outcome of interest was the proportion of patients with obesity prescribed DOACs.</div></div><div><h3>Results</h3><div>A total of 1826 patients were included in our analysis. Most patients were of White race (85.8 %) and approximately half were female. Pulmonary embolism was the most common VTE type (62.2 %). A total of 1018 patients were prescribed DOAC therapy (55.8 %), 524 warfarin therapy (28.7 %), and 284 enoxaparin (15.6 %). Logistic regression analysis revealed that the utilization of DOACs exhibited a significant upward trend from 2017 to 2022 (odds ratio [OR] 1.85 to 14.08 compared to 2014), but not from 2015 to 2016 (OR 1.30 to 1.52). Patients with BMI ≥ 40 and ≥ 50 were twice and 4-times as likely to be prescribed warfarin than DOACs, respectively.</div></div><div><h3>Conclusion</h3><div>Between 2017 and 2022, the proportion of patients with obesity prescribed DOACs for the treatment of VTE increased significantly. This suggests an increasing likelihood to prescribe DOACs in this patient population despite the lack of safety and efficacy data from randomized controlled trials except for very heavy patients.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"245 ","pages":"Article 109216"},"PeriodicalIF":3.7,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142688976","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 : 2024-11-16DOI: 10.1016/j.thromres.2024.109224
Juan Francisco García Granado , Francisco Javier Rodríguez Esparragón , Jesús María González Martín , Sara E. Cazorla Rivero , Ayoze Nauzet González Hernández
Purpose
Endothelial progenitor cells (EPCs) are biomarkers of neurovascular repair in cerebral vascular disease (CVD). Low quantification of EPCs and/or their dysfunction has been associated with stroke severity and post-stroke functionality. This systematic review (SR) and meta-analysis aimed to analyze whether EPC quantification contributes to stroke severity and functional prognosis.
Methods
Articles were selected from the PubMed, ScienceDirect, and Ovid MEDLINE databases, according to the guidelines of the PRISMA 2020 [1] statement. Detailed observational studies of samples from subjects with a clinical diagnosis of CVD (ischemic stroke-IS, hemorrhagic stroke-HS, or transient ischemic attack-TIA) aged >45 years during 2003–2023 were included. Evaluation of study quality was based on the Critical Appraisal Skills Programme checklist(Santamaría, 2017 [2]).
Results
We included 22 articles in our SR. Patients with IS and good functional outcomes had higher EPC levels during the first week of admission than those with worse functional outcomes. Higher EPC levels were associated with reduced infarct growth, improved NIHSS scores at 48 h (OR 0.8; 95 % CI: 0.72–0.90; p < 0.0002) 7 (r = −0.607; p < 0.0001), and 90 days (r = −0.570; p < 0.0001), with a negative correlation between EPC levels and NIHSS score (overall pooled r = −0,32, 95 % CI: −0.39-0.24), and good functional outcomes with better mRS scores at 24 h, 3, 6, and 12 months (overall pooled SMD 4.51, CI 95 %: 0.70–0.83). Lower EPC quantification and worse functional outcomes during admission were predictors of IS recurrence. Higher EPC levels were associated with better functional outcomes and lower bleeding volumes in patients with HS and were protective markers for the progression high-risk TIA.
Conclusion
EPCs seems to be predictive biomarkers of better clinical outcomes in patients with CVD, exhibiting lower severity (NIHSS) and better functional prognosis (mRS).
{"title":"Endothelial and circulating progenitor cells as prognostic biomarkers of stroke: A systematic review and meta-analysis","authors":"Juan Francisco García Granado , Francisco Javier Rodríguez Esparragón , Jesús María González Martín , Sara E. Cazorla Rivero , Ayoze Nauzet González Hernández","doi":"10.1016/j.thromres.2024.109224","DOIUrl":"10.1016/j.thromres.2024.109224","url":null,"abstract":"<div><h3>Purpose</h3><div>Endothelial progenitor cells (EPCs) are biomarkers of neurovascular repair in cerebral vascular disease (CVD). Low quantification of EPCs and/or their dysfunction has been associated with stroke severity and post-stroke functionality. This systematic review (SR) and meta-analysis aimed to analyze whether EPC quantification contributes to stroke severity and functional prognosis.</div></div><div><h3>Methods</h3><div>Articles were selected from the PubMed, ScienceDirect, and Ovid MEDLINE databases, according to the guidelines of the PRISMA 2020 [<span><span>1</span></span>] statement. Detailed observational studies of samples from subjects with a clinical diagnosis of CVD (ischemic stroke-IS, hemorrhagic stroke-HS, or transient ischemic attack-TIA) aged >45 years during 2003–2023 were included. Evaluation of study quality was based on the Critical Appraisal Skills Programme checklist(Santamaría, 2017 [<span><span>2</span></span>]).</div></div><div><h3>Results</h3><div>We included 22 articles in our SR. Patients with IS and good functional outcomes had higher EPC levels during the first week of admission than those with worse functional outcomes. Higher EPC levels were associated with reduced infarct growth, improved NIHSS scores at 48 h (OR 0.8; 95 % CI: 0.72–0.90; <em>p</em> < 0.0002) 7 (<em>r</em> = −0.607; <em>p</em> < 0.0001), and 90 days (<em>r</em> = −0.570; p < 0.0001), with a negative correlation between EPC levels and NIHSS score (overall pooled r = −0,32, 95 % CI: −0.39-0.24), and good functional outcomes with better mRS scores at 24 h, 3, 6, and 12 months (overall pooled SMD 4.51, CI 95 %: 0.70–0.83). Lower EPC quantification and worse functional outcomes during admission were predictors of IS recurrence. Higher EPC levels were associated with better functional outcomes and lower bleeding volumes in patients with HS and were protective markers for the progression high-risk TIA.</div></div><div><h3>Conclusion</h3><div>EPCs seems to be predictive biomarkers of better clinical outcomes in patients with CVD, exhibiting lower severity (NIHSS) and better functional prognosis (mRS).</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"245 ","pages":"Article 109224"},"PeriodicalIF":3.7,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142688980","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 : 2024-11-15DOI: 10.1016/j.thromres.2024.109215
David Green MD, PhD
Venoms have primarily been used to prepare antivenoms for the treatment of snake bites, but they have constituents that might serve other medical needs. These include metalloproteinases, serine proteases, phospholipases, and C-type lectin-like proteins. Some of the products that have been prepared from venoms are procoagulants employed as topical hemostatics, and either applied directly to bleeding wounds or used as adjuncts to surgical procedures to assist in controlling blood loss. Venoms are also a valuable source of laboratory reagents helpful in diagnosing specific coagulation factor deficiencies, identifying lupus anticoagulants, or managing therapeutic anticoagulation. In addition, the unique properties of certain venom components have led to their use as antithrombotic agents. This review describes how snake venoms have provided insight into coagulation mechanisms and generated products to improve human health. Venomous snakes are dangerous but we must learn to safely share our planet with them, not least because studies of their venoms might lead to the discovery of valuable biomolecules.
毒液主要用于制备治疗蛇咬伤的抗蛇毒血清，但其成分也可满足其他医疗需求。这些成分包括金属蛋白酶、丝氨酸蛋白酶、磷脂酶和 C 型凝集素样蛋白。从毒液中制备的一些产品是作为局部止血剂使用的促凝血剂，可直接涂抹在出血的伤口上，或作为外科手术的辅助用药，以帮助控制失血。毒液也是实验室试剂的重要来源，有助于诊断特定凝血因子缺乏症、确定狼疮抗凝物或管理治疗性抗凝血。此外，某些蛇毒成分的独特性质也促使它们被用作抗血栓药物。本综述介绍了蛇毒如何让人们深入了解凝血机制，并产生改善人类健康的产品。毒蛇是危险的，但我们必须学会安全地与它们分享我们的星球，尤其是因为对它们毒液的研究可能会发现有价值的生物分子。
{"title":"Hematology products from snake venoms","authors":"David Green MD, PhD","doi":"10.1016/j.thromres.2024.109215","DOIUrl":"10.1016/j.thromres.2024.109215","url":null,"abstract":"<div><div>Venoms have primarily been used to prepare antivenoms for the treatment of snake bites, but they have constituents that might serve other medical needs. These include metalloproteinases, serine proteases, phospholipases, and C-type lectin-like proteins. Some of the products that have been prepared from venoms are procoagulants employed as topical hemostatics, and either applied directly to bleeding wounds or used as adjuncts to surgical procedures to assist in controlling blood loss. Venoms are also a valuable source of laboratory reagents helpful in diagnosing specific coagulation factor deficiencies, identifying lupus anticoagulants, or managing therapeutic anticoagulation. In addition, the unique properties of certain venom components have led to their use as antithrombotic agents. This review describes how snake venoms have provided insight into coagulation mechanisms and generated products to improve human health. Venomous snakes are dangerous but we must learn to safely share our planet with them, not least because studies of their venoms might lead to the discovery of valuable biomolecules.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"245 ","pages":"Article 109215"},"PeriodicalIF":3.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682889","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 : 2024-11-13DOI: 10.1016/j.thromres.2024.109214
Madeline Abbott (Grossman) , Anna Bustin O'Brien , Kelsie Ellis , Hilary Whitworth , Christopher Thom
Objectives
The purpose of this study was to describe the enoxaparin dose required by preterm neonates and infants to achieve therapeutic anti-Xa levels.
Study design
Retrospective chart review of preterm infants, <12 weeks postnatal age, born before 37 weeks gestation, receiving subcutaneous (SUBQ) enoxaparin every 12 h (q12h) with an anti-Xa goal of 0.5–1 units/mL. The primary endpoint was the enoxaparin dose required to achieve a therapeutic anti-Xa level. Secondary endpoints included initial enoxaparin dose and the frequency of achieving therapeutic anti-Xa levels with the initial dose, index thrombus progression, formation of new thrombi, and suspected or confirmed bleeding.
Results
Fifty-six patients were included for analysis. At time of enoxaparin initiation, the median gestational age, post-menstrual age, and weight were 34 weeks and 2 days, 38 weeks and 4 days, and 2.5 kg (kg), respectively. The median dose required to achieve a therapeutic anti-Xa was 2 mg/kg (IQR 1.7–2.6 mg/kg) SUBQ q12h. The median initial enoxaparin dose of 1.7 mg/kg SUBQ q12h aligned with formulary recommendations. Twenty-three patients (41 %) achieved a therapeutic anti-Xa with the initial dose. Follow-up ultrasounds were available for 38 patients, of which 3 (8 %) showed progression of the index thrombus and 5 (13 %) showed formation of a new thrombus. One patient discontinued enoxaparin due to pulmonary hemorrhage, necessitating protamine administration.
Conclusions
Preterm neonates appear to require a median enoxaparin dose of 2 mg/kg subcutaneously every 12 h to achieve therapeutic anti-Xa levels.
{"title":"Optimizing therapeutic enoxaparin in preterm neonates and infants","authors":"Madeline Abbott (Grossman) , Anna Bustin O'Brien , Kelsie Ellis , Hilary Whitworth , Christopher Thom","doi":"10.1016/j.thromres.2024.109214","DOIUrl":"10.1016/j.thromres.2024.109214","url":null,"abstract":"<div><h3>Objectives</h3><div>The purpose of this study was to describe the enoxaparin dose required by preterm neonates and infants to achieve therapeutic anti-Xa levels.</div></div><div><h3>Study design</h3><div>Retrospective chart review of preterm infants, <12 weeks postnatal age, born before 37 weeks gestation, receiving subcutaneous (SUBQ) enoxaparin every 12 h (q12h) with an anti-Xa goal of 0.5–1 units/mL. The primary endpoint was the enoxaparin dose required to achieve a therapeutic anti-Xa level. Secondary endpoints included initial enoxaparin dose and the frequency of achieving therapeutic anti-Xa levels with the initial dose, index thrombus progression, formation of new thrombi, and suspected or confirmed bleeding.</div></div><div><h3>Results</h3><div>Fifty-six patients were included for analysis. At time of enoxaparin initiation, the median gestational age, post-menstrual age, and weight were 34 weeks and 2 days, 38 weeks and 4 days, and 2.5 kg (kg), respectively. The median dose required to achieve a therapeutic anti-Xa was 2 mg/kg (IQR 1.7–2.6 mg/kg) SUBQ q12h. The median initial enoxaparin dose of 1.7 mg/kg SUBQ q12h aligned with formulary recommendations. Twenty-three patients (41 %) achieved a therapeutic anti-Xa with the initial dose. Follow-up ultrasounds were available for 38 patients, of which 3 (8 %) showed progression of the index thrombus and 5 (13 %) showed formation of a new thrombus. One patient discontinued enoxaparin due to pulmonary hemorrhage, necessitating protamine administration.</div></div><div><h3>Conclusions</h3><div>Preterm neonates appear to require a median enoxaparin dose of 2 mg/kg subcutaneously every 12 h to achieve therapeutic anti-Xa levels.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"245 ","pages":"Article 109214"},"PeriodicalIF":3.7,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142688882","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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