Background: A recent Phase 2/3 study in Japanese patients showed that caplacizumab was effective in treating immune-mediated thrombotic thrombocytopenic purpura (iTTP), with a low rate of iTTP recurrence. ADAMTS13 activity is monitored weekly during caplacizumab treatment to guide discontinuation of caplacizumab and consequently avoid exacerbations or relapse. The aim of this study was to assess changes in ADAMTS13 activity/inhibitor levels during caplacizumab treatment in this patient population.
Methods: A post hoc analysis of the Phase 2/3 study in Japanese patients was conducted. Patients ≥ 18 years old with confirmed iTTP received 10 mg of caplacizumab daily in conjunction with therapeutic plasma exchange (TPE) and immunosuppression for 30 days post-TPE. Outcomes included time to recovery of ADAMTS13 activity, ADAMTS13 activity level at treatment end, incidence of ADAMTS13 inhibitor re-elevation (ie, inhibitor boosting) during treatment, time to platelet count recovery, number of days of TPE, and safety. Outcomes according to presence of inhibitor boosting were also assessed.
Results: Nineteen patients had confirmed iTTP and were included in this analysis. Median (95% confidence interval) time to recovery of ADAMTS13 activity to ≥ 10%, ≥ 20%, and ≥ 60% was 14.6 (5.9-24.8), 18.5 (5.9-31.8), and 47.5 (18.5-60.9) days, respectively. Median (range) ADAMTS13 activity level at caplacizumab treatment end was 62.0% (29.0-101.0). Nine patients had ADAMTS13 inhibitor boosting. Delayed response of ADAMTS13 activity was observed in patients with inhibitor boosting. The median time to platelet count response and median number of TPE days were shorter in patients with inhibitor boosting compared with patients without inhibitor boosting. Rituximab was administered to almost all patients with inhibitor boosting (88.9%), after completion of TPE. Patients without inhibitor boosting who were treated with rituximab received it prior to completion of TPE. Only one patient experienced a recurrence, which occurred shortly after caplacizumab discontinuation due to an adverse event.
Conclusions: In patients with iTTP, caplacizumab with TPE and immunosuppression may reduce the risk of ADAMTS13 inhibitor boosting if rituximab is administered early in the iTTP treatment period. Early administration of rituximab in addition to caplacizumab may prevent iTTP recurrence with inhibitor boosting.
{"title":"Frontline use of rituximab may prevent ADAMTS13 inhibitor boosting during caplacizumab treatment in patients with iTTP: post hoc analysis of a phase 2/3 study in Japan.","authors":"Kazunori Imada, Yoshitaka Miyakawa, Satoshi Ichikawa, Hitoji Uchiyama, Yasunori Ueda, Yasuhiro Hashimoto, Masashi Nishimi, Masako Tsukamoto, Sayaka Tahara, Masanori Matsumoto","doi":"10.1186/s12959-024-00642-3","DOIUrl":"10.1186/s12959-024-00642-3","url":null,"abstract":"<p><strong>Background: </strong>A recent Phase 2/3 study in Japanese patients showed that caplacizumab was effective in treating immune-mediated thrombotic thrombocytopenic purpura (iTTP), with a low rate of iTTP recurrence. ADAMTS13 activity is monitored weekly during caplacizumab treatment to guide discontinuation of caplacizumab and consequently avoid exacerbations or relapse. The aim of this study was to assess changes in ADAMTS13 activity/inhibitor levels during caplacizumab treatment in this patient population.</p><p><strong>Methods: </strong>A post hoc analysis of the Phase 2/3 study in Japanese patients was conducted. Patients ≥ 18 years old with confirmed iTTP received 10 mg of caplacizumab daily in conjunction with therapeutic plasma exchange (TPE) and immunosuppression for 30 days post-TPE. Outcomes included time to recovery of ADAMTS13 activity, ADAMTS13 activity level at treatment end, incidence of ADAMTS13 inhibitor re-elevation (ie, inhibitor boosting) during treatment, time to platelet count recovery, number of days of TPE, and safety. Outcomes according to presence of inhibitor boosting were also assessed.</p><p><strong>Results: </strong>Nineteen patients had confirmed iTTP and were included in this analysis. Median (95% confidence interval) time to recovery of ADAMTS13 activity to ≥ 10%, ≥ 20%, and ≥ 60% was 14.6 (5.9-24.8), 18.5 (5.9-31.8), and 47.5 (18.5-60.9) days, respectively. Median (range) ADAMTS13 activity level at caplacizumab treatment end was 62.0% (29.0-101.0). Nine patients had ADAMTS13 inhibitor boosting. Delayed response of ADAMTS13 activity was observed in patients with inhibitor boosting. The median time to platelet count response and median number of TPE days were shorter in patients with inhibitor boosting compared with patients without inhibitor boosting. Rituximab was administered to almost all patients with inhibitor boosting (88.9%), after completion of TPE. Patients without inhibitor boosting who were treated with rituximab received it prior to completion of TPE. Only one patient experienced a recurrence, which occurred shortly after caplacizumab discontinuation due to an adverse event.</p><p><strong>Conclusions: </strong>In patients with iTTP, caplacizumab with TPE and immunosuppression may reduce the risk of ADAMTS13 inhibitor boosting if rituximab is administered early in the iTTP treatment period. Early administration of rituximab in addition to caplacizumab may prevent iTTP recurrence with inhibitor boosting.</p><p><strong>Trial registration: </strong>NCT04074187.</p>","PeriodicalId":22982,"journal":{"name":"Thrombosis Journal","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11297770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction: Outcomes of deep venous thrombosis management and associated factors among patients in tertiary hospitals in Addis Ababa, Ethiopia: a multicenter retrospective cohort study.","authors":"Seble Birhane, Melak Gedamu Beyene, Fishatsion Tadesse, Assefa Mulu Baye","doi":"10.1186/s12959-024-00639-y","DOIUrl":"10.1186/s12959-024-00639-y","url":null,"abstract":"","PeriodicalId":22982,"journal":{"name":"Thrombosis Journal","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11293091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141861031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Inherited antithrombin, protein C, and protein S deficiency increase the risk of venous thromboembolism. The presence of defects can be identified by clinical laboratory assays. In most Chinese clinical laboratories, the screening tests for antithrombin, protein C, and protein S deficiency are their activity assays. Ensuring appropriate pre-analytical storage conditions for activity tests is essential. This study aimed to assess the effects of storage conditions on antithrombin, protein C, and protein S activity in frozen plasma.
Methods: We collected the remaining plasma of 29 patients. The baseline of antithrombin, protein C, and protein S activity values were tested within 4 h. Then, each sample was sub-packaged into 4 EP tubes, and was stored at -20 °C for 3 days, -20 °C for 7 days, -80 °C for 3 days, and - 80 °C for 7 days, respectively. After thawing, samples were tested by two systems.
Results: The percentage deviation of antithrombin and protein C activity assay was<10% compared with the initial values. Protein S activity showed a significant reduction in frozen plasma, with a deviation > 10%. Some samples, initially within the normal range, were classified as abnormal after freezing storage.
Conclusions: Our study indicated that antithrombin and protein C remain stable when stored at -20 °C or -80 °C in a week. We argued that Protein S activity is not stable in frozen plasma. The use of frozen-thawed plasma for PS activity assay may result in overdiagnosis of protein S deficiency.
背景:遗传性抗凝血酶、蛋白 C 和蛋白 S 缺乏症会增加静脉血栓栓塞的风险。临床实验室检测可确定是否存在缺陷。在大多数中国临床实验室中,抗凝血酶、蛋白 C 和蛋白 S 缺乏症的筛查试验是其活性测定。确保活性检测的适当分析前储存条件至关重要。本研究旨在评估储存条件对冷冻血浆中抗凝血酶、蛋白 C 和蛋白 S 活性的影响:方法:我们收集了 29 名患者的剩余血浆。然后将每个样本分装到 4 个 EP 管中,分别在 -20 °C 下保存 3 天、-20 °C 下保存 7 天、-80 °C 下保存 3 天和 -80 °C 下保存 7 天。解冻后,用两个系统对样本进行检测:抗凝血酶和蛋白 C 活性检测的偏差率为 10%。结果:抗凝血酶和蛋白 C 活性测定的偏差百分比为 10%,一些最初在正常范围内的样本在冷冻储存后被归类为异常:我们的研究表明,抗凝血酶和蛋白 C 在-20 °C或-80 °C储存一周后仍保持稳定。我们认为,蛋白 S 活性在冷冻血浆中并不稳定。使用冷冻解冻血浆进行 PS 活性检测可能会导致蛋白 S 缺乏症的过度诊断。
{"title":"Effect of frozen storage conditions on antithrombin protein C and protein S activity assay stability.","authors":"Houmei Feng, Danyu Song, Qiang Xu, Xiaohui Cai, Jianru Liu, Yang Zhang, Zhou Zhou","doi":"10.1186/s12959-024-00640-5","DOIUrl":"10.1186/s12959-024-00640-5","url":null,"abstract":"<p><strong>Background: </strong>Inherited antithrombin, protein C, and protein S deficiency increase the risk of venous thromboembolism. The presence of defects can be identified by clinical laboratory assays. In most Chinese clinical laboratories, the screening tests for antithrombin, protein C, and protein S deficiency are their activity assays. Ensuring appropriate pre-analytical storage conditions for activity tests is essential. This study aimed to assess the effects of storage conditions on antithrombin, protein C, and protein S activity in frozen plasma.</p><p><strong>Methods: </strong>We collected the remaining plasma of 29 patients. The baseline of antithrombin, protein C, and protein S activity values were tested within 4 h. Then, each sample was sub-packaged into 4 EP tubes, and was stored at -20 °C for 3 days, -20 °C for 7 days, -80 °C for 3 days, and - 80 °C for 7 days, respectively. After thawing, samples were tested by two systems.</p><p><strong>Results: </strong>The percentage deviation of antithrombin and protein C activity assay was<10% compared with the initial values. Protein S activity showed a significant reduction in frozen plasma, with a deviation > 10%. Some samples, initially within the normal range, were classified as abnormal after freezing storage.</p><p><strong>Conclusions: </strong>Our study indicated that antithrombin and protein C remain stable when stored at -20 °C or -80 °C in a week. We argued that Protein S activity is not stable in frozen plasma. The use of frozen-thawed plasma for PS activity assay may result in overdiagnosis of protein S deficiency.</p>","PeriodicalId":22982,"journal":{"name":"Thrombosis Journal","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11285460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141793578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-29DOI: 10.1186/s12959-024-00638-z
Jia-Long Li, Kristine J S Kwan, Xue-Guang Lin, Jie Wang, Bo Chen, Yi-Jie Lu, Bo Wang, Shi-Shuai Xie, Jiong Zhou, Bo Yu, Ying Deng, Shuai Jiang, Jing-Dong Tang
Objective: Thromboangiitis obliterans (TAO) remains clinical challenging due to its rarity and underwhelming management outcomes. This study aimed to describe a novel TAO rabbit model that demonstrates a closer resemblance to TAO.
Methods: Thirty-six New Zealand rabbits underwent the surgical implantation of calibrated gelatin sponge particles (CGSPs) into their right femoral artery. The CGSPs were soaked in different solutions to simulate different types of thrombi: normal (NT; normal saline); inflammatory TAO thrombus (TAO; dimethylsulfoxide [DMSO]), and DMSO with methotrexate (MTX). All groups underwent clinical assessment, digital subtraction angiography (DSA) and histopathological analysis at time points day 0 (immediate), week 1 (acute), week 2 (subacute), and week 4 (chronic).
Results: The TAO rabbit presented with signs of ischemia of the right digit at week 4. On DSA, the TAO rabbits exhibited formation of corkscrew collaterals starting week 1. On H&E staining, gradual CGSP degradation was observed along with increased red blood cell aggregation and inflammatory cells migration in week 1. On week 2, disorganization of the tunica media layer and vascular smooth muscle cell (VSMC) proliferation was observed. In the TAO rabbit, migrated VSMCs, inflammatory cells, and extracellular matrix with collagen-like substances gradually occluded the lumen. On week 4, the arterial lumen of the TAO rabbit was filled with relatively-organized VSMC and endothelial cell clusters with less inflammatory cells. Neorevascularization was found in the MTX-treated group.
Conclusion: The novel TAO rabbit model shows a closer resemblance to human TAO clinically, radiographically, and histopathologically. Histological analysis of the IT progression in the TAO model suggests that it is of VSMC origin.
目的:血栓闭塞性脉管炎(TAO)由于其罕见性和治疗效果不佳,在临床上仍具有挑战性。本研究旨在描述一种新型 TAO 兔模型,该模型与 TAO 更为相似:方法:36 只新西兰兔通过手术将校准明胶海绵颗粒(CGSPs)植入右股动脉。CGSP浸泡在不同的溶液中,以模拟不同类型的血栓:正常血栓(NT;生理盐水);炎性TAO血栓(TAO;二甲基亚砜[DMSO]);以及含有甲氨蝶呤(MTX)的二甲基亚砜。所有组别都在第0天(即刻)、第1周(急性)、第2周(亚急性)和第4周(慢性)进行了临床评估、数字减影血管造影(DSA)和组织病理学分析:结果:TAO 兔在第 4 周出现右手指缺血症状。在 DSA 上,TAO 兔从第 1 周开始出现开瓶器状血管袢的形成。在 H&E 染色上,第 1 周观察到 CGSP 逐渐降解,红细胞聚集和炎性细胞迁移增加。第 2 周,观察到血管内膜中层紊乱和血管平滑肌细胞(VSMC)增殖。在 TAO 兔身上,移行的 VSMC、炎症细胞和含有胶原样物质的细胞外基质逐渐堵塞了管腔。第 4 周,TAO 兔的动脉管腔内充满了相对有序的 VSMC 和内皮细胞簇,炎性细胞较少。结论:结论:新型 TAO 兔模型在临床、影像学和组织病理学方面与人类 TAO 更为相似。对 TAO 模型中 IT 进展的组织学分析表明,它是由 VSMC 引起的。
{"title":"The Buerger's rabbit model: a closer step to unravelling thromboangiitis obliterans?","authors":"Jia-Long Li, Kristine J S Kwan, Xue-Guang Lin, Jie Wang, Bo Chen, Yi-Jie Lu, Bo Wang, Shi-Shuai Xie, Jiong Zhou, Bo Yu, Ying Deng, Shuai Jiang, Jing-Dong Tang","doi":"10.1186/s12959-024-00638-z","DOIUrl":"10.1186/s12959-024-00638-z","url":null,"abstract":"<p><strong>Objective: </strong>Thromboangiitis obliterans (TAO) remains clinical challenging due to its rarity and underwhelming management outcomes. This study aimed to describe a novel TAO rabbit model that demonstrates a closer resemblance to TAO.</p><p><strong>Methods: </strong>Thirty-six New Zealand rabbits underwent the surgical implantation of calibrated gelatin sponge particles (CGSPs) into their right femoral artery. The CGSPs were soaked in different solutions to simulate different types of thrombi: normal (NT; normal saline); inflammatory TAO thrombus (TAO; dimethylsulfoxide [DMSO]), and DMSO with methotrexate (MTX). All groups underwent clinical assessment, digital subtraction angiography (DSA) and histopathological analysis at time points day 0 (immediate), week 1 (acute), week 2 (subacute), and week 4 (chronic).</p><p><strong>Results: </strong>The TAO rabbit presented with signs of ischemia of the right digit at week 4. On DSA, the TAO rabbits exhibited formation of corkscrew collaterals starting week 1. On H&E staining, gradual CGSP degradation was observed along with increased red blood cell aggregation and inflammatory cells migration in week 1. On week 2, disorganization of the tunica media layer and vascular smooth muscle cell (VSMC) proliferation was observed. In the TAO rabbit, migrated VSMCs, inflammatory cells, and extracellular matrix with collagen-like substances gradually occluded the lumen. On week 4, the arterial lumen of the TAO rabbit was filled with relatively-organized VSMC and endothelial cell clusters with less inflammatory cells. Neorevascularization was found in the MTX-treated group.</p><p><strong>Conclusion: </strong>The novel TAO rabbit model shows a closer resemblance to human TAO clinically, radiographically, and histopathologically. Histological analysis of the IT progression in the TAO model suggests that it is of VSMC origin.</p>","PeriodicalId":22982,"journal":{"name":"Thrombosis Journal","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11285203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141793579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-24DOI: 10.1186/s12959-024-00633-4
Zhencan Lin, Hao Sun, Meiyi Chen, Deng Li, Zhiqing Cai, Yimin Wang, Jie Xu, Ruofan Ma
Purpose: This study aims to investigate the potential role of Caprini risk assessment model (RAM) in predicting the risk of venous thromboembolism (VTE) in patients undergoing total hip or knee arthroplasty (THA/TKA). No national study has investigated the role of Caprini RAM after primary THA/TKA.
Methods: Data from The National Sample of Healthcare Cost and Utilization Project (HCUP) in 2019 were utilized for this study. The dataset consisted of 229,134 patients who underwent primary THA/TKA. Deep vein thrombosis (DVT) and pulmonary embolism (PE) were considered as VTE. The incidence of thrombosis was calculated based on different Caprini scores, and the risk of the Caprini indicator for VTE events was evaluated using a forest plot.
Results: The prevalence of VTE after primary THA/TKA in the U.S. population in 2019 was found to be 4.7 cases per 1000 patients. Age, body mass index (BMI), and Caprini score showed a positive association with the risk of VTE (P < 0.05). The receiver operating characteristic (ROC) curve analysis indicated that a Caprini score of 9.5 had a sensitivity of 47.2% and a specificity of 82.7%, with an area under the curve (AUC) of 0.693 (95% CI, 0.677-0.710). The highest Youden index was 0.299. Multivariate logistic regression analysis revealed that malignancy, varicose vein, positive blood test for thrombophilia, history of thrombosis, COPD, hip fracture, blood transfusion, and age were significant risk factors for VTE. Based on these findings, a new risk stratification system incorporating the Caprini score was proposed.
Conclusions: Although the Caprini score does not seem to be a good predictive model for VTE after primary THA/TKA, new risk stratification for the Caprini score is proposed to increase its usefulness.
{"title":"Utilization of the Caprini risk assessment model(RAM) to predict venous thromboembolism after primary hip and knee arthroplasty: an analysis of the Healthcare Cost and Utilization Project(HCUP).","authors":"Zhencan Lin, Hao Sun, Meiyi Chen, Deng Li, Zhiqing Cai, Yimin Wang, Jie Xu, Ruofan Ma","doi":"10.1186/s12959-024-00633-4","DOIUrl":"10.1186/s12959-024-00633-4","url":null,"abstract":"<p><strong>Purpose: </strong>This study aims to investigate the potential role of Caprini risk assessment model (RAM) in predicting the risk of venous thromboembolism (VTE) in patients undergoing total hip or knee arthroplasty (THA/TKA). No national study has investigated the role of Caprini RAM after primary THA/TKA.</p><p><strong>Methods: </strong>Data from The National Sample of Healthcare Cost and Utilization Project (HCUP) in 2019 were utilized for this study. The dataset consisted of 229,134 patients who underwent primary THA/TKA. Deep vein thrombosis (DVT) and pulmonary embolism (PE) were considered as VTE. The incidence of thrombosis was calculated based on different Caprini scores, and the risk of the Caprini indicator for VTE events was evaluated using a forest plot.</p><p><strong>Results: </strong>The prevalence of VTE after primary THA/TKA in the U.S. population in 2019 was found to be 4.7 cases per 1000 patients. Age, body mass index (BMI), and Caprini score showed a positive association with the risk of VTE (P < 0.05). The receiver operating characteristic (ROC) curve analysis indicated that a Caprini score of 9.5 had a sensitivity of 47.2% and a specificity of 82.7%, with an area under the curve (AUC) of 0.693 (95% CI, 0.677-0.710). The highest Youden index was 0.299. Multivariate logistic regression analysis revealed that malignancy, varicose vein, positive blood test for thrombophilia, history of thrombosis, COPD, hip fracture, blood transfusion, and age were significant risk factors for VTE. Based on these findings, a new risk stratification system incorporating the Caprini score was proposed.</p><p><strong>Conclusions: </strong>Although the Caprini score does not seem to be a good predictive model for VTE after primary THA/TKA, new risk stratification for the Caprini score is proposed to increase its usefulness.</p>","PeriodicalId":22982,"journal":{"name":"Thrombosis Journal","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11267675/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141761052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thrombocytopenia frequently occurs in patients with sepsis. Disseminated intravascular coagulation (DIC) may be a possible cause of thrombocytopenia owing to its high prevalence and association with poor outcomes; however, it is important to keep the presence of other diseases in mind in sepsis practice. Thrombotic microangiopathy (TMA), which is characterized by thrombotic thrombocytopenic purpura, Shiga toxin-producing Escherichia coli hemolytic uremic syndrome (HUS), and complement-mediated HUS, is characterized by thrombocytopenia, microangiopathic hemolytic anemia, and organ damage. TMA has become widely recognized in recent years because of the development of specific treatments. Previous studies have reported a remarkably lower prevalence of TMA than DIC; however, its epidemiology is not well defined, and there may be cases in which TMA is not correctly diagnosed, resulting in poor outcomes. Therefore, it is important to differentiate DIC from TMA. Nevertheless, differentiating between DIC and TMA remains a challenge as indicated by previous reports that most patients with TMA can be diagnosed as DIC using the universal coagulation scoring system. Several algorithms to differentiate sepsis-related DIC from TMA have been suggested, contributing to improving the care of septic patients with thrombocytopenia; however, it may be difficult to apply these algorithms to patients with coexisting DIC and TMA, which has recently been reported. This review describes the disease characteristics, including epidemiology, pathophysiology, and treatment, of DIC, TMA, and other diseases with thrombocytopenia and proposes a novel practical approach flow, which is characterized by the initiation of the diagnosis of TMA in parallel with the diagnosis of DIC. This practical flow also refers to the longitudinal diagnosis and treatment flow with TMA in mind and real clinical timeframes. In conclusion, we aim to widely disseminate the results of this review that emphasize the importance of incorporating consideration of TMA in the management of septic DIC. We anticipate that this practical new approach for the diagnostic and treatment flow will lead to the appropriate diagnosis and treatment of complex cases, improve patient outcomes, and generate new epidemiological evidence regarding TMA.
{"title":"Practical approach to thrombocytopenia in patients with sepsis: a narrative review","authors":"Kasumi Satoh, Takeshi Wada, Akihito Tampo, Gaku Takahashi, Kota Hoshino, Hironori Matsumoto, Takayuki Taira, Satoshi Kazuma, Takamitsu Masuda, Takashi Tagami, Hiroyasu Ishikura","doi":"10.1186/s12959-024-00637-0","DOIUrl":"https://doi.org/10.1186/s12959-024-00637-0","url":null,"abstract":"Thrombocytopenia frequently occurs in patients with sepsis. Disseminated intravascular coagulation (DIC) may be a possible cause of thrombocytopenia owing to its high prevalence and association with poor outcomes; however, it is important to keep the presence of other diseases in mind in sepsis practice. Thrombotic microangiopathy (TMA), which is characterized by thrombotic thrombocytopenic purpura, Shiga toxin-producing Escherichia coli hemolytic uremic syndrome (HUS), and complement-mediated HUS, is characterized by thrombocytopenia, microangiopathic hemolytic anemia, and organ damage. TMA has become widely recognized in recent years because of the development of specific treatments. Previous studies have reported a remarkably lower prevalence of TMA than DIC; however, its epidemiology is not well defined, and there may be cases in which TMA is not correctly diagnosed, resulting in poor outcomes. Therefore, it is important to differentiate DIC from TMA. Nevertheless, differentiating between DIC and TMA remains a challenge as indicated by previous reports that most patients with TMA can be diagnosed as DIC using the universal coagulation scoring system. Several algorithms to differentiate sepsis-related DIC from TMA have been suggested, contributing to improving the care of septic patients with thrombocytopenia; however, it may be difficult to apply these algorithms to patients with coexisting DIC and TMA, which has recently been reported. This review describes the disease characteristics, including epidemiology, pathophysiology, and treatment, of DIC, TMA, and other diseases with thrombocytopenia and proposes a novel practical approach flow, which is characterized by the initiation of the diagnosis of TMA in parallel with the diagnosis of DIC. This practical flow also refers to the longitudinal diagnosis and treatment flow with TMA in mind and real clinical timeframes. In conclusion, we aim to widely disseminate the results of this review that emphasize the importance of incorporating consideration of TMA in the management of septic DIC. We anticipate that this practical new approach for the diagnostic and treatment flow will lead to the appropriate diagnosis and treatment of complex cases, improve patient outcomes, and generate new epidemiological evidence regarding TMA.","PeriodicalId":22982,"journal":{"name":"Thrombosis Journal","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141740684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: This research is one of the pioneering randomized clinical trials (RCTs) aimed at assessing the effectiveness and safety of rivaroxaban in treating left ventricular thrombus (LVT) in patients who have experienced acute coronary syndrome (ACS).
Materials and methods: This is a randomized, controlled, interventional, open-label study. The patients were randomly divided into warfarin and rivaroxaban groups. We performed transthoracic echocardiography at the start of the study and again after three months to measure the thrombus area in square millimeters. The morphology of the thrombus was categorized into mural and round, and the mobility was classified into immobile, semi-mobile and hypermobile. We also monitored for adverse events including bleeding, systemic embolic occurrences, rehospitalization, and major adverse cardiac events (MACE).
Results: The study included fifty-two patients in the intention-to-treat analysis, with an equal split between the rivaroxaban and warfarin groups (26 patients each). The average follow-up duration was three months. The thrombus resolution rates in the rivaroxaban (76.9%) and warfarin (69.2%) groups, as well as the thrombus size reduction, did not show statistical significance between groups. All semi-mobile or hypermobile thrombi transformed into immobile and all of the round LVTs changed into a mural in both rivaroxaban and warfarin groups. No significant difference was observed in bleeding complications and rehospitalization between the two groups.
Conclusion: The trial demonstrated that rivaroxaban is as effective as warfarin in terms of thrombus resolution rate, reduction in thrombus size, bleeding risk, and rehospitalization rate. Our findings suggest that rivaroxaban is a viable alternative to warfarin for managing left ventricular thrombus.
{"title":"Evaluation of the efficacy and safety of rivaroxaban compared to warfarin in patients with left ventricular apical thrombus: a randomized clinical trial.","authors":"Pejman Mansouri, Zahra Azamian Jazi, Mohammad Hadi Mansouri, Hooman Dehghan, Reihaneh Zavar, Seyedeh Melika Hashemi, Fereshteh Sattar, Masoumeh Sadeghi, Afshin Amirpour, Morteza Abdar","doi":"10.1186/s12959-024-00632-5","DOIUrl":"10.1186/s12959-024-00632-5","url":null,"abstract":"<p><strong>Introduction: </strong>This research is one of the pioneering randomized clinical trials (RCTs) aimed at assessing the effectiveness and safety of rivaroxaban in treating left ventricular thrombus (LVT) in patients who have experienced acute coronary syndrome (ACS).</p><p><strong>Materials and methods: </strong>This is a randomized, controlled, interventional, open-label study. The patients were randomly divided into warfarin and rivaroxaban groups. We performed transthoracic echocardiography at the start of the study and again after three months to measure the thrombus area in square millimeters. The morphology of the thrombus was categorized into mural and round, and the mobility was classified into immobile, semi-mobile and hypermobile. We also monitored for adverse events including bleeding, systemic embolic occurrences, rehospitalization, and major adverse cardiac events (MACE).</p><p><strong>Results: </strong>The study included fifty-two patients in the intention-to-treat analysis, with an equal split between the rivaroxaban and warfarin groups (26 patients each). The average follow-up duration was three months. The thrombus resolution rates in the rivaroxaban (76.9%) and warfarin (69.2%) groups, as well as the thrombus size reduction, did not show statistical significance between groups. All semi-mobile or hypermobile thrombi transformed into immobile and all of the round LVTs changed into a mural in both rivaroxaban and warfarin groups. No significant difference was observed in bleeding complications and rehospitalization between the two groups.</p><p><strong>Conclusion: </strong>The trial demonstrated that rivaroxaban is as effective as warfarin in terms of thrombus resolution rate, reduction in thrombus size, bleeding risk, and rehospitalization rate. Our findings suggest that rivaroxaban is a viable alternative to warfarin for managing left ventricular thrombus.</p>","PeriodicalId":22982,"journal":{"name":"Thrombosis Journal","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11264466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141727815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-17DOI: 10.1186/s12959-024-00628-1
Yimeng Wang, Yanmin Yang, Lulu Wang, Han Zhang, Jiang-Shan Tan, Yuyuan Shu
Background: This study aimed to describe the status of antithrombotic therapy at discharge and prognosis in patients with atrial fibrillation (AF) and chronic coronary syndrome (CCS) who underwent percutaneous coronary intervention (PCI).
Methods: This was an observational, prospective study. The primary endpoint was major adverse cardiovascular events (MACE), including all-cause death, myocardial infarction, stroke/transient ischemic attach (TIA), systemic embolism or ischemia-driven revascularization. Bleeding events were collected according to the Thrombolysis in Myocardial Infarction (TIMI) criteria.
Results: Between 2017 and 2019, a cohort of 516 patients (mean age 66, [SD 9], of whom 18.4% were female) with AF and CCS who underwent PCI were evaluated, with a median followed-up time of 36 months (Interquartile range: 22-45). MACE events occurred in 13.0% of the patients, while the TIMI bleeding events were observed in 17.4%. Utilization of TAT (triple antithrombotic therapy) (P < 0.001) and oral anticoagulation (OAC) therapy (P < 0.001) increased through years. History of heart failure (HF) (Hazard ratio [HR], 1.744; 95% confidence interval [CI], 1.011-3.038) and TAT (HR, 2.708; 95%CI, 1.653-4.436) had independent associations with MACE events. OAC (HR, 10.378; 95%CI, 6.136-17.555) was identified as a risk factor for bleeding events. A higher creatine clearance (HR, 0.986; 95%CI, 0.974-0.997) was associated with a lower incidence of bleeding events.
Conclusions: Antithrombotic therapy has been improved among patients with AF and CCS who underwent PCI these years. History of HF and TAT were independently associated with MACE events. Higher creatine clearance was protective factor of bleeding events, while OAC was a risk factor for TIMI bleeding events.
研究背景本研究旨在描述接受经皮冠状动脉介入治疗(PCI)的心房颤动(AF)和慢性冠状动脉综合征(CCS)患者出院时的抗血栓治疗情况和预后:这是一项前瞻性观察研究。主要终点是主要不良心血管事件(MACE),包括全因死亡、心肌梗死、中风/短暂性脑缺血、全身性栓塞或缺血导致的血管再通。出血事件根据心肌梗死溶栓治疗(TIMI)标准收集:2017年至2019年期间,共评估了516名接受PCI治疗的房颤和CCS患者(平均年龄66岁,[SD 9],其中18.4%为女性),中位随访时间为36个月(四分位间范围:22-45)。13.0%的患者发生了MACE事件,17.4%的患者发生了TIMI出血事件。TAT(三联抗栓疗法)的使用情况(P 结论:近年来,接受PCI治疗的房颤和CCS患者的抗血栓治疗得到了改善。心房颤动病史和 TAT 与 MACE 事件独立相关。较高的肌酸清除率是出血事件的保护因素,而OAC则是TIMI出血事件的风险因素。
{"title":"Antithrombotic therapy at discharge and prognosis in patients with chronic coronary syndrome and atrial fibrillation who underwent PCI: a real-world study.","authors":"Yimeng Wang, Yanmin Yang, Lulu Wang, Han Zhang, Jiang-Shan Tan, Yuyuan Shu","doi":"10.1186/s12959-024-00628-1","DOIUrl":"10.1186/s12959-024-00628-1","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to describe the status of antithrombotic therapy at discharge and prognosis in patients with atrial fibrillation (AF) and chronic coronary syndrome (CCS) who underwent percutaneous coronary intervention (PCI).</p><p><strong>Methods: </strong>This was an observational, prospective study. The primary endpoint was major adverse cardiovascular events (MACE), including all-cause death, myocardial infarction, stroke/transient ischemic attach (TIA), systemic embolism or ischemia-driven revascularization. Bleeding events were collected according to the Thrombolysis in Myocardial Infarction (TIMI) criteria.</p><p><strong>Results: </strong>Between 2017 and 2019, a cohort of 516 patients (mean age 66, [SD 9], of whom 18.4% were female) with AF and CCS who underwent PCI were evaluated, with a median followed-up time of 36 months (Interquartile range: 22-45). MACE events occurred in 13.0% of the patients, while the TIMI bleeding events were observed in 17.4%. Utilization of TAT (triple antithrombotic therapy) (P < 0.001) and oral anticoagulation (OAC) therapy (P < 0.001) increased through years. History of heart failure (HF) (Hazard ratio [HR], 1.744; 95% confidence interval [CI], 1.011-3.038) and TAT (HR, 2.708; 95%CI, 1.653-4.436) had independent associations with MACE events. OAC (HR, 10.378; 95%CI, 6.136-17.555) was identified as a risk factor for bleeding events. A higher creatine clearance (HR, 0.986; 95%CI, 0.974-0.997) was associated with a lower incidence of bleeding events.</p><p><strong>Conclusions: </strong>Antithrombotic therapy has been improved among patients with AF and CCS who underwent PCI these years. History of HF and TAT were independently associated with MACE events. Higher creatine clearance was protective factor of bleeding events, while OAC was a risk factor for TIMI bleeding events.</p>","PeriodicalId":22982,"journal":{"name":"Thrombosis Journal","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11253490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141634582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-16DOI: 10.1186/s12959-024-00635-2
Haichuan Guo, Chengsi Li, Hao Wu, Meixin Ma, Ruoxuan Zhu, Maolin Wang, Bin Yang, Naihao Pan, Yanbin Zhu, Juan Wang
Background: The association of low-density lipoprotein cholesterol (LDL-C) and lymphocyte counts with the development of deep vein thrombosis (DVT) has been demonstrated in many fields but remains lacking in open wedge high tibial osteotomy (OWHTO). This study aimed to assess the predictive value of LDL-C to lymphocyte count ratio (LLR) in screening for postoperative new-onset DVT.
Methods: Clinical data were retrospectively collected from patients who underwent OWHTO between June 2018 and May 2023. The limited restricted cubic spline (RCS) was conducted to evaluate the nonlinear relationship between LLR and the risk of postoperative new-onset DVT. The receiver operating characteristic (ROC) curves were plotted and the predictive value of biomarkers was assessed. After adjusting for intergroup confounders by propensity score matching, the univariate logistic regression was applied to assess the association between LLR and DVT.
Results: 1293 eligible patients were included. RCS analysis showed a linear positive correlation between LLR and the risk of DVT (P for overall = 0.008). We identified LLR had an area under the curve of 0.607, accuracy of 74.3%, sensitivity of 38.5%, and specificity of 80.7%, and LLR > 1.75 was independently associated with a 1.45-fold risk of DVT (95% CI: 1.01-2.08, P = 0.045). Furthermore, significant heterogeneities were observed in the subgroups of age, BMI, diabetes mellitus, hypertension, Kellgren-Lawrence grade, the American Society of Anesthesiologists (ASA) score, and intraoperative osteotomy correction size.
Conclusion: LLR is a valuable biomarker for predicting postoperative new-onset DVT in patients with OWHTO, and routine screening is expected to yield positive benefits.
{"title":"Low-density lipoprotein cholesterol-to-lymphocyte count ratio (LLR) is a promising novel predictor of postoperative new-onset deep vein thrombosis following open wedge high tibial osteotomy: a propensity score-matched analysis.","authors":"Haichuan Guo, Chengsi Li, Hao Wu, Meixin Ma, Ruoxuan Zhu, Maolin Wang, Bin Yang, Naihao Pan, Yanbin Zhu, Juan Wang","doi":"10.1186/s12959-024-00635-2","DOIUrl":"10.1186/s12959-024-00635-2","url":null,"abstract":"<p><strong>Background: </strong>The association of low-density lipoprotein cholesterol (LDL-C) and lymphocyte counts with the development of deep vein thrombosis (DVT) has been demonstrated in many fields but remains lacking in open wedge high tibial osteotomy (OWHTO). This study aimed to assess the predictive value of LDL-C to lymphocyte count ratio (LLR) in screening for postoperative new-onset DVT.</p><p><strong>Methods: </strong>Clinical data were retrospectively collected from patients who underwent OWHTO between June 2018 and May 2023. The limited restricted cubic spline (RCS) was conducted to evaluate the nonlinear relationship between LLR and the risk of postoperative new-onset DVT. The receiver operating characteristic (ROC) curves were plotted and the predictive value of biomarkers was assessed. After adjusting for intergroup confounders by propensity score matching, the univariate logistic regression was applied to assess the association between LLR and DVT.</p><p><strong>Results: </strong>1293 eligible patients were included. RCS analysis showed a linear positive correlation between LLR and the risk of DVT (P for overall = 0.008). We identified LLR had an area under the curve of 0.607, accuracy of 74.3%, sensitivity of 38.5%, and specificity of 80.7%, and LLR > 1.75 was independently associated with a 1.45-fold risk of DVT (95% CI: 1.01-2.08, P = 0.045). Furthermore, significant heterogeneities were observed in the subgroups of age, BMI, diabetes mellitus, hypertension, Kellgren-Lawrence grade, the American Society of Anesthesiologists (ASA) score, and intraoperative osteotomy correction size.</p><p><strong>Conclusion: </strong>LLR is a valuable biomarker for predicting postoperative new-onset DVT in patients with OWHTO, and routine screening is expected to yield positive benefits.</p>","PeriodicalId":22982,"journal":{"name":"Thrombosis Journal","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11250942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141627738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-12DOI: 10.1186/s12959-024-00636-1
Limei Lu, Ya Shen, Yuping Pan
Background: Deep vein thrombosis (DVT) is common in patients undergoing gynecological surgery. We aimed to investigate the preventive efficacy in DVT of graduated compression stockings (GCS) alone and in combination with intermittent pneumatic compression (GCS + IPC) after gynecological surgery.
Methods: In November 2022, studies on the use of GCS and GCS + IPC for the prevention of DVT after gynecological surgery were searched in seven databases. After literature screening and data extraction based on specific inclusion and exclusion criteria, preventive efficacies, including the risk of DVT and anticoagulation function, of GCS and GCS + IPC were compared. Finally, sensitivity analysis and Egger's test were performed to evaluate the stability of the meta-analysis.
Results: Six publications with moderate quality were included in this meta-analysis. The results showed that GCS + IPC significantly reduced DVT risk (P = 0.0002) and D-dimer levels (P = 0.0005) compared with GCS alone. Sensitivity analysis and Egger's test showed that the combined results of this study were stable and reliable.
Conclusions: Compared with GCS alone, GCS + IPS showed a higher preventive efficacy against DVT in patients following gynecological surgery.
{"title":"Combination of graduated compression stockings and intermittent pneumatic compression is better in preventing deep venous thrombosis than graduated compression stockings alone for patients following gynecological surgery: a meta-analysis.","authors":"Limei Lu, Ya Shen, Yuping Pan","doi":"10.1186/s12959-024-00636-1","DOIUrl":"10.1186/s12959-024-00636-1","url":null,"abstract":"<p><strong>Background: </strong>Deep vein thrombosis (DVT) is common in patients undergoing gynecological surgery. We aimed to investigate the preventive efficacy in DVT of graduated compression stockings (GCS) alone and in combination with intermittent pneumatic compression (GCS + IPC) after gynecological surgery.</p><p><strong>Methods: </strong>In November 2022, studies on the use of GCS and GCS + IPC for the prevention of DVT after gynecological surgery were searched in seven databases. After literature screening and data extraction based on specific inclusion and exclusion criteria, preventive efficacies, including the risk of DVT and anticoagulation function, of GCS and GCS + IPC were compared. Finally, sensitivity analysis and Egger's test were performed to evaluate the stability of the meta-analysis.</p><p><strong>Results: </strong>Six publications with moderate quality were included in this meta-analysis. The results showed that GCS + IPC significantly reduced DVT risk (P = 0.0002) and D-dimer levels (P = 0.0005) compared with GCS alone. Sensitivity analysis and Egger's test showed that the combined results of this study were stable and reliable.</p><p><strong>Conclusions: </strong>Compared with GCS alone, GCS + IPS showed a higher preventive efficacy against DVT in patients following gynecological surgery.</p>","PeriodicalId":22982,"journal":{"name":"Thrombosis Journal","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11245769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141601867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}