Thrombosis Update最新文献

{"title":"The interplay between inflammation and thrombosis in COVID-19: Mechanisms, therapeutic strategies, and challenges","authors":"Li Ma,&nbsp;Joanne Willey","doi":"10.1016/j.tru.2022.100117","DOIUrl":"10.1016/j.tru.2022.100117","url":null,"abstract":"<div><p>Coronavirus disease 2019 (COVID-19), caused by a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can cause life-threatening pathology characterized by a dysregulated immune response and coagulopathy. While respiratory failure induced by inflammation is the most common cause of death, micro-and macrovascular thrombosis leading to multiple organ failure are also causes of mortality. Dysregulation of systemic inflammation observed in severe COVID-19 patients is manifested by cytokine release syndrome (CRS) - the aberrant release of high levels of proinflammatory cytokines, such as IL-6, IL-1, TNFα, MP-1, as well as complement. CRS is often accompanied by activation of endothelial cells and platelets, coupled with perturbation of the balance between the pro-and antithrombotic mechanisms, resulting in thrombosis. Inflammation and thrombosis form a vicious circle, contributing to morbidity and mortality. Treatment of hyperinflammation has been shown to decrease thrombosis, while anti-thrombotic treatment also downregulates cytokine release. This review highlights the relationship between COVID-19-mediated systemic inflammation and thrombosis, the molecular pathways involved, the therapies targeting these processes, and the challenges currently encountered.</p></div>","PeriodicalId":34401,"journal":{"name":"Thrombosis Update","volume":"8 ","pages":"Article 100117"},"PeriodicalIF":0.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666572722000219/pdfft?md5=f79d481acb4ac1194c057376d268f18e&pid=1-s2.0-S2666572722000219-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44333445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Downregulation of thrombomodulin-thrombin-activated protein C pathway as a mechanism for SARS-CoV-2 induced endotheliopathy and microvascular thrombosis","authors":"S. Agarwal ,&nbsp;C.T. Cohen ,&nbsp;M. Zobeck ,&nbsp;P.M. Jacobi ,&nbsp;S.E. Sartain","doi":"10.1016/j.tru.2022.100116","DOIUrl":"10.1016/j.tru.2022.100116","url":null,"abstract":"<div><p>There is emerging evidence of microvascular thrombosis and thrombotic microangiopathy (TMA) induced by COVID-19, presumably from endothelial injury. Thrombomodulin (TM) is an endothelial glycoprotein that plays a dual role in maintaining healthy endothelium-as a natural anticoagulant by binding thrombin to activate protein C (APC) and a negative regulator of the alternate complement pathway (AP). TM is shed into the plasma as soluble TM (sTM) during endothelial injury.</p><p>We hypothesize that SARS-CoV-2 spike proteins cause direct microvascular endothelial injury, leading to TM shedding, decreased activation of PC, and consequently, microvascular thrombosis in COVID-19. We conducted this study twofold: 1) <em>in vivo</em>, we assessed endothelial injury (by measuring sTM) and AP activation by quantifying Ba (cleavage product of AP component Factor B) in a cohort of critically ill COVID-19 pediatric patients and the implications on clinical outcomes; and 2)<em>in vitro,</em> we investigated endothelial injury (TM shedding) by SARS-COV-2 spike proteins and the subsequent functional consequence in activated PC (APC) levels and Ba levels.</p><p>sTM and Ba in plasma samples from SARS-CoV-2 positive patients admitted to Texas Children's Hospital Pediatric Intensive Care Unit (n = 33) and from healthy controls (n = 38) were measured by ELISA. <em>In vitro,</em> confluent glomerular microvascular endothelial cells (GMVECs) were incubated for 48 h in the presence or absence (control) of purified SARS-CoV-2 spike proteins, S1 and S2. TM from the cell lysates while Ba and APC from the cell supernatants were measured by ELISA. sTM and Ba levels were significantly higher in the COVID-19 pediatric patients compared to healthy controls (p &lt; 0.01 and p &lt; 0.001, respectively). Among the COVID-19 patients, elevated sTM was associated with increased vasopressor use (p = 0.01) and elevated Ba was associated with increased duration of mechanical ventilation (p = 0.04). <em>In vitro</em>, surface bound TM and soluble APC were significantly lower in GMVECs after addition of spike proteins (p &lt; 0.05), while Ba was undetectable in both control and spike proteins exposed GMVECs.</p><p>In conclusion, we provide evidence of endothelial injury in COVID-19 pediatric patients and demonstrate a potential pathway of SARS-CoV-2 induced thrombosis. Decreased surface-bound TM results in lower amount of thrombin-TM complex, hence lesser activation of PC, likely leading to a pro-thrombotic state. These findings in GMVECs could explain the vulnerability of kidneys to COVID-19-induced TMA.</p></div>","PeriodicalId":34401,"journal":{"name":"Thrombosis Update","volume":"8 ","pages":"Article 100116"},"PeriodicalIF":0.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666572722000207/pdfft?md5=a1b4b1be35b9b0b7ed8e178dfe19d1d2&pid=1-s2.0-S2666572722000207-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44689326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using weighted harmonic mean for prediction of APTT in the mixing test","authors":"Mitsuhiro Uchiba,&nbsp;Masao Matsuoka","doi":"10.1016/j.tru.2022.100114","DOIUrl":"https://doi.org/10.1016/j.tru.2022.100114","url":null,"abstract":"<div><h3>Background</h3><p>The mixing test of activated partial thromboplastin time (APTT) is used for differentiating factor deficiency (FD), lupus anticoagulant (LAC), and acquired hemophilia A (AHA). However, the interpretation of the mixing test is not fully standardized.</p></div><div><h3>Objectives</h3><p>The aim of this study was to determine whether the weighted harmonic mean predicts the APTT in mixture of a mixing test samples and is useful for the differentiation of FD, LAC, and AHA.</p></div><div><h3>Patients/methods</h3><p>We examined 27 FD, 26 LAC, and 18 AHA samples. Harmonic means of APTT were calculated from the clotting times with and without 2 h incubation. We defined the index of harmonic mean (IHM) as the ratio of the actual APTT to the predicted APTT calculated by the harmonic mean. We defined IHM of the measured immediate after mixing samples and of delayed (after 2 h of incubation) measured samples as IHMi and IHMd respectively.</p></div><div><h3>Results</h3><p>Actual APTT and predicted APTT were correlated in the FD group. Both IHMi and IHMd in the FD group were equal or lower than 1.02, whereas those in the LAC group were higher than 1.02. In the AHA group, the IHMd was higher than 1.02, whereas half of the IHMi were equal or lower than 1.02. Time dependent inhibition evaluated by IHMd/IHMi was not observed in the LAC group, whereas it was observed in 77% of participants in the AHA group.</p></div><div><h3>Conclusions</h3><p>The harmonic mean was potentially useful in predicting APTT in the mixing test, and the IHM calculated from the predicted APTT had differentiation potency for FD and LAC, and for FD and AHA. IHM was also available for partial differentiation of LAC to AHA.</p></div>","PeriodicalId":34401,"journal":{"name":"Thrombosis Update","volume":"8 ","pages":"Article 100114"},"PeriodicalIF":0.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666572722000189/pdfft?md5=6106d24d8777844293cd53466f8e5c56&pid=1-s2.0-S2666572722000189-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"137276198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The thrombotic spectrum of B-thalassemia","authors":"Mavra Vasilopoulou,&nbsp;Christos Stafylidis,&nbsp;Marianna Politou","doi":"10.1016/j.tru.2022.100102","DOIUrl":"https://doi.org/10.1016/j.tru.2022.100102","url":null,"abstract":"<div><p>B-thalassemia is one of the most common recessive monogenic disorders, characterized by phenotypic diversity, lifelong treatment and severe complications. Apart from anemia, extramedullary erythropoiesis with skeletal deformities, iron overload and organ damage, hypercoagulability with subsequent thromboembolic events (TEE) has also been recognized as a fundamental feature of the disease. The pathophysiological mechanisms involved in TEE include damaged thalassemic RBC membranes as well as platelet and endothelial activation. Additionally, the fluctuation in the severity of the disease and therapeutic choices seem to influence the hemostatic balance in these patients, as transfusion-independence and splenectomy are documented risk factors for TEE. Insufficient data exist for the management and prevention of thrombotic risk in thalassemia and an imperative need to develop explicit guidelines emerges. In this review, we provide an insight in the pathophysiology of thrombosis in β-thalassemia, further discussing the available clinical evidence for optimal treatment strategies.</p></div>","PeriodicalId":34401,"journal":{"name":"Thrombosis Update","volume":"7 ","pages":"Article 100102"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666572722000062/pdfft?md5=07b07d9d8317ee33e8499be053931ec4&pid=1-s2.0-S2666572722000062-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72256305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Feasibility study of the Fearon Algorithm in anticoagulation service guided warfarin management","authors":"John Saunders ,&nbsp;Sara R. Vazquez ,&nbsp;Aubrey E. Jones ,&nbsp;J. Michael Fearon ,&nbsp;Paul Wegener ,&nbsp;Aaron Wilson ,&nbsp;Daniel M. Witt","doi":"10.1016/j.tru.2022.100105","DOIUrl":"10.1016/j.tru.2022.100105","url":null,"abstract":"<div><h3>Background</h3><p>Patients receiving warfarin who spend a lower proportion of time in therapeutic international normalized ratio (INR) range (TTR) have a higher risk of both bleeding complications and thromboembolic events. Using warfarin dosing algorithms is one intervention associated with improved INR stability.</p></div><div><h3>Objective</h3><p>To determine the feasibility of an individualized warfarin dosing algorithm (Fearon Algorithm) under anticoagulation management service (AMS) care and compare measures of INR control using the algorithm with standard care.</p></div><div><h3>Methods</h3><p>A pre/post intervention feasibility study consisting of the 12 months prior to patient enrollment (pre-study phase) and 6 months in which patients used the Fearon Algorithm under the supervision of an AMS pharmacist (AMS phase). The primary study outcome was the change in individual TTR.</p></div><div><h3>Results</h3><p>A total of 30 patients were enrolled in the study, 26 (87%) of whom successfully completed the AMS study phase using the Fearon Algorithm. Median corrected individual TTR increased significantly from 53% (IQR: 39%, 64%) during the year prior to enrollment to 63% (IQR: 57%, 73%) during the AMS phase (p &lt; 0.01) The uncorrected TTR also increased significantly from 52% (IQR: 39%, 64%) to 61% (IQR: 57%, 72%) (p &lt; 0.01). The Fearon Algorithm specified a smaller warfarin tablet strength in half the patients.</p></div><div><h3>Conclusion</h3><p>The Fearon Algorithm is feasible for an AMS to implement in patients receiving long-term warfarin therapy and appears to improve TTR.</p></div>","PeriodicalId":34401,"journal":{"name":"Thrombosis Update","volume":"7 ","pages":"Article 100105"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666572722000098/pdfft?md5=82b74936348d4288a8176e5ac06a5d19&pid=1-s2.0-S2666572722000098-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45688249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thrombosis post-mRNA-based SARS-CoV-2 vaccination (BNT162b2) – Time to think beyond thrombosis with thrombocytopenia syndrome (TTS)","authors":"Zohaib Yousaf ,&nbsp;Fateen Ata ,&nbsp;Riyadh Ali Mohammed Hammamy","doi":"10.1016/j.tru.2022.100104","DOIUrl":"10.1016/j.tru.2022.100104","url":null,"abstract":"<div><p>The COVID-19 pandemic has affected the global socioeconomic and healthcare infrastructure. Vaccines have been the cornerstone in limiting the global spread of the pandemic. However, the mass scale vaccination has resulted in some unanticipated adverse events. Arguably the most serious of these has been the development of widespread thrombosis with viral-vectored vaccines. We present a case of extensive thrombosis associated with the messenger RNA (m-RNA) vaccine.</p></div>","PeriodicalId":34401,"journal":{"name":"Thrombosis Update","volume":"7 ","pages":"Article 100104"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666572722000086/pdfft?md5=7aa4b9e3224a8c5fb865b3c52ec0bc14&pid=1-s2.0-S2666572722000086-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48086436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Successful treatment of acquired von Willebrand syndrome in multiple myeloma","authors":"Sandra Marten ,&nbsp;Raphael Teipel ,&nbsp;Oliver Tiebel ,&nbsp;Karolin Trautmann-Grill","doi":"10.1016/j.tru.2022.100108","DOIUrl":"10.1016/j.tru.2022.100108","url":null,"abstract":"<div><p>Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder characterized by quantitative or qualitative defects of the von Willebrand factor (vWF) with laboratory findings and clinical presentations similar to those of inherited von Willebrand disease (vWD). In contrast to the inherited form, the bleeding disorder is not due to genetic defects of von Willebrand factor. The prevalence of AVWS is poorly defined. Data from reviews, international registry and reference laboratories in Germany suggest a rate of approximately one case of AVWS in every 30–40 samples from patients with confirmed bleeding disorders. An association with different disorders has been described.</p><p>Multiple myeloma (MM) is a malignant plasma cell disorder defined by the accumulation of monoclonal plasma cells in the bone marrow or extramedullary lesions and often accompanied with a monoclonal paraprotein in blood and/or urine.</p><p>Symptomatic myeloma disease requiring treatment is usually characterized by renal failure, anemia or destructive bone lesions. Bleeding due to AVWS as a leading symptom of the disease is uncommon.</p><p>Here we report the case of a patient with MM presenting with significant bleeding from AVWS as primary symptom. Bleeding lasted for several years before diagnostic work-up including a bone marrow puncture revealed MM. Myeloma-specific treatment resulted in an adequate hematological response characterized by decreasing monoclonal paraprotein-levels and AVWS was resolved.</p></div>","PeriodicalId":34401,"journal":{"name":"Thrombosis Update","volume":"7 ","pages":"Article 100108"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666572722000128/pdfft?md5=2cb9838d226967d7f7050e9ce56f96f7&pid=1-s2.0-S2666572722000128-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46448038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New insights into neonatal hemostasis","authors":"Gili Kenet ,&nbsp;Assaf Arie Barg ,&nbsp;Ulrike Nowak-Göttl","doi":"10.1016/j.tru.2022.100103","DOIUrl":"10.1016/j.tru.2022.100103","url":null,"abstract":"<div><p>Hemostasis is a dynamic process that starts in utero. Neonates, especially those who are born preterm, are at high risk of bleeding. The perinatal period is also associated with increased thrombosis risk as compared to older children. The coagulation system evolves with age, and the decreased levels of coagulation factors along with hypo-reactive platelets are counterbalanced by the increased activity of von Willebrand factor, high hematocrit and MCV as well as low levels of coagulation inhibitors that promote hemostasis. This review will address the concept and manifestations of developmental hemostasis with respect to the pathogenesis of severe bleeding or thrombosis in neonates. A special focus will be shared regarding intracerebral hemorrhages and perinatal arterial ischemic stroke. Hemostatic challenges associated with pathogenesis, diagnosis and treatment will be discussed.</p></div>","PeriodicalId":34401,"journal":{"name":"Thrombosis Update","volume":"7 ","pages":"Article 100103"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666572722000074/pdfft?md5=8eb01a4711c9cf8da1073185eb160e6d&pid=1-s2.0-S2666572722000074-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48918357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Similarities of antiphospholipid antibodies in HIT and APS patients with heparin-platelet factor 4 antibodies","authors":"Imene Hocine","doi":"10.1016/j.tru.2022.100106","DOIUrl":"10.1016/j.tru.2022.100106","url":null,"abstract":"<div><p>Heparin-induced thrombocytopenia (HIT) is a prothrombotic autoimmune disorder confirmed by the existence of Heparin-Platelet Factor 4 (HPF4) antibodies. The aim of this work is to study the possible relationship between anti-HPF4 and antiphospholipid antibodies (aPLs) that may explain the discrepancies observed in patients with a suspected HIT (HIT group) with positive immunoassay (HPF4-Elisa) and negative functional assay (heparin-induced platelet aggregation test). So, we performed H-PF4 antibodies research in 31 APS confirmed patients (APL group). All tests performed have been compared to normal controls (n = 34). We found anti-H-PF4 in 7/31 patients of APL group. In parallel, we search for aPLs in 9/34 patients tested positive for anti-HPF4 in HIT group, all of them were positive. All specificities were observed in the two anti-HPF4 positive groups (aβ2GP1 IgM/IgG/IgA, aCL (IgM/IgG/IgA, aPS-PT IgM/IgG). The most associated antibodies with anti-HPF4 are the anti ß2Glycoprotein1 (Odds ratio = 50.1). We suggest that the presence of aPLs in HIT group with anti-HPF4 could be the cause of the discrepancies. In addition, we performed the Heparin Neutralization Assay (HNA) which is specific for anti-HPF4, neutralization was obtained for patients exposed to heparin. Furthermore, we suggest that we should performed a larger cohort to confirm the causal relationship of aPLs and also to expand the tests allowing the differentiation between these autoantibodies.</p></div>","PeriodicalId":34401,"journal":{"name":"Thrombosis Update","volume":"7 ","pages":"Article 100106"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666572722000104/pdfft?md5=f8055d993cde80746f4ddcf16e8975c3&pid=1-s2.0-S2666572722000104-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49325671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implementation of a care pathway for deep vein thrombosis: What's the benefit?","authors":"Jorn S. Heerink,&nbsp;Nathalie Péquériaux,&nbsp;Ruud Oudega,&nbsp;Mathijn de Jong,&nbsp;Hendrik Koffijberg,&nbsp;Ron Kusters","doi":"10.1016/j.tru.2022.100109","DOIUrl":"https://doi.org/10.1016/j.tru.2022.100109","url":null,"abstract":"","PeriodicalId":34401,"journal":{"name":"Thrombosis Update","volume":"7 ","pages":"Article 100109"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266657272200013X/pdfft?md5=2abfc043021da48fcacbf7bead9fdf0e&pid=1-s2.0-S266657272200013X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72217069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}