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lördag 4 mars 2023

ADAMTS-13 ja COVID-19. PubMed haku


Microvascular dysfunction in COVID-19: the MYSTIC study.
Rovas A, Osiaevi I, Buscher K, Sackarnd J, Tepasse PR, Fobker M, Kühn J, Braune S, Göbel U, Thölking G, Gröschel A, Pavenstädt H, Vink H, Kümpers P. Angiogenesis. 2021 Feb;24(1):145-157. doi: 10.1007/s10456-020-09753-7. Epub 2020 Oct 14. PMID: 33058027 Free PMC article.
METHODS: Hospitalized adult patients with moderate-to-severe or critical COVID-19 (n = 23) were enrolled non-consecutively in this prospective, observational, cross-sectional, multi-center study. ...CONCLUSIONS: Our data clearly show severe alterations …
Prognostic value of von Willebrand factor and ADAMTS13 in patients with COVID-19: A systematic review and meta-analysis.
Xu X, Feng Y, Jia Y, Zhang X, Li L, Bai X, Jiao L. Thromb Res. 2022 Oct;218:83-98. doi: 10.1016/j.thromres.2022.08.017. Epub 2022 Aug 18. PMID: 36027630 Free PMC article. Review.
The estimated pooled means indicated increased plasma levels of VWF:Ag, VWF:Rco, and VWF:Ag/ADAMTS13:Ac ratio, and decreased plasma levels of ADAMTS13:Ac in COVID-19 patients with unfavorable outcomes when compared to those with favorable outcomes (com …
Background: Endotheliopathy and coagulopathy appear to be the main causes for critical illness and death in patients with coronavirus disease 2019 (COVID-19). The adhesive ligand von Willebrand factor (VWF) has been involved in immunothrombosis responding to endothelial injury. Here, we reviewed the current literature and performed meta-analyses on the relationship between both VWF and its cleaving protease ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13) with the prognosis of COVID-19. Methods: We searched MEDLINE, Cochrane Library, Web of Science, and EMBASE databases from inception to 4 March 2022 for studies analyzing the relationship between VWF-related variables and composite clinical outcomes of patients with COVID-19. The VWF-related variables analyzed included VWF antigen (VWF:Ag), VWF ristocetin cofactor (VWF:Rco), ADAMTS13 activity (ADAMTS13:Ac), the ratio of VWF:Ag to ADAMTS13:Ac, and coagulation factor VIII (FVIII). The unfavorable outcomes were defined as mortality, intensive care unit (ICU) admission, and severe disease course. We used random or fixed effects models to create summary estimates of risk. Risk of bias was assessed based on the principle of the Newcastle-Ottawa Scale. Results: A total of 3764 patients from 40 studies were included. The estimated pooled means indicated increased plasma levels of VWF:Ag, VWF:Rco, and VWF:Ag/ADAMTS13:Ac ratio, and decreased plasma levels of ADAMTS13:Ac in COVID-19 patients with unfavorable outcomes when compared to those with favorable outcomes (composite outcomes or subgroup analyses of non-survivor versus survivor, ICU versus non-ICU, and severe versus non-severe). In addition, FVIII were higher in COVID-19 patients with unfavorable outcomes. Subgroup analyses indicated that FVIII was higher in patients admitting to ICU, while there was no significant difference between non-survivors and survivors. Conclusions: The imbalance of the VWF-ADAMTS13 axis (massive quantitative and qualitative increases of VWF with relative deficiency of ADAMTS13) is associated with poor prognosis of patients with COVID-19.
Increased VWF and Decreased ADAMTS-13 in COVID-19: Creating a Milieu for (Micro)Thrombosis.
Favaloro EJ, Henry BM, Lippi G. Semin Thromb Hemost. 2021 Jun;47(4):400-418. doi: 10.1055/s-0041-1727282. Epub 2021 Apr 23. PMID: 33893632 Review.
However, ADAMTS-13 deficiency may result from other pathological processes. Of relevance is the recent finding that COVID-19 (coronavirus disease 2019) is associated with both increased levels and activity of VWF as well as generally decreased  (or occasionally normal) activity levels of ADAMTS-13. Thus, in COVID-19 there is an alteration in the VWF/ADAMTS-13 axis, most often described by increased VWF/ADAMTS-13 ratio (or reduced ADAMTS-13/VWF ratio). COVID-19 is also associated with high prothrombotic risk. Thus, the imbalance of VWF and ADAMTS-13 in COVID-19 may be providing a milieu that promotes (micro)thrombosis, in a clinical picture resembling a secondary thrombotic microangiopathy in some patients. This review therefore assesses the literature on VWF, ADAMTS-13, and COVID-19. Whenever reported in COVID-19, VWF has always been identified as raised (compared with normal reference ranges or control populations). Reports have included VWF level (i.e., VWF antigen) and in some cases one or more VWF "activity" (e.g., collagen binding; platelet glycoprotein Ib [GPIb] binding, using ristocetin cofactor or more modern versions including VWF:GPIbR [recombinant] and VWF:GPIbM [mutant]). Whenever reported, ADAMTS-13 has been reported as "normal" or reduced; however, it should be recognized that "normal" levels may still identify a relative reduction in individual cases. Some reports also discuss the raised VWF/ADAMTS-13 (or reduced ADAMTS-13/VWF) ratio, but very few provide actual numerical data.
The ADAMTS13-von Willebrand factor axis in COVID-19 patients.
Mancini I, Baronciani L, Artoni A, Colpani P, Biganzoli M, Cozzi G, Novembrino C, Boscolo Anzoletti M, De Zan V, Pagliari MT, Gualtierotti R, Aliberti S, Panigada M, Grasselli G, Blasi F, Peyvandi F. J Thromb Haemost. 2021 Feb;19(2):513-521. doi: 10.1111/jth.15191. Epub 2020 Dec 18. PMID: 33230904 Free PMC article.
BACKGROUND: Severe coronavirus disease 2019 (COVID-19) is characterized by an increased risk of thromboembolic events, with evidence of microthrombosis in the lungs of deceased patients. ...CONCLUSIONS: We found a significant alteration of the V …
ADAMTS13 regulation of VWF multimer distribution in severe COVID-19.
Ward SE, Fogarty H, Karampini E, Lavin M, Schneppenheim S, Dittmer R, Morrin H, Glavey S, Ni Cheallaigh C, Bergin C, Martin-Loeches I, Mallon PW, Curley GF, Baker RI, Budde U, O'Sullivan JM, O'Donnell JS; Irish COVID-19 Vasculopathy Study (iCVS) investigators. J Thromb Haemost. 2021 Aug;19(8):1914-1921. doi: 10.1111/jth.15409. Epub 2021 Jun 20. PMID: 34053187 Free PMC article.
OBJECTIVES: This study investigated the hypothesis that ADAMTS-13 regulation of VWF multimer distribution may be impaired in severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection contributing to the o … We observed markedly increased VWF collagen-binding activity in patients with severe COVID-19 compared to controls (median 509.1 versus 94.3 IU/dl). Conversely, plasma ADAMTS-13 activity was significantly reduced (median 68.2 IU/dl). In keeping with an increase in VWF:ADAMTS-13 ratio, abnormalities in VWF multimer distribution were common in patients with COVID-19, with reductions in high molecular weight VWF multimers. Terminal sialylation regulates VWF susceptibility to proteolysis by ADAMTS-13 and other proteases. We observed that both N- and O-linked sialylation were altered in severe COVID-19. Furthermore, plasma levels of the ADAMTS-13 inhibitors interleukin-6, thrombospondin-1, and platelet factor 4 were significantly elevated.
Distinctive Biomarker Features in the Endotheliopathy of COVID-19 and Septic Syndromes.
Fernández S, Moreno-Castaño AB, Palomo M, Martinez-Sanchez J, Torramadé-Moix S, Téllez A, Ventosa H, Seguí F, Escolar G, Carreras E, Nicolás JM, Richardson E, García-Bernal D, Carlo-Stella C, Moraleda JM, Richardson PG, Díaz-Ricart M, Castro P. Shock. 2022 Jan 1;57(1):95-105. doi: 10.1097/SHK.0000000000001823. PMID: 34172614 Free PMC article.
Biomarkers distinguishing different COVID-19 phenotypes from sepsis syndrome remain poorly understood. ...METHODS: Patients with COVID-19 pneumonia (n = 49) were classified into moderate, severe, or critical (life-threatening) disease. Plasma samples were collected within 48 to 72 h of hospitalization to analyze endothelial activation markers, including soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1), von Willebrand Factor (VWF), A disintegrin-like and metalloprotease with thrombospondin type 1 motif no. 13 (ADAMTS-13) activity, thrombomodulin (TM), and soluble TNF receptor I (sTNFRI); heparan sulfate (HS) for endothelial glycocalyx degradation; C5b9 deposits on endothelial cells in culture and soluble C5b9 for complement activation; circulating dsDNA for neutrophil extracellular traps (NETs) presence, and α2-antiplasmin and PAI-1 as parameters of fibrinolysis. We compared the level of each biomarker in all three COVID-19 groups and healthy donors as controls (n = 45). Results in critically ill COVID-19 patients were compared with other intensive care unit (ICU) patients with septic shock (SS, n = 14), sepsis (S, n = 7), and noninfectious systemic inflammatory response syndrome (NI-SIRS, n = 7). … All analyzed biomarkers were increased in COVID-19 patients versus controls (P < 0.001), except for ADAMTS-13 activity that was normal in both groups. The increased expression of sVCAM-1, VWF, sTNFRI, and HS was related to COVID-19 disease severity (P < 0.05). Several differences in these parameters were found between ICU groups: SS patients showed significantly higher levels of VWF, TM, sTNFRI, and NETS compared with critical COVID-19 patients and ADAMTS-13 activity was significantly lover in SS, S, and NI-SIRS versus critical COVID-19 (P < 0.001). Furthermore, α2-antiplasmin activity was higher in critical COVID-19 versus NI-SIRS (P < 0.01) and SS (P < 0.001), whereas PAI-1 levels were significantly lower in COVID-19 patients compared with NI-SIRS, S, and SS patients (P < 0.01). Conclusions: COVID-19 patients present with increased circulating endothelial stress products, complement activation, and fibrinolytic dysregulation, associated with disease severity. COVID-19 endotheliopathy differs from SS, in which endothelial damage is also a critical feature of pathobiology. These biomarkers could help to stratify the severity of COVID-19 disease and may also provide information to guide specific therapeutic strategies to mitigate endotheliopathy progression.
Low ADAMTS13 Activity Correlates with Increased Mortality in COVID-19 Patients.
Sweeney JM, Barouqa M, Krause GJ, Gonzalez-Lugo JD, Rahman S, Gil MR. TH Open. 2021 Mar 9;5(1):e89-e103. doi: 10.1055/s-0041-1723784. eCollection 2021 Jan. PMID: 33709050 Free PMC article.
The causes of coagulopathy associated with coronavirus disease 2019 (COVID-19) are poorly understood. We aimed to investigate the relationship between von Willebrand factor (VWF) biomarkers, intravascular hemolysis, coagulation, and organ damage in …
COVID-19 associated coagulopathy: Mechanisms and host-directed treatment.
Plášek J, Gumulec J, Máca J, Škarda J, Procházka V, Grézl T, Václavík J. Am J Med Sci. 2022 Jun;363(6):465-475. doi: 10.1016/j.amjms.2021.10.012. Epub 2021 Nov 6. PMID: 34752741 Free PMC article. Review.
Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is associated with specific coagulopathy that frequently occurs during the different phases of coronavirus disease 2019 (COVID-19
Impaired exercise capacity in post-COVID-19 syndrome: the role of VWF-ADAMTS13 axis.
Prasannan N, Heightman M, Hillman T, Wall E, Bell R, Kessler A, Neave L, Doyle A, Devaraj A, Singh D, Dehbi HM, Scully M. Blood Adv. 2022 Jul 12;6(13):4041-4048. doi: 10.1182/bloodadvances.2021006944. PMID: 35543533 Free PMC article.
Post-COVID syndrome (PCS), or long COVID, is an increasingly recognized complication of acute SARS-CoV-2 infection, characterized by persistent fatigue, reduced exercise tolerance, chest pain, shortness of breath, and cognitive slowing. Acute COVID-19 is strongly linked with an increased risk of thrombosis, which is a prothrombotic state quantified by an elevated von Willebrand factor (VWF) antigen (Ag)/ADAMTS13 ratio that is associated with severity of acute COVID-19 infection. We investigated whether patients with PCS also had evidence of a prothrombotic state associated with symptom severity. In a large cohort of patients referred to a dedicated post-COVID-19 clinic, thrombotic risk, including VWF(Ag)/ADAMTS13 ratio, was investigated. An elevated VWF(Ag)/ADAMTS13 ratio (≥1.5) was present in nearly one-third of the cohort and was 4 times more likely to be present in patients with impaired exercise capacity, as evidenced by desaturation ≥3% and/or an increase in lactate level >1 from baseline on a 1-minute sit-to-stand test and/or a 6-minute walk test (P < .0001). Of 276 patients, 56 (20%) had impaired exercise capacity, of which 55% (31/56) had a VWF(Ag)/ADAMTS13 ratio ≥1.5 (P < .0001). Factor VIII and VWF(Ag) were elevated in 26% and 18%, respectively, and support a hypercoagulable state in some patients with PCS. These findings suggest possible ongoing microvascular/endothelial dysfunction in the pathogenesis of PCS and suggest a role for antithrombotic therapy in the treatment of these patients.
ADAMTS13 factor deficiency in severe COVID-19 may not be immune mediated - report from a pilot study.
George A, Deepika C, Mohan G, Srishail R, Rajendran V, Shastry S, Balakrishnan JM, Rao S. Clin Hemorheol Microcirc. 2022;82(2):193-198. doi: 10.3233/CH-221514. PMID: 35754264
BACKGROUND: The assessment of ADAMTS13 factor activity and inhibitor levels was conducted in severe COVID-19 patients as an observational study. ..Results: A total of 14 patients were included and the average ADAMTS13 activity level at the time of admission was 28.54±30.74% (range 1.83-86.67%) which was reduced compared to controls (88.09±14.77). Nine patients had reduced ADAMTS13 factor activity (<40%) and 77.7% among them had severe deficiency (<10% activity). ADAMTS13 inhibitor was positive (>15 IU/mL) only in two patients and an overall mean value was 8.15±5.8. Elevated D-Dimer and length of hospital stay had significant correlation with ADAMTS13 activity (-0.247 and 0.306 respectively). No features of thrombotic microangiopathy were observed and hence no plasma exchange was performed. Conclusion: Reduced ADAMTS13 factor activity without inhibitor development may give a clue to the disease progress in COVID-19. …

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