CLINICAL RESEARCH
Association of von Willebrand factor Ag-to-ADAMTS13 ratio with early sepsis-related mortality
,
 
,
 
,
 
,
 
,
 
 
 
More details
Hide details
1
Department of Internal Medicine, Hematology Unit, Faculty of Medicine, Menoufia University, Menoufia, Egypt
 
2
Department of Internal Medicine, Hematology Unit, Faculty of Medicine, Zagazig, Egypt
 
3
Departement of Biochemistry, Faculty of Medicine, Menoufia University, Menoufia, Egypt
 
 
Submission date: 2021-04-19
 
 
Final revision date: 2021-07-27
 
 
Acceptance date: 2021-07-28
 
 
Publication date: 2021-09-20
 
 
Arch Med Sci Civil Dis 2021;6(1):117-124
 
KEYWORDS
TOPICS
ABSTRACT
Introduction:
Sepsis is a highly complex syndrome with highly heterogeneous clinical manifestations, which makes it difficult to detect and treat. Von Willebrand factor (vWF) functions differently depending on its multimeric size and adhesive properties, which are regulated by ADAMTS 13. Thus, a decrease in ADAMTS 13 activity results in the persistence of ultralarge vWF and the formation of microvascular thrombi, ischaemia, and organ failure. The aim of the study was to identify the role of von Willebrand factor antigen-to-ADAMTS 13 ratio in predicting early sepsis-related mortality.

Material and methods:
This is a cohort of 70 sequentially selected adults with sepsis. The patients were classified into two groups: A (survivors) and B (non-survivors) based upon their survival within 7 days of hospital admission.

Results:
VWF Ag, ADAMTS13, and vWF/ADAMTS13 ratio were significant predictors of early hospital mortality. For vWF Ag at a cut-off level of ≥ 3560 ng/l, sensitivity was 76% and specificity was 88.9%. For ADAMTS at a cut-off level of ≤ 210 ng/l, sensitivity was 84% and specificity was reported as 68.9%. For vWF/ADAMTS ratio at a cut off level of ≥ 17, sensitivity was 80% and specificity was 84.4%. There was a statistically highly significant positive correlation between non-survival and levels of vWF and vWF/ADAMTS 13 ratio, and there was a statistically highly significant negative correlation between non-survival and ADAMTS 13 level.

Conclusions:
High vWF/Ag and vWF/Ag/ADAMTS13 ratios on day 1 of admission are associated with increased early (7 days) sepsis-related mortality.

 
REFERENCES (29)
1.
Shankar-Hari M, Ambler M, Mahalingasivam V, Jones A, Rowan K, Rubenfeld GD. Evidence for a causal link between sepsis and long-term mortality: a systematic review of epidemiologic studies. Crit Care 2016; 20: 101.
 
2.
Strandberg G, Walther S, Agvald Öhman C, Lipcsey M. Mortality after severe sepsis and septic shock in Swedish intensive care units 2008-2016 – a nationwide observational study. Acta Anaesthesiol Scand 2020; 64: 967-75.
 
3.
Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) Mervyn. Acta Medica Okayama 2016; 315: 801-10.
 
4.
Prescott HC, Langa KM, Liu V, Escobar GJ, Iwashyna TJ. Increased 1-year healthcare use in survivors of severe sepsis. Am J Respir Crit Care Med 2014; 190: 62-9.
 
5.
Raymond S, Holden DC, Mira JC, Stortz JA, Loftus J, Mohr AM. Microbial recognition and danger signals in sepsis and trauma. Biochim Biophys Acta 2017; 1863: 2564-73.
 
6.
Gragnano F, Sperlongano S, Golia E, et al. The role of von Willebrand factor in vascular inflammation: from pathogenesis to targeted therapy. Mediators Inflamm 2017; 2017: 5620314.
 
7.
Samraj RS, Zingarelli B, Wong HR. Role of biomarkers in sepsis care. Shock 2013; 40: 358-65.
 
8.
Mostel Z, Perl A, Marck M, et al. Post-sepsis syndrome – an evolving entity that afflicts survivors of sepsis. Mol Med 2019; 26: 6.
 
9.
Chen L, Deng H, Cui H, et al. Inflammatory responses and inflammation-associated diseases in organs. Oncotarget 2018; 9: 7204-18.
 
10.
Caraballo C, Jaimes F. Organ dysfunction in sepsis: an ominous trajectory from infection to death. Yale J Biol Med 2019; 92: 629-40.
 
11.
Sheats MK. A comparative review of equine SIRS, sepsis, and neutrophils. Front Veterinary Sci 2019; 6: 69.
 
12.
Philippe A, Chocron R, Gendron N, et al. Circulating von Willebrand factor and high molecular weight multimers as markers of endothelial injury predict COVID-19 in-hospital mortality. Angiogenesis 2021; 24: 505-17.
 
13.
South K, Roberts L, Morris L, et al. Severity-stratified and longitudinal analysis of VWF/ADAMTS13 imbalance, altered fibrin crosslinking and inhibition of fibrinolysis as contributors to COVID-19 coagulopathy. medRxiv 2020; 5: 1-22.
 
14.
Pipe SW, Montgomery RR, Pratt KP, Lenting PJ, Lillicrap D. Life in the shadow of a dominant partner: the FVIII-VWF association and its clinical implications for hemophilia A. Blood 2016; 128: 2007-16.
 
15.
Lerolle N, Dunois-Lardé C, Badirou I, et al. von Willebrand factor is a major determinant of ADAMTS-13 decrease during mouse sepsis induced by cecum ligation and puncture. J Thromb Haemostasis 2009; 7: 843-50.
 
16.
Singh K, Kwong AC, Madarati H, et al. Characterization of ADAMTS13 and von Willebrand factor levels in septic and non-septic ICU patients. PLoS One 2021; 16: e0247017.
 
17.
Shoeib SA, Abd ElHalim AF, Abd ElHafez MA, Dawod AA, Abd ElMohsen EA, ElBaz SA. Serum soluble glycoprotein VI (sGPVI) to predict the 28th day in-hospital mortality in adult patients with sepsis. Egypt J Hospital Med 2020; 80: 820-6.
 
18.
Dempfle CEH, Lorenz S, Smolinski M, et al. Utility of activated partial thromboplastin time waveform analysis for identification of sepsis and overt disseminated intravascular coagulation in patients admitted to a surgical intensive care unit. Crit Care Med 2004; 32: 520-4.
 
19.
Katoch T, Singh A, Suri V, Sethi S, Sachdeva N, Naseem S. Diagnostic performance of biomarkers in maternal sepsis: a prospective observational study. Int J Gynecol Obstetrics 2021; 154: 312-7.
 
20.
Benediktsson S, Frigyesi A, Kander T. Routine coagulation tests on ICU admission are associated with mortality in sepsis: an observational study. Acta Anaesthesiol Scand 2017; 61: 790-6.
 
21.
Massion PB, Peters P, Ledoux D, et al. Persistent hypocoagulability in patients with septic shock predicts greater hospital mortality: impact of impaired thrombin generation. Intensive Care Med 2012; 38: 1326-35.
 
22.
Zheng R, Pan H, Wang JF, Yu XS, Chen ZQ, Pan JY. The association of coagulation indicators with in-hospital mortality and 1-year mortality of patients with sepsis at ICU admissions: a retrospective cohort study. Clin Chim Acta 2020; 504: 109-18.
 
23.
Orati JA, Almeida P, Santos V, Ciorla G, Lobo SM. Serum C-reactive protein concentrations in early abdominal and pulmonary sepsis. Rev Brasil Terapia Intensiva 2013; 25: 6-11.
 
24.
Peetermans M, Meyers S, Liesenborghs L, et al. Von Willebrand factor and ADAMTS13 impact on the outcome of Staphylococcus aureus sepsis. J Thromb Haemostasis 2020; 18: 722-31.
 
25.
Freund Y, Lemachatti N, Krastinova E, et al. Prognostic accuracy of sepsis-3 criteria for in-hospital mortality among patients with suspected infection presenting to the emergency department. JAMA 2017; 317: 301-8.
 
26.
Toker AK, Kose S, Turken M. Comparison of SOFA Score, SIRS, qSOFA, and qSOFA + L criteria in the diagnosis and prognosis of sepsis. Eurasian J Med 2021; 53: 40-7.
 
27.
Gaini S, Relster MM, Pedersen C, Johansen IS. Prediction of 28-days mortality with sequential organ failure assessment (SOFA), quick SOFA (qSOFA) and systemic inflammatory response syndrome (SIRS) – a retrospective study of medical patients with acute infectious disease. Int J Infect Dis 2019; 78: 1-7.
 
28.
Rudd KE, Seymour CW, Aluisio AR, et al. Association of the quick sequential (sepsis-related) organ failure assessment (qSOFA) score with excess hospital mortality in adults with suspected infection in low- and middle-income countries. JAMA 2018; 319: 2202-11.
 
29.
Song JU, Sin CK, Park HK, Shim SR, Lee J. Performance of the quick sequential (sepsis-related) organ failure assessment score as a prognostic tool in infected patients outside the intensive care unit: a systematic review and meta-analysis. Crit Care 2018; 22: 1-13.
 
ISSN:2451-0637
Journals System - logo
Scroll to top