Plasma ADAMTS13 activity parallels the APACHE II score, reflecting an early prognostic indicator for patients with severe acute pancreatitis

Morioka, Chie; Uemura, Mamoru; Matsuyama, Toyoki; Matsumoto, Masanori; Kato, Seiji; Ishikawa, Masatoshi; Ishizashi, Hiromichi; Fujimoto, Masao; Sawai, Masayoshi; Yoshida, Motoyuki; Mitoro, Akira; Yamao, Junichi; Tsujimoto, Tatsuhiro; Yoshiji, Hitoshi; Urizono, Yasuyuki; Hata, Masaharu; Nishino, Kimihiro; Okuchi, Kazuo; Fujimura, Yoshihiro; Fukui, Hiroshi

doi:10.1080/00365520802179933

Cited by 32 publications

(21 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The other variables used in the study, such as use of mechanical ventilation, length of stay (LOS), vasopressor agents and number of organ failure on admission, also showed correlations with low ADAMTS13 levels but these correlations were not statistically significant. The positive correlation between ADAMTS13 and APACHE II has been shown previously, but this was done in patients with severe acute pancreatitis [25].…”

Section: Discussionmentioning

confidence: 95%

Prognostic value of ADAMTS13 in patients with severe sepsis and septic shock

Azfar

Khan

Habib

et al. 2017

CIM

View full text Add to dashboard Cite

Prognostic value of ADAMTS13 in patients with severe sepsis and septic shock Abstract Purpose: ADAMTS13 level was evaluated as a predictor of mortality in patients with severe sepsis and septic shock, and compared with Acute Physiology and Chronic Health Evaluation II (APACHE II) scores.Methods: This prospective observational study was conducted in the Medical and Surgical Intensive Care Units of King Khalid University Hospital. Detailed clinical evaluations were performed on 84 patients (56.08±18.18 years of age) with severe sepsis and septic shock. ADAMTS13 levels were determined (three blood samples at 24 hours intervals) and APACHE II scores, hematological profiles, indices of organ hypo-perfusion, renal functions and coagulation profiles were recorded. Primary outcome was 30 days ICU mortality and secondary outcomes were its comparison with APACHE II score, length of ICU stay and use of vasopressor agents.Results: Hypertension (53.6%) and diabetic mellitus (45.2%) were the commonest comorbidities. The median ADAMTS13 levels were 336.65, 339.35 and 313.9, respectively. ROC analysis showed maximum area under the curve for second ADAMTS13 (AUC=0.760) compared with first (AUC=0.660) and third samples (AUC=0.707) and APACHE II scores (AUC=0.662). Patients were divided into low and high ADAMTS13 groups according to the best cut-off point. Mortality was high in the low ADAMTS13 level group [OR=4.5]and was significantly associated with age, DBP, ADAMTS13, APACHE II score, DIC score and platelet count. ADAMTS13 (OR=5.3), APACHE II (OR=4.13) and DIC scores (OR=7.32) were significant risk factors for mortality.Conclusions: Low ADAMTS13 was associated with increased mortality in patients with severe sepsis and septic shock and was comparable to APACHE II scores for predicting mortality.

show abstract

Section: Discussionmentioning

confidence: 95%

Prognostic value of ADAMTS13 in patients with severe sepsis and septic shock

Azfar

Khan

Habib

et al. 2017

CIM

View full text Add to dashboard Cite

show abstract

“…10,11,13,26,27 Elevated VWF levels in plasma in these syndromes may be the result of enhanced release of ULVWF and reduced processing of ULVWF and/or VWF by ADAMTS13. The importance of reduced ADAMTS13 activity in plasma in these diseases or other chronic inflammatory conditions is not known.…”

Section: Discussionmentioning

confidence: 99%

“…7 In distinction, deficiency of ADAMTS13 increases plasma levels of ULVWF and causes thrombotic thrombocytopenic purpura, a disorder of thrombotic microangiopathy. 8 Several epidemiologic studies have demonstrated reduced plasma ADAMTS13 activity in inflammatory conditions, including aging, 9 systemic inflammation, 10 pancreatitis, 11 and sepsis. 12,13 It remains uncertain, however, whether ADAMTS13 contributes to disease pathogenesis or rather simply serves as an inflammation-associated marker.…”

Section: Introductionmentioning

confidence: 99%

ADAMTS13 reduces vascular inflammation and the development of early atherosclerosis in mice

Gandhi

Khan

Lentz

et al. 2012

Blood

View full text Add to dashboard Cite

ADAMTS13, a metalloprotease, plays a pivotal role in preventing spontaneous microvascular thrombosis by cleaving hyperactive ultra large von Willebrand factor multimers into smaller, less active multimers. Reduced ADAMTS13 activity in plasma has been described in many diseases associated with systemic inflammation. It remains uncertain, however, whether ADAMTS13 contributes to disease pathogenesis or rather simply serves as an inflammation-associated marker. We hypothesized that, by decreasing vascular inflammation, ADAMTS13 reduces the development of early atherosclerotic plaques. Using intravital fluorescence microscopy, we observed excessive leukocyte adhesion and accelerated atherosclerotic plaque formation at the carotid sinus of Adamts13 ؊/؊ /ApoE ؊/؊ mice compared with ApoE ؊/؊ mice fed a high-fat Western diet. At 4 months of age, there was a significant increase in atherosclerosis in the aorta and aortic sinus of Adamts13 ؊/؊ / ApoE ؊/؊ mice compared with ApoE ؊/؊ mice. Interestingly, we detected a 2-fold increase in macrophage recruitment to the atherosclerotic plaque of the Adamts13 ؊/؊ /ApoE ؊/؊ mice compared with ApoE ؊/؊ mice, suggesting that the atherosclerotic lesions in these mice were not only larger but also more inflammatory. These findings reveal a new functional role for the antithrombotic enzyme ADAMTS13 in reducing excessive vascular inflammation and plaque formation during early atherosclerosis. (Blood. 2012; 119(10):2385-2391) Introduction ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type I repeats-13) is a zinc-containing protease that is synthesized primarily by hepatic stellate cells 1,2 and, to a lesser extent, by endothelial cells, 3 both of which secrete ADAMTS13 into the bloodstream. The only known substrate for ADAMTS13 is von Willebrand factor (VWF), a hemostatic glycoprotein that is stored as ultra large VWF (ULVWF) multimers in platelet ␣-granules and endothelial storage granules called Weibel-Palade bodies. 4 ULVWF multimers, which can be as large as 20 000 kDa and are considered to be the most hyperactive and thrombogenic form of VWF, 4,5 are not present in blood plasma under normal conditions. However, on endothelial cell activation or injury, ULVWF multimers are released into the circulation from WeibelPalade bodies. During the process of secretion, ULVWF remains transiently bound to the endothelial surface where they are cleaved by ADAMTS13 into smaller, less active VWF multimers, thereby reducing its thrombotic potential. 6 The essential role of VWF in hemostasis is evidenced clinically in patients with von Willebrand disease, a bleeding disorder caused by a lack of functional VWF. 7 In distinction, deficiency of ADAMTS13 increases plasma levels of ULVWF and causes thrombotic thrombocytopenic purpura, a disorder of thrombotic microangiopathy. 8 Several epidemiologic studies have demonstrated reduced plasma ADAMTS13 activity in inflammatory conditions, including aging, 9 systemic inflammation, 10 pancreatitis, 11 and sepsis. 12,13 It remains uncertain, ...

show abstract

“…The elevated plasma VWF level is primarily a consequence of endothelial cell activation, but other mechanisms may be involved. Several recent studies have shown that systemic inflammation is also associated with reduced activity of the VWF-processing enzyme ADAMTS13 activity in syndromes such as acute systemic inflammation caused by endotoxin, 9 acute pancreatitis, 10 severe sepsis and septic shock, 11 sepsis-induced disseminate intravascular coagulation, 12 and sepsis-induced organ dysfunction. [13][14][15] It is therefore likely that in addition to enhanced release of VWF, delayed or reduced VWF processing by ADAMTS13 contributes to the elevated level and adhesiveness of VWF in these inflammatory disorders.…”

Section: Introductionmentioning

confidence: 99%

Oxidative modification of von Willebrand factor by neutrophil oxidants inhibits its cleavage by ADAMTS13

Chen

Wang

et al. 2010

Blood

133

124

View full text Add to dashboard Cite

Elevated plasma von Willebrand factor (VWF) and low ADAMTS13 activity have been reported in several inflammatory states, including sepsis and acute respiratory distress syndrome. One hallmark of inflammation is neutrophil activation and production of reactive oxygen species, including superoxide radical, hydrogen peroxide, and hypochlorous acid (HOCl). HOCl is produced from hydrogen peroxide and chloride ions through the action of myeloperoxidase. HOCl can oxidize methionine to methionine sulfoxide and tyrosine to chlorotyrosine. This is of interest because the ADAMTS13 cleavage site in VWF, the Tyr 1605 -Met 1606 peptide bond, contains both oxidation-prone residues. We hypothesized that HOCl would oxidize either or both of these residues and possibly inhibit ADAMTS13-mediated cleavage. We therefore treated ADAMTS13 substrates with HOCl and examined their oxidative modification by mass spectrometry. Met 1606 was oxidized to the sulfoxide in a concentration-dependent manner, with complete oxidation at 75M HOCl, whereas only a miniscule percentage of Tyr 1605 was converted to chlorotyrosine. The oxidized substrates were cleaved much more slowly by ADAMTS13 than the nonoxidized substrates. A similar result was obtained with multimeric VWF. Taken IntroductionDuring acute inflammation, endothelial cells are activated by inflammatory cytokines such as interleukin-1 and tumor necrosis factor-␣. Activated endothelial cells release von Willebrand factor (VWF) and expose P-selectin on the cell surface, a result of exocytosis of Weibel-Palade bodies, the major endothelial storage granules. 1,2 On a longer time scale, other adhesion molecules, such as E-selectin and intracellular adhesion molecule-1, are synthesized and exposed on the cell surface. 3 These molecules provide an adhesive surface for neutrophils, which attach to and roll on the endothelium, then become activated and migrate through the vessel wall into the surrounding tissues.Although a fraction of the VWF remains transiently attached to the activated endothelium, most is secreted into the plasma. 4,5 Elevated VWF levels in plasma have been described in diseases associated with systemic inflammation, such as acute lung injury/acute respiratory distress syndrome 6,7 and sepsis. 8 In each of these disorders, increased plasma VWF levels correlated independently with increased risk of death. The elevated plasma VWF level is primarily a consequence of endothelial cell activation, but other mechanisms may be involved. Several recent studies have shown that systemic inflammation is also associated with reduced activity of the VWF-processing enzyme ADAMTS13 activity in syndromes such as acute systemic inflammation caused by endotoxin, 9 acute pancreatitis, 10 severe sepsis and septic shock, 11 sepsis-induced disseminate intravascular coagulation, 12 and sepsis-induced organ dysfunction. [13][14][15] It is therefore likely that in addition to enhanced release of VWF, delayed or reduced VWF processing by ADAMTS13 contributes to the elevated level and adhesiveness of VW...

show abstract

Plasma ADAMTS13 activity parallels the APACHE II score, reflecting an early prognostic indicator for patients with severe acute pancreatitis

Abstract: Plasma ADAMTS13:AC was closely related to the APACHE II score. This intimate relationship may serve as an early prognostic indicator for SAP patients. The imbalance between decreased ADAMTS13:AC and increased UL-VWFM could contribute to SAP pathogenesis through enhanced thrombogenesis.

Cited by 32 publications

References 39 publications

Prognostic value of ADAMTS13 in patients with severe sepsis and septic shock

Prognostic value of ADAMTS13 in patients with severe sepsis and septic shock

ADAMTS13 reduces vascular inflammation and the development of early atherosclerosis in mice

Oxidative modification of von Willebrand factor by neutrophil oxidants inhibits its cleavage by ADAMTS13

Contact Info

Product

Resources

About