Document Detail


Association between thrombotic microangiopathy and reduced ADAMTS13 activity in malignant hypertension.
MedLine Citation:
PMID:  18332284     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The thrombotic microangiopathy observed in malignant hypertension is similar to that of thrombotic thrombocytopenic purpura, which is associated with a deficiency of ADAMTS13, a von Willebrand factor (VWF)-cleaving protease that cleaves large prothrombogenic multimers. We hypothesized that ADAMTS13 is deficient in malignant hypertension and that the severity of thrombotic microangiopathy is associated with decreased ADAMTS13 activity. We included 20 patients with malignant and 20 patients with severe hypertension, and 20 matched normotensive individuals served as control subjects. VWF, active VWF, and free hemoglobin were assessed to explore predictors of ADAMTS13 activity. Patients with malignant hypertension had lower ADAMTS13 activity (80%; interquartile range: 53% to 130%) compared with control subjects (99% interquartile range: 82% to 129%; P<0.01) but not compared with patients with severe hypertension (P=0.14). ADAMTS13 activity negatively correlated with lactic dehydrogenase levels after logarithmic transformation (r=-0.65; P<0.001) and was associated with platelet count (r=0.34; P=0.04) and the presence of schistocytes (r=-0.37; P=0.02). Apart from the association with thrombotic microangiopathy, ADAMTS13 was inversely associated with creatinine (r=-0.42; P=0.008). Increasing levels of VWF were associated with a decrease in ADAMTS13 activity (r=-0.34; P=0.03). There was no significant association between ADAMTS13 activity and other parameters, including blood pressure. In conclusion, ADAMTS13 is decreased in malignant hypertension and associated with the severity of thrombotic microangiopathy, likely because of the release of VWF after endothelium stimulation. A severe deficiency could not be demonstrated. More studies are needed to identify the role of ADAMTS13 in the thrombotic microangiopathy and ischemic complications of malignant hypertension.
Authors:
Bert-Jan H van den Born; Niels V van der Hoeven; Evelyn Groot; Peter J Lenting; Joost C M Meijers; Marcel Levi; Gert A van Montfrans
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Publication Detail:
Type:  Journal Article     Date:  2008-03-10
Journal Detail:
Title:  Hypertension     Volume:  51     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2008 Apr 
Date Detail:
Created Date:  2008-03-21     Completed Date:  2008-04-16     Revised Date:  2008-10-07    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  862-6     Citation Subset:  IM    
Affiliation:
Department of Internal and Vascular Medicine, Academic Medical Centre, Meibergdreef 9, Room F4-222, PO Box 22660, 1100 DD, Amsterdam, the Netherlands. b.j.vandenborn@amc.uva.nl
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MeSH Terms
Descriptor/Qualifier:
ADAM Proteins / blood*
Acute Disease
Adult
Case-Control Studies
Endothelium, Vascular / metabolism
Female
Hemoglobins / metabolism
Humans
Hypertension, Malignant / complications*,  metabolism*
Hypertension, Renal / complications,  metabolism
Kidney Failure / complications,  metabolism
Male
Microcirculation
Prospective Studies
Severity of Illness Index
Thrombosis / blood*,  complications*
von Willebrand Factor / metabolism
Chemical
Reg. No./Substance:
0/Hemoglobins; 0/von Willebrand Factor; EC 3.4.24.-/ADAM Proteins; EC 3.4.24.-/ADAMTS13 protein, human
Comments/Corrections
Comment In:
Hypertension. 2008 Oct;52(4):e32; author reply e33   [PMID:  18695140 ]

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