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The Impact of Antiproteinuric Therapy on the Prothrombotic State in Patients with Overt Proteinuria.
MedLine Citation:
PMID:  21972946     Owner:  NLM     Status:  Publisher    
Background: Overt proteinuria is a strong risk factor for thromboembolism due to changes in levels of various coagulation proteins and urinary antithrombin loss. The described coagulation disturbances in these patients are based on outdated studies conducted primarily in the 1970's and 80's. Whether these coagulation disturbances resolve with antiproteinuric therapy has yet to be studied. Methods: A total of 32 patients with overt proteinuria (median 3.7 g/d; interquartile range 1.5-5.6) were enrolled in this intervention crossover trial designed to assess optimal antiproteinuric therapy with sodium restriction, losartan and diuretics. Levels of various pro- and anticoagulant proteins, and two thrombin generation assays (i.e., Calibrated Automated Thrombogram [CAT] and prothrombin fragment 1+2) of placebo period were compared to maximum anti-proteinuric therapy period. As secondary analysis, coagulation measurements of the placebo period in these patients were compared to 32 age and sex matched healthy controls. Results: During maximum treatment median proteinuria was significantly lower (median, 0.9 g/d; interquartile range, 0.6-1.4; P<0.001) as compared to placebo period. Similarly, levels of various liver-synthesized pro- and anticoagulant proteins, activated protein C resistance, as well as prothrombin fragment 1+2 levels were significantly lower during maximum treatment versus placebo period. However, Von Willebrand and factor VIII levels were similar. Based on the higher levels of procoagulant proteins (i.e., fibrinogen, factor V, VIII and Von Willebrand) and both thrombin generation assays, patients were substantially more prothrombotic than healthy controls (P<0.004). Conclusions: Antiproteinuric therapy ameliorates the protrombotic state. Proteinuric patients are in a more prothrombotic state, as compared to healthy controls.
B K Mahmoodi; A B Mulder; F Waanders; H M H Spronk; R Mulder; M C J Slagman; L Vogt; G Navis; H Ten Cate; H C Kluin-Nelemans; G D Laverman
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-10-4
Journal Detail:
Title:  Journal of thrombosis and haemostasis : JTH     Volume:  -     ISSN:  1538-7836     ISO Abbreviation:  -     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-10-6     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101170508     Medline TA:  J Thromb Haemost     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 International Society on Thrombosis and Haemostasis.
Division of Hemostasis and Thrombosis, Department of Hematology, University Medical Center Groningen, Groningen Department of Laboratory Medicine, University Medical Center Groningen, Groningen Department of Nephrology, University Medical Center Groningen, Groningen Department of Internal Medicine, Laboratory for Clinical Thrombosis and Haemostasis, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.
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