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Peak thrombin generation and subsequent venous thromboembolism: the Longitudinal Investigation of Thromboembolism Etiology (LITE) study.

TitlePeak thrombin generation and subsequent venous thromboembolism: the Longitudinal Investigation of Thromboembolism Etiology (LITE) study.
Publication TypeJournal Article
Year of Publication2009
AuthorsLutsey PL, Folsom AR, Heckbert SR, Cushman M
JournalJ Thromb Haemost
Volume7
Issue10
Pagination1639-48
Date Published2009 Oct
ISSN1538-7836
KeywordsAdult, Aged, Biomarkers, Blood Coagulation Factors, Case-Control Studies, Ethnic Groups, Factor VIII, Female, Fibrin Fibrinogen Degradation Products, Humans, Male, Middle Aged, Partial Thromboplastin Time, Prospective Studies, Risk Factors, Thrombin, United States, Venous Thromboembolism
Abstract

BACKGROUND: Thrombin is an enzyme that is essential for the acceleration of the coagulation cascade and the conversion of fibrinogen to clottable fibrin.

OBJECTIVES: We evaluated the relationship of basal peak thrombin generation with the risk of future venous thromboembolism (VTE), and determined whether associations were independent of other coagulation markers.

METHODS: The Longitudinal Investigation of Thromboembolism Etiology (LITE) study investigated VTE in two prospective population-based cohorts: the Atherosclerosis Risk in Communities (ARIC) study and the Cardiovascular Health Study (CHS). Peak thrombin generation was measured on stored plasma in a nested case-control sample (434 cases and 1004 controls). Logistic regression was used to estimate the relationship of peak thrombin generation with VTE, adjusted for age, sex, race, center, and body mass index. Mediation was evaluated by additionally adjusting for factor VIII and D-dimer.

RESULTS: Relative to the first quartile of peak thrombin generation, the odds ratio (OR) of VTE for those above the median was 1.74 [95% confidence interval (CI) 1.28-2.37]. The association was modestly attenuated by adjustment for FVIII and D-dimer (OR 1.47, 95% CI 1.05-2.05). Associations appeared to be stronger for idiopathic than for secondary VTE. Elevated peak thrombin generation more than added to the VTE risk associated with FV Leiden or low activated partial thromboplastin time.

CONCLUSIONS: In this prospective study of two independent cohorts, elevated basal peak thrombin generation was associated with subsequent risk of VTE, independently of established VTE risk factors.

DOI10.1111/j.1538-7836.2009.03561.x
Alternate JournalJ Thromb Haemost
PubMed ID19656279
PubMed Central IDPMC2763356
Grant ListN01HC55020 / HL / NHLBI NIH HHS / United States
N01HC55018 / HL / NHLBI NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
R01 HL059367 / HL / NHLBI NIH HHS / United States
N01 HC015103 / HC / NHLBI NIH HHS / United States
N01-HC-55016 / HC / NHLBI NIH HHS / United States
N01-HC-55018-22 / HC / NHLBI NIH HHS / United States
R01 HL59367 / HL / NHLBI NIH HHS / United States
N01HC55022 / HL / NHLBI NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
N01-HC-85086 / HC / NHLBI NIH HHS / United States
N01HC55015 / HL / NHLBI NIH HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
T32 HL007779 / HL / NHLBI NIH HHS / United States
N01 HC-55222 / HC / NHLBI NIH HHS / United States
R01 HL059367-08 / HL / NHLBI NIH HHS / United States
N01-HC-55015 / HC / NHLBI NIH HHS / United States
T32 HL007779-08 / HL / NHLBI NIH HHS / United States
N01-HC-75150 / HC / NHLBI NIH HHS / United States
N01HC55016 / HL / NHLBI NIH HHS / United States
N01HC55019 / HL / NHLBI NIH HHS / United States
N01HC75150 / HL / NHLBI NIH HHS / United States
N01-HC-85079 / HC / NHLBI NIH HHS / United States
R01 HL059367-09 / HL / NHLBI NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
N01HC55021 / HL / NHLBI NIH HHS / United States
N01 HC045133 / HC / NHLBI NIH HHS / United States
N01 HC035129 / HC / NHLBI NIH HHS / United States
T32 HL07779 / HL / NHLBI NIH HHS / United States