title: Biological variation in tPA-induced plasma clot lysis time.
abstract: Hypofibrinolysis is a risk factor for venous and arterial thrombosis, and can be assessed by using a turbidimetric tPA-induced clot lysis time (CLT) assay. Biological variation in clot lysis time may affect the interpretation and usefulness of CLT as a risk factor for thrombosis. Sufficient information about assay variation and biological variation in CLT is not yet available. Thus, this study aimed to determine the analytical, within-subject and between-subject variation in CLT. We collected blood samples from 40 healthy individuals throughout a period of one year (average 11.8 visits) and determined the CLT of each plasma sample in duplicate. The mean (± SD) CLT was 83.8 (± 11.1) minutes. The coefficients of variation for total variation, analytical variation, within-subject variation and between-subject variation were 13.4%, 2.6%, 8.2% and 10.2%, respectively. One measurement can estimate the CLT that does not deviate more than 20% from its true value. The contribution of analytical variation to the within-subject variation was 5.0%, the index of individuality was 0.84 and the reference change value was 23.8%. The CLT was longer in the morning compared to the afternoon and was slightly longer in older individuals (> 40 years) compared to younger (≤40 years) individuals. There was no seasonal variation in CLT and no association with air pollution. CLT correlated weakly with fibrinogen, C-reactive protein, prothrombin time and thrombin generation. This study provides insight into the biological variation of CLT, which can be used in future studies testing CLT as a potential risk factor for thrombosis.
authors: Department of Hematology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors: Simone
authors: S
authors: Talens
authors: Joyce J M C
authors: JJ
authors: Malfliet
authors: Goran
authors: G
authors: Rudež
authors: Henri M H
authors: HM
authors: Spronk
authors: Nicole A H
authors: NA
authors: Janssen
authors: Piet
authors: P
authors: Meijer
authors: Cornelis
authors: C
authors: Kluft
authors: Moniek P M
authors: MP
authors: de Maat
authors: Dingeman C
authors: DC
authors: Rijken
mesh_terms: D000328:Adult; D000368:Aged; D000397:Air Pollution / Q000009:adverse effects; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D005260:Female; D063285:Fibrin Clot Lysis Time; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D008875:Middle Aged; D011517:Prothrombin Time; D012016:Reference Values; D012307:Risk Factors; D013917:Thrombin / Q000378:metabolism; D013927:Thrombosis / Q000097:blood / Q000209:etiology; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D005340:Fibrinogen; D002097:C-Reactive Protein; D013917:Thrombin; D010959:Tissue Plasminogen Activator