title: Increased factor XIa levels in patients with a first acute myocardial infarction: the introduction of a new thrombin generation based factor XIa assay.
abstract: OBJECTIVE
  One of the contributing mechanisms in acute myocardial infarction (AMI) is plasma hypercoagulability. Recently, it was suggested that factor XI activation might play a role in atherothrombosis. To quantify factor XIa plasma levels, we developed a new thrombin generation based assay and hypothesized that in AMI patients factor XIa levels are increased during the acute thrombotic event.
  
  
  METHODS
  A prospective cohort study was performed including 56 patients with first AMI. Blood was collected upon admission and after 6 months. Reference blood samples were obtained from 30 apparently healthy control subjects. Plasma samples were diluted (1:5) in factor XI deficient plasma and factor XIa plasma levels were established using a reference curve (0-12.5 pM factor XIa) and an inhibitory anti-factor XIa antibody. The established FXIa concentrations were related to the 1-year outcome.
  
  
  RESULTS
  Factor XIa plasma concentrations were significantly increased in AMI patients on admission compared to 6 months after the event (3.7 pM [2.7-5.5] vs. 2.8 [1.9-4.3], median ± IQR; P=0.001) and compared to healthy controls (3.7 pM [2.7-5.5] vs. 2.7 [1.6-4.2], median ± IQR; P=0.004). However, a high factor FXIa level at baseline was not significantly associated with a recurrent cardiovascular event (OR 1.26, 95%CI 0.33-4.7).
  
  
  CONCLUSIONS
  This study presents the first application of a new thrombin generation based factor XIa assay, showing significantly increased factor XIa levels in AMI patients on admission compared to 6 months after the event and compared to healthy controls. The factor XIa concentration was not associated with the risk of recurrence.
authors.affiliation: Laboratory for Clinical Thrombosis and Haemostasis, Department of Internal Medicine, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, The Netherlands. Electronic address: rinske.loeffen@maastrichtuniversity.nl.
authors.forename: R
authors.initials: R
authors.lastname: Loeffen
authors.affiliation: Laboratory for Clinical Thrombosis and Haemostasis, Department of Internal Medicine, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: van Oerle
authors.affiliation: Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: P G
authors.initials: PG
authors.lastname: de Groot
authors.affiliation: Department for Cardiovascular Medicine, Division of Cardiology, University of Münster, Münster, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Waltenberger
authors.affiliation: Department of Cardiology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.
authors.forename: H J
authors.initials: HJ
authors.lastname: Crijns
authors.affiliation: Laboratory for Clinical Thrombosis and Haemostasis, Department of Internal Medicine, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, The Netherlands.
authors.forename: H M H
authors.initials: HM
authors.lastname: Spronk
authors.affiliation: Laboratory for Clinical Thrombosis and Haemostasis, Department of Internal Medicine, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, The Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: ten Cate
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D001780:Blood Coagulation Tests / Q000379:methods*; D015331:Cohort Studies; D015945:Factor XIa / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000175:diagnosis*; D011446:Prospective Studies; D012008:Recurrence; D015203:Reproducibility of Results; D018570:Risk Assessment / Q000379:methods; D012680:Sensitivity and Specificity; D013917:Thrombin / Q000276:immunology*
chemical_list: D015415:Biomarkers; D015945:Factor XIa; D013917:Thrombin