Factor XIII A-subunit concentration predicts outcome in stroke subjects and vascular outcome in healthy, middle-aged men.
There is growing evidence for a role of factor XIII (FXIII) in vascular disease. FXIII measures were determined in (i) a nested case-control study from the Second Northwick Park Heart Study of 63 men with myocardial infarction (MI) and 124 age-matched controls and (ii) in a case-control study of 475 subjects with acute stroke and 461 controls followed up for 54 months for mortality. In both studies, measures of FXIII A- and B-subunit antigen, FXIII activity and prothrombin fragments (F1 + 2) were made. An in vitro model was used to investigate the effects of thrombin activity on FXIII A- and B-subunit antigen levels. In study 1, patients clinically free of coronary artery disease who later developed MI had lower adjusted FXIII A-subunit levels at recruitment (129.2%vs 113.3%, P = 0.007). In study 2, stroke patients with large vessel disease had lower A-subunit antigen levels (102.1%vs 127.2%, P < 0.001), but higher F1 + 2 levels (0.941%vs 0.753%, P < 0.05), than subjects with small vessel disease. Levels of FXIII A-subunit (100%vs 117%, P < 0.0001) were lower and F1 + 2 higher (1.020%vs 0.702%, P < 0.0001) in stroke patients who had died compared with those still alive at the end of the follow-up period. Low concentrations of FXIII A-subunit antigen predicted vascular outcome in otherwise healthy subjects and relate to both size of infarct and poor post-stroke survival in patients with acute ischaemic stroke. Low in vitro concentrations of FXIII A-subunit antigen wererelated to increased thrombin generation and, thus, increased risk of thrombotic events.
Unit of Molecular Vascular Medicine, Leeds General Infirmary, University of Leeds, UK. hanspeter.kohler@insel.ch
Hans P
HP
Kohler
Robert A S
RA
Ariëns
Andrew J
AJ
Catto
Angela M
AM
Carter
George J
GJ
Miller
Jackie A
JA
Cooper
Michael W
MW
Mansfield
Kristina F
KF
Standeven
Peter J
PJ
Grant
D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D004739:England / Q000453:epidemiology; D005176:Factor XIII / Q000032:analysis*; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood*; D010446:Peptide Fragments / Q000032:analysis; D011379:Prognosis; D011446:Prospective Studies; D011498:Protein Precursors / Q000032:analysis; D011516:Prothrombin / Q000032:analysis; D020521:Stroke / Q000097:blood* / Q000401:mortality; D015996:Survival Rate
D015415:Biomarkers; D010446:Peptide Fragments; D011498:Protein Precursors; C064015:factor XIII subunit A; C029733:prothrombin fragment 1; C044183:prothrombin fragment 2; D011516:Prothrombin; D005176:Factor XIII; C054380:factor XIIIb