Plasma levels of factor XIIa and factor VIIa are increased but not related in primary hyperlipidaemia.
The lipolysis of triglyceride-rich lipoproteins may provide a surface that supports the activation of factor XII (FXII) with subsequent activation of factor VII (FVII). Plasma levels of activated FVII (FVIIa) but not activated FXII (FXIIa) are increased in the post-prandial state when there is a transient increase in triglyceride levels. We compared plasma levels of FXIIa antigen in control subjects (n = 33) and in patients with chronically elevated lipids (primary hyperlipidaemia, n = 49), with FVIIa and markers of thrombin generation. Results are given as median (first and third quartiles). Plasma levels of FXIIa [2.34 (1.68-3.32) ng/ml versus 1.53 (0.93-1.86) ng/ml, P = 0.0002], FVIIa [3.02 (2.15-4.64) ng/ml versus 2.20 (1.66-2.56) ng/ml, P = 0.0004], thrombin-antithrombin complexes [3.08 (2.16-5.54) microg/I versus 2.13 (1.46-2.84) microg/l, P = 0.005] and prothrombin fragment 1 + 2 (Pro F1 + 2) [1.28 (1.08-1.50) nmol/l versus 0.92 (0.65-1.08) nmol/l, P = 0.0001] were increased compared with controls irrespective of the type of hyperlipidaemia. In hyperlipdaemic subjects, levels of Pro F1 + 2 were correlated with FVIIa (r = 0.56, P = 0.0002) and FXIIa (r = 0.31, P = 0.03). These results suggest increased activation of both FVII and FXII in hyperlipidaemic subjects, which correlates with increased thrombin generation. Given the lack of correlation between levels of FXIIa and FVIIa, it remains to be established whether the increase in FXIIa is responsible for increased FVIIa activity in this subject group.
Cardigan
R A
RA
Department of Haematology, University College London Medical School, UK. rebecca.cardigan@nbs.nhs.uk
Crook
M
M
Mackie
I J
IJ
Machin
S J
SJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000990:Antithrombin III / Q000032:analysis; D004789:Enzyme Activation; D015942:Factor VIIa / Q000032:analysis*; D015956:Factor XIIa / Q000032:analysis*; D005215:Fasting / Q000097:blood; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications; D006949:Hyperlipidemias / Q000097:blood*; D015228:Hypertriglyceridemia / Q000097:blood / Q000150:complications; D008066:Lipolysis; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000032:analysis; D010447:Peptide Hydrolases / Q000032:analysis; D011516:Prothrombin / Q000032:analysis; D013917:Thrombin / Q000096:biosynthesis; D019851:Thrombophilia / Q000097:blood / Q000209:etiology; D014280:Triglycerides / Q000097:blood
D008074:Lipoproteins; D010446:Peptide Fragments; D014280:Triglycerides; C046193:antithrombin III-protease complex; C045879:prothrombin fragment 1.2; D000990:Antithrombin III; D011516:Prothrombin; D010447:Peptide Hydrolases; D015942:Factor VIIa; D015956:Factor XIIa; D013917:Thrombin