Summary
Antibodies against phospholipid-binding plasma proteins, such as β2-glycoprotein I (β2-GPI) and prothrombin, are associated with thromboembolic events in patients with
systemic lupus erythematosus and also in subjects with no evident underlying diseases.
We wanted to examine whether increased levels of antibodies to negatively-charged
phospholipids (cardiolipin), to phospholipid-binding plasma proteins β2-GPI and prothrombin and to oxidised low-density lipoprotein (LDL) were associated
with risk of deep venous thrombosis or pulmonary embolism in subjects with no previous
thrombosis. The antibodies were measured in stored serum samples from 265 cases of
deep venous thrombosis of the lower extremity or pulmonary embolism occurring during
a median follow-up of about 7 years and from 265 individually matched controls. The
study subjects were middle-aged men participating in a cancer prevention trial of
alpha-tocopherol and beta-carotene and the cases of thromboembolic events were identified
from nationwide Hospital Discharge Register.
The risk for thrombotic events was significantly increased only in relation to antiprothrombin
antibodies. As adjusted for body mass index, number of daily cigarettes and history
of chronic bronchitis, myocardial infarction and heart failure at baseline, the odds
ratio per one unit of antibody was 6.56 (95% confidence interval 1.73-25.0). The seven
highest individual optical density-unit values of antiprothrombin antibodies were
all confined to subjects with thromboembolic episodes.
In conclusion, the present nested case-control study showed that high autoantibody
levels against prothrombin implied a risk of deep venous thrombosis and pulmonary
embolism and could be involved in the development of the thrombotic processes.