ORAL COMMUNICATIONS H-4: Physiological and Population Studies: 2
53 FAMILIAL DYSFIBRINOGENEMIA AND
THROMBOPHILIA. STRUCTURAL DEFECTS AND
IMPAIRED FIBRINOLYSIS.
‘Haverkate F and ‘Samama MM
‘Gaubius Laboratory, TNO-PG, Leiden, The Netherlands, and
*Hotel Dieu, Paris, France.
Amongst 250 cases of dysfibrinogenemia reported, 26 are
significantly associated with thrombophilia. To establish first a
possible association between familial dystibrinogenemia and
thrombophilia, we collected data of 187 relatives of 26 probands
with thromhophilic dysfibrinogenemia. Kaplan-Meier analysis
confirmed an association hetween defective structure and
thrombophilia which was predominantly venous thrombosis at
young age.
To investigate an association between thrombophilia and
structural defects and malfunction of the ahnormal fibrinogen, we
(including J. Koopman and J. Grimbergen) determined by DNA
sequencing the molecular defects in abnormal fibrinogen of, 11
unrelated patients with thromhophilic dysfibrinogenemia. Our
54 EPIDEYTOLOGY OF PLASMA D-DIMER, tPA A:JI) VON
WILLEBRAND FACTOR ANTIGENS: GLASGOW MONICA STIJDY.
Lowe GDO, Rumley A, Lee AJ and Tunstall-Pedoe HD
IJniversityDepartment of Medicine, Royal Infirm-
ary, Glasgow and Cardiovascular Epidemiology
JJnit , IJniversityof Dundee, 1J.Y.
Recent studies suggest that plasma D-dimer, tPA
and von Willebrand factor antigens are predic-
tors of cardiovascular events: it is therefore
important to define their relationships to bio-
logical, demographic and coronary risk factors
in the general population. We studied this in a
random sample of 603 men and women aged 25-64
years (Second Glasgow MONICA Survey), using
ELISA assays (from AGEN, Biopool and DAY0 resp-
ectively). All variables increased significantly
with age and the menopause; and decreased bet-
ween 09.00 and 17.00 hours. D-dimer was higher
in women, while tPA and VWF were higher in men.
In men, all three variables were higher in smok-
ers than non-smokers, and in those with preval-
ent coronary heart disease compared to those
55 FIBRINOLYTIC ACTIVITY IS NOT IMPAIRED IN REGULAR
SMOKERS AND SNUFF DIPPERS - THE NORTHERN
SWEDEN MONICA STUDY
lEliasson M, 2 Asolund K, 3 Evrin P-E, 1Lundblad D
Dept’s. of Internal Medicine. lLuleB Hosoital and *UmeB
University Hospital and 3Clinical Chemistry, Central Hospital,
Boden. Sweden
Population studies of tobacco use with specific assays for
fibrinolytic variables are lacking. Our aim was to study if
regular smoking or snuff dipping was associated with changes
in tissue plasminogen activator (tPA) activity or plasminogen
activator inhibitor type 1 (PAI-1) activity in a randomly selected
population sample. As a part of the WHO MONICA Project, 1
583 randomly selected men and women between 25 and 64
years were examined. 1 266 (80.0%) could be classified
accordina to well defined tobacco habits. 581 were non-
tobacco isers, 238 ex-smokers, 356 current cigarette smokers
and 90 snuff dippers. Tobacco use was not allowed during the
hour preceding the examination. Self-reported tobacco use
was validated by cotinine measurements.
19
results, added to those of others demonstrate that thrombosis is
predominantly associated with defects at the C-terminal end of the
Aol-chain or y-chain, or at the N-terminal site of the BP-chain of
fibrinogen.
A mechanism to explain thrombophilia is a decreased lysis of
abnormal fihrin as a consequence of defectivebinding to fibrin of
fihrinolytic enzymes. A defective binding of t-PA was associated
with defects at the N-terminal site of the BP-chain (2 cases), and
a defective hinding of plasminogen to the C-terminal end of the
Aor-chain (I case). Another mechanism to explain thrombosis is
a defective binding of thromhin to abnormal fibrin assoc.iated with
defects in the N-terminal site of the BP-chain (2 cases) of
fibrinogen. Consequently, thrombosis is not associated with a
defect in one particular region of the fibrinogen molecule.
We conclude that an association between thrombosis and
dysfihrinogenemia is plausible in some cases assuming a
malfunction of fibrin in fibrinolysis or thromhin binding. Why a
particular molecular defect leads to malfunction of fibrin is still
unclear.
without. All three variables correlated with
cholesterol and triglyceride in women, as did
tPA in men. tPA also correlated with body mass
index, blood pressure and gamma glutamyl trans-
peptidase (the latter perhaps being a marker of
liver metabolism/blood flow). Multivariate mod-
els for each variable are presented. We conclude
that age, sex, time of day and coronary risk
factors be considered when interpreting plasma
leve.lsof D-dimer, tPA and VWF; and that risk
factors may operate partly through endothelial
disturbance and fibrin turnover. Prospective
studies are in progress to further assess these
variables in prediction of coronary risk.
(Supported by a grant from the Scottish Office
Home and Health Department).
Results. No significant differences in tPA activity was found
between different groups of tobacco habits. Nor were there any
significant univariate linear correlations between tPA activity
and different measurements of tobacco exposure, except that
tPA activity in men was .26 IUlml lower (95% Cl .07 to -.60.
p=.O4) in the highest quintile of cigarettes consumption
compared to the lowest quintile. In a multiple linear regression
with age, anthropometric variables, blood pressure, serum
lipids and insulin included, there was no influence of smoking
or snuff use on tPA activity.
PAI- activity did not differ between groups. No significant
univariate or multivariate relations were found between
tobacco exposure and PAI- activity. Still, male smokers in the
highest quintile of cigarettes consumption had 5.7 U/ml higher
PAI- activity (95% Cl 4.3 to 7.1, p=.OO6) than those in the
lowest quintile.
Conclusion. Regular cigarette smoking and snuff dipping are
no major predictors of impaired fibrinolysis. A minor influence
can not be excluded but may be restricted to men smoking a
large numbers of cigarettes.