Current Research
by Dr Laura
Bertolacinni, Louise Gergel Fellow
The antiphospholipid
syndrome (APS) is a disease also called 'sticky blood' syndrome in which
the blood has a tendency to clot spontaneously. This clotting disorder can
affect any vessel in the body or even, during pregnancy can be a major
cause of miscarriages and fetal death. The majority of people with APS are
aged between 20 and 50 years, although all age groups can be affected. It
seems to be more frequent in women than men because of its effect on
pregnancy.
There are two main blood tests that are used for diagnosis: 1) the anticardiolipin
test (aCL) and 2) the lupus anticoagulant test (LA). Although these
tests are the most clinically useful, there are a small number of people
with APS (about 20%) in whom one or other test will be negative.
International research
efforts are directed in 3 broad based aspects – the basic mechanisms of
the disease (why patients develop the condition in the first place and why
some patients develop thrombosis and others not), the clinical
ramifications of the disease (a condition which can potentially affect any
organ must impinge on all branches on medicine) and methods to improve and
‘fine tune’ treatment.
The common thread
linking patients with APS is the presence of antibodies. Antibodies would
normally have the task of defending against foreign invaders such as
viruses or bacteria but in this disease, antibodies known as
“antiphospholipid antibodies” (aPL) react to self-molecules,
particularly phospholipid-protein complexes. The association between aPL
and thrombosis is strong, but the exact mechanism for the thrombosis
remains uncertain. aPL have been shown to alter platelets, clotting
proteins and the blood vessel lining itself (endothelium).
One attractive theory is that these antibodies affect the clotting
proteins of the blood. Recently, we have identified new targets for the
aPL, which are being extensively investigated in our laboratory.
Antibodies to prothrombin (a coagulation protein) have been shown to be
specific markers for thrombosis. Most
significantly, we have also shown that some patients with APS related
clinical features, which are negative for aCL and LA had antiprothrombin
antibodies, suggesting that testing for these antibodies could be of added
clinical benefit. Antibodies to Factor XII, another protein involved in
the clotting process, have also been found in patients with APS and their
immunological characteristics are being investigated.
Further reading
1.
Bertolaccini ML, Hughes GR. Antiphospholipid antibody testing:
which are most useful for diagnosis? Rheum Dis Clin North Am 2006; 32:
455-63
2.
Bertolaccini ML, Khamashta MA. Laboratory diagnosis and management
challenges in the antiphospholipid syndrome. Lupus 2006; 15: 172-8
3.
Khamashta MA. Hughes syndrome. Antiphospholipid syndrome. Khamashta
MA, ed. London: Springer-Verlag, 2006
