Friday, June 27, 2008

Treatment of Antiphospholipid Antibody Syndrome

The spectrum of the antiphospholipid syndrome
allows for the stratification of risks and therapeutic
options. Among patients with antiphospholipid antibodies,
the risk of thrombosis at some future time
is moderate in women with pregnancy loss alone,
higher among those in whom thrombosis occurs,
and extremely high in patients with the rare but devastating
syndrome of rapidly progressive, multistage
vascular occlusion, known as catastrophic
antiphospholipid syndrome.


By contrast, asymptomatic
persons who are incidentally found to have
positive antibody tests are at the lowest risk for any
of these events. A high titer of auto antibodies, especially
lupus anticoagulant, increases the likelihood
of thrombosis, as do smoking, the use of oral
contraceptives, surgery, immobilization, pregnancy,
and heritable pro coagulant states. Another measure
of complexity is that patients with antiphospholipid
antibodies who do not have recurrent thrombosis
but who do have livedo reticularis, thrombocytopenia,
cardiac-valve vegetation, a multiple sclerosis–
like condition, or progressive cognitive dysfunction
do not fulfill the usual criteria for the diagnosis of the antiphospholipid syndrome. In these patients,
the risk of thrombosis, and hence the urgency of
treatment with an anticoagulant agent, is unknown.
Thrombosis and fetal loss can also be caused
by mutations involving factor V (factor V Leiden),
prothrombin, or methylenetetrahydrofolate reductase,
or by deficiencies of protein C, protein S, or antithrombin
III. Opinions differ, but the concomitant
presence of two or more prothrombotic risk
factors may increase the risk. Thus, a precise diagnosis
requires an expensive and inconvenient panel
of tests. Very few clinical clues differentiate the various
types of thrombophilia. Arthralgia, leukopenia,
thrombocytopenia, livedo reticularis, or a rheumatic
illness (or a family history of rheumatic illness) increases
the likelihood that the antiphospholipid
syndrome is the cause of a newly diagnosed thrombosis.
Two tests, a standardized enzyme-linked immunosorbent
assay for anticardiolipin antibodies
and a clotting test for lupus anticoagulant, readily
and inexpensively confirm or rule out the antiphospholipid
syndrome. Population studies usually identify
the antiphospholipid syndrome and factor V
Leiden as the most common causes of thrombophilia,
each accounting for about 20 percent of cases
of recurrent thrombosis among young patients.
Approximately 15 percent of women with recurrent
pregnancy loss have the antiphospholipid syndrome.
The antiphospholipid syndrome and the
genetic thrombophilias are proportionately less frequent
among persons 65 years of age or older, because
with increased age, atherosclerosis and cancer
are more frequent causes of thrombosis.
A heterogeneous clinical picture has led to discrepant
recommendations for treatment of the
antiphospholipid syndrome. Corticosteroids, prescribed
in the 1980s because of the association of
the syndrome with lupus, proved ineffective in preventing
pregnancy loss.
4
In pregnant women with
a history of recurrent fetal loss, low doses of unfractionated
heparin (5000 U administered subcutaneously
twice daily) are as effective, with respect to the
outcomes of pregnancy, as high doses (10,000 U or
more twice daily).
5
Patients with previous thrombosis
require high doses. Prospective dose-ranging
studies of warfarin for the treatment of thrombosis
in patients who are not pregnant have not
been done. A 1995 report of a retrospective study
concluded that anticoagulant therapy that results in
an international normalized ratio (INR) of 3.0 or
higher affords better protection against recurrence
than does less intense anticoagulant therapy.