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Giornale Italiano di Cardiologia Pratica
It J Practice Cardiol
Dicembre 2003
sed this problem by studying a large
series of women with previous VTE,
part of which while using OC (4). The
prevalence of the two commonest
thrombophilic mutations in the heterozigous
form was respectively 19.3% for
FV and 9.6% for F II mutation, while
2.7% were carriers of both defects. In
absence of such mutations the odds ratio
for VTE related only to use of OC
was 2.4, but was heightened to 41 in
carriers of the FV, to 58.6 in carriers of
the F II mutation, and to 86.5 in the
few carriers of both defects (4). We also
found an increase of VTE risk under
the pill (by 3.5) in women with high
prothrombin levels and a normal genotype(9).
Recurrences of venous
thromboembolism
VTE is a chronic recurrent disease (10).
In the Olmsted County study (1), the
cumulative incidence of the first VTE
recurrence was 16.6% in two years,
23% in 5 years and 30% in 10 years.
However, the absolute hazard of recurrence
per 1000 patients/days correspondently
declined from 30 at 90
days to 20 at 2 years, and was as low
as 5 at 10 years. Similar figures had
been reported also by other Authors
(11, 12) and were confirmed in a recent
meta-analysis (13).
The cumulative incidence of fatal PE after
a first episode of DVT is about 2.6%
(11). In a systematic review by Douketis
et al. (14) the rate of fatal PE during effective
treatment of acute DVT was
0.4%, and remained 0.3 per 100
pts/years after anticoagulant therapy.
Among patients presenting with PE,
however, the case-fatality rate of recurrent
DVT or PE was as high as 26.4%.
Thus, patients presenting with PE are at
higher risk of death in case of a recurrent
episode than those presenting
with DVT. Regarding the post-Thrombotic
Syndrome (PTS) its cumulative incidence
has been shown to be 22.8%
after 2 years, 28% after 5 y and 29%
after 8 y (12). The development of PTS
appeared to be strongly associated with
ipsilateral DVT recurrences.
What are the risk factors for
recurrences?
Main risk factors for recurrences are
"idiopathic" versus "secondary" VTE,
permanent versus transient risk circumstances
at first episode (13), a history of
previous VTE, presence of primary
thrombophilic states either congenital
(mainly AT III, Protein C and S deficiences)
or acquired (LAC and antiphospholipid
syndrome). However, the two
commonest thrombophilic mutations
(abnormal Factor V and Factor II) are
still open to debate as significant factors
for recurrences (16), except for the
combined heterozigous (17) or the single
homozigous defects.
Malignancy is an important risk factor
for recurrences. Even during effective
oral anticoagulant therapy a higher rate
of thrombotic recurrences, together
with a significantly higher bleeding risk
has been observed (18, 19).
Can VTE recurrences be
predicted?
The levels of D-Dimer three months after
stopping oral anticoagulation showed
a high negative predictive value
(NPV) for VTE recurrences (20). In a
further study of our group (21) altered
D-Dimer at 1 month testing after discontinuation
of anticoagulation was associated
with a higher rate of recurrence,
expecially in those subjects with an
idiopathic first DVT episode, and/or
with thrombophilia. The NVP for recurrences
of the 1-month D-Dimer level
was as high as 96% in the patients with
thrombophilia.
The extent of persistent residual vein
thrombosis (RVT) after a first DVT episode
also appears to be a dependable
predictor of recurrences (20, 21). This
result needs some interpretation for
what concerns the contralateral recurrences,
that amount to almost 50% of
the total. We tried therefore to couple
the two mentioned criteria, namely D-
Dimer and RVT and found that the
predictive power of RVT was greatly
enhanced by a combined D-Dimer
measurement (mx recurrence rate of