What is the true risk of
thrombosis in patients carrying thrombogenic mutations?
Giuseppe Famularo
Department of Medical Sciences, San Camillo Hospital, Rome, Italy
Correspondence: Dr. Giuseppe Famularo, Department of Medical
Sciences, san Camillo Hospital, Circonvallazione Gianicolense,
00100 Rome, Italy. Tel/Fax +39-6-7847528. E-mail: gfamularo@uni.net
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Aznar and colleagues report that
carriers of the prothrombin G20210A variant and factor V Leiden
have an increased risk of venous thromboembolism, particularly if
they receive oral contraceptives.1 However, their data
are not as convincing as they look. The relation between the
prevalence of the most common thrombogenic mutations and the
probability of recurrent venous thrombosis is not linear,
suggesting that the actual risk of recurrence is also dependent on
a number of other genetic or acquired conditions and their
severity. The use of oral contraceptives adds significantly to the
risk but other concurrent factors could have a comparable or even
greater impact. For example, patients with the antiphospholipid
syndrome or the lupus anticoagulant (LAC) and those with
hyperhomocysteinemia have a particularly elevated risk of
thrombosis and this appears to be independent of whether they are
taking oral contraceptives.2,3 To establish with
confidence the actual thrombogenic potential of prothrombin
G20210A and factor V Leiden mutations, this segment of population
(i.e. those positive for antiphospholipid antibody or LAC and
those with hyperhomocysteinemia) should be not included in the
analysis of data. The apparent paradox associated with being
carriers of factor V Leiden mutation, i.e. an increased prevalence
of deep-vein thrombosis with a lower propensity to develop
pulmonary embolism once patients have thrombosis,4
indirectly suggests that other genetic or acquired conditions are
the major determinant of the clinical risk of patients with such
variants as prothrombin G20210A and Leiden mutations rather than
the presence of thrombogenic mutations per se.
In my opinion, it would be appropriate for any reassurance that
the data reported by Aznar and colleagues will be re-analyzed
after adjustment for the blood levels of homocysteine and the
presence of antiphospholipid antibodies and LAC. Even information
about pregnancy-related disorders should be provided.
