Discussion
This 17-year-old Caucasian male’s challenging presentation of DVT and
saddle PE occurred in the setting of trauma, immobilization, obesity,
and double-heterozygosity for FVL/PT-G20210A with concurrent APS. Given
the persistence of his APS in the setting of double-heterozygosity for
FVL/PT-G20210A, despite resolution of his previous provoking trauma and
immobilization, he will be continued on therapeutic anticoagulation with
enoxaparin for least 6 months.
The risks of VTE associated with either FVL or PT-G20210A mutations have
been described in a multitude of studies. However, the risk in patients
with double-heterozygosity for FVL/PT-G20210A has been more difficult to
understand due to lack of power in many studies given the rarity of both
polymorphisms together.6 In the meta-analysis by
Simone et al, the risk of initial VTE in patients with
double-heterozygosity for FVL/PT-G20210A was increased when compared to
patients without either mutation or with PT-G20210A heterozygosity
alone.7 There is conflicting evidence on VTE
recurrence risk in patients with double-heterozygosity for
FVL/PT-G20210A. An investigation in the Netherlands reported no increase
in risk of VTE recurrence for patients with double-heterozygosity
relative to patients without known FVL or PT-G20210A in a population in
the Netherlands.1 However, the relative risk of VTE
recurrence was reported as high as 3.7 for patients with double
heterozygosity compared to patients with a single FVL mutation in a
population in Italy.8 It has also been demonstrated
that patients with double-heterozygosity for FVL/PT-G20210A may present
with the first episode of VTE at a significantly younger age than
patients with VTE associated with no genetic risk factors or single gene
defects alone (34.7 vs 40.6 years, P<0.01). Despite some
differing reports of recurrence risk, there is data to support the use
of lifelong anticoagulation for patients with double-heterozygosity
alone.
Our patient has the additional risk factor of APS, which with concurrent
double heterozygosity of FVL/PT-G20210A has been described in at least
one case of catastrophic antiphospholipid syndrome as a contributor to
disease. For APS alone, there is conflicting evidence for the use of
aspirin for primary prevention of arterial and venous thromboembolism,
although The European Alliance of Associations for Rheumatology (EULAR)
has recommended primary prevention for even asymptomatic patients with
APS and a high-risk profile (presence of persistent LA or any
combination of two or more of LA/aCL antibody/aβ2GPI antibody) with
low-dose aspirin since 2019.4,10 There is limited
evidence for secondary prevention of venous thromboembolism in patients
with APS, as would apply to our patient, but warfarin monotherapy is
typically utilized with a target international normalized ratio of
2.0-3.0. In the event of recurrent venous thrombosis in a patient with
APS while on warfarin, EULAR recommends consideration of warfarin
combined with low-dose aspirin or extended therapeutic
enoxaparin.4,10. Family discussion regarding the
benefits and risks of indefinite anticoagulation with warfarin after 6
months is ongoing for the patient in this case.
Much of the literature examining risk of VTE with genetic mutations
specifically exclude individuals with inciting factors, such as trauma,
which was an important provoking factor for this patient. This case also
highlights the importance of evaluation for thrombophilia in patients in
select circumstances with extensive thrombus burden, even in the setting
of known risk factors such as trauma and obesity, as the results may
have lifelong clinical implications.
Legend: FIGURE 1 Patient’s chest computed tomography at initial
diagnosis of saddle PE with thrombus extending into the left and right
pulmonary arteries.
Conflict of Interest: The authors declare that there is no
conflict of interest.Acknowledgements: We are grateful to Dr. Pamela Camacho for her
clinical care of this patient.References
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