Background and general principles of heritable thrombophilia
Thrombophilia testing is not appropriate and should not be
carried out unless the results may influence clinical
Thrombophilia is a multifactorial condition with heritable,
acquired and circumstantial components which interact to give rise
to an increased risk for VTE. VTE most commonly manifests as deep
vein thrombosis (DVT) in the leg. This may progress to pulmonary
embolism (PE) if the clot dislodges and travels to the lung. The
incidence of venous thromboembolism (VTE) in the general population
increases with age.
Up to 50% of individuals with VTE may have an identifiable
heritable thrombophilia. This has led to a large demand for
thrombophilia testing, despite the fact that there is frequently a
lack of evidence in the literature that this testing has clinical
utility. In most cases patient management is unlikely to be altered
by the presence or absence of a thrombophilia risk factor.
Heritable thrombophilias include factor V Leiden (F5 gene
c.1601G>A) and a prothrombin gene variant (F2 gene c.*97G>A)
- PGV, both of which are common in Caucasians but generally rare in
other ethnic groups, and deficiencies of antithrombin (AT), protein
C (PC) and protein S (PS), all of which are rare.
The majority of the VTE events occurring in individuals with
heritable thrombophilia are provoked by one or more predisposing
factors, eg surgery, immobility, increasing age, pregnancy,
combined oral contraceptive pill, malignancy.
The magnitude of risk associated with a positive thrombophilia
test result is often perceived by the patient to be greater than it
actually is, with associated negative psychological impact.
Testing for heritable thrombophilia is not indicated in
unselected patients who present with a first episode of VTE.
Initiation and intensity of anticoagulant therapy following a
diagnosis of acute VTE is not generally influenced by the presence
or absence of a heritable thrombophilia. Patients with PC or PS
deficiency, however, should have initiation of anticoagulation with
low molecular weight heparin for an adequate period of time
Decisions regarding duration of anticoagulation should be made
taking into account whether or not a first VTE was provoked and
considering the risk of anticoagulant therapy related bleeding,
regardless of whether or not a heritable thrombophilia is known to
Finding a common heritable thrombophilia (heterozygosity for FV
Leiden or PGV) does not typically predict the likelihood of VTE
recurrence. There is a higher recurrence risk in patients with AT,
PC, or PS deficiency or with multiple defects.
Evidence suggests that thrombophilia testing does not reduce the
risk of VTE recurrence in clinical practice.
Patients who have recurrently normal D-dimers after completion
of anticoagulation therapy have a comparatively low risk of VTE