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Background and general principles of heritable thrombophilia

Thrombophilia testing is not appropriate and should not be carried out unless the results may influence clinical management.

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 alongside Warfarin.

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 be present.

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 recurrence.