Thrombophilia, risk factors and prevention

ABSTRACT

Introduction: Fifty-three years after the first description of an inherited prothrombotic condition (antithrombin deficiency), our knowledge on hereditary and acquired causes of hypercoagulability that can predispose carriers to venous thromboembolism (VTE) has greatly improved.

Areas covered: Main causes of hereditary thrombophilia are summarized alongside new prothrombotic mutations recently discovered. The main causes of acquired thrombophilia, and namely, antiphospholipid antibody syndrome and hyperhomocysteinemia, are also discussed together with other common acquired prothrombotic states characterized by an increase of procoagulant factors and/or a decrease of natural anticoagulants. Finally, suggestions for thromboprophylaxis in carriers of hereditary thrombophilia according to current guidelines/evidence are made for the most challenging high-risk situations (i.e. surgery, pregnancy, contraception, cancer, economy class syndrome) as well as for the prevention of post-thrombotic syndrome.

Expert opinion: A carrier of inherited thrombophilia should be evaluated in the framework of other (genetic and/or acquired) coexisting risk factors for first or recurrent VTE when assessing the need and duration of prevention (primary prophylaxis). Prevention strategies should be tailored to each patient and every situational risk factor. The knowledge of the carriership status of severe thrombophilia in the proband can be important to provide asymptomatic relatives with adequate counseling on thrombophilia screening or primary thromboprophylaxis.

KEYWORDS:

• Deep vein thrombosis
• inherited and acquired thrombophilia
• pregnancy
• pulmonary embolism
• thromboprophylaxis
• venous thromboembolism

Article highlights

• Thrombophilia is a clinical condition defined as either an inherited or acquired abnormality of hemostasis predisposing to venous thromboembolism (VTE).

• Hereditary and acquired thrombophilia determine a prothrombotic state. Acquired disorders foster a prothrombotic state via elevated procoagulant factors, reduced anticoagulants, pro-inflammatory/autoimmune mechanisms.

• Hereditary thrombophilia is divided into mild or severe according to the thrombotic risk associated with the genetic abnormalities.

• New genetic gain-of-function defects responsible for severe thrombophilia have been identified, and namely, pseudo-homozygosity for activated protein C resistance, factor IX Padua and resistance to antithrombin.

• Individual’s ABO blood group is the most common genetic risk factor for VTE to remember.

• The main acquired thrombophilia conditions are antiphospholipid antibody syndrome, hyperhomocysteinemia, acquired increased levels of procoagulant factors and/or decreased levels of natural anticoagulants.

• A subject with thrombophilia should be evaluated in the framework of other (genetic and/or acquired) coexisting risk factors for first or recurrent VTE when assessing the need and duration of prevention (primary prophylaxis).

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.