Thrombophilic States

  • Adriana Guigova
  • Tony Philip


The concept of hereditary thrombophilia was first described by Egeberg in 1965. At that time, he noted that members of his family had suffered from recurrent thrombotic events and that this predisposition was inherited in an autosomal dominant fashion. Since his initial observation, our current understanding of the pathogenesis of thromboembolism has evolved significantly. The current model for pathologic thrombus formation emphasizes the interaction of acquired and genetic risk factors in the pathogenesis of venous and arterial thromboembolism. When the sum total of thrombotic potential exceeds compensatory antithrombotic mechanisms, then symptomatic thromboembolism occurs. This multi-hit hypothesis of venous thromboembolism proposed by Frits Rosendaal in 1999 still provides a useful framework when assessing the etiology of thromboembolism in individual patients and helps inform therapy. Thrombophilia refers to congenital or acquired predispositions to thrombus formation. Here, we review the currently established hereditary and acquired thrombophilias. We will review genetic thrombophilic conditions such as factor V Leiden, the prothrombin gene 20210 mutation, protein C and S deficiency, antithrombin deficiency, hyperhomocysteinemia, and the methylenetetrahydrofolate reductase (MTHFR) mutation. We will also discuss important acquired risk factors such as surgery, trauma, immobility, malignancy, rheumatologic diseases and infections, pregnancy and the postpartum period, hormonal therapies and chemotherapeutic agents, as well as the antiphospholipid antibody syndrome, paroxysmal nocturnal hemoglobinuria (PNH), JAK2-associated myeloproliferative neoplasms, and anatomic predispositions to thrombosis such as May-Thurner syndrome. A focus on the appropriate testing, timing, and the implications of such states being present will be made for each thrombophilic state.


Inherited thrombophilias Factor V Leiden mutation Protein C deficiency Protein S deficiency Antithrombin III Antiphospholipid antibody syndrome Homocysteine Polycythemia vera May-Thurner syndrome Acquired thrombophilia 


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of Hematology/Oncology, Department of MedicineZucker School of Medicine at Hofstra/Northwell, Northwell HealthLake SuccessUSA

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