, Benjamin Hohlfelder2 and Samuel Z. Goldhaber3
(1)
Cardiovascular Division, Harvard Medical School Brigham and Women’s Hospital, Boston, Massachusetts, USA
(2)
Department of Pharmacy Services, Brigham and Women’s Hospital, Boston, Massachusetts, USA
(3)
Thrombosis Research Group, Harvard Medical School Brigham and Women’s Hospital, Boston, Massachusetts, USA
Abstract
Risk factors for venous thromboembolism (VTE) include inherited thrombophilias, lifestyle-related risk factors, and acquired conditions of endothelial injury, stasis, and hypercoagulability. The majority of VTE patients presents with a combination of multiple risk factors that result in venous thrombosis. Common acquired risk factors include advanced age, malignancy, immobility, inflammation, and recent trauma, surgery, and hospitalization. Thrombophilia testing is most helpful when the results will assist in decision-making for prevention or treatment of VTE.
Keywords
Hypercoagulable statesRisk factorsThrombophiliaVenous thromboembolismSelf-Assessment Questions
1.
Which of the following factors increases the risk of recurrent venous thromboembolism (VTE)?
(a)
Factor V Leiden heterozygosity
(b)
Prothrombin gene mutation homozygosity
(c)
Compound heterozygosity for Factor V Leiden and prothrombin gene mutation
(d)
Suffering an idiopathic (unprovoked) VTE
2.
Thrombophilia testing is indicated in which of the following clinical scenarios?
(a)
A 82-year-old man with pulmonary embolism (PE) after a fall complicated by a right hip fracture
(b)
A 56-year-old woman with left lower extremity deep vein thrombosis (DVT) following right mastectomy for breast cancer
(c)
The younger sister of a 23-year-old non-smoking woman with left calf DVT following initiation of a combination oral contraceptive pill
(d)
A 19-year-old collegiate baseball pitcher with right upper extremity DVT following spring training sessions
3.
Which of the following problems with thrombophilia testing may occur during the acute diagnosis and treatment phase of a patient with PE?
(a)
A false positive result for prothrombin gene mutation testing
(b)
A false negative result for factor V Leiden mutation testing
(c)
A false positive result for protein S deficiency
(d)
A false negative result for protein C deficiency
Recognition of risk factors is a critical step in the assessment of a patient’s risk for developing an initial VTE and recurrent events. Inherited thrombophilias, lifestyle-related risk factors, and acquired conditions of endothelial injury, stasis, and hypercoagulability contribute to an individual’s risk for VTE (Table 2.1). The majority of patients with VTE presents with a combination of multiple risk factors that result in venous thrombosis. Illustrating this point, the patient in the Clinical Vignette has numerous VTE risk factors, including hypertension, coronary artery disease, obesity, smoking, immobility, and recent acute infectious illness.
Table 2.1
Major risk factors for venous thromboembolism (VTE)
Inherited |
Factor V Leiden mutation (activated protein C resistance) |
Prothrombin gene mutation 20210 |
Deficiency of protein C, protein S, or antithrombin |
Family history of VTE |
Lifestyle |
Smoking |
Obesity |
Diet (high red meat, low fish and vegetable consumption) |
Stress |
Acquired |
Advancing age |
Prior history of VTE |
Recent surgery, trauma, or hospitalization |
Long-haul air travel |
Malignancy |
Hyperhomocysteinemia (less commonly inherited secondary to a mutation in methylenetetrahydrofolate reductase) |
Pregnancy, oral contraceptive pills, or hormone replacement therapy |
Atherosclerotic cardiovascular disease and associated factors (including diabetes, dyslipidemia, hypertension) |
Pacemaker or implantable cardiac defibrillator leads and indwelling venous catheters |
Chronic medical illness (including heart failure, chronic obstructive pulmonary disease, chronic kidney disease) |
Lupus anticoagulant, antiphospholipid antibodies, anti-β2 glycoprotein-1 antibodies, or anticardiolipin antibodies |
Immobility |
Inflammatory |
Acute infectious illness |
Blood transfusion and erythropoiesis-stimulating agents |
Chronic inflammation (including systemic vasculitides, inflammatory bowel disease) |
Clinical Vignette
A 68-year-old woman with past medical history of hypertension and coronary artery disease status post coronary artery bypass graft surgery 5 years prior developed left leg discomfort and edema 1 week following discharge from the hospital for community acquired pneumonia. She was obese and an active smoker. She admitted to spending most of her time in bed watching television since returning home from the hospital. In the Emergency Department, a venous ultrasound demonstrated left popliteal vein DVT (Fig. 2.1).
Fig. 2.1
Venous ultrasound demonstrating non-compressibility of the left popliteal vein (POP V) (ovals) consistent with the diagnosis of acute deep vein thrombosis (DVT) in a 68-year-old woman recently discharged from the hospital after admission for pneumonia who had risk factors for venous thromboembolism (VTE) including obesity, smoking, immobility, coronary artery disease, and age
Inherited Thrombophilias
Inherited thrombophilias should be suspected in patients with VTE at a young age, multiple family members with VTE, VTE in unusual locations, idiopathic or recurrent VTE, or a history of recurrent miscarriages. The prevalence of specific inherited thrombophilias varies according to population demographics. In the general population, inherited thrombophilias are less frequent than “traditional” VTE risk factors, such as cancer, immobility, and obesity [1]. However, in patients who have experienced an initial episode of VTE or have a family history of VTE, the prevalence of inherited thrombophilia increases.
Testing for inherited thrombophilias is often performed to assess the risk of recurrent VTE in a patient with an initial event. However, only a subset of inherited thrombophilias significantly increase the risk of VTE recurrence. While deficiencies of protein C, protein S, or antithrombin consistently increase the risk of recurrent VTE, more common inherited thrombophilias such as factor V Leiden and the prothrombin gene mutation do not appear to increase the risk of recurrence [2]. In a study evaluating the impact of factor V Leiden and the prothrombin gene mutation on VTE recurrence, heterozygosity for either factor V Leiden or the prothrombin gene mutation was not associated with an increased risk of VTE recurrence [3]. Furthermore, compound heterozygosity and homozygosity for either factor V Leiden or prothrombin gene mutation did not increase the risk of recurrent VTE.
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