Basis of management is treatment of a thrombotic event with anticoagulation. Treatment for FVL individuals is the same as non-affected patients for the initial thrombotic event. For homozygotes or those with recurrent events, lifetime anticoagulation is considered.
First Steps after Confirming Diagnosis
- First VTE Event
- Routine anticoagulation, as for VTE in any other patient
- Duration of therapy is not clear
- Long term anticoagulation not indicated for uncomplicated heterozygotes
- Can consider long term anticoagulation for homozygotes, recurrent VTE, coexistent non-modifiable risk factors, multiple thrombophilic disorders
- VTE during Pregnancy
- routine anticoagulation, as for VTE in any other pregnant patient
Diet, Exercise, and Lifestyle Interventions
- Target BMI 20-25.
- Avoid prolonged immobility .
- Smoking cessation.
- Risks and benefits of hormonal contraceptives, HRT and SERMs should be considered on an individual level . No current guidelines exist for their use in thrombophilia patients.
Re-assessment of treatment plan when risk factor status changes (e.g. surgery, pregnancy, use of hormonal contraception, HRT or SERMS).
Follow up testing/screening/monitoring
Maintain high index of suspicion for VTE.
Care team members
- Genetic counselor and/or Geneticist
- High risk OB
Generally N/A (unless indicated due to specific VTE event)
May be beneficial to female patients with multiple pregnancy loses secondary to thrombophilia
- Anticoagulants as appropriate for specific VTE events
Contraindicated (or use with caution)
- Estrogen contraceptives
- SERMs (especially Tamoxifen)
Surgery and/or procedures
Occasional patients with recurrent DVT who are not candidates for anticoagulation may benefit from inferior vena cava filter placement to prevent life-threatening PE.
Treatments and interventions to avoid
Long term anticoagulation in FVL heterozygotes with no history of VTE should be avoided because risk of bleeding is higher than risk of VTE
Effect of the condition on fertility
No evidence that the condition has any effect on fertility
Effect of the condition on pregnancy, delivery and/or the postpartum period
- 2-5 fold increased risk of fetal loss
- Risk of recurrent, early-onset and severe preeclampsia
- Possible 3-5 fold increased risk of intrauterine growth restriction (IUGR) (but some studies found no association)
- Interventions to reduce risk:
- Use of low molecular weight heparin (LMWH) during pregnancy is not routinely recommended but can be considered with appropriate risk/benefit discussion with the patient.
- No evidence that anticoagulation therapy reduces the risk of other pregnancy complications associated with FVL, including preeclampsia and IUGR.
Effect of pregnancy on manifestations of the condition
- Pregnancy is a known risk factor for thrombosis and FVL patients have higher risk of VTE event during pregnancy
- Prophylactic LMWH or unfractionated heparin during pregnancy followed by 4-6 week course of warfarin postpartum is recommended for patients with:
- History of unprovoked VTE
- History of estrogen provoked VTE
- Multiple thrombophilia disorders
- When indicated, routine anticoagulation, as for VTE in any other pregnant patient
- Incidence of venous thrombosis:
- Heterozygotes: 0.19% - 0.49% per year
- Homozygotes: 1.3% per year
- VTE risk in FVL heterozygotes is 7 fold higher than general population risk
- VTE risk in homozygotes is 80 fold higher than general population.
Factors affecting expression (variable expressivity)
- Risk of VTE event is higher amoong individuals with a family history of thrombosis as compared those without a family history of thrombosis. This suggests additional inherited thrombophilic factors that have not yet been identified.
- Additional environmental risk factors are present in 50% of FVL patients with VTE.
Effect on longevity/lifespan
No increase in mortality or change in life-expectancy, assuming appropriate monitoring and treatment.
Effect on function and quality of life
Overall function and quality of life remains high given that most patients are asymptomatic
Expected response to therapy
FVL has no effect on response to standard anticoagulation
How do genetic test results alter prognosis?
- Homozygotes have a much higher incidence of initial VTE, recurrent VTE and early-onset VTE (<50 years old).
- Homozygotes can be considered for lifetime anticoagulation therapy after their first VTE event depending on individual risks of bleeding.
Pre-symptomatic or Asymptomatic Patients
- Long term anticoagulation is not recommended for heterozygotes with no history of VTE because the yearly risk of major bleeding (1-3%) exceeds the risk of a thrombotic event (0.2-0.5%).
- Long term anticoagulation may be considered for asymptomatic homozygotes since their risk of VTE is highe., However, there is no evidence that it is beneficial from a cost-benefit perspective.
- Prophylactic short-term anticoagulation should be considered when patients are at a higher risk, such as undergoing surgery or prolonged immobilization.
- There is no evidence that prophylaxis is beneficial in pregnant patients. However, patients can be offered a 4 to 6 week course of anticoagulation following delivery as this is the time of highest risk.
Consensus Statements and Guidelines
Jobin S, Kalliainen L, Adebayo L, Agarwal Z, Card R, Christie B, Haland T, Hartmark M, Johnson P, Kang M, Lindvall B, Mohsin S, Morton C. Venous thromboembolism prophylaxis. Bloomington (MN): Institute for Clinical Systems Improvement (ICSI); 2012: 51.
Geerts W, Bergqvist D, Pineo G, Heit J, Samama C, Lassen M, Colwell C. Prevention of venous thromboembolism: American College of Chest Physicians evidence-based clinical practice guidelines (8th edition). Chest. 2008;133(6):381S-453S.
ACOG Committee on Practice Bulletins. Prevention of Deep Vein Thrombosis and Pulmonary Embolism. Obstet Gynecol. 2007;101(2): 429-440.