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Factor V Leiden Thrombophilia

Most common inherited thrombophilia caused by an activated protein C resistance mutation in factor V.

Written by: Saygı Hospital Health Guide Editorial Board
Last updated:

This content has been compiled by the Saygı Hospital Health Guide Editorial Board and is periodically reviewed by a specialist physician.

References (5)

This content is for informational purposes only and does not constitute medical advice. You can book an appointment at our Hematoloji department. Book Appointment →

What is Factor V Leiden Thrombophilia?

Factor V Leiden (FVL) is the most common inherited thrombophilia in populations of European descent (carrier frequency 3-8% in heterozygotes). It is a single-base substitution (1691 G>A) in the F5 gene replacing arginine with glutamine at position 506 (R506Q), one of the cleavage sites where activated protein C (APC) inactivates factor Va. The mutated factor Va is degraded more slowly, resulting in prolonged thrombin generation and a hypercoagulable state called APC resistance.

Heterozygous FVL increases venous thromboembolism (VTE) risk approximately 3-7 fold, while homozygous FVL increases risk 20-80 fold. The lifetime VTE risk in heterozygotes without other factors remains modest (5-10%), so most carriers never have an event. Risk multiplies with concurrent factors: estrogen-containing oral contraceptives, hormone replacement therapy, pregnancy, postpartum, surgery, immobilization, and other thrombophilias.

Diagnosis is by APC resistance screening (modified clotting assay) followed by genetic testing for F5 R506Q if abnormal. Most carriers do not require prophylactic anticoagulation; thromboprophylaxis is targeted to high-risk situations (major surgery, pregnancy in selected cases, prolonged immobilization). After a first VTE, decisions about extended anticoagulation depend on whether the event was provoked, additional risk factors, and personal/family history rather than carrier status alone.

Symptoms

Most carriers asymptomatic
Deep vein thrombosis (leg swelling, pain)
Pulmonary embolism (sudden dyspnea, chest pain, hemoptysis)
Cerebral venous thrombosis (headache, seizures, focal deficit)
Mesenteric or portal vein thrombosis (abdominal pain)
Recurrent unexplained miscarriage (debated association)
Thrombosis with oral contraceptives, HRT, or pregnancy
Postoperative VTE
Postpartum VTE
Catheter-related thrombosis
Family history of VTE
Unusual-site thrombosis (Budd-Chiari, retinal vein)
Stroke in young adults (rare)
Recurrent superficial thrombophlebitis
Severe homozygous: VTE in childhood or adolescence

Risk Factors

Factor V Leiden mutation (heterozygous or homozygous)
Family history of VTE
European ancestry
Estrogen oral contraceptives, HRT
Pregnancy and postpartum
Surgery, especially orthopedic and abdominal
Immobilization, long-haul travel
Cancer
Trauma
Antiphospholipid syndrome (compound risk)
Other inherited thrombophilias (prothrombin G20210A, AT/protein C/S deficiency)
Obesity
Smoking
Age
Compound heterozygosity (FVL + prothrombin) markedly increases risk

When to See a Doctor?

If you experience any of the following symptoms, seek medical attention promptly:

  • Personal history of VTE for thrombophilia evaluation
  • Family history of VTE in young relatives
  • Recurrent unexplained miscarriage
  • Pre-pregnancy counseling with known FVL
  • Considering oral contraceptives or HRT with FVL or family history
  • Major surgery planned in known carrier
  • Unusual-site thrombosis
  • Cerebral or mesenteric venous thrombosis

Treatment Methods

01
Hematology referral for evaluation
02
Indications for testing: first VTE in young patient, unprovoked VTE, recurrent VTE, unusual site, strong family history, considering hormonal therapy in family
03
APC resistance ratio (modified, factor V deficient plasma) as screening test
04
Genetic testing for F5 R506Q to confirm and define heterozygous vs homozygous
05
Pre-test and post-test genetic counseling
06
Acute VTE: standard anticoagulation (DOAC, LMWH, or warfarin) — same as non-carriers
07
Duration: 3 months for provoked event; extended/indefinite for unprovoked, recurrent, or homozygous with major event
08
Avoid combined estrogen-progestin contraceptives in carriers with VTE history; progestin-only or non-hormonal contraception preferred
09
Pregnancy: no routine anticoagulation in heterozygous without prior VTE; antepartum and postpartum prophylaxis (LMWH) if prior VTE, family history, homozygous, or compound thrombophilia
10
Surgical prophylaxis: standard VTE prophylaxis with mechanical and pharmacologic measures; extended duration in major orthopedic surgery
11
Long-haul travel: hydration, mobilization, compression stockings; LMWH only in selected high-risk individuals
12
Family screening guided by symptomatic family member; cascade testing controversial in asymptomatic relatives
13
Patient education on VTE warning signs, hormonal therapy avoidance, surgery and pregnancy planning
14
Lifestyle: smoking cessation, weight management, regular activity
15
Avoid prolonged immobilization, dehydration
16
Coordinate with obstetrics, gynecology, surgery as needed
17
Genetic counseling for compound thrombophilia (FVL + prothrombin G20210A) markedly increased risk
18
Surveillance after VTE: signs of post-thrombotic syndrome, recurrence
19
Adherence and bleeding risk discussion if on long-term anticoagulation
20
Vaccinations for splenectomy not relevant here; routine adult vaccines per guidelines

Which Department to Visit?

You can visit our Hematoloji department for these complaints. Our specialist physicians will create the most suitable treatment plan for you.

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Health Disclaimer: The information on this page is prepared for general informational purposes only. It does not replace medical diagnosis and treatment. Please consult your physician for your complaints. Saygı Hospital does not accept responsibility for actions taken based on the information on this page.