What is the management approach for individuals with inherited thrombosis (blood clotting) disorders?

Management of Inherited Thrombosis Disorders

The management of inherited thrombosis requires anticoagulation therapy with duration based on the specific thrombophilia type, with indefinite treatment recommended for patients with severe thrombophilias such as antithrombin, protein C, or protein S deficiencies. 1

Diagnostic Approach

• Testing for Factor V Leiden and prothrombin G20210A mutations is recommended in individuals with a first venous thrombosis episode under age 50, venous thrombosis in unusual sites, recurrent venous thrombosis, or a strong family history of thrombotic disease 2
• Inherited thrombophilia is detected in 10-59% of children with venous thromboembolism (VTE) and should be considered in patients with unexplained thrombotic events 1
• For suspected inherited platelet function disorders, a staged diagnostic approach is recommended, beginning with first-step tests available in most laboratories worldwide 3
• Patients testing positive for Factor V Leiden should be evaluated for other thrombophilias, particularly prothrombin G20210A mutation 2

Risk Assessment and Stratification

• The lifetime risk for venous thromboembolism in Factor V Leiden heterozygotes is approximately 10% and for homozygotes is over 80% 2
• Risk factors for thrombosis should be identified and ameliorated when possible (e.g., arrhythmias, ventricular dysfunction, prolonged immobilization) 3
• In patients with inherited thrombophilia, the co-existence of prothrombotic risk factors significantly increases the likelihood of developing thrombotic complications 4
• Carriers of factor V Leiden have an increased risk of thrombosis: 0.30-0.56 events per 100 patient-years 1

Anticoagulation Management

• The American Heart Association recommends a target INR of 2.5 (range 2.0-3.0) for all treatment durations, balancing bleeding risk against thrombosis risk when considering indefinite anticoagulation 2
• For severe thrombophilias (antithrombin, protein C, or protein S deficiencies), indefinite anticoagulation therapy is recommended 1
• Direct oral anticoagulants (DOACs) are now being used for VTE treatment in patients with inherited thrombophilia, though evidence in patients with well-characterized thrombophilia is still being gathered 5
• In patients with antithrombin deficiency who develop VTE while on prophylactic anticoagulation, antithrombin concentrate augmentation may be necessary 6

Special Considerations

Pregnancy Management

• Pregnancy in women with inherited thrombophilia requires a multidisciplinary approach involving hematologists and maternal/fetal medicine experts 1
• Women with thrombophilia and personal history of VTE should consider thromboprophylaxis during the postpartum period 2
• Low molecular weight heparins are the drugs of choice during pregnancy, but may be inadequate in some patients with severe thrombophilias like antithrombin deficiency 6

Hormonal Contraception

• Combined oral contraceptives produce a 30-fold increase in thrombotic risk when Factor V Leiden mutation is present, compared to a 4-fold increase with COCs alone 2
• Women with a personal history of venous thromboembolism should avoid combined oral contraceptives regardless of Factor V Leiden status 2
• Factor V Leiden is considered a "known thrombogenic mutation" and is listed as an absolute contraindication to combined oral contraceptive use in current contraceptive guidelines 2

Pediatric Patients

• Risk factors for pediatric VTE include inherited thrombophilia, central venous access devices, malignancy, and age-related factors 1
• The age distribution of VTE in children is bimodal with peaks in infancy and adolescence 1
• Treatment approaches should be adapted to the pediatric population, with DOACs now approved for some pediatric indications 1

Long-distance Travel

• For long-distance travelers with genetic thrombophilia, frequent ambulation, calf muscle exercise, sitting in an aisle seat, and properly fitted below-knee graduated compression stockings (15-30 mmHg at ankle) are recommended 2

Family Screening

• Screening of first-degree relatives of patients with high-risk thrombophilias (antithrombin, protein C, or protein S deficiency) should be considered 1
• Screening of asymptomatic female relatives is particularly important before starting hormonal contraception or during pregnancy planning 1
• The American College of Medical Genetics recommends against routine screening for Factor V Leiden in asymptomatic women contemplating or using oral contraceptives 2

Monitoring and Follow-up

• Patients with a palliated single ventricle should be monitored for thrombosis with periodic transthoracic echocardiography as part of routine follow-up assessments 3
• Serial clinical assessment and monitoring for changes in anatomic and hemodynamic thrombotic risk factors are indicated because risk factors may change over time 3
• When using DOACs in patients with inherited thrombophilia, be aware that they can interfere with thrombophilia testing, potentially causing overestimation of antithrombin activity and clot-based assays used for proteins C and S 5