Factor VII Deficiency: Diagnosis and Management
Diagnosis
Factor VII deficiency is diagnosed by an isolated prolonged prothrombin time (PT) with a normal activated partial thromboplastin time (aPTT), followed by specific Factor VII coagulant activity (FVII:C) assay. 1, 2
Diagnostic Algorithm
First-line testing: PT and aPTT are performed in all patients with suspected bleeding disorders 3
- PT will be prolonged while aPTT remains normal—this is the only congenital bleeding disorder with this pattern 2
Confirmatory testing: Specific FVII:C assay to quantify factor VII levels 4, 2
- Severe deficiency: FVII:C <1%
- Moderate deficiency: FVII:C 1-5%
- Mild deficiency: FVII:C 5-20% 5
Molecular diagnosis: FVII gene sequencing can identify specific mutations on chromosome 13, though this is typically second-line testing 4, 2
Critical Diagnostic Pitfall
There is no consistent correlation between FVII:C levels and bleeding severity—some patients with undetectable FVII may be asymptomatic, while others with 10-15% levels may bleed significantly. 4, 2 Clinical phenotype must guide management decisions, not laboratory values alone. 1
Management of Acute Bleeding
Recombinant activated factor VII (rFVIIa) is the primary treatment for acute bleeding episodes in Factor VII deficiency. 1
Dosing for Acute Bleeding
- Standard dose: 15-30 mcg/kg every 4-6 hours until hemostasis is achieved 3, 1
- Most bleeding episodes respond to single "intermediate" doses (median 60 mcg/kg) 5
Treatment Duration by Bleeding Type
Hemarthroses, muscle/subcutaneous hematomas, epistaxis, gum bleeding: Single-day replacement therapy is typically sufficient 5
Menorrhagia: Single or multiple-dose schedules lead to favorable outcomes 5
Life-threatening bleeds (CNS, gastrointestinal): Require prolonged treatment courses and consideration of short- or long-term prophylaxis 5
Alternative Therapies When rFVIIa Unavailable
Fresh frozen plasma (FFP): Requires large volumes (20 mL/kg initially, then 3-6 mL/kg maintenance) with risks of transfusion-associated circulatory overload and TRALI 3, 1
Plasma-derived FVII concentrates: Effective alternative when rFVIIa is not accessible 3, 1
Prothrombin complex concentrates (PCCs): Can be used but contain variable FVII content and carry thrombotic risk 6
Perioperative Management
For surgical procedures, administer rFVIIa 15-30 mcg/kg immediately before surgery and continue every 4-6 hours throughout the perioperative period. 1
Surgical Prophylaxis Protocol
- Pre-operative dose: 15-30 mcg/kg given immediately before incision 3, 1
- Intraoperative: Continue dosing every 4-6 hours 1
- Post-operative: Maintain treatment until wound healing is secure 3
- Target levels: Aim to maintain FVII activity sufficient for hemostasis, though laboratory monitoring is not validated for determining therapeutic adequacy 3, 1
Clinical assessment of hemostasis must guide management as no validated laboratory tests exist to determine therapeutic levels. 3, 1
Long-term Prophylaxis Indications
Prophylactic treatment should be initiated for specific high-risk populations. 3, 1
Who Requires Prophylaxis
Newborns with severe deficiency: High risk of early gastrointestinal and CNS bleeding 3, 1
Patients with history of severe bleeding: Particularly those with recurrent CNS hemorrhage, severe hemarthroses, or surgery-related bleeding 3, 1, 5
Women with severe menorrhagia: Those with bleeding refractory to other measures 3, 1
Safety Considerations and Monitoring
Thrombotic Risk
Exercise caution in patients with prothrombotic risk factors including advanced atherosclerotic disease, crush injury, septicemia, or DIC where tissue factor may be expressed. 3, 1
- Thrombotic events have been reported in older patients with cardiovascular risk factors treated with rFVIIa 3
- The risk appears lower in congenital FVII deficiency compared to acquired hemophilia, but vigilance is required 3, 7
Inhibitor Development
Inhibitory antibodies to rFVIIa are rare but have been reported in FVII-deficient patients. 3, 1, 7
- Two inhibitors were detected among repeatedly treated patients in the STER registry (one post-rFVIIa, one post-pdFVII) 5
- Monitor for decreased treatment efficacy suggesting possible inhibitor development 5
Liver Transplantation
Liver transplantation is curative but should be reserved exclusively for the most severely affected patients who fail medical management or experience life-threatening complications. 3, 1
- Medical management with factor replacement is strongly preferred 3
- Transplantation consideration only after documented failure of optimal medical therapy 3, 1
- During transplant surgery, factor replacement is required intraoperatively and for 1-3 days post-operatively 3
Clinical Phenotype Considerations
Women comprise an excess of symptomatic patients, with menorrhagia affecting two-thirds of women of fertile age. 4, 2
Surgery-related bleeding is frequent and often serves as the diagnostic event in previously asymptomatic individuals. 2 This underscores the importance of pre-operative screening in patients with family history or suggestive bleeding history, even if previously asymptomatic.