Overview of recommendations

• Recommendation for analysis of FVII activity

  • For analysis of factor VII activity, human tissue or recombinant thromboplastin as clotting activator is preferred.

• Recommendation for definition of FVII deficiency

  • FVII:C > 50%: Normal

  • FVII:C 35-50%: Low FVII level

  • FVII:C < 35%: FVII deficiency

• Recommendation for FVII genotyping

  • In clinically severe factor VII deficiency, genotyping allows for prenatal counseling and is recommended. In moderate, mild or asymptomatic cases, genotyping is not recommended for routine care.

• Recommendation for classification

  • Severity of factor VII deficiency should be classified according to bleeding phenotype in addition to factor level.

• Recommendations for antifibrinolytics

  • Tranexamic acid can be applied as monotherapy for treatment or prevention of mild bleeding or as adjunctive therapy to factor replacement in more severe cases.

  • Intravenous injection with tranexamic acid 10 mg/kg body weight every 8 hours or an oral dose of tranexamic acid 20-25 mg/kg 3-4 times daily. Maximum daily dose of tranexamic acid is 4–6 g. As tranexamic acid is excreted in the urine it should not be used in renal tract bleeding.

• Recommendation for substitution therapy during major surgery

  • Substitution therapy should only be given to high-risk patients defined as:

    • Factor VII level < 10%

    • Factor VII level 10-20 % and a history of trauma induced excessive bleeding and/or frequent nosebleeds

    • Significant bleeding history (joint or intracranial bleeds) irrespective of FVII level

    • Pediatric patients (see pediatric section)

  • rFVIIa is recommended as the preferred substitution therapy

  • rFVIIa can be administered as bolus injections or continuous infusion

• Recommendation for long-term prophylactic factor replacement therapy

  • Long-term prophylactic factor replacement therapy should be considered in severe FVII deficiency with severe bleeding phenotype.

  • rFVIIa initially 15-30 µg/kg 2 -3 times weekly followed by individualized dose tailoring is suggested.

• Recommendation for follow-up in adult patients

  • High-risk patients should be offered annual follow-up visits at a comprehensive hemophilia care center.

• Recommendations for pregnancy and delivery

  • All patients with FVII deficiency should receive tranexamic acid at start of delivery or prior to caesarean section.

  • Irrespective of mode of delivery, rFVIIa or other hemostatic agents should be available in the case of hemorrhages.

  • Prophylactic treatment with rFVIIa during vaginal delivery and caesarean section should only be considered in high-risk patients.

  • rFVIIa is given 15-30 μg/kg prior to and post-partum every 4-6 hours for at least 3 days.

• Pediatric recommendations

  • Pediatric reference ranges must be used when evaluating the levels of Factor VII in children.

  • Vitamin K deficiency and liver disease should be ruled out before the diagnosis of factor VII deficiency can be made in children.

  • Particularly young children may benefit from higher doses and more frequent administration of rFVIIa compared to adults.

  • Prophylactic treatment with factor concentrates should be considered early in severe FVII deficiency with a severe bleeding pattern.