About the Condition

Description/definition:

Factor X deficiency

Congenital/hereditary factor X deficiency

  • Autosomal recessive disorder, reported in 1 in 1 million persons.
  • Bleeding manifestations may present at any age.
  • May be further classified into:
    • Type I disease (low coagulant activity and low immunological antigen levels).
    • Type II disease (low coagulant activity and normal/borderline low antigen levels).
  • No clear link between the genotype/location of the mutation and the phenotypic expression of the disease.

Acquired factor X deficiency

  • Factor X deficiency:
    • Amyloid light-chain amyloidosis – occurs in up to 14% of patients with amyloidosis.
    • Severe liver disease – associated with other clotting factor deficiencies.
    • Vitamin K deficiency – associated with other clotting factor deficiencies.
  • Factor X Inhibitor (extremely rare):
    • Immune-mediated
    • No underlying condition in 35%
    • Reported in:
      • Burns
      • Respiratory infections
      • Exposure to topical thrombin

Pathophysiology:

Congenital FX deficiency caused by mutations in the F10 gene that encodes for factor X (homozygous or compound heterozygous).

Acquired FX deficiency in AL amyloidosis caused by binding on amyloid fibrils primarily in the liver and spleen.

Note: Other causes of bleeding in AL amyloidosis include:

  • Vascular fragility from amyloid infiltration of blood vessels
  • Presence of a thrombin inhibitor
  • Dysfibrinogenemia
  • Disseminated intravascular coagulation and fibrinolysis
  • Acquired coagulation factor deficiencies, including:
    • Acquired von Willebrand disease
    • Deficiency of FII, FV, FVII, FIX, FX, FXI, and/or FXII

Diagnosis:

Consider diagnosis of factor X deficiency in a patient with:

  • Congenital deficiency:
    • Bleeding early in life
    • Elevated PT and aPTT
  • Acquired deficiency:
    • Recent onset of bleeding symptoms, especially in older adults.
    • Lack of previous bleeding symptoms especially in association with previous hemostatic challenges.
    • No family history of congenital/inherited deficiency of FV (or other coagulation factor deficiencies).
    • Elevated PT and aPTT.

Confirm diagnosis:

  • Congenital deficiency:
    • Correction of prolonged PT and aPTT by normal plasma (mixing study).
    • Reduced factor X activity in specific factor assay.
  • Acquired deficiency:
    • Mixing study:
      • If inhibitor, no correction of prolonged PT and aPTT with normal plasma (mixing study).
      • If amyloidosis, correction of prolonged PT and aPTT with normal.
    • Reduced factor X activity in specific factor assay.

Other supplemental (non-screening) assays include:

  • Russell Viper Venom (RVV) assay:
    • A metalloproteinase that activates factor X directly and can therefore detect factor X deficiency in plasma samples.
    • Chromogenic assays (spectrophotometric detection of a substrate sensitive to activated factor X).
    • Immunological assays (e.g. an enzyme-linked immunosorbent assay [ELISA] that measures factor X antigen).

Notes:

  • In congenital FX deficiency, there is a strong correlation between FX activity and severity of disease manifestation. In contrast, the correlation is weaker in patients with acquired FX deficiency.
  • Bleeding manifestations are similar in congenital and acquired FX deficiency. Most common bleeding manifestations include mucocutaneous bleeds (particularly epistaxis), hemarthroses (soft tissue and joint bleeding), GI bleeding, and heavy menstrual bleeding.

Treatment:

General principles of management:

  • Treat active bleeding.
  • Eradicate inhibitor if present.
  • Treat underlying condition.

Treatment of active bleeding:

  • For patients with severe bleeding or undergoing major surgery, factor X replacement therapy with either of the following:
    • Prothrombin complex concentrate (PCC) 
      • Plasma-derived, virally inactivated.
      • PCCs typically include three or four coagulation factors (factors II, IX, and X, with or without factor VII), and most also include one or more other factors with anticoagulant activity, such as heparin, antithrombin, protein C, protein S, and/or protein Z.
      • Most PCCs contain about equivalent activities of factor IX and X activities and increase plasma levels by about 1.5%/IU/Kg body weight.
      • PCC 20-30 factor IX units/kg with additional PCC 10-20 units/kg at 24 hour intervals (half life of FX is about 30 hours), if needed, adjusted to maintain factor X activity at >20%.
      • Potential increased risk of thrombosis.
    • Factor X concentrate (Coagadex)
      • Plasma-derived
      • FDA approved for use in adults and children with hereditary factor X deficiency:
        • Routine prophylaxis
        • On-demand treatment
        • Perioperative management of bleeding
    • If PCC and factor X concentrate are unavailable, consider fresh frozen plasma (FFP) 15-25 mL/kg.
  • Other treatment considerations:
    • Tranexamic acid:
      • Should be considered for patients with mild bleeding or undergoing minor surgery.
      • Most effective for bleeding involving mucocutaneous surfaces.
      • Use with caution if given concurrently with activated clotting factor concentrates.
      • Contraindicated in patients with urinary tract bleeding.

Eradication of inhibitor

  • In rare cases of autoimmune acquired FX deficiency.

Treatment of underlying conditions (if applicable)

  • Treat amyloidosis if present.

Note: The above recommendations are established for congenital FX deficiency. There is no standardized treatment for acquired FX deficiency. Limited, variable success has been achieved with vitamin K plus
FFP, PCCs (with dosing frequency and disease severity each playing a
role in treatment efficacy), dual-factor concentrate, or recombinant
activated factor VIIa with oral corticosteroids.

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