Factor Deficiencies, Uncommon

Factor Deficiencies, Uncommon

 

Factors V, VII, X, XI, XII and XIII, high molecular weight kininogen (HMWK) and prekallikrein are the most frequently occurring uncommon factor deficiencies.

Deficiency of factor XI

  • Inheritance
    • Autosomal recessive
  • Presentation
    • Often asymptomatic
    • Can be associated with excessive bleeding, usually related to injury (tooth extraction, tonsillectomy, nasal surgery)
  • Pathophysiology
    • Factors XI, XII, HMWK and prekallikrein are referred to as contact factors
    • Factor XI is activated which then activates IX

Deficiency of factor XII

  • Inheritance
    • Autosomal recessive
  • Presentation
    • Asymptomatic
  • Pathophysiology
    • Factor XII is activated to XIIa by protein and protein surface extractions
    • XIIa activates XI, which then activates IX

Deficiency of factor XIII

  • Inheritance
    • Autosomal recessive
  • Presentation
    • Most common – umbilical cord bleeding  
  • Pathophysiology
    • Most significant role in tensile strength and integrity of fibrin clot

Deficiency of HMWK (Fitzgerald factor)

  • Inheritance
    • Autosomal recessive
  • Presentation
    • Generally asymptomatic  
  • Pathophysiology
    • HMWK is involved in the activation of the intrinsic pathway, which is initiated when trauma occurs to a blood vessel (such as exposure of blood to collagen in damaged vessel wall or in vitro by contact with a syringe or test tube)
    • HMWK functions as a cofactor, binding to prekallikrein and factor XI, thus accelerating their activation by factor XIIa
    • Individuals have normal hemostasis and no excessive bleeding in spite of PTT often >100 seconds

Deficiency of prekallikrein (Fletcher factor)

  • Inheritance
    • Autosomal recessive
  • Presentation
    • Completely asymptomatic
  • Pathophysiology
    • Hemostasis is normal and excessive bleeding absent in spite of partial thromboplastic time (PTT) often >100 seconds

Deficiency of factor V

  • Inheritance
    • Rare autosomal recessive disorders
      • May rarely be found as a combined defect with factor VIII
  • Presentation
    • Most common – moderate bleeding tendency with ecchymosis, epistaxis, gingival bleeding and hemorrhage following minor lacerations
  • Pathophysiology
    • Activated factor V combines with activated factor X to cleave prothrombin to thrombin

Deficiency of factor VII

  • Inheritance
    • Autosomal recessive
  • May be associated with other factor deficiencies
  • Presentation
    • May be associated with bilirubin disorders, mental retardation, microcephaly and cleft palate
    • Mucosal bleeding, but bleeding will be more severe if associated with other factor deficiencies
  • Pathophysiology
    • Activated factor VII activates both factors IX and X

Deficiency of factor X

  • Inheritance
    • Autosomal recessive
  • Presentation
    • Most common – moderate to severe bleeding
      • Primarily of soft tissues, joints, mucous membranes, umbilical cord
  • Pathophysiology
    • Activated factor X complexes with activated factor V to cleave prothrombin to thrombin

Deficiency of fibrinogen

  • Inheritance
    • Autosomal recessive
  • Several genetic mutations associated with the disease
    • Varies from hypo- to afibrinogenemia
  • Presentation
    • Varies from asymptomatic to moderate bleeding
  • Pathophysiology
    • Fibrinogen is activated to fibrin by thrombin
    • Fibrin is a stabilizing factor in the clotting sequence

Deficiency of prothrombin (factor II)

  • Autosomal recessive disorder
    • Types I and II variants
  • Presentation
    • Mild to moderate mucocutaneous and soft tissue bleeding
      • Significant surgical bleeding
  • Pathophysiology
    • Prothrombin is activated to thrombin by factor Va and factor Xa complex
    • Thrombin is a potent platelet activator

See Also