Coagulation
Hereditary bleeding disorders
Factor II (prothrombin) deficiency

Authors: Kendall Crookston, M.D., Ph.D., Lizabeth Rosenbaum, M.D. and Julie Gober-Wilcox, M.D. (see Authors page)

Revised: 28 April 2016, last major update August 2010

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PubMed Search: Factor II (prothrombin) deficiency [title]

Definition / General
  • Congenital deficiency of prothrombin (factor II) that results in reduced prothrombin activity and normal or reduced prothrombin antigen levels
  • Prothrombin (factor II) is a vitamin-K dependent cofactor which is activated by factor Xa to form thrombin, which then converts fibrinogen to fibrin

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Coagulation cascade

Terminology
  • Hypoprothrombinemia (type I deficiency) is a decrease in the overall synthesis of prothrombin and is characterized by reduced prothrombin activity and antigen levels
  • Dysprothrombinemia (type II deficiency) is the synthesis of dysfunctional prothrombin molecules and is characterized by reduced activity and normal antigen levels
Epidemiology
  • Rare; fewer than 100 cases have been reported
  • Prevalence rate of approximately 1:2,000,000 in the general population
Sites
  • Mucocutaneous and soft tissue bleeding (see below)
Etiology
  • 40 different mutations in the prothrombin gene have been identified, the majority of which are missense mutations (~80%). However, insertion or deletion mutations (~10%) and nonsense mutations (~4%) have also been identified.
  • The gene is transmitted in an autosomal recessive pattern with homozygous, heterozygous or compound heterozygous genotypes
  • Homozygous individuals have functional prothrombin levels of 2 - 25%
  • Heterozygous patients have prothrombin levels of 40 - 60%
  • Biologic half life is 48 - 120 hours
Clinical Features
  • Complete deficiency is incompatible with life
  • Severe hemorrhage typically occurs when levels are < 5%
  • Need levels of 10 - 40% for surgical hemostasis
  • Patients have lifelong history or family history of bleeding; varies from asymptomatic to minor bleeding to severe bleeding (depending on the mutation)
  • Also easy bruising, postoperative bleeding, epistaxis, menorrhagia, miscarriage, postpartum hemorrhage, hemarthroses and intracranial bleeding (if severe deficiency)
Laboratory
  • Prolonged PT and PTT that correct with mixing study (1:1 mixture of patient and normal pooled plasma)
  • Type I (true deficiency) patients will have both activity and antigen levels < 10%
  • Type II patients will have normal antigen levels and low activity
Treatment
  • Recombinant factor VIIa, alternatively 10 - 20 ml fresh frozen plasma/kg, then 3 ml/kg every 12 - 24 hours as necessary
  • Plasma infusion for recurrent bleeding episodes every 3 - 5 weeks
  • Prothrombin complex concentrates may be used for serious bleeding
Differential Diagnosis