Coagulation
Hereditary bleeding disorders
Factor II (prothrombin) deficiency
Last author update: 1 August 2010
Last staff update: 16 September 2020
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PubMed Search: Factor II (prothrombin) deficiency [title]
Table of Contents
Definition / general | Terminology | Epidemiology | Sites | Etiology | Diagrams / tables | Clinical features | Laboratory | Treatment | Differential diagnosis | Additional referencesCite this page: Crookston K, Rosenbaum LS, Gober-Wilcox J. Factor II (prothrombin) deficiency. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/coagulationfactorIIdef.html. Accessed April 16th, 2024.
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
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
Diagrams / tables
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Coagulation cascade
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
- Acquired prothrombin deficiency due to severe liver disease, vitamin K deficiency, or anti-prothrombin antibodies (antiphospholipid syndrome)
- Must rule out other coagulation factor deficiencies that cause prolonged PT and PTT : e.g. factor V deficiency or factor X deficiency
Additional references
