What is factor 11 (coagulation factor XI) deficiency?

Factor XI Deficiency: Clinical Features and Management

Factor XI deficiency is a rare autosomal recessive bleeding disorder characterized by variable bleeding tendency that doesn't always correlate with factor XI plasma levels, with a particularly high prevalence in the Ashkenazi Jewish population.

Overview and Epidemiology

Factor XI deficiency is a rare bleeding disorder with the following characteristics:

• Prevalence: Approximately 1 in 100,000 in the general population 1
• Higher prevalence: Particularly common in Ashkenazi Jews 2, 3
• Inheritance pattern: Autosomal recessive with variable expression 4

Pathophysiology

• Factor XI is part of the intrinsic coagulation pathway
• Activated by thrombin, contributing to the amplification phase of coagulation 2
• Deficiency leads to an injury-related bleeding diathesis 2
• Bleeding occurs especially in areas of high fibrinolytic activity 2

Clinical Presentation

The bleeding tendency in Factor XI deficiency is notably variable:

• Severity classification:

  • Severe deficiency: Factor XI levels <15-20%
  • Moderate deficiency: Factor XI levels 20-40%
  • Mild deficiency: Factor XI levels >40%

• Bleeding characteristics:

  • Typically mild to moderate bleeding symptoms 4
  • Primarily injury-related or surgery-provoked bleeding 2
  • No spontaneous bleeds observed in pediatric populations 5
  • Bleeding tendency does not consistently correlate with Factor XI levels 4, 2

• Common bleeding manifestations:

  • Excessive bleeding after surgery or trauma
  • Mucosal bleeding (epistaxis, menorrhagia)
  • Triggered intracranial hemorrhage (rare but reported in children) 5

Diagnosis

Diagnosis of Factor XI deficiency involves:

1. Laboratory testing:

   • Prolonged activated partial thromboplastin time (aPTT)
   • Normal prothrombin time (PT)
   • Normal thrombin time
   • Specific Factor XI activity assay showing reduced levels

2. Genetic testing:

   • Particularly useful in populations with known mutations
   • Five specific mutations identified in Ashkenazi Jewish and Basque populations 2

Management

Management strategies for Factor XI deficiency include:

Acute Bleeding Management

• Antifibrinolytic agents (tranexamic acid) are often first-line therapy, especially for minor bleeding 3, 5
• Fresh frozen plasma (FFP) is the mainstay treatment for more significant bleeding 3
• Factor XI concentrates may be used in specific situations, though they carry thrombotic risk, especially in older patients 3
• Recombinant activated factor VII (rFVIIa) in combination with tranexamic acid has been used successfully 2

Surgical Management

• Prophylactic hemostatic preparation is crucial for surgical procedures:
  • Studies show 25% excessive bleeding rate in surgeries without hemostatic preparation vs. no complications when appropriate prophylaxis is used 5
  • Options include tranexamic acid, FFP, or factor XI concentrates depending on severity and procedure type 3, 5

Special Considerations

• Pediatric patients:

  • Generally favorable outcomes with proper management 5
  • No spontaneous bleeds reported in pediatric populations 5
  • Triggered intracranial hemorrhage can occur and requires prompt treatment 5

• Pregnancy and childbirth:

  • Women may experience menorrhagia and postpartum hemorrhage 4
  • Requires specialized management during delivery

Monitoring and Follow-up

• Regular assessment of bleeding symptoms
• Factor XI levels do not reliably predict bleeding risk 4
• Individual bleeding history is more predictive of future bleeding risk than factor levels

Emerging Therapeutic Approaches

• Novel non-replacement therapies are under investigation 4
• Factor XI as a potential antithrombotic target with minimal bleeding risk 6

Clinical Pearls and Pitfalls

• Key pitfall: Relying solely on Factor XI levels to predict bleeding risk
• Important consideration: Factor XI deficiency has a more variable bleeding tendency than hemophilia A or B 3
• Critical action: Always provide hemostatic preparation before surgical procedures 5
• Special population: Consider testing in patients of Ashkenazi Jewish descent with unexplained bleeding tendency 2, 3

Factor XI deficiency represents a unique bleeding disorder with variable clinical expression that requires individualized assessment and management strategies based on the patient's specific bleeding history and planned interventions.