What does a low coagulation factor V activity level indicate?

Low Factor V Activity: Clinical Significance and Diagnostic Approach

A low coagulation factor V activity level indicates a bleeding disorder that can range from mild to severe, requiring further diagnostic evaluation to determine the specific type of factor V deficiency and its clinical implications.

Understanding Factor V and Its Deficiency

Factor V is an essential glycoprotein in the coagulation cascade that acts as a cofactor for the prothrombinase complex, which converts prothrombin to thrombin during clot formation 1. Low Factor V activity can be caused by:

• Congenital Factor V deficiency: A rare autosomal recessive bleeding disorder with an estimated incidence of 1 in 1 million people 1
• Acquired Factor V deficiency: Can occur in the setting of:
  • Rheumatologic disorders
  • Malignancies
  • Antibiotic use
  • Exposure to topical bovine thrombin 2
• Combined deficiencies: Such as combined Factor V and Factor VIII deficiencies 3

Clinical Manifestations

The bleeding phenotype associated with Factor V deficiency varies considerably:

• Common presentations:

  • Mucosal bleeding (epistaxis, menorrhagia, gingival bleeding)
  • Postoperative hemorrhage
  • Easy bruising

• Less common but serious manifestations:

  • Hemarthroses (joint bleeding)
  • Intramuscular hemorrhage
  • Intracranial hemorrhage (ICH) - occurs in approximately 8% of homozygous Factor V deficiency cases 3

Interestingly, the correlation between Factor V levels and bleeding severity is limited, with many patients having milder bleeding phenotypes than expected based on their Factor V levels 4. This may be partly explained by the finding that patients with Factor V deficiency often have lower levels of tissue factor pathway inhibitor (TFPI), which may serve as a compensatory mechanism 4.

Diagnostic Approach

Initial Screening Tests

When Factor V deficiency is suspected, the following initial tests should be performed:

• Complete blood count (CBC): Usually normal in isolated Factor V deficiency
• Prothrombin time (PT): Prolonged
• Activated partial thromboplastin time (aPTT): Prolonged 5

Both PT and aPTT are prolonged because Factor V participates in both the intrinsic and extrinsic coagulation pathways.

Confirmatory Testing

• Factor V activity assay: The definitive test for diagnosing Factor V deficiency
  • Severe deficiency: <1% activity
  • Moderate deficiency: 1-5% activity
  • Mild deficiency: 5-30% activity 1

Additional Testing

If Factor V deficiency is confirmed, consider:

• Factor V antigen levels: To distinguish between quantitative and qualitative defects
• Genetic testing: To identify specific mutations in the F5 gene 6
• Testing for other coagulation factors: Particularly Factor VIII, to rule out combined deficiencies 3

Differential Diagnosis

Low Factor V activity should prompt consideration of:

1. Von Willebrand Disease Type 2N: Can present with reduced Factor VIII levels due to impaired binding of Factor VIII to von Willebrand factor 3

2. Disseminated Intravascular Coagulation (DIC): Can cause consumption of multiple coagulation factors including Factor V 3

3. Liver Disease: Impairs synthesis of multiple coagulation factors

4. Vitamin K Deficiency: Primarily affects Factors II, VII, IX, and X, but may indirectly impact Factor V levels

Clinical Implications and Management

The management of Factor V deficiency depends on the severity of bleeding and the clinical context:

• For minor bleeding or prophylaxis before procedures:

  • Fresh frozen plasma (FFP): The mainstay of treatment as no Factor V-specific concentrate is widely available 2
  • Antifibrinolytic agents (e.g., tranexamic acid): Particularly useful for mucosal bleeding

• For severe or refractory bleeding:

  • Prothrombin complex concentrates
  • Recombinant activated Factor VII
  • Platelet transfusions (platelets contain approximately 20% of the body's Factor V in alpha-granules) 2

Special Considerations

• Asymptomatic patients: Many individuals with Factor V deficiency, even those with undetectable Factor V activity, may be asymptomatic and discovered incidentally during preoperative screening or routine examinations 6

• Genetic counseling: Important for patients with congenital Factor V deficiency, as it follows an autosomal recessive inheritance pattern 1

• Monitoring: Regular follow-up with a hematologist is recommended for patients with known Factor V deficiency

Pitfalls to Avoid

• Misdiagnosis: Factor V deficiency can be misdiagnosed as other coagulation disorders due to similar laboratory findings
• Sample handling: Improper sample collection or handling can lead to falsely low Factor V levels
• Incomplete evaluation: Failure to distinguish between congenital and acquired causes can lead to inappropriate management

Recent research has identified novel regulators of plasma Factor V levels, including CLEC4M as a clearance receptor, which may provide new insights into the pathophysiology and potential therapeutic targets for Factor V deficiency 7.