What treatment is recommended for a patient with normal von Willebrand factor (VWF) levels but a low VWF antigen activity ratio of 0.7, similar to her mother's condition?

Treatment for Patient with Normal VWF Levels and Low VWF:Ag Activity Ratio

For a patient with normal von Willebrand factor (VWF) levels but a low VWF antigen activity ratio of 0.7, desmopressin (DDAVP) is the recommended first-line treatment when intervention is needed for bleeding or surgical procedures.

Understanding the Diagnosis

This clinical presentation suggests Type 2M von Willebrand Disease (VWD), characterized by:

• Normal VWF antigen levels
• Decreased VWF activity
• VWF:RCo/VWF:Ag ratio of 0.7 (borderline low)
• Family history (mother with similar findings)

According to the International Society on Thrombosis and Haemostasis (ISTH) guidelines, a VWF:RCo/VWF:Ag ratio of <0.7 is considered diagnostic for Type 2 VWD variants 1. The patient's ratio of 0.7 is at the borderline threshold between Type 1 and Type 2 VWD.

Treatment Algorithm

1. For Minor Bleeding Episodes or Minor Procedures:

• First-line: Desmopressin (DDAVP) at 0.3 μg/kg IV or subcutaneously 2, 3
• Monitor response with post-administration VWF levels
• Target VWF:RCo levels >50 IU/dL for most procedures

2. For Major Bleeding Episodes or Major Surgical Procedures:

• First-line: VWF-containing concentrates if desmopressin response is inadequate
• Dosing based on weight and severity of bleeding
• Target VWF:RCo levels >50 IU/dL for most procedures and ≥80 IU/dL for major surgery 2

3. Adjunctive Therapy:

• Tranexamic acid can be used as adjunctive therapy for mucosal bleeding

Special Considerations

Pregnancy and Childbirth

If the patient is female and of reproductive age, special planning is needed for pregnancy:

• Close monitoring during pregnancy as VWF levels may change
• Consultation with high-risk obstetrics and hematology
• Preparation of a delivery plan with target VWF:RCo ≥50 IU/dL for vaginal delivery and ≥80 IU/dL for cesarean section 2

Neuraxial Anesthesia Considerations

For patients requiring neuraxial anesthesia:

• VWF activity of ≥50 IU/dL is generally acceptable for administration of a spinal anesthetic 1
• For epidural catheter insertion and removal, similar thresholds apply

Monitoring and Follow-up

• Regular hematology follow-up to monitor bleeding symptoms
• Periodic VWF testing to assess disease status
• Assessment of iron status if history of bleeding
• Response to desmopressin should be documented to guide future treatment decisions

Common Pitfalls to Avoid

1. Inadequate testing: A single normal result does not exclude a bleeding disorder; repeat testing may be necessary due to variability in VWF levels 2

2. Dismissing symptoms: Up to 75% of specialists formally register patients with convincing bleeding history even with normal laboratory results 2

3. Failure to consider family history: The hereditary nature of VWD makes family history crucial in diagnosis and management

4. Environmental factors affecting test results: Stress, exercise, inflammation, and hormonal factors can temporarily increase VWF levels, potentially masking a bleeding disorder 2

5. Sample handling issues: Improper processing or storage of blood samples can affect VWF assay results 1

This patient's borderline VWF:RCo/VWF:Ag ratio of 0.7, combined with a family history (mother with similar findings), strongly suggests a mild form of Type 2 VWD that requires appropriate management to prevent bleeding complications, particularly before surgical procedures or during pregnancy.