What is the next step in managing a patient with a low von Willebrand antigen activity ratio, history of significant hemorrhages, and intermittent thrombocytopenia?

Management of a Patient with Low von Willebrand Antigen Activity Ratio and History of Hemorrhages

The next step in managing this 65-year-old woman with a von Willebrand antigen activity ratio of 0.69, significant hemorrhages, and intermittent thrombocytopenia should be specialized VWD testing including VWF multimer analysis to determine the specific subtype of von Willebrand disease. 1

Diagnostic Evaluation

Initial Assessment

• The patient's VWF:RCo/VWF:Ag ratio of 0.69 is concerning as ratios below 0.7 suggest a qualitative VWF defect (Type 2 VWD) 1
• Her history of significant hemorrhages post-thyroidectomy and post-gum graft, along with intermittent thrombocytopenia, strongly supports a bleeding disorder diagnosis 1
• The family history of significant hemorrhages with platelet drops in her mother suggests a hereditary component 1

Recommended Laboratory Tests

• Complete specialized VWD testing including: 1
  • VWF multimer distribution analysis to identify potential loss of high-molecular-weight multimers 1
  • VWF collagen binding (VWF:CB) assay to further characterize VWF function 1
  • Ristocetin-induced platelet aggregation (RIPA) to distinguish between Type 2A, 2B, and platelet-type VWD 2

Differential Diagnosis

Type 2 VWD Variants

• Type 2A: Characterized by selective deficiency of high-molecular-weight VWF multimers and decreased VWF-dependent platelet adhesion 1
• Type 2B: Features increased VWF affinity for platelet GP Ib with potential thrombocytopenia, which aligns with this patient's presentation 1, 3
• Type 2M: Shows decreased VWF-dependent platelet adhesion without selective deficiency of high-molecular-weight multimers 1
• Platelet-type VWD (pseudo-VWD): Often misdiagnosed as Type 2B VWD, characterized by hyperresponsive platelets and thrombocytopenia 2

Acquired von Willebrand Syndrome (AVWS)

• Consider AVWS given the patient's age and intermittent thrombocytopenia 1
• AVWS can be associated with various conditions including essential thrombocythemia 4
• The normal ristocetin test with platelets at 155 doesn't rule out AVWS or VWD 1

Management Plan

Immediate Steps

1. Refer to a hematologist with expertise in bleeding disorders 1
2. Complete specialized VWF testing as outlined above 1
3. Screen for underlying conditions that could cause AVWS 1

Treatment Options Based on Diagnosis

• If Type 1 VWD is confirmed: Desmopressin (DDAVP) is the treatment of choice 5, 6

  • Monitor for potential side effects including hyponatremia 3
  • Limit fluid intake from 1 hour before to 8 hours after administration 3

• If Type 2 VWD (especially 2B) or Type 3 VWD is confirmed: 5, 6

  • VWF-containing concentrates are preferred over desmopressin
  • Desmopressin is contraindicated in Type 2B due to risk of thrombocytopenia and thrombosis 3

• If Platelet-type VWD is confirmed: 2

  • Platelet concentrates should be administered instead of VWF/FVIII preparations

Important Considerations

• VWF:RCo/VWF:Ag ratio <0.7 is the key threshold for distinguishing Type 2 from Type 1 VWD 1
• Intermittent thrombocytopenia strongly suggests Type 2B VWD or platelet-type VWD 1, 2
• Family history of bleeding with platelet drops supports a hereditary form rather than acquired 1
• Treatment must be tailored based on the specific VWD subtype to avoid potential complications 3, 5
• Misdiagnosis between Type 2B VWD and platelet-type VWD is common but has important treatment implications 2