What are the next steps for a postmenopausal patient with intermittent thrombocytopenia, chronically low ferritin and iron levels, and a family history of bleeding disorders, after a local laboratory cancelled a von Willebrand factor (VWF) multimer test?

Management of Suspected von Willebrand Disease with Intermittent Thrombocytopenia and Iron Deficiency

For a postmenopausal patient with intermittent thrombocytopenia (120-150), chronic iron deficiency, and family history of bleeding disorders, you should refer the patient to a specialized hematology center for comprehensive von Willebrand Disease (VWD) testing including VWF:RCo/VWF:Ag ratio and alternative multimer analysis, as the clinical presentation strongly suggests Type 2B VWD. 1

Diagnostic Approach

The patient's presentation has several hallmark features suggestive of Type 2B von Willebrand Disease:

1. Intermittent thrombocytopenia - Characteristic of Type 2B VWD due to enhanced binding of abnormal VWF to platelets 1, 2
2. Chronic iron deficiency - Common in VWD patients due to bleeding, particularly in women 3
3. Family history of bleeding - Elevated bleeding assessment tool scores in four family members strongly supports a hereditary bleeding disorder 1

Initial Laboratory Testing

When the local laboratory cancels a multimer test, pursue these alternatives:

• Request the following tests from a specialized coagulation laboratory:

  • VWF antigen (VWF:Ag)
  • VWF activity (VWF:RCo or newer assays like VWF:GPIbR, VWF:GPIbM)
  • Factor VIII activity (FVIII:C)
  • VWF:RCo/VWF:Ag ratio - critical for distinguishing Type 1 from Type 2 variants 1
  • VWF multimer analysis (at specialized center) 4

• Consider newer alternative assays with improved sensitivity:

  • VWF:GPIbR (uses recombinant GPIb with ristocetin)
  • VWF:GPIbM (uses gain-of-function mutant GPIb without ristocetin) 1

Specific Considerations for Type 2B VWD

Type 2B VWD should be strongly suspected based on:

• Thrombocytopenia - A hallmark feature of Type 2B VWD 1, 2, 5
• Iron deficiency - Studies show 16.1% of women with iron deficiency anemia and menorrhagia have VWD 3
• Family history - Critical diagnostic criterion per ISTH and American Society of Hematology 1

Laboratory findings typically include:

• VWF:RCo <30 IU/dL
• VWF:Ag 30-200 IU/dL
• VWF:RCo/VWF:Ag ratio <0.5-0.7
• Loss of high molecular weight multimers 1

Management Recommendations

1. Refer to specialized hematology center with expertise in diagnosing complex bleeding disorders
2. Continue iron supplementation until definitive diagnosis, as iron deficiency is common in VWD patients 3
3. Screen first-degree relatives given the hereditary nature of VWD 1
4. Consider genetic testing to confirm diagnosis and specific variant 1

Important Caveats

• Multimer analysis is crucial for proper subtyping of VWD, especially for Type 2 variants 1, 4
• DDAVP is contraindicated in Type 2B VWD as it can worsen thrombocytopenia 1
• Thrombocytopenia in Type 2B VWD is due to enhanced binding of abnormal VWF to platelets, causing their clearance 5
• VWF half-life is reduced in Type 2B VWD regardless of multimer representation or thrombocytopenia 5

The combination of intermittent thrombocytopenia, iron deficiency despite being postmenopausal, and family history of bleeding strongly points to Type 2B VWD, which requires specialized testing for confirmation and appropriate management 1, 2.