What is the appropriate diagnosis and management for a 20-year-old female with menorrhagia, recent epistaxis, and a mildly prolonged INR, considering the possibility of von Willebrand disease?

Von Willebrand Disease: Diagnosis and Management in a Young Woman with Menorrhagia

For a 20-year-old female presenting with menorrhagia, epistaxis, and mildly prolonged INR, proceed directly to von Willebrand disease-specific testing with VWF:Ag, VWF:RCo, and Factor VIII levels, as this clinical presentation strongly suggests VWD and warrants immediate diagnostic evaluation. 1

Clinical Presentation and Diagnostic Approach

Key Clinical Features Suggesting VWD

The combination of menorrhagia since menarche, recurrent epistaxis, and easy bruising represents the classic mucocutaneous bleeding pattern of von Willebrand disease. 2, 3 This triad occurs in over 70% of women with VWD and significantly impacts quality of life. 4, 5

When evaluating bleeding history, specifically ask about:

• Menorrhagia present since menarche 4
• Easy bruising greater than 5 cm occurring 1-2 times per month 4
• Frequent gum bleeding with flossing or brushing 4
• Epistaxis occurring 1-2 times per month 4
• Excessive bleeding with dental extractions, surgery, or childbirth (if applicable) 4

Physical Examination Priorities

Focus the examination on identifying ecchymoses, hematomas, and petechiae while excluding alternative diagnoses. 2 Specifically evaluate for signs of liver disease (jaundice), splenomegaly, joint and skin laxity (Ehlers-Danlos syndrome), telangiectasia (hereditary hemorrhagic telangiectasia), and perform gynecologic examination to identify anatomic lesions causing menorrhagia. 2

Laboratory Testing Algorithm

Initial VWD-Specific Testing Panel

Order these three tests together as the initial evaluation: 1

• VWF antigen (VWF:Ag) - measures the quantity of von Willebrand factor protein 1
• VWF ristocetin cofactor activity (VWF:RCo) - assesses functional ability of VWF to bind platelets 1
• Factor VIII coagulant activity (FVIII) - evaluates factor VIII levels carried by VWF 1

These three tests establish the diagnosis and suggest VWD type and severity. 2, 1 The NHLBI/NIH guidelines provide a grade B recommendation for ordering all three tests together when VWD is suspected based on mucocutaneous bleeding history. 2, 1

Additional First-Line Tests

Include these tests to evaluate for alternative diagnoses and complications: 6

• Complete blood count with platelets and peripheral smear (to assess for thrombocytopenia and anemia from chronic blood loss) 6
• PT/INR (already noted as mildly prolonged in this patient) 6
• aPTT (to evaluate intrinsic pathway) 6
• ABO blood group (Type O patients have 25-60% lower VWF levels than Type AB) 1, 6
• Iron studies (to evaluate for iron deficiency from chronic menorrhagia) 6

Interpreting Initial Results

Abnormal results suggesting VWD include: 2, 1

• Low VWF:Ag levels
• Low VWF:RCo levels
• Low Factor VIII levels
• VWF:RCo to VWF:Ag ratio below 0.5-0.7 (suggests Type 2 VWD variants) 2, 1

Reflexive/Specialized Testing

If initial testing shows abnormalities, proceed to VWF multimer analysis to determine VWD subtype. 2, 1 Do not order multimer analysis as part of initial screening - this technically complex test should only be performed when initial results are abnormal. 2, 1

Critical Testing Considerations and Pitfalls

Factors That Affect VWF Levels

Test timing is crucial because VWF levels are affected by: 1

• Stress, exercise, and inflammation (falsely elevate VWF levels) 1
• Pregnancy and estrogen therapy (increase VWF levels) 1
• Menstrual cycle phase (levels fluctuate throughout cycle) 5, 7
• ABO blood group (Type O has 25% lower baseline levels) 1

Perform testing when the patient is not acutely stressed, inflamed, or on hormonal therapy to avoid false-negative results. 1, 7 If the patient is already on hormonal treatment for menorrhagia, testing should ideally be performed before treatment or after discontinuation, as hormonal therapy can mask the diagnosis. 7

Sample Handling Requirements

Proper specimen handling is essential to avoid false results: 1

• Transport at room temperature 1
• Separate plasma promptly 1
• Freeze at or below -40°C if not tested within 2 hours 1

Common Diagnostic Errors to Avoid

Do not rely solely on PT and aPTT to rule out bleeding disorders - these tests will miss von Willebrand disease and mild platelet function disorders. 8 The mildly prolonged INR in this patient may reflect Factor VIII deficiency secondary to VWD, but normal coagulation studies do not exclude the diagnosis. 8

Do not order bleeding time or PFA-100 tests for VWD screening - these have conflicting data regarding sensitivity and specificity and are not recommended by current guidelines. 1, 6

Management of VWD-Related Menorrhagia

Treatment Options Based on Age and Reproductive Status

For a 20-year-old woman of reproductive age, surgical intervention (hysterectomy) is not appropriate. 4 Medical management options include: 4, 3

First-line hormonal therapy:

• Combined oral contraceptives 4, 3
• Levonorgestrel intrauterine device (Mirena) - effective and should be considered prior to surgical management 5, 3

Hemostatic agents for acute bleeding or breakthrough episodes:

• Desmopressin (DDAVP) - intranasal or subcutaneous administration for mild to moderate Type 1 VWD with Factor VIII levels greater than 5% 9, 4, 3
• Tranexamic acid (antifibrinolytic agent) 4, 3
• Epsilon-aminocaproic acid (antifibrinolytic agent) 4

For severe bleeding or patients unresponsive to DDAVP:

• Virally inactivated plasma-derived clotting factor concentrates containing both VWF and Factor VIII 3

Desmopressin Use in VWD

According to FDA labeling, desmopressin is indicated for patients with mild to moderate classic von Willebrand disease (Type 1) with Factor VIII levels greater than 5%. 9 It should be administered 30 minutes prior to scheduled procedures to maintain hemostasis. 9 Patients least likely to respond are those with severe homozygous VWD with Factor VIII coagulant activity and VWF antigen levels less than 1%. 9

Monitoring During Treatment

During desmopressin administration, check bleeding time, Factor VIII coagulant activity, ristocetin cofactor activity, and von Willebrand factor antigen to ensure adequate levels are achieved. 9

Multidisciplinary Management

Coordinate care between hematology and gynecology to ensure optimal outcomes and prevent unnecessary surgical interventions that carry increased bleeding risk in VWD patients. 5 Failure to diagnose underlying VWD leads to continued menorrhagia, diminished quality of life, and unnecessary gynecologic procedures (D&C, endometrial ablation, hysterectomy) that may be complicated by hemorrhage. 4

Prevalence Context

Von Willebrand disease occurs in approximately 11-16% of women with menorrhagia, making it a significant but often overlooked cause of excessive menstrual bleeding. 4, 10, 7 This diagnosis should not be missed, as appropriate treatment can dramatically improve quality of life and prevent complications.