What further workup is needed for a patient with easy bruising and abnormal coagulation labs, including elevated factor VIII activity, von Willebrand factor (VWF) antigen, and ristocetin cofactor, with a normal activated partial thromboplastin time (APTT) and slightly elevated international normalized ratio (INR)?

Further Workup for Abnormal Coagulation Labs in a Patient with Easy Bruising

For a patient with easy bruising and elevated factor VIII activity, von Willebrand factor (VWF) antigen, and ristocetin cofactor with normal APTT and slightly elevated INR, repeat VWF testing 2-3 times over several weeks is essential as VWF is an acute phase reactant that can produce falsely elevated results.

Initial Assessment of Elevated VWF Parameters

The patient's laboratory results show:

• Elevated factor VIII activity
• Elevated VWF antigen
• Elevated ristocetin cofactor
• Normal APTT
• Slightly elevated INR

These findings present an unusual pattern, as elevated VWF parameters typically don't cause easy bruising. Several important considerations must be addressed:

Repeat Testing for VWF Parameters

• VWF is an acute phase reactant that can vary in response to clinical status 1, 2
• Testing must be repeated up to 3 times to ensure reliable results 1
• Tests should be performed in laboratories experienced with these assays 1

Additional First-Line Testing

• Complete blood count with platelet count 2
• Platelet function studies 2
• Bleeding assessment tool (BAT) to quantify bleeding symptoms 2

Differential Diagnosis Considerations

Von Willebrand Disease Variants

Despite elevated VWF parameters, certain VWD variants should be considered:

• Type 2B VWD: Can present with increased VWF parameters but abnormal function 3
• Type 2N VWD: Can show normal or elevated VWF antigen but decreased affinity for factor VIII 2

Other Potential Causes

• Acute phase reaction causing transiently elevated VWF levels 1, 2
• Platelet function disorders not detected by standard testing 4
• Rare variants with increased ristocetin sensitivity 5

Recommended Further Workup

1. Repeat VWF Testing:

   • Repeat VWF antigen, ristocetin cofactor, and factor VIII levels 2-3 times over several weeks 1, 2
   • Ensure proper specimen handling to avoid false results 1

2. Additional Laboratory Tests:

   • VWF multimer analysis to assess qualitative defects 2, 6
   • Platelet function testing including light transmission aggregometry with multiple agonists 2
   • Evaluation of other coagulation factors (II, V, VII, X, XI, XIII) 2

3. Specialist Consultation:

   • Consultation with a pediatric hematologist is recommended when there is significant concern for a bleeding disorder 1, 2
   • Hematology consultation is valuable as up to 60-70% of patients with mild-moderate bleeding symptoms may have a bleeding disorder of unknown cause even after initial testing 2

Important Considerations

False Positive Results

• Inappropriate specimen handling commonly leads to false-positive results 1
• Prolongation of PT/INR can occur due to various factors unrelated to primary bleeding disorders 1

Timing of Testing

• Avoid testing during acute illness or inflammation which can elevate VWF levels 2
• Consider testing family members if a hereditary disorder is suspected 2

Pre-Surgical Planning

• If the patient requires surgery, comprehensive hemostatic evaluation should be completed beforehand 2, 7
• For patients with confirmed VWD, desmopressin may be used to maintain hemostasis during surgical procedures 7

Follow-up Recommendations

• Schedule follow-up testing in 2-4 weeks when patient is not acutely ill
• Document all bleeding episodes with detailed descriptions
• Consider genetic testing if initial workup is inconclusive but clinical suspicion remains high
• Establish a clear threshold for hematology referral based on test results and clinical symptoms

By following this systematic approach to further workup, the underlying cause of the patient's easy bruising can be properly identified, leading to appropriate management strategies to reduce morbidity and improve quality of life.