Should we stop testing for bleeding disorders based on a normal RIPA (Ristocetin-Induced Platelet Aggregation) test result in a patient with a significant family history of bleeding disorders?

Further Testing is Necessary Despite Normal RIPA in a Patient with Strong Family History of Bleeding Disorders

Normal RIPA testing alone is insufficient to rule out bleeding disorders in a patient with multiple family members having elevated bleeding assessment tool scores, and further testing should be pursued.

Understanding the Significance of Family History in Bleeding Disorders

When evaluating a patient with a significant family history of bleeding disorders (19 family members with at least 5 having increased bleeding assessment tool scores), the normal RIPA test result represents only one piece of the diagnostic puzzle. Family history is a critical component in the assessment of bleeding disorders:

• A positive family history is considered a very important clinical consideration for assessment of mild bleeding disorders, with nearly all clinicians (98%) including this in their initial bleeding assessment 1
• The American Academy of Pediatrics recognizes that family history of a specific bleeding disorder might necessitate testing for that condition, even when initial tests are normal 1

Comprehensive Diagnostic Approach

First-Line Testing to Consider:

• Complete blood count (CBC) and ferritin analysis (persistent iron deficiency may suggest a bleeding phenotype)
• Coagulation screening: PT, aPTT, Clauss fibrinogen
• Von Willebrand factor (VWF) testing:
  • VWF antigen (VWF:Ag)
  • VWF activity assays
  • Factor VIII coagulant activity

Second-Line Testing:

• Platelet function testing beyond RIPA
• VWF multimer analysis (essential for subtyping von Willebrand Disease) 2
• Specific factor assays (particularly factors VIII, IX, and XI)
• VWF collagen binding assay (VWF:CB)

Why Normal RIPA Is Not Sufficient

1. RIPA has limitations:

   • RIPA primarily evaluates platelet-VWF interaction and can miss other bleeding disorders
   • Normal RIPA does not exclude all types of von Willebrand Disease or other bleeding disorders 2

2. Multiple testing is often required:

   • Von Willebrand factor is an acute phase reactant; its levels can vary in response to clinical status, resulting in falsely elevated results
   • Testing may need to be repeated up to 3 times to ensure reliable results 1

3. Family history significance:

   • With 5 family members having elevated bleeding assessment tool scores, there is a strong likelihood of an inherited bleeding disorder that may require specialized testing

Potential Diagnoses to Consider

1. Von Willebrand Disease variants:

   • Some variants may have normal RIPA but still present with bleeding symptoms 3, 4
   • Type 2N VWD presents with normal VWF:RCo and VWF:Ag but low FVIII:C 2

2. Platelet function disorders:

   • Some platelet function disorders may have normal RIPA but abnormal responses to other agonists 1

3. Bleeding Disorder of Unknown Cause (BDUC):

   • If no recognized hemostatic defect is found despite positive bleeding history, patients are considered to have BDUC 1
   • These patients still require management for bleeding symptoms

Management Implications

Identifying the specific bleeding disorder has important implications:

• Guides prophylactic treatment before procedures
• Informs genetic counseling
• Determines appropriate hemostatic agents (DDAVP vs. factor concentrates)
• Influences management of pregnancy and childbirth in female patients

Conclusion

Given the strong family history of bleeding disorders (5 family members with elevated bleeding assessment tool scores), a single normal RIPA test is insufficient to rule out a bleeding disorder. Further testing is warranted to identify potential bleeding disorders that may not be detected by RIPA alone. Consultation with a hematologist specializing in bleeding disorders is recommended to guide additional testing.