What is the most likely diagnosis for a newborn with persistent bleeding after circumcision, a family history of a bleeding disorder affecting the mother and brother, and no laboratory results available?

Von Willebrand Disease (VWD)

The most likely diagnosis is Von Willebrand disease (VWD), given the persistent post-circumcision bleeding and positive family history affecting both the mother and brother, which indicates an autosomal inheritance pattern affecting both sexes equally. 1

Key Diagnostic Reasoning

Why VWD is Most Likely (Answer B)

• VWD is the most common inherited bleeding disorder, affecting approximately 1 in 1,000 people and occurring equally in males and females 2, 1
• Post-circumcision bleeding is a classic presentation of VWD and represents one of the hallmark bleeding symptoms that should raise immediate suspicion 1, 3
• The family history pattern is pathognomonic: Both the mother and brother are affected, which is consistent with autosomal dominant inheritance (most common in Type 1 VWD) 1
• VWD causes mucocutaneous bleeding due to deficiency or dysfunction of von Willebrand factor, which mediates platelet adhesion and carries factor VIII 2

Why NOT Hemophilia A (Answer A)

• Hemophilia A is X-linked recessive and would not affect the mother 1
• Males inherit hemophilia from carrier mothers who are typically asymptomatic (though rare exceptions exist with skewed X-inactivation or Turner syndrome) 4
• The maternal involvement makes hemophilia A essentially impossible in this clinical scenario 1

Why NOT DIC (Answer C)

• DIC requires an underlying trigger such as sepsis, trauma, hypoxia, or systemic illness 1
• DIC does not have a familial inheritance pattern 1
• The clinical presentation describes isolated bleeding without evidence of systemic illness or consumptive coagulopathy

Why NOT Platelet Disorder (Answer D)

• While platelet function disorders can present with similar mucocutaneous bleeding, they are much rarer than VWD 1
• The specific presentation of post-circumcision bleeding combined with the family history pattern more strongly suggests VWD 1
• Platelet disorders would be a secondary consideration if VWD testing returns normal 3

Critical Clinical Pearls

Diagnostic Challenges Without Labs

• Standard coagulation studies (PT/aPTT) do not reliably detect VWD, especially in mild cases 1, 3
• Normal PT, aPTT, platelet count, and fibrinogen do not exclude VWD 3
• Specific testing is required: VWF antigen, VWF ristocetin cofactor activity, and factor VIII levels must all be ordered simultaneously 3

Immediate Management Considerations

• Bleeding after circumcision requires prompt hemostatic intervention while awaiting diagnostic confirmation
• Local compression may be insufficient in VWD due to impaired platelet adhesion 2
• Consultation with pediatric hematology is warranted due to the complexity of VWD diagnosis and need for specialized testing 1, 3

Testing Pitfalls to Avoid

• VWF is an acute phase reactant and levels can be falsely elevated during stress, illness, or in the immediate neonatal period 1
• Repeated testing may be required for reliable diagnosis 1
• Proper sample handling is essential: atraumatic blood draw, room temperature transport, and prompt processing 3

Next Steps in Clinical Practice

When VWD is suspected based on clinical presentation:

• Order all three VWD assays simultaneously: VWF antigen, VWF ristocetin cofactor activity, and factor VIII coagulant activity 3
• Definitive diagnosis requires VWF ristocetin cofactor activity <30 IU/dL, or 30-50 IU/dL with supportive clinical/family history 3
• If initial testing is normal but clinical suspicion remains high, platelet function testing should be the next step 3
• Immediate referral to pediatric hematology is indicated for abnormal results requiring subtyping or strong bleeding history with normal tests 3