Factor XIII Deficiency
The correct answer is C. Factor 13 deficiency. This newborn's presentation of delayed umbilical cord separation with bleeding and normal PT, PTT, platelet count, and platelet function—but prolonged clot formation time—is pathognomonic for Factor XIII deficiency 1.
Why Factor XIII Deficiency is the Answer
Factor XIII deficiency is the only coagulation disorder that presents with completely normal routine coagulation screening tests (PT, PTT, platelet count, and platelet function) because these tests only measure clot formation, not clot stability 1, 2. Factor XIII is responsible for cross-linking fibrin polymers to create mechanically stable clots 3. Without it, clots form normally but dissolve prematurely, leading to delayed bleeding 3.
Classic Clinical Presentation
- Delayed umbilical cord separation (beyond 2-3 weeks) with bleeding from the umbilical stump is the hallmark neonatal presentation of Factor XIII deficiency 1, 4, 5
- This occurs in approximately 80-90% of affected infants 5
- The bleeding is characteristically delayed because the initial clot forms normally but then breaks down due to mechanical instability 1, 3
Laboratory Pattern
- PT: Normal (extrinsic pathway intact) 1, 2
- PTT: Normal (intrinsic pathway intact) 1, 2
- Platelet count and function: Normal (primary hemostasis intact) 1, 2
- Clot solubility test: Abnormal (clot dissolves in 5M urea or 1% monochloroacetic acid) 2, 5
- Factor XIII activity assay: Low or absent (definitive diagnostic test) 1, 2
Why the Other Options Are Incorrect
A. Factor VIII Deficiency (Hemophilia A)
Factor VIII deficiency would prolong the PTT, not leave it normal 1, 6. Factor VIII is part of the intrinsic coagulation pathway, and its deficiency causes prolonged PTT with normal PT 6. The explicitly normal PTT in this case rules out Factor VIII deficiency 1.
B. Von Willebrand Disease
Von Willebrand disease would typically show abnormal platelet function testing and may prolong the PTT in severe cases 1, 6. The platelet function is explicitly normal in this case, excluding von Willebrand disease 1. Additionally, von Willebrand disease does not typically cause severe umbilical stump bleeding in newborns 6.
D. Thrombocytopenia
Thrombocytopenia is definitively ruled out by the normal platelet count 1, 6. By definition, thrombocytopenia requires a low platelet count, which is not present in this case 6.
Diagnostic Approach
Initial Screening
When routine coagulation tests (PT, PTT, platelet count) are normal but clinical bleeding occurs, Factor XIII deficiency must be specifically considered and tested for 1, 4:
- Order Factor XIII activity assay (not detected by routine panels) 1, 2
- Perform clot solubility test (5M urea test) as a rapid screening method 2, 5
- Consider Factor XIII antigen assay to distinguish type I (quantitative) from type II (qualitative) deficiency 2
Critical Pitfall
The most common diagnostic error is failing to consider Factor XIII deficiency because routine coagulation tests are normal 4, 2. Factor XIII is the only coagulation factor deficiency that cannot be detected by classical hemostatic screening tests 4. A newborn with persistent umbilical stump bleeding and normal routine coagulation tests should be screened for Factor XIII deficiency 4, 5.
Management Implications
- Prophylactic Factor XIII concentrate is required for surgical procedures and trauma 1
- Genetic counseling is recommended as this is typically an autosomal recessive disorder 1
- Long-term prophylaxis with cryoprecipitate or plasma-derived Factor XIII concentrate provides excellent prognosis 3
- Intracranial hemorrhage is a major concern in untreated patients, occurring in up to 30% of cases 3, 5