What is the most likely diagnosis for a baby with delayed separation of the umbilical cord and bleeding from the site, with normal coagulation labs including Prothrombin Time (PT), Partial Thromboplastin Time (PTT), platelet count, and function, but a delay in bleeding time?

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Factor XIII Deficiency

The most likely diagnosis is Factor XIII deficiency (Option C), as this is the classic presentation of delayed umbilical cord separation with bleeding and normal routine coagulation studies.

Clinical Reasoning

Factor XIII deficiency presents with a pathognomonic triad that matches this case perfectly:

  • Delayed umbilical cord separation (typically beyond 2-3 weeks in term infants) with bleeding from the umbilical stump 1
  • Normal PT, PTT, platelet count, and platelet function 1
  • Prolonged bleeding time as the only abnormal routine test 1

Factor XIII is a transglutaminase that cross-links fibrin polymers, stabilizing the clot. Critically, Factor XIII activity is not detected by routine coagulation panels (PT/PTT) because these tests only measure clot formation time, not clot stability 1. The clot forms normally but dissolves prematurely due to inadequate cross-linking.

Why Other Options Are Incorrect

Factor VIII deficiency (Hemophilia A) would prolong the PTT, not leave it normal. The PTT is explicitly normal in this case 2, 1.

Von Willebrand disease would typically show:

  • Prolonged PTT in severe cases (Type 3 VWD) due to low Factor VIII 3
  • Abnormal platelet function testing, particularly with ristocetin cofactor activity 3
  • The platelet function is explicitly stated as normal here 2

Thrombocytopenia is explicitly ruled out by the normal platelet count stated in the question 2.

Diagnostic Approach

When evaluating bleeding with normal routine coagulation studies:

  • Factor XIII activity assay must be specifically ordered, as it is often overlooked in routine coagulation panels 1
  • The American Society of Hematology recommends comprehensive evaluation for rare bleeding disorders when routine studies are normal but clinical bleeding occurs 1
  • Factor XIII deficiency has an incidence of approximately 1 in 2 million but should be suspected with this classic presentation 1

Clinical Context of Delayed Cord Separation

Normal umbilical cord separation occurs at 7-10 days in term infants 4. Delayed separation beyond 3 weeks suggests:

  • Leukocyte adhesion deficiency (associated with recurrent infections and neutrophil dysfunction) 5, 6
  • Factor XIII deficiency (associated with bleeding manifestations) 1
  • Immunodeficiency syndromes 5

The presence of bleeding from the umbilical site strongly points toward Factor XIII deficiency rather than immunologic causes 1, 5.

Management Implications

Factor XIII deficiency requires:

  • Prophylactic Factor XIII concentrate for surgical procedures and trauma 1
  • Tranexamic acid as adjunctive therapy for mucosal bleeding 1, 3
  • Genetic counseling, as this is typically an autosomal recessive disorder 1

The bleeding time prolongation occurs because the clot that forms is mechanically unstable and breaks down under shear stress, mimicking a platelet function defect despite normal platelet count and function 1.

References

Guideline

Bleeding Disorder Diagnosis and Management

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Management of Suspected von Willebrand Disease with Elevated PT and aPTT

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

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This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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