What coagulation factor is affected in a newborn patient with delayed separation of the umbilical cord and bleeding, normal Prothrombin Time (PT), Partial Thromboplastin Time (PTT), platelet count, and function, but delayed clotting time?

Factor XIII Deficiency

The answer is C - Factor XIII deficiency. This clinical presentation of delayed umbilical cord separation with bleeding, normal PT, PTT, platelet count and function, but prolonged clot time is pathognomonic for Factor XIII deficiency 1, 2.

Why Factor XIII Deficiency is the Correct Answer

Factor XIII is the only coagulation factor that stabilizes fibrin clots after they form, and its deficiency is uniquely detected by prolonged clot time rather than PT or PTT 1. Here's the diagnostic reasoning:

• Normal PT and PTT exclude deficiencies in the intrinsic, extrinsic, and common pathways (Factors II, V, VII, VIII, IX, X, XI, XII), as these would prolong PT and/or PTT 1, 2
• Normal platelet count and function exclude thrombocytopenia (option D) and platelet disorders 3, 2
• Factor XIII acts after thrombin converts fibrinogen to fibrin, cross-linking fibrin strands to create a stable clot 1
• Standard coagulation tests (PT/PTT) measure clot formation up to fibrin generation but do not assess clot stability, which requires Factor XIII 1

Classic Clinical Presentation

Delayed umbilical cord separation (beyond 2-3 weeks) with bleeding is a hallmark presentation of Factor XIII deficiency 4, 5:

• The umbilical stump requires stable fibrin clot formation for proper separation and hemostasis 4
• Without Factor XIII, clots form initially (normal PT/PTT) but then break down, causing delayed separation and bleeding 5
• This presentation has been documented in multiple case series of severe Factor XIII deficiency 4, 5

Why Other Options Are Incorrect

Factor VIII Deficiency (Option A - Hemophilia A)

• Would prolong PTT, not leave it normal 3
• Factor VIII is part of the intrinsic pathway, and its deficiency causes prolonged PTT with normal PT 3
• The normal PTT in this case excludes Factor VIII deficiency 3

Von Willebrand Disease (Option B)

• Would cause prolonged bleeding time and potentially prolonged PTT, but not isolated prolonged clot time 3
• Von Willebrand factor affects platelet adhesion (primary hemostasis) and carries Factor VIII 3
• Normal platelet function in this case excludes von Willebrand disease 3
• Does not typically cause severe umbilical stump bleeding in newborns 3

Thrombocytopenia (Option D)

• Explicitly excluded by normal platelet count 3, 2
• Would not cause isolated prolonged clot time with normal PT/PTT 2

Important Clinical Pitfall

Do not confuse delayed umbilical cord separation as a normal variant 4, 5:

• Normal cord separation occurs at 7-10 days in term infants 6
• Separation beyond 3 weeks with bleeding should raise suspicion for Factor XIII deficiency or leukocyte adhesion defects 4, 5
• While delayed separation can occur with prematurity, sepsis, or antibiotic use, bleeding from the site with normal routine coagulation studies is specific for Factor XIII deficiency 6, 7

Diagnostic Confirmation

The diagnosis is confirmed by specific Factor XIII activity assay 1:

• Clot solubility test in 5M urea or 1% monochloroacetic acid shows rapid clot dissolution in Factor XIII deficiency 1
• Factor XIII activity level <1% indicates severe deficiency 1