What is the diagnosis and management for a newborn with umbilical bleeding, normal Prothrombin Time (PT), activated Partial Thromboplastin Time (aPTT), platelet count, and platelet function, but increased clot lysis, with a family history of similar condition?

Factor XIII Deficiency

This newborn has Factor XIII deficiency, and you must immediately administer fresh frozen plasma (FFP) at 10-20 mL/kg every 12 hours to stop the umbilical bleeding, then establish lifelong prophylaxis to prevent the nearly 30% risk of fatal intracranial hemorrhage. 1, 2, 3

Diagnostic Confirmation

Factor XIII deficiency is the only coagulation disorder that presents with normal PT, aPTT, platelet count, and platelet function but demonstrates increased clot lysis. 1, 4, 5

• The classic presentation is umbilical stump bleeding in the first weeks of life, often with a positive family history suggesting autosomal recessive inheritance 2, 3, 6
• Routine coagulation tests (PT, aPTT) only measure clot formation time, not clot stability, which is why they remain normal in Factor XIII deficiency 4
• The clot solubility test (5M urea or 2% acetic acid) is diagnostic when the clot dissolves in <16 hours, though it may miss mild deficiencies 2, 7
• Order a specific Factor XIII activity assay for definitive diagnosis, as this is not included in routine coagulation panels 1, 4
• Thromboelastography (TEG) with streptokinase is more sensitive than solubility tests, showing increased Lys60 at Factor XIII levels <40% 7

Immediate Management

Do not delay treatment while awaiting confirmatory testing if clinical suspicion is high. 1, 2

• Administer FFP 10-20 mL/kg immediately to stop active umbilical bleeding 1
• Avoid all intramuscular injections, including vitamin K, until Factor XIII levels are corrected, as these cause large intramuscular hematomas 1
• Avoid invasive procedures (venipuncture, circumcision) until diagnosis is confirmed and Factor XIII activity is >10% 1
• Collaborate immediately with pediatric hematology if available 1

Long-Term Prophylaxis

Lifelong prophylaxis is mandatory due to the 30% risk of intracranial hemorrhage without treatment. 2, 3

• Target trough Factor XIII activity of 10-20 IU/dL, which is achievable with 25-35 IU/kg every 4-6 weeks 2
• FFP 10-20 mL/kg every 2-4 weeks is an alternative if Factor XIII concentrate is unavailable 1
• Factor XIII concentrate (plasma-derived or recombinant) is preferred over FFP for long-term prophylaxis due to lower volume and viral transmission risk 2, 3
• The half-life of Factor XIII is approximately 9-12 days, allowing for infrequent dosing 2, 3

Surgical and Procedural Management

Before any surgical intervention or invasive procedure, ensure Factor XIII activity is >10%. 1

• For major surgery or trauma, target Factor XIII levels of 20-30% 2
• Tranexamic acid may be used as adjunctive therapy for mucosal bleeding or procedures 1
• Consider platelet transfusion during problematic bleeds, as platelets contain Factor XIII and provide cellular hemostatic support 2

Family Counseling

Provide genetic counseling regarding autosomal recessive inheritance. 1, 4

• Screen the sibling with similar history for Factor XIII deficiency 2
• Both parents are likely heterozygous carriers with Factor XIII activity 30-60%, which is usually asymptomatic 2
• Future pregnancies carry a 25% risk of affected offspring 4

Critical Pitfalls to Avoid

• Do not assume vitamin K deficiency based on umbilical bleeding alone; vitamin K deficiency would show prolonged PT, which is explicitly absent in this case 1
• Do not rely solely on clot solubility tests, as they may be normal at Factor XIII levels between 9-40%, which still carries bleeding risk 7
• Do not use INR to guide management, as it is designed exclusively for warfarin monitoring and has no validity in Factor XIII deficiency 8
• Do not delay prophylaxis initiation; intracranial hemorrhage can occur as early as 2 months of age 3