What is the appropriate management for a newborn with burns, hepatomegaly, and bleeding at multiple sites, with normal Prothrombin Time (PT) and Partial Thromboplastin Time (PTT) after administration of Fresh Frozen Plasma (FFP) and Vitamin K?

Management of Newborn with Burns, Hepatomegaly, and Bleeding with Normal PT/PTT

This newborn requires immediate investigation for underlying liver disease and factor deficiency, with administration of vitamin K and consideration of specific factor replacement or fresh frozen plasma if bleeding persists despite normal coagulation studies. 1, 2

Initial Assessment and Diagnosis

The clinical presentation of a term newborn with hepatomegaly and multi-site bleeding with normal PT/PTT after FFP and vitamin K administration suggests several critical possibilities:

• Hepatic synthetic dysfunction causing factor deficiency that is not fully corrected by standard therapy 1
• Factor XIII deficiency or other rare factor deficiencies not detected by PT/PTT 1
• Platelet dysfunction or thrombocytopenia requiring specific evaluation 1
• Underlying metabolic or infectious liver disease causing ongoing coagulopathy 1

Immediate Management Algorithm

Step 1: Laboratory Evaluation

• Obtain complete coagulation profile: fibrinogen level (Clauss method), platelet count, factor XIII level, and thromboelastography if available 1, 3
• Assess liver function: transaminases, bilirubin, albumin, and ammonia to evaluate hepatic synthetic capacity 1
• Check for infection: blood cultures, viral hepatitis panel, and metabolic screening 1

Step 2: Targeted Therapy Based on Findings

If fibrinogen <1.0 g/L:

• Administer cryoprecipitate (preferred) or fibrinogen concentrate, as FFP has relatively low fibrinogen content 4, 5
• Target fibrinogen >1.0 g/L to prevent microvascular bleeding 5, 3

If platelet count <50 × 10⁹/L:

• Transfuse platelets to maintain count >50 × 10⁹/L (or >100 × 10⁹/L if ongoing bleeding) 1
• Initial dose: 10-15 mL/kg of platelet concentrate 1

If factor XIII deficiency suspected (normal PT/PTT with bleeding):

• Administer specific factor XIII concentrate or cryoprecipitate 1
• This is a critical diagnosis as PT/PTT do not detect factor XIII deficiency 1

Step 3: Additional Vitamin K Administration

Despite prior vitamin K administration, consider:

• Repeat vitamin K1 (phytonadione) 1 mg intramuscularly or slow intravenous if there is evidence of vitamin K-dependent factor deficiency 2, 6
• For neonates at high risk of hemorrhage (hepatic disease), the intramuscular or slow intravenous route is preferred over oral 7, 6
• Higher doses may be necessary in the context of liver disease 2

Step 4: Fresh Frozen Plasma Considerations

If coagulopathy persists despite initial FFP:

• Administer additional FFP at 10-15 mL/kg, as further doses may be required 1
• Important caveat: FFP may be insufficient in severe hepatic dysfunction, as the liver cannot synthesize adequate clotting factors even with replacement 8
• Monitor for volume overload and transfusion-related acute lung injury (TRALI), particularly with repeated FFP doses 1, 4

Critical Pitfalls to Avoid

• Do not assume normal PT/PTT excludes coagulopathy: Factor XIII deficiency, platelet dysfunction, and fibrinogen depletion can cause bleeding with normal screening tests 1, 4
• Do not rely solely on FFP for fibrinogen replacement: FFP contains only ~2 g fibrinogen per 4 units, making cryoprecipitate or fibrinogen concentrate more effective 4, 5
• Do not give oral vitamin K to critically ill neonates: The intramuscular or intravenous route is essential for reliable absorption in sick infants 7, 6
• Do not overlook underlying liver disease: Hepatomegaly with bleeding suggests primary hepatic pathology requiring specific investigation and treatment 1

Ongoing Management

• Admit to neonatal intensive care for continuous monitoring and management 1, 3
• Repeat coagulation studies every 4-6 hours initially to guide further therapy 1, 2
• Address the underlying cause: Treat infection, metabolic disease, or other hepatic pathology as identified 1
• Monitor for complications: Hypothermia, acidosis, and hypocalcemia can worsen coagulopathy 1, 3

Special Considerations for Neonates

• Neonatal coagulation factors are physiologically lower than adult levels, making interpretation challenging 7, 6
• Breast-fed infants are at higher risk for vitamin K deficiency bleeding and may require repeated dosing 7, 6
• Prothrombin complex concentrate (PCC) is generally not recommended as first-line therapy in neonates, though it may be considered if FFP fails and specific factor concentrates are unavailable 1, 9