When should a baby born to a mother with protein S deficiency be evaluated for inherited thrombophilia?

When to Evaluate a Baby Born to a Mother with Protein S Deficiency

Routine thrombophilia testing should not be performed in neonates born to mothers with protein S deficiency unless the infant develops clinical signs of thrombosis. 1, 2

Key Principles for Neonatal Evaluation

Defer Testing in Asymptomatic Infants

• Protein S levels are physiologically low in all neonates, making interpretation of deficiency testing unreliable during the newborn period. 2
• Testing should be deferred until at least 6 months of age (and ideally not until after puberty or outside of acute illness) when protein S levels normalize to adult ranges. 2
• For asymptomatic individuals with a family history of protein S deficiency, clinical surveillance is the appropriate management strategy rather than routine testing or prophylactic anticoagulation. 1

Immediate Evaluation Only for Symptomatic Neonates

Urgent evaluation is warranted only if the neonate develops clinical manifestations of thrombosis, including: 3

• Arterial thrombosis: Poor perfusion, absent pulses, limb discoloration, or signs suggesting aortic thrombosis
• Venous thrombosis: Limb swelling, superior vena cava syndrome, or renal vein thrombosis
• Purpura fulminans: Extensive skin necrosis with disseminated intravascular coagulation (suggests homozygous protein S deficiency)
• Cerebral sinovenous thrombosis: Seizures, altered mental status, or focal neurological deficits

Management of Symptomatic Neonates

If thrombosis occurs, immediate intervention includes: 1

• Administration of fresh frozen plasma (FFP) 10-20 mL/kg every 12 hours to provide protein S replacement until clinical lesions resolve
• Protein concentrate when available (preferred over FFP)
• After stabilization, long-term options include vitamin K antagonists, low molecular weight heparin, protein replacement therapy, or liver transplantation for severe cases 1

Risk Stratification Context

Understanding Maternal Risk Does Not Equal Neonatal Risk

• The mother's protein S deficiency increases her own thrombotic risk, particularly postpartum (1.76% risk with family history of VTE), but this does not automatically translate to immediate neonatal thrombotic risk. 1
• Heterozygous protein S deficiency (which the infant has a 50% chance of inheriting) typically does not manifest with thrombosis in childhood unless additional risk factors are present. 4, 5
• Pediatric thrombotic events in protein S deficiency are uncommon, with a review showing mean age of first thrombosis at 10 years when it does occur. 5

When to Consider Later Testing

Testing may be considered at 6 months of age or older if: 2

• There is a strong family history of early thrombotic events (before age 50)
• The child develops unexplained thrombosis
• Pre-procedural risk assessment is needed for major surgery
• The family requests testing for reproductive planning purposes (though this is typically deferred until adolescence)

Common Pitfalls to Avoid

• Do not order protein S levels in the immediate neonatal period as physiologically low levels will lead to false-positive results and unnecessary parental anxiety. 2
• Do not initiate prophylactic anticoagulation in asymptomatic neonates based solely on maternal history—the risks of anticoagulation outweigh benefits in this population. 1
• Do not confuse maternal postpartum thromboprophylaxis needs (which are real and evidence-based) with neonatal management needs (which are observation-based unless symptomatic). 4, 1