Causes of Thrombocytopenia in a 1-Month-Old Preterm Infant
In a 1-month-old preterm infant, thrombocytopenia is most commonly caused by late-onset sepsis or necrotizing enterocolitis (NEC), which typically presents after 72 hours of life and leads to severe, prolonged thrombocytopenia. 1, 2, 3
Timing-Based Classification
Late-Onset Thrombocytopenia (>72 hours of life)
At one month of age, your preterm infant falls into the late-onset category, where the differential diagnosis is distinctly different from early thrombocytopenia:
Primary causes to investigate:
Sepsis - This is the leading cause of late-onset thrombocytopenia in preterm neonates, causing severe thrombocytopenia (platelets <50 × 10⁹/L) that is prolonged and often requires platelet transfusion 2, 3
Necrotizing enterocolitis (NEC) - Nearly always associated with late-onset thrombocytopenia in preterm infants, presenting with severe and prolonged platelet reduction 1, 2, 3
Ongoing infection - Bacterial infections acquired postnatally rapidly lead to severe thrombocytopenia in this population 3
Less Common but Important Causes
Immune-Mediated Thrombocytopenia
Neonatal alloimmune thrombocytopenia (NAIT) - While NAIT typically presents at birth or within the first 7 days with platelet counts <100 × 10⁹/L (most <50 × 10⁹/L), it should be considered if thrombocytopenia is severe and isolated without other explanation 4, 5
Maternal immune thrombocytopenia - Can cause neonatal thrombocytopenia through transplacental passage of maternal antiplatelet antibodies 6
Prematurity-Related Factors
Impaired megakaryocytopoiesis - Preterm neonates have inherently compromised platelet production capacity, making them vulnerable to prolonged thrombocytopenia 2
Chronic hypoxia - Intrauterine hypoxia and placental insufficiency are frequent causes of early-onset thrombocytopenia in preterm neonates, though less likely at one month unless there are ongoing hypoxic insults 2, 7
Thrombocytopenia associated with prematurity itself - Approximately half of all sick preterm neonates develop thrombocytopenia during their NICU course 2
Critical Diagnostic Approach
Immediate evaluation should focus on:
Rule out sepsis/NEC first - Obtain blood cultures, complete blood count with differential, and assess for clinical signs of infection or NEC, as these are by far the most common causes at this age 1, 2, 3
Assess severity - Platelet count <50 × 10⁹/L warrants urgent transcranial ultrasonography to evaluate for intracranial hemorrhage 5
Review coagulation studies - Normal coagulation studies with isolated severe thrombocytopenia excludes vitamin K deficiency and hemophilia A, pointing toward immune causes or consumptive processes 5
Consider immune workup if sepsis/NEC excluded - If infection is ruled out and thrombocytopenia is severe and isolated, pursue HPA genotyping of mother, neonate, and father, plus maternal serum alloantibody testing to evaluate for NAIT 4, 5
Common Pitfalls
Assuming all preterm thrombocytopenia is benign - While early-onset thrombocytopenia in preterm infants is usually mild and self-resolving, late-onset thrombocytopenia at one month is nearly always pathological and requires investigation 2, 3
Missing NAIT - This is the most important cause of severe thrombocytopenia in term neonates and can occur in preterm infants; delayed diagnosis increases risk of intracranial hemorrhage and long-term neurological disability 3, 6
Delaying sepsis workup - Given that sepsis and NEC account for the vast majority of late-onset thrombocytopenia in preterm infants, these must be excluded first before pursuing other diagnoses 1, 2, 3