Peripheral Multilineage Haemophagocytosis in an Extremely Premature Infant With <i>Escherichia col</i><i>i</i> Sepsis

An extremely premature girl was born following spontaneous labour at 24 weeks of gestation. The mother's urine culture revealed a resistant strain of Escherichia coli. The neonate was intubated due to respiratory insufficiency, and intermittent phototherapy was initiated. One week postpartum, the infant's blood culture yielded a positive result for Staphylococcus aureus infection, most likely attributed to a line-associated bloodstream infection. Consequently, antibiotic therapy with flucloxacillin and gentamicin was started. A week later, C-reactive protein levels rose to 81.1 mg/L, the girl developed circulatory insufficiency, and blood appeared in the endotracheal tube. Haematological analysis showed thrombocytopenia (83 × 109/L), anaemia (4.7 mmol/L), and leucocytosis (25 × 109/L). Microscopic evaluation revealed erythrophagocytosis, thrombophagocytosis, lymphophagocytosis and intra- and extra-cellular bacteria in the peripheral smear (May–Grünwald Giemsa stain, magnification ×400) (Figure 1). Additionally, vacuolation and toxic granulation was present in ≥50% of neutrophils. Direct antiglobulin tests were negative. Antibiotic therapy was switched to meropenem, which improved the girl's condition. Haemophagocytosis was not observed on subsequent smears. The blood culture was positive for E. coli infection only 2 days later. Haemophagocytosis in the peripheral blood is rare, particularly in neonates, but it is an important diagnostic clue [1]. It is most commonly associated with haemolytic disease of the newborn, but can also be triggered by severe infections, such as bacterial sepsis, viral infections, and fungal or parasitic diseases [2]. In this case, the presence of E. coli likely triggered a hyperinflammatory response, leading to the observed erythro-, thrombo-, and lymphophagocytosis in the peripheral smear [3]. The finding of intracellular bacteria in blood smears is concerning, as it may indicate overwhelming infection [4], requiring urgent intervention. Timely recognition of haemophagocytosis and bacterial presence on blood smears can be lifesaving, especially given the limited material available for laboratory analysis in neonates. Once the underlying infection is brought under control, the haemophagocytic activity typically subsides. All authors contributed to the laboratory evaluation of the patient. Jorik H. Amesz wrote the manuscript under supervision of Madeleen Bosma. The authors would like to kindly thank E.C. van Weers for her contribution. The authors declare no conflicts of interest. The data are available from the corresponding author upon reasonable request.