Pathologic Findings of Sepsis-associated Disseminated Intravascular Coagulation in a Neonate

To the Editors: A Japanese male infant, the firstborn of a dichorionic diamniotic twin pregnancy, was admitted to our neonatal intensive care unit for management of extremely low birth weight at 23 weeks of gestation, with a birth weight of 576 g. On admission, a peripherally inserted central catheter (PICC) was maintained for treatment and parenteral nutrition. However, the ductus arteriosus was refractory to treatment and failed to close, and the infant exhibited poor digestion, which prevented the removal of the PICC line. On the day of life (DOL) 26, the infant showed worsening respiratory status, elevated C-reactive protein (7.65 mg/dL), and a decreased platelet count (1000/μL). Considering the possibility of catheter-related bloodstream infection and sepsis-associated disseminated intravascular coagulation (DIC), we replaced the PICC, obtained blood culture samples, and removed the PICC line to initiate treatment. Despite the administration of antibiotics, anticoagulation therapy and other supportive measures, the infant died on DOL 28. After his death, the PICC tip and blood cultures obtained on DOL 26 yielded methicillin-resistant coagulase-negative staphylococci. On the day of the infant’s passing, with the consent of the parents, we performed a necropsy of the lungs and heart. This examination revealed diffusely scattered thrombi within the cardiac chambers and interalveolar blood vessels, surrounded by significant infiltration of neutrophils (Fig. 1A–F).FIGURE 1.: A: Heart. Magnification 2 × 2.5. Vegetation attached to the endocardium is observed, with a high degree of neutrophil infiltration evident in both the endocardium and the vegetation. B: The area enclosed by the dotted line in (A) is shown at 10 × 2.5 magnification. A high degree of neutrophil infiltration is also visible here. C: Lung. Magnification 2 × 2.5. A blood vessel is located in the center of the image, occupied by red blood cells and fibrin clots, suggesting the presence of a thrombus. The center of the thrombus is highly infiltrated with neutrophils. D: The area enclosed by the dotted line in (C) is shown at 10 × 2.5 magnification. Fibrin clots, red blood cells and neutrophil infiltration are observed. E: Lung blood vessel. Magnification 2 × 2.5. A vegetation/thrombus within the blood vessel. The vessel wall is necrotic, and its boundaries are unclear. F: The area enclosed by the dotted line in (E) is shown at 20 × 2.5 magnification. Fibrin clots, red blood cells and neutrophil infiltration are visible.It has been previously reported that neonates are more prone to developing DIC than adults, with infection recognized as one of the major underlying causes, accounting for approximately 16% of all DIC cases. In sepsis-associated DIC, the continuous consumption of coagulation factors and platelets leads to microcirculatory thrombosis, which can contribute to multiple organ failure and death due to sepsis.1,2 Few studies have provided pathological images of neonatal DIC.1 To our knowledge, this is the first report to present pathological images of sepsis-associated DIC. Neutrophil extracellular traps (NETs) are an important concept related to sepsis-associated DIC. As part of the innate immune response to infection, NETs are released when neutrophils encounter infectious microorganisms, and are composed of neutrophil granule proteins, cell-free DNA and histones. Although NETs serve as an important host defense mechanism, they also promote thrombus formation and can adsorb several proteins involved in thrombosis. Activation of coagulation can trigger DIC. Studies on patients with sepsis have suggested that increased NET formation is significantly associated with the incidence of sepsis-induced DIC and mortality in these patients.3–5 The histopathological findings of DIC observed in this case, which showed thrombus formation accompanied by neutrophil infiltration consistent with clinically observed sepsis-associated DIC, are significant because this pathology is rare and suggests the contribution of NETs to DIC. In the future, we believe that further investigation of sepsis-associated DIC pathology specimens, including immunostaining for fibrin and nuclear components, will deepen our understanding of the involvement of NETs.