Sepsis-induced coagulopathy in preterm neonates with Gram-positive sepsis presents with hypercoagulation and reduced platelet activation compared with healthy preterm neonates

Dimitra Gialamprinou; Christos-Georgios Kontovazainitis; Abraham Pouliakis; Alexandra Fleva; Maria Markopoulou; Maria-Elina Bessina; Georgios N Katsaras; Ilias Chatziioannidis; Anastasia Giannakou; Emmanuel Roilides; Elisavet Diamanti; Georgios Mitsiakos

doi:10.1016/j.rpth.2023.100100

Sepsis-induced coagulopathy in preterm neonates with Gram-positive sepsis presents with hypercoagulation and reduced platelet activation compared with healthy preterm neonates

Res Pract Thromb Haemost. 2023 Mar 7;7(2):100100. doi: 10.1016/j.rpth.2023.100100. eCollection 2023 Feb.

Affiliations

¹ Second Neonatal Department and Neonatal Intensive Care Unit (NICU), Aristotle University of Thessaloniki, "Papageorgiou" University Hospital, Thessaloniki, Greece.
² Second Department of Pathology, National and Kapodistrian University of Athens, "Attikon" University Hospital, Athens, Greece.
³ Immunology and Histocompatibility Department, "Papageorgiou" University Hospital, Thessaloniki, Greece.
⁴ Third Department of Pediatrics, Aristotle University of Thessaloniki, "Hippokration" University Hospital, Thessaloniki, Greece.

Abstract

Background: Neonatal sepsis is frequently accompanied by coagulopathy and thrombocytopenia attributed to the cross-link between inflammation and coagulation. However, sepsis-induced coagulopathy and platelet function in septic preterm neonates remain to be elucidated. In addition, there is no robust evidence for a causal relationship between thrombocytopenia and bleeding in preterm neonates with sepsis.

Objective: This single-center prospective cohort study aimed to assess sepsis-induced coagulopathy and platelet function in preterm neonates during sepsis.

Methods: We included 25 preterm neonates with Gram-positive sepsis born at gestational age 24 + 1 to 34 + 3 and studied in comparison to 30 healthy counterparts. Coagulation was assessed using conventional coagulation tests (CCTs) and rotational thromboelastometry (ROTEM). Platelet function was evaluated by flow cytometry. The study was conducted at 3-time points, at 1st, at 2nd to 3rd, and at 5th to 7th day of sepsis, respectively.

Results: Compared with healthy controls, neonates with Gram-positive sepsis present in ROTEM a hypercoagulable state; a higher maximum clot firmness (MCF) and higher amplitudes of intrinsic rotational thromboelastometry (INTEM) (INTEM MCF: median, 71; P .004 and INTEM A10: median, 67; P .005, respectively), extrinsic rotational thromboelastometry (EXTEM) (EXTEM MCF: median, 70; P .02 and EXTEM A10: median, 67; P .02, respectively), and rotational thromboelastometry assay for fibrin formation (FIBTEM) (FIBTEM MCF: median, 25; P < .001 and FIBTEM A10: median, 23; P .002, respectively). Conversely, CCTs exhibited hypocoagulation. Thrombocytopenia in preterm neonates with Gram-positive sepsis is not associated with an increased bleeding risk. In Gram-positive sepsis, platelets display increased glycoprotein (GP) surface receptors' expression (GPIb: median, 2.8; P .03, GPIIb: median, 3.1; P .004, and GPIIIa: median, 3.9; P .008, respectively) and reduced activation (P-selectin: median, 1; P < .001). A higher expression of platelets GP and improved degranulation capacity were recorded in patients in higher gestational age groups of >32 weeks of gestation. Platelet GPIb expression is age-dependent in healthy neonates.

Conclusion: Neonatal Gram-positive sepsis is characterized by a progressive hypercoagulation along with increased GP expression, reduced platelet activation, and thrombocytopenia without bleeding. Platelet GP expression and degranulation capacity are age-dependent among neonates with sepsis. Platelet GP expression is age-dependent among healthy counterparts.

Keywords: Gram-positive bacterial infections; blood coagulation disorders; blood platelets; flow cytometry; infant; newborn; sepsis.