Effectiveness and Safety of 4-factor Prothrombin Complex Concentrate (4PCC) in Neonates With Intractable Bleeding or Severe Coagulation Disturbances: A Retrospective Study of 37 Cases

Abstract

Background: To date, clinical experience with prothrombin complex concentrate (PCC) in the neonatal population has been limited. Aim: The objective of this study was to describe our experience regarding the effectiveness and safety of PCC administration in newborns with severe bleeding or coagulopathy resistant to conventional therapy. Methodology: We retrospectively analyzed data from 37 neonates with intractable bleeding or severe coagulation disturbances. All patients received intravenous bolus administration of 20 or 30 u/kg of PCC per dose, as a rescue procedure. Results: Hemostasis was achieved in the majority of neonates and we observed statistically significant improvement in prothrombin time, international normalized ratio, and activated partial thromboplastin time (P<0.001, P=0.044, P<0.001, respectively). Thirteen neonates survived, whereas 24 did not survive. In those who survived, PCC had been administered earlier (<24 h) in the disease process compared with those who died (P=0.043). Neither acute adverse events nor thromboembolic complications were observed in all neonates. Conclusions: In our study, PCC seemed to be a safe and effective intervention for hemostasis and early intervention was more effective as a rescue therapy, without any adverse event. Further prospective controlled trials are required to determine optimal dose and timing of PCC administration in neonates.

The Vascular Endothelium and Coagulation: Homeostasis, Disease, and Treatment, with a Focus on the Von Willebrand Factor and Factors VIII and V

“…Both processes evolve throughout the neonatal period until adulthood, with significant quantitative and qualitative differences in the levels of the various proteins that participate in coagulation and fibrinolysis [ 82 , 86 , 91 , 92 , 93 , 94 ]. This variability, observed in neonates at different gestational stages [ 87 , 95 , 96 ], could be accounted for by differences in liver maturity or by the varying vitamin K concentrations observed in childbearing women [ 97 , 98 ]. All the components of the hemostatic system are present at childbirth but always at lower levels than at later developmental stages [ 80 , 81 , 84 , 86 , 87 , 99 ].…”

British Society for Haematology guideline for anticoagulant management of pregnant individuals with mechanical heart valves

“…An INR above the age-appropriate reference range should be managed with IV vitamin K (30 μg/ kg by slow IV infusion) rather than the standard neonatal prophylactic dose and FFP or 20-30 IU/kg PCC should be considered. 64,65…”

“…Close liaison with the neonatology team is required and a coagulation screen should be performed on the newborn. An INR above the age‐appropriate reference range should be managed with IV vitamin K (30 μg/kg by slow IV infusion) rather than the standard neonatal prophylactic dose and FFP or 20–30 IU/kg PCC should be considered 64,65 …”

Direct Oral Anticoagulant Reversal in the Pediatric Emergency Department

“…In adult studies looking at the use of 4PCC for nonspecific DOAC reversal, there was good hemostatic efficacy with low incidence of subsequent thrombotic events, although all-cause mortality was still fairly high 16–18 . There are no pediatric studies using 4PCC for DOAC-related bleeding; however, there are data for use of prothrombin concentrates in pediatric patients with major bleeding events 19,20 . There are no comparative studies directly between targeted antidotes and 4PCC in either the adult or pediatric populations.…”