What is the risk of Necrotizing Enterocolitis (NEC) in infants on anticoagulation therapy?

From the Guidelines

Infants on anticoagulation therapy do not appear to have an increased risk of necrotizing enterocolitis (NEC) based on current evidence, though data specifically addressing this concern is limited. When anticoagulation is medically necessary for conditions like thrombosis or congenital heart disease, the benefits typically outweigh potential risks. Common anticoagulants used in infants include low molecular weight heparin (enoxaparin, typically 1.5 mg/kg every 12 hours for term infants and 1.7 mg/kg every 12 hours for preterm infants) and unfractionated heparin (starting at 28 units/kg/hour after an initial bolus of 75 units/kg) 1. While administering these medications, clinicians should monitor for signs of NEC including abdominal distension, bloody stools, feeding intolerance, and lethargy. The theoretical concern about anticoagulation increasing NEC risk stems from the possibility that anticoagulants might exacerbate intestinal bleeding if mucosal injury occurs. However, the pathophysiology of NEC primarily involves intestinal inflammation, bacterial translocation, and ischemia rather than coagulation abnormalities. Regular monitoring of anti-factor Xa levels (target range 0.5-1.0 units/mL for therapeutic dosing) is essential to maintain appropriate anticoagulation while minimizing bleeding risks. If NEC develops while an infant is on anticoagulation, the risk-benefit of continuing therapy should be reassessed with potential dose adjustment or temporary discontinuation depending on the indication for anticoagulation.

Some key points to consider in the management of infants on anticoagulation therapy include:

• The use of anticoagulants in pediatric patients is based on limited evidence, and most guidelines are extrapolated from adult data 1.
• The management of venous thromboembolism in pediatric patients involves the use of anticoagulants, with low molecular weight heparin and unfractionated heparin being common choices 1.
• The diagnosis and management of complicated intra-abdominal infection in adults and children, including NEC, involve the use of broad-spectrum antibiotics and supportive care 1.
• The selection of specific antimicrobial therapy for pediatric patients with complicated intra-abdominal infection should be based on considerations of the origin of infection, severity of illness, and safety of the antimicrobial agents in specific pediatric age groups 1.

In terms of the risk of NEC in infants on anticoagulation therapy, the current evidence does not suggest an increased risk, but clinicians should remain vigilant and monitor for signs of NEC, as the pathophysiology of the condition is complex and multifactorial 1.

From the Research

Risk of NEC in Infants on Anticoagulation

• The risk of necrotizing enterocolitis (NEC) in infants on anticoagulation is a complex issue, and there is limited research directly addressing this topic 2, 3.
• However, studies have investigated the use of anticoagulants in pediatric patients, including infants, and the pathophysiology of NEC 4, 5, 6.
• Research has shown that coagulopathy and mesenteric thrombosis are common in premature neonates with NEC, suggesting a potential link between coagulation and the development of NEC 6.
• A study on coagulation gene expression profiling in infants with NEC found significant changes in the expression of genes involved in the coagulation and anticoagulation systems, with an overall procoagulant effect 6.
• Another study investigated the use of low-dose low-molecular-weight heparin in active ulcerative colitis, which may have implications for the treatment of NEC, but more research is needed to fully understand its effects 5.
• The use of direct oral anticoagulants (DOACs) in pediatric patients, including infants, is being investigated, and preliminary results suggest that DOACs may be at least as efficient and safe as traditional anticoagulants for the treatment and prevention of thrombotic events 2.
• However, there is currently no direct evidence to support the use of anticoagulants in infants with NEC, and more research is needed to fully understand the risks and benefits of anticoagulation therapy in this population 3, 4.