P0374 - Although Easier Is it Safe? Low molecular weight heparin anticoagulation in infants with mechanical prosthetic valves

Introduction: Anticoagulation in children with mechanical prosthetic valves lacks evidence-based recommendations and as a result, children receive adult-based oral vitamin K antagonists (VKA) regimens. Low molecular weight heparin (LMWH) has been proposed as an alternative treatment in adults with mechanical prosthetic valves and VKA failure or intolerance. We report the successful use of LMWH in infants following mechanical valve replacement in whom satisfactory therapeutic anticoagulation could not be achieved with VKA.

Case Description: Four pediatric patients underwent surgical replacement of systemic atrioventricular valves with mechanical prostheses at a single pediatric tertiary medical center between 2016 and 2019. Indications for replacement were unsuccessful congenital valve repair (3 patients) and native valve MSSA endocarditis (1 patient). Average age at valve replacement was 6.7 months (range 1-15 months). Satisfactory anticoagulation was defined as an international normalized ratio of 2.5-3.5 (INR; VKA therapy) or LMWH level 0.5-1 IU/mL (LMWH therapy) and percent of time therapeutic greater than 65%. In these patients, initial VKA therapy lasted an average 63 days (range 9-186 days) with an average 22% time in therapeutic range (TTR; range 7-37%; Figure 1) and 0.91 INRs per anticoagulation day (range 0.78-1.04; Figure 2). Due to unsatisfactory anticoagulation, all patients were transitioned to twice-daily LMWH therapy and subsequently were therapeutic an average 96% of days (range 95-99%) with 0.11 LMWH levels per anticoagulation day (range 0.11-0.24). Two LMWH patients have transitioned back to VKA therapy with an average 67% TTR and 0.16 INRs per anticoagulation days. One patient was transitioned at 5 months of age after 2 months on LMWH and the other remained on LMWH for 19 months until 33 months old. Including two patients remaining on LMWH, average LMWH duration was 12 months (range 2-25 months). Of note, during this time period, one additional infant underwent mechanical valve replacement (6 months old) and was adequately anticoagulated with VKA only (TTR 55% and 0.47 INRs per day for the first 3 months before improvement). All patients additionally received low-dose aspirin. There were no major bleeding or thromboembolic events.

Discussion: We successfully managed four infants with systemic atrioventricular valve replacement on therapeutic LMWH without evidence of adverse events. VKA anticoagulation in infants is challenged by variable dose response rates, inconsistent dietary vitamin K, frequent intercurrent illnesses, and difficulty with laboratory monitoring. On LMWH, these four patients reliably achieved therapeutic anticoagulation goals with less frequent monitoring labs than VKA therapy. Further collaborative investigation is needed to establish the efficacy and safety of a LMWH anticoagulation strategy in young children with mechanical valve prostheses.

Conclusion: LMWH may be a safe alternative therapy to achieve satisfactory anticoagulation chronically or until VKA treatment is more likely to be successful.