Anticoagulation Therapy in Children

Abstract

Venous thromboembolism (VTE) is very uncommon in children and adolescents compared with older adults, though its incidence has significantly increased over the past two decades. Given the rarity of the condition, the data on pediatric VTE lag behind the adult experience and consequently the management of VTE in children is, in large part, modeled on the adult strategies. This approach has certain limitations, given that young children have developmental particularities of the hemostatic system and differences in the pharmacokinetics and pharmacodynamics of various anticoagulant agents. The most commonly used anticoagulants in children continue to be the heparins and the vitamin K antagonists. Direct intravenous thrombin inhibitors, argatroban, bivalirudin, have very limited pediatric use. The non-vitamin K antagonist oral anticoagulant drugs (novel oral anticoagulants) present potential advantages in terms of efficacy, safety, and convenience, though pediatric data are limited to preclinical and small phase I trials. There are several ongoing phase I, II, and III trials for dabigatran rivaroxaban, apixaban, and edoxaban, the results of which are likely to change the future management of pediatric thromboses.

Bivalirudin for Maintenance Anticoagulation During Venovenous Extracorporeal Membrane Oxygenation for COVID-19

“…Unfractionated heparin remains the mainstay of continuous anticoagulation therapy in patients on ECMO support due to its rapid onset of action, widespread availability, and the ability to reverse its action with protamine. 5 However, inherent limitations exist, including the requirement of the cofactor antithrombin III through which its action is mediated, unpredictable kinetics requiring frequent dose adjustments, and the highly antigenic nature of heparin that may trigger HIT. 7 COVID-19 may exacerbate variations in heparin sensitivity secondary to reduced antithrombin III levels.…”

“…However, heparin carries inherent limitations that predispose to persistent fluctuations in dose sensitivity and heparin-induced thrombocytopenia (HIT). 5 Direct thrombin inhibitors, of which bivalirudin is a member, produce transient inhibition of thrombin to mitigate the cleavage of fibrinogen to its active form. Furthermore, they offer potential advantages during ECMO due to their ability to exert this effect by directly attaching to and inhibiting both freely circulating and fibrin-bound thrombin.…”

Accidental apixaban intoxication in a 23-month-old child: a case report

“…Despite multiple ongoing studies on apixaban in the pediatric population [12][13][14][15], there is currently no available data on apixaban pharmacokinetics and pharmacodynamics properties among children. As previously reported, the apixaban plasma concentration vs. time profile exhibited a multiphasic elimination profile, with an initial rapid decline followed by a more gradual terminal phase [4].…”

FDA approval summary: Dalteparin for the treatment of symptomatic venous thromboembolism in pediatric patients

“…The FDA granted approval of dalteparin for pediatric patients with and without cancer to be as inclusive as possible because of (a) pediatric trial data to support dosing, efficacy, and safety in both populations, (b) in clinical practice, the same therapeutic goals are pursued for patients with and without cancer, (c) the risk of therapy is potentially greater in cancer patients, and ing complications. [14][15][16] In the dalteparin safety population, there was only one neonate. Given the unique safety considerations in neonates, there was insufficient safety data to allow for an adequate assessment of safety in neonates, and therefore the approval was limited to patients over the age of 1 month.…”