Antithrombotic Therapy in Children: LMWH Therapy in Pediatric Patients

Treatment of Heparin-Induced Bleeding: If anticoagulation with heparin needs to be discontinued for clinical reasons, termination of the heparin infusion will usually suffice because of the rapid clearance of heparin. If an immediate effect is required, IV protamine sulfate rapidly neutralizes heparin activity by virtue of its positive charge. The dose of protamine sulfate required to neutralize heparin is based on the amount of heparin received in the previous 2 h (Table 3). Protamine sulfate can be administered in a concentration of 10 mg/mL at a rate not to exceed 5 mg/min. Patients with known hypersensitivity reactions to fish and those who have received protamine-containing insulin or previous protamine therapy may be at risk of hypersensitivity reactions to protamine sulfate.
LMWH Therapy in Pediatric Patients
Potential Advantages of LMWH for Children: LMWHs have several potential advantages over initial short-term heparin therapy for DVT or PE, as well as the traditional 3 months of oral anticoagulants review canadian family pharmacy online. The potential advantages of LMWH for children include predictable pharmacokinetics that result in minimal monitoring, which is critically important in pediatric patients with poor or nonexistent venous access; subcutaneous administration; lack of interference by other drugs or diet such as exists for coumadin; reduced risk of heparin-induced thrombocytopenia; and probable reduced risk of the osteoporosis that occurs with long-term heparin use.
Mechanism of Action: Like heparin, anticoagulant activities of LMWHs are mediated by catalysis of AT.
Therapeutic Range: Therapeutic doses of LMWH are extrapolated from adults and are based on an anti-factor Xa levels. The guideline for therapeutic LMWHs is an anti-factor Xa level of 0.50 to 1.0 U/mL in a sample taken 4 to 6 h following a subcutaneous injection.
Doses: The doses of LMWH required to achieve adult therapeutic anti-factor Xa levels in pediatric patients have been assessed for two LMWHs, enoxaparine (Lovenox; Rhone-Poulenc; Collegeville, PA) and reviparin (Clivarin, Knoll BASF Pharma; Ludwigshasen, Germany). A weight-adjusted nomogram was used to adjust LMWH doses into the therapeutic range (two level IV studies). Therapeutic doses of LMWH are age dependent, with infants having increased requirements (Table 4). The doses required for older children are similar to the weight-adjusted requirements for adults (Table 4). Potentially, LMWH may be used for several months. However, when this route of treatment is chosen, sensitive tests of bone density should be considered to monitor for early signs of osteoporosis.

Table 3—Reversal of Heparin Therapy

Time Since Last Heparin Dose, min Protamine Dose, mg/100 U of Heparin Received
<30 1.0 mg/100
30-60 0.5-0.75
60-120 0.375-0.5
>120 0.25-0.375

Table 4—Dosing ofReviparin and Enoxaparin

Weight-Dependent Dose of Reviparin Weight <5 kg Weight >5 kg
Initial treatment dose 150 U/kg/dose q!2h 100 U/kg/dose ql2h
Initial prophylactic dose 50 U/kg/dose ql2h 30 U/kg/dose ql2h
Age-Dependent Dose of Enoxaparin
Age <2 mo Age >2 mo
Initial treatment dose 1.5 mg/kg/dose ql2h 1.0 mg/kg/dose ql2h
Initial prophylactic dose 0.75 mg/kg/dose ql2h 0.5 mg/kg/dose ql2h