A dose-finding study of Tinzaparin in pediatric patients

Abstract number: P1887

Kuhle^* S., Massicotte^* M. P., Dinyari† M., Andrew^* M., Chan^* A. K. C., Mitchell^* D., Vegh^* P., Mitchell^* L.

†Canada ^*The Hospital for Sick Children, Canada;

Background  

Low-molecular-weight heparins (LMWHs) are increasingly being used for treatment of thromboembolic events (TE) in children. The LMWH Tinzaparin (Innohep®, LEO Pharma) offers the further advantage of once-daily dosing. To date, Tinzaparin has not been studied in children and appropriate dosing over ages is unknown.

Objectives  

To investigate dosages required to achieve therapeutic anti-Xa levels (0.5–1.0 IU mL^-1) using Tinzaparin in children of all age groups.

Study design  

Open label prospective cohort study. The outcome was the dose required to achieve therapeutic anti-Xa levels in each of the five age groups.

Study population  

Non-selected children (>36 weeks gestational age – 16 years) with objectively confirmed TE, requiring therapeutic anti-coagulation being treated at the Hospital for Sick Children, Toronto, Canada.

Intervention  

All children received an initial dose of 175 anti-Xa IU kg^-1 subcutaneously. Anti-Xa levels were measured 4 h after injection. During the course of the study, the protocol was amended and the initial dose for children < 3 months of age was increased to 250 anti-Xa IU kg^-1. If the therapeutic range was not achieved following the initial dose, dose adjustments were made guided by a standardized nomogram.

Results  

Thirty-seven children were enrolled and 35 received drug. All children had significant comorbidities including congenital heart disease, cancer and organ transplant. The median time to achieve target anti-Xa levels was as follows: 0–2 months (2 days); 2–12 months (2 days); 1–5 years (3.5 days); 5–10 years (1.5 days); 10–16 years (1 day). The relationship between age and maintenance dose is shown in Fig. 1.

Conclusion  

There is an age-dependent requirement for dosage of Tinzaparin with younger children requiring a higher dose per kg body weight. Younger children (0–5 years) require longer to achieve target anti-Xa levels. The efficacy and safety of Tinzaparin in treatment of TE in children needs to be determined in carefully designed clinical trials.

Figure 1