Safety and efficacy of nadroparin in children: an observational study.

The incidence of venous thrombosis is rising rapidly in children.[1,2] This
rise is the result of improved pediatric care over the past decades, resulting
in an increase in the survival of critically ill children and and increased use
of central venous catheters in children. When a venous thrombus occurs there is
an indication for therapeutic anticoagulant treatment (anti Xa levels 0.5-1.0
IU/mL). Inhibition of the coagulation system gives the opportunity to resolve
the clot. If children are at high risk for venous thrombosis preventive
measures can be taken by prophylactic anticoagulant treatment (anti-Xa levels
0.1-0.4 IU/mL). This inhibits the coagulation system in a lesser way compared
to therapeutic anticoagulant treatment and prevents formation of a thrombus.
In the Netherlands each year 400 children receive off-label therapeutic and
prophylactic nadroparin treatment, without any information on the
pharmacokinetics/-dynamics (PK/PD) and therefore optimal and safe dosage
regimen. As a result, these children are prone to suboptimal treatment with a
risk for thrombosis, a lack of thrombus resolution or major bleeding.
Therefore, we designed an observational study during standard care to objectify
the PK/PD in children.

Therapeutic nadroparin administration:
Primary objective:
To develop evidence-based dosing regimens of nadroparin for children in
different age groups by means of the objectification of the PK/PD of nadroparin.
Secondary objective:
1) Investigate the relation between anti Xa levels and thrombus resolution
within 3 months after the start of nadroparin treatment
Investigate the relation between anti Xa levels and bleeding during treatment
with nadroparin until 24 hours after termination of nadroparin
Prophylactic nadroparin administration:
Primary objective:
To develop evidence-based dosing regimens of nadroparin for children in
different age groups by means of the objectification of the PK/PD of nadroparin.
Secondary objective:
1) Investigate the relation between anti Xa levels and new or recurrent
thrombosis during treatment with nadroparin
2) Investigate the relation between anti Xa levels and bleeding during
treatment with nadroparin until 24 hours after termination of nadroparin

A national observational prospective study

As mentioned above, each year 400 children receive off label nadroparin
treatment without any information on PK/PD and therefore optimal and safe
therapeutic or prophylactic dosage regimen. Despite this off label treatment,
dosage recommendations have been provided. As a result, these children are
prone to suboptimal treatment with a risk of a new thrombosis, a lack of
thrombus resolution, or major bleeding. This bleeding has an impact on the
morbidity and survival of these children. Therefore, we will perform an
observational study during standard care to objectify the PK/PD in children.
With the development of evidence-based therapeutic dosing regimens for children
in different age groups (2 months - 3 years, 4 - 11 years and >= 12 years), and
evidence-based prophylactic dosing regimens for children for nadroparin we can
ensure these vulnerable children an effective treatment without toxicity, and
therefore less complications. To avoid the burden of venepunctures we aim to
include mainly children with central venous or arterial access, or an
intravenous cannula and combine blood samples with standard blood samples.