H e m a t o lo g y E d u c a t io n - European Hematology Association

Based on the data obtained from the recent metaanalyses
and systematic reviews, at least the symptomatic
propositus should be screened in a specialized
coagulation unit for prothrombotic defects, 60-63 such as
antithrombin-, protein C-, or protein S-deficiency.
Furthermore, since the rate of combined IT associated
with a first symptomatic onset is not negligible in the
pediatric population, especially when the family history
is positive for thrombosis, 64 non-major risk factors such
as the factor V G1691A mutation or the prothrombin
G20210A variant should be included in a screening program.
Since a second VTE after a first episode of spontaneous
VTE, i.e., thrombosis in the absence of further
secondary causes, has indicated a subgroup of pediatric
patients suffering from combined prothrombotic risk
factors to be at high risk of recurrent thrombosis, 38 the
latter approach to search for multiple risk factors is
stressed.
With respect to the Mendelian theory of inheritance,
approximately 50% of siblings of a symptomatic
propositus suffering from a combined prothrombotic
defect carry one single risk factor, while 25% carry two
or more gene mutations/polymorphisms. Thus, based
on the fact that an effective primary prophylactic anticoagulant
therapy is available in risk situations, IT
screening programs must be individually discussed in
selected non-symptomatic siblings and further first
degree family members in high risk families such as
antithrombin-, protein C-, or protein S-deficiency carriers,
or in cases in which combined IT are identified.
Treatment modalities
Adult patients with a first thrombotic episode will
receive oral anticoagulation for at least three months
after venous thrombosis, six to 12 months when the
deep venous thrombosis was idiopathic, and at least six
to 12 months after pulmonary embolism. 75 Decisions on
extending anticoagulant therapy are individually based
on the perceived risks of VTE recurrence and anticoagulant-related
bleeding. Whether long-term continuation
of anticoagulant treatment should be considered after a
first VTE in carriers of a thrombophilic trait is still a matter
of debate. 75 In children with a first VTE, randomized
therapeutic trials are missing and treatment guidelines
are mainly adapted from adults. 76,77 More than in adults,
the prolonged use of anti-coagulant treatment in a physically
active age group must be weighed against the risk
of bleeding. Data from the meta-analyses mentioned
above will help physicians to decide, along with parents
and patients, in which cases a prolonged anticoagulant
treatment may be justified, 60-62,77 or practically, if pediatric
patients additionally carrying genetic trait with
chronic conditions associated with VTE might require
secondary anti-coagulant in high risk situations, e.g.,
post-operatively, prolonged immobilization, or dehydration.
The findings based on the analyses of risk
increase underscore the hypothesis that in cases in
which the temporary risk factors recur, the risk of a second
VTE in children is probably less likely if IT is not
present. 56,60
Until results from randomized trials are available for
anticoagulant treatment and duration of symptomatic
index patients, children with clinically- and imagingproven
VTE are treated according to recommendations
based on small-scale studies in children and guidelines
adapted from adult patient protocols. 76,77 Unfractionated
heparin, low-molecular weight heparins, and vitamin Kantagonists
are the commonly used antithrombotic
drugs, whereas newly developed antithrombotic agents
such as argatroban, bivalirudin or fondaparinux are
under discussion and are increasingly administered in
small pediatric clinical trials. 76-79 Keeping in mind the low
level of evidence for treatment-related recommendations
in the pediatric population, it must be pointed out
here that there is an urgent need for each pediatric
patient with an early VTE manifestation to receive secondary
anti-coagulation prophylaxis in clinical risk situations
prone to thromboembolism, for example,
catheterization, dehydration, hematologic malignancies,
38,80-82 or prolonged immobilization, respectively.
Since randomized treatment trials are lacking, doses and
durations of secondary anti-coagulation should be individually
adapted to patient’s risk.
Conclusions
Apart from a risk stratification in children with VTE
based on clinically-acquired circumstances along with
acquired and genetic thrombophilic risk factors, future
evidence-based prospective anticoagulant/antithrombotic
treatment trials including newly available anticoagulants
are mandatory. 79 In addition, a worldwide pediatric
expert consensus on standardized clinical outcome
measurements, imaging methods to be used, and determination
of follow-up intervals is urgently requested.
The effective prevention of thrombosis-related complications
in children, such as the post-thrombotic syndrome,
will considerably reduce the burden and the
costs associated with the disease. 83
References
London, United Kingdom, June 9-12, 2011
1. Andrew M, David M, Adams M, et al. Venous thromboembolic
complications (VTE) in children: first analyses of the
Canadian Registry of VTE. Blood. 1994;83:1251-1257.
2. Schmidt B, Andrew M. Neonatal thrombosis: report of a
prospective Canadian and international registry. Pediatrics.
1995;96:939-943.
3. Journeycake JM, Buchanan GR. Thrombotic complications of
central venous catheters in children. Cur Opin Hematol.
2003;10:369-374.
4. Revel-Vilk S. Central venous line-related thrombosis in children.
Acta Haematol. 2006;115:201-206.
5. Normann S, deVeber G, Fobker M, et al. Role of endogenous
testosterone concentration in pediatric stroke. Ann Neurol.
2009;66:754-758.
6. Nowak-Göttl U, von Kries R, Göbel U. Neonatal symptomatic
thromboembolism in Germany: two year survey. Arch Dis
Child Fetal Neonatal Ed. 1997a;76:F163-F167.
7. Revel-Vilk S, Sharathkumar A, Massicotte P, et al. Natural history
of arterial and venous thrombosis in children treated with
low molecular weight heparin: a longitudinal study by ultrasound.
J Thromb Haemost. 2004;2:42-46.
8. Journeycake J, Eshelman D, Buchanan GR. Post-thrombotic
syndrome is uncommon in childhood cancer survivors. J
Pediatr. 2006;148:275-277.
9. Goldenberg NA. Long-term outcomes of venous thrombosis
in children. Cur Opin Hematol. 2005;12:370-376.
10. Kuhle S, Koloshuk B, Marzinotto V, et al. A cross-sectional
study evaluating post-thrombotic syndrome in children.
Thromb Res. 2003;111:227-233.
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