“[I
use] unapproved drugs on children all the time,”
admits Dr Patricia Massicotte, a professor in the Department
of Pediatrics, Stollery Children’s Hospital, University
of Alberta. “Although the drugs have been studied
in adults, they haven’t been studied in a proper
way for use in children,” she explains.
Dr Massicotte’s comment, though
startling, is a reality faced by many pediatricians.
The lack of clinical research in kids does not apply
just to drug therapy. Understanding of disease processes,
symptoms, effective treatments and prognoses for diseases
in children is woefully inadequate, especially in diseases
that are more common in adults and have been well studied
in this population. Often the assumption, or perhaps
the hope, is that what applies to the big guy will apply
to the little guy.
But the difference between kids and
adults is not size alone, as Dr Massicotte pointed out
in a review of pulmonary thromboembolism (PTE) in children,
published in the March 2005 Issue of Pediatric Radiology.
NOT
ALL BAD
It’s not always bad being the little guy.
For one, as you might expect, the incidence of PTE in
children is much lower than in adults. And when it does
appear, it’s more commonly due to an identifiable
congenital defect, malignancy or disease. Only 4% of
thrombosis in kids is idiopathic compared with 30% in
adults. Central venous lines, often necessary for the
care of ill children, “appear to be the most important
acquired risk factor in the development of venous thrombosis
and pulmonary embolism,” say the study authors
in their article.
Research in adult patients has led
to important clinical findings that can ultimately aid
in diagnosis. The same does not hold true for children,
unfortunately. What’s more, PTE is often not even
considered during diagnosis, as it is not held to be
a childhood disease.
And while cardinal signs and symptoms
of PTE in kids are similar to adults, “dyspnea
and tachypnea may be less commonly seen,” explain
the researchers in their article. They suggest that
this probably “reflects a better physiologic reserve.”
PINT-SIZED
PTE
There are a number of radiographic tests that
may be helpful in confirming the presence or absence
of pediatric PTE. However, the ‘gold standard,’
pulmonary angiography, is seen as invasive, risky and
expensive in adults, never mind children. “Protocols
are usually extrapolated from adult studies with little
justification for their applicability to children,”
say the authors, reinforcing the need for more research.
For example, although D-dimer, a marker for recent thrombosis,
along with clinical evaluation can exclude PTE in adults,
it “is not nearly as useful when assessing PTE
in children,” says Dr Massicote.
As a result, many cases of PTE may
go undiagnosed. Pediatric autopsy studies show an incidence
of PTE ranging from 0.73-4.2%, depending on the population.
The Canadian Paediatric Thrombophilia Registry (a database
of PTE and DVT cases in children aged one month to 18
years) reports that PTE accounts for only 0.86 events
per 10,000 hospitalizations.
THROMBO
TREATMENTS
Thromboembolism management options for kids include
supportive care, anticoagulant therapy with heparin
and thrombolysis. There are three thrombolytic agents
that are currently in use: streptokinase (with no recommendation
in children), urokinase (off the market), and tissue
plasminogen activator (TPA, most commonly used). All
are plasminogen activators that convert plasminogen
to plasmin, which dissolves blood clots.
However because blood-clotting systems
are still developing, “plasminogen concentrations
are decreased in infants and in many pediatric diseases,
reducing the efficacy of these agents somewhat,”
say the researchers. To counter this, “many experts
using TPA in infants and children will administer fresh
frozen plasma as a plasminogen source before or during
TPA.”
Because
the epidemiology, symptoms and treatment of PTE are
different in children compared with adults, child-focused,
“evidence-based guidelines for diagnosis, treatment
and longterm followup are urgently required,”
the report concludes. “Pediatric research using
a good clinical design and multicentred is really needed
because children are dying from undetected blood clots,”
warns Dr Massicotte.
Pediatr
Radiol Mar, 2005;35(3):258-74
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