Pediatric Clinics of North America - CIPERJ

352 ADAMS & WENTZEL
A dual-energy x-ray absorptiometry scan should be performed when LMWH
is used for extensive periods of time because chronic use of LMWH can result
in osteopenia.
Patients who have vascular malformations and who develop a serious
thrombotic event, such as a pulmonary embolism, require anticoagulation
therapy indefinitely [59,60]. In the acute phase, these patients can be treated
with LMWH or regular heparin, then converted to an oral vitamin K antagonist,
such as warfarin. Some patients who have acute thromboembolic
events may require the placement of an inferior or superior vena caval filter
in addition to anticoagulation therapy.
Antifibrinolytic agents, such as e-aminocaproic acid and tranexamic acid,
are used to treat the hemorrhagic coagulopathy that can occur in patients
who have vascular lesions [61]. Both agents attach to the lysine-binding sites
of plasminogen and plasmin, displacing plasminogen from its fibrin surface.
Tranexamic acid is more potent and has a longer half-life than e-aminocaproic
acid. Widespread use of antifibrinolytic agents is limited secondary to
concerns of increased risk for thrombosis, but there are no retrospective
or prospective studies concerning the use of these agents in children who
have vascular malformations. Furthermore, antiplatelet agents, such as
aspirin, ticlopidine, and clopidogrel, have shown little clinical benefit but
further, more definitive studies are needed. Compression garments reduce
the amount of blood trapping within the vascular lesion and probably decrease
LIC. Other nonpharmacologic supportive therapies include massage,
physical therapy, and hydrotherapy.
Novel approaches
Vascular malformations are a challenging group of disorders for physicians.
Treatment mainly has been surgical or through interventional procedures.
Particular attention to new sclerosing agents and embolization
techniques will be important in improving the management of these patients.
Such agents, however, need to address the pathophysiologic differences in
these malformations, because agents effective for arterial malformations
may not be effective for lymphatic malformations or VMs.
As with vascular tumors, medical therapy needs to be targeted to the limited
knowledge of the pathophysiology of these malformations. One exciting
area with great potential is the recent discovery of genetic alterations within
these lesions [62]. Some genetic alterations could serve as therapeutic targets
and thus aid in treatment options. For example, the PTEN gene mutation
has been identified in patients who have extensive AVMs and other anomalies
[63]. Rapamycin or other mTOR inhibitors are predicted to be effective
agents in disorders in which the PTEN/mTOR/STAT3 pathway is affected
[63]. New antithrombotic agents with effectiveness similar to LMWH need
to be investigated because life-long anticoagulation is needed after a significant
thrombotic event has occurred. At present, clear and agreed-on medical