Pediatric Clinics of North America - CIPERJ

318 GOLDENBERG & BERNARD
neonatal CSVT cases and the cumulative incidence of such sequelae in childhood
(ie, non-neonatal) CSVT ranged widely between 8% and 47%. In the
aforementioned pediatric series of RVT and CSVT, the proportion of children
who received anticoagulation and the duration of the anticoagulation
course varied considerably across studies. With regard to portal vein thrombosis,
few pediatric series reporting outcomes have been published; however,
it seems that the risk for developing recurrent gastrovariceal bleeding in this
population is substantial, occurring in many cases even after surgical interventions
have been undertaken to reduce portal hypertension [57]. For PE in
childhood, long-term outcomes, such as chronic pulmonary hypertension
and pulmonary function, have yet to be established.
An additional VTE outcome of interest is residual thrombus burden. To
date, data (principally in adults) suggest that the persistence of thrombosis
after a therapeutic course of anticoagulation of appropriate duration does
not increase the risk for recurrent VTE, including PE, appreciably. Some evidence
[58] indicates, however, that persistent thrombosis is associated with
the development of venous valvular insufficiency, an important risk factor
for (albeit an imperfect correlate of) [59] the development of PTS. The prevalence
of residual thrombosis despite adequate anticolagulation in neonatal
VTE has ranged from 12% in a small series of premature newborns who had
CRT [46] to 62% in full-term neonatal VTE survivors [4]. Among primarily
older children, the prevalence of persistent thrombosis has ranged broadly
from 37% to 68% in the few longitudinal studies that have used systematic
radiologic evaluation of thrombus evolution [5,16].
The ability to predict clinically relevant long-term outcomes of VTE at diagnosis
and during the acute and subacute phases of treatment is essential to
establishing a future risk-stratified approach to antithrombotic management
in children. Early work defined strong associations of homozygous anticoagulant
deficiencies and APA syndrome with recurrent VTE. Over the past several
years, the presence of multiple thromophilia traits has been identified as
prognostic for recurrent VTE [42], and the radiologic finding of complete
veno-occlusion at diagnosis of DVT is associated with an increased risk for
persistent thrombosis [60] (which, in turn, is associated with the development
of venous valvular insufficiency [58], as discussed previously). Most recently,
plasma FVIII activity greater than 150 U/dL and D-dimer concentration
greater than 500 ng/mL at the time of diagnosis of VTE in children and after
3 to 6 months of standard anticoagulation are shown to predict a composite
adverse thrombotic outcome, characterized by persistent thrombosis, recurrent
VTE, or the development of PTS [5], adding to evidence for the prognostic
usefulness of these markers in adult VTE [61–63].
Future directions
VTE has emerged in recent years as a critical pediatric concern with acute
and chronic sequelae. Important and highly clinically relevant questions on