Discussion
Our experience in children demonstrates that CDT, in combination with
systemic anticoagulation, is a safe and effective treatment modality for
life- or limb-threatening thrombosis. Of the 29 patients that were
included in the analysis there was only one major19and three non-major bleeding events that were described. The major bleed
involved a precipitous drop in the hemoglobin of a neonate following the
interventional procedure that required multiple blood transfusions,
while the minor bleeds only required temporary cessation of CDT and
anticoagulation to resolve. This review also provides descriptive
information that may help pediatric hematologists and IRs prepare the
post-procedural expectations of staff and patients, including
post-procedural decline in hemoglobin (2.3 g/dL), and platelets (50,000
cells/dL), with ~25% of patients requiring a
transfusion after the procedure.
The rate of complete thrombus resolution of 34.5% in our patient cohort
compares favorably to other studies evaluating outcomes of LE DVT in
children. Specifically, the findings by Avila et al. noted a complete
resolution rate between 19.6 and 30.9% in neonates and non-neonates at
the end of therapy images.21 Our thrombosis resolution
rate is notable due to the extent of thromboses that were included in
our study, with 93% having multiple segments of occlusion, and those
patients who are selected for thrombolysis at our institution have
increased vascular compromise, secondary to extensive thrombosis,
compared to those treated with anticoagulation alone. Our findings also
add to the evidence that Hispanic patients affected with vascular
disease have worse outcomes (in our case, thrombus resolution) than
those patients that identify as non-Hispanic,22-24with no Hispanic identifying patients experiencing thrombus resolution
compared to 45.5% of non-Hispanic patients. This may suggest the need
for more aggressive interventional and medical approaches in Hispanic
children with LE or IVC DVT.
Patients that received the anticoagulant rivaroxaban during their
treatment course had a 6-fold increase in the rate of thrombus
resolution, which remained significant after controlling for ethnicity.
The direct oral anticoagulant rivaroxaban is becoming increasingly used
for VTE in children,25 with the advantages of not
requiring laboratory monitoring and the ease of oral administration.
While we cannot conclude on reasons for the enhanced efficacy of this
drug, it may be secondary to better compliance over other agents in our
population. Our data suggests that the medication should be considered
for anticoagulation in children affected with extensive LE and IVC
thrombosis, especially in the adolescent age range due to ease of dosing
regimen. It is important to note, however, that rivaroxaban is not
currently approved by the FDA for use in children. The risk factor of
estrogen-containing oral hormonal therapy (a reversable thrombosis risk
factor upon cessation of the medication) was also associated with
thrombus resolution.
In general, most devices used in pediatrics are considered
“off-label,” as they do not have specific pediatric approval. The use
of Angiojet for patients less than 18 years of age has not received
approval via the FDA, and studies are not available in the pediatric
population. A thorough review of the literature does not suggest a
detrimental safety profile for device use in the less than 18-year-old
population, and multiple studies have documented use of the Angiojet in
this population without significant incident.26,27 It
is important to note that patients can have temporary bradyarrhythmia as
a result of the use of this device, regardless of which vascular
territory it is being used in.28
Based on the analysis of our data, the use of Angiojet as part of
interventional therapy during pediatric thrombolysis trends to
improved resolution of the thrombus burden. While this might be a part
of the impact of aggressive utilization of tPA, as this trend was also
noted with relatively better thrombus clearance and less progression in
our “on-table” tPA administration only cohort, the use of the
thrombolytic function of the Angiojet with “lace and lyse” delivery of
tPA may be a superior modality for interventional thrombolysis. The use
of tPA in this cohort can assist with thrombus clearance and potentially
avoid mandated ICU stays associated with CDT. Furthermore, these results
will lead us to consider changing our practice to using the Angiojet
device with “on-table” tPA when the circumstances permit.
In addition, as has been noted in multiple adult studies, the use of tPA
for venous thrombolysis carries a relatively low risk profile in the
pediatric population.29-32 One does need to be careful
in this population as pediatric patients process tPA differently than
adults. It is known that neonates and young infants have lower
plasminogen levels than older children and adults33which may lead to inadequate fibrinolysis unless plasminogen is
supplemented.34
There is a valid concern with respect to intra-procedural blood loss
with the use of thrombectomy or thrombolysis devices. All utilized
devices carry some risk of direct or indirect blood loss with their
utilization; e.g. the hemolytic side effect of the Angiojet and the
potential for blood loss with other aspiration devices. We did note that
our patients experienced decrease in their hemoglobin
(>2g/dL) regardless of whether it required intervention.
Limitations of this study include its retrospective nature and limited
sample size. As treatment decisions were not randomized but at the
discrepancy of the treating physicians, it is difficult to make direct
comparisons of treatment approaches between patients. This review does,
however, provide a baseline understanding for this important and growing
population and allows our institution and others the ability to develop
systematic and uniform approaches to pediatric patients with extensive
LE and IVC thrombosis. We will continue to evaluate outcomes and adverse
events with pediatric thrombolysis moving forward, including the use of
a dedicated outcomes survey.
In conclusion, the experience at our pediatric institution demonstrates
that tPA administration, whether by CDT or as an intra-procedural bolus,
in combination with anticoagulation is an effective and safe approach to
extensive pediatric LE and IVC thrombosis. The improved thrombosis
resolution rate with rivaroxaban needs additional future investigation,
though is encouraging for pediatric patients requiring thrombolysis for
acute thrombosis. Future prospective and multi-institutional studies are
needed to develop a widely accepted and optimized approach to pediatric
thrombolysis.
Conflict of Interest Statement: The authors of this manuscript
have no conflicts to disclose; no funding was received for this work.
Data sharing statement : The data that support the findings of
this study are available from the corresponding author upon reasonable
request.