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Thrombosis in children with bt shunts, glenns and fontans
1. Thrombosis in children with BT shunts, Glenns and Fontans
Paul Monagle *
Department of Haematology, Royal Children’s Hospital Chair, Head of Department of Pathology, University of Melbourne,
Flemington Rd. Melbourne, Victoria 3052, Australia
Available online 22 November 2005
Abstract
Children with congenital heart disease (CHD) constitute a major proportion of children seen in tertiary hospitals with thromboembolic
disease (TE). Three common surgical procedures are the Blalock–Taussig (BT) shunt, Glenn shunt and the Fontan surgery. All of these
procedures can result in TE. There are few well designed studies in the literature determining the epidemiology of TE in these cohorts,
however, TE has been diagnosed in children, especially following the BT shunt and the Fontan surgery. The best approach to treat or prevent
TE complications in these cohorts of children has not been determined. Clinical studies are urgently required to provide evidence based
recommendations for treatment and prophylaxis of TE.
D 2005 Elsevier Ireland Ltd. All rights reserved.
Keywords: Pediatrics; Congenital heart disease; Blalock–Taussig shunts; Glenn shunts; Fontan procedure; Thrombosis
Congenital heart disease (CHD), with a wide spectrum of
severity, affects approximately 1% of all live births. The
majority of congenital cardiac structural abnormalities occur
in otherwise healthy children and total correction of the
cardiac lesion usually results in a normal productive lifespan.
Thromboembolic disease (TE) has been termed the new
epidemic of pediatric tertiary care hospitals. Nowhere is this
more evident than in cardiac and cardiac surgical children.
Improved survival for these children over the last decade has
been the result of tremendous advances in surgical techni-
ques, availability of new drugs and new applications for old
drugs, and developments in critical and supportive care.
Despite this, one of the most frequent complications seen in
survivors of CHD is TE, which include venous, arterial and
intracardiac TEs, pulmonary embolism, and embolism to the
central nervous system. Venous TEs in children with CHD
have a mortality of approximately 7%. Morbidity in the form
of post phlebitic syndrome and recurrent venous TEs
occurred in 23% of children.
Children with CHD constitute a major proportion of
children seen in tertiary hospitals with TE. Recent data show
that almost 50% of infants less than 6 months, and 30% of
older children who suffer venous TE have underlying
cardiac disorders. Similarly, almost 70% of infants (<6
months) and 30% children who suffer arterial TE have
underlying cardiac defects. In addition, the majority of
children on primary anticoagulant prophylaxis are being
treated for complex CHD or severe acquired cardiac illness.
Three common cardiac surgical procedures are Blalock–
Taussig (BT) shunts, Glenn procedures, and Fontan surgery. In
many patients these surgeries will be performed sequentially.
The initial BTshunt during the neonatal period, followed by a
Glenn procedure as the first stage towards a final Fontan
procedure which is the definitive palliative surgery. Throm-
bosis can occur as a complication of each procedure, however
the implications of thrombosis differ for each surgical
procedure, as does the management and potential outcome.
There remains little conclusive evidence to support the optimal
treatment strategies for thrombotic complications of these
procedures. This paper will discuss thrombosis as a compli-
cation of each of these surgical procedures.
1. Blalock–Taussig (BT) shunt
BT shunts are commonly performed in the neonatal
period to increase pulmonary blood flow. BT shunts may be
1058-9813/$ - see front matter D 2005 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.ppedcard.2005.09.003
* Tel.: +61 3 93455919; fax: +61 3 93491819.
E-mail address: paul.monagle@rch.org.au.
Progress in Pediatric Cardiology 21 (2005) 17 – 21
www.elsevier.com/locate/ppedcard
2. performed as a single palliative procedure with planned later
more definitive surgery, or as part of a more complex
surgical intervention (e.g. Norwood procedure). In classic
BT shunts, the subclavian artery is anastomosed directly to
the ipsilateral pulmonary artery. The procedure is usually
performed on right side, unless there is a right sided aortic
arch, in which case the shunt is performed on the left. In
contrast, for a modified BT shunt a Gore-tex tube graft is
placed between the subclavian artery and the ipsilateral
pulmonary artery. The Gore-tex tube may be as small as 3
mm diameter, depending on the size of the infant, but is
usually 3.5 or 4 mm in diameter.
The natural history of BT shunts has been assessed using
angiography. Godart et al. assessed BT shunt growth and
development of stenosis and distortion in 78 patients at a
mean follow up time of 51 months [1]. They found that
growth of the pulmonary arteries occurred but did not
exceed the normal growth of the pulmonary arterial tree.
However, a shunt procedure could cause distortion and
stenosis of the pulmonary artery which may have important
implications for future corrective surgical intervention.
Patients with BT shunts may have reduced peripheral
pulses in the ipsilateral arm, and may have measurably
reduced growth of the arm. This can be of significance when
assessing for post thrombotic syndrome which may occur in
the upper limbs secondary to central venous thrombosis (see
Fig. 1).
Blockage of the BT shunt will compromise pulmonary
blood flow and is often a major clinical event requiring
immediate surgery. The incidence of thrombotic occlusion
of BT shunts in the literature ranges from 1 to 17% [2–
16]. Risk factors for patency and stenosis include the age
of the patient and graft size [2,3]. Diagnosis is usually
clinical, although echocardiography, and angiography can
be of value.
There is no consistent approach to the prevention of
thrombosis of BT shunts. Many investigators use antith-
rombotic therapy beginning with therapeutic doses of
heparin and followed by low dose aspirin (1 to 10 mg/kg/
day) [15], although others recommend intraoperative hep-
arin with no further anticoagulation [16]. There is no data
from randomized trials to demonstrate clinical superiority of
either approach.
Children who develop acute BT shunt occlusion usually
require some form of intervention which include thrombo-
lytic therapy and/or stenting. Local thrombolytic therapy
with tissue plasminogen activator and streptokinase have
been used successfully in some children [9,17]. Angioplasty,
balloon dilation, stent implantation [6,18] and repeat surgery
[2,4] are other therapeutic options. The latter usually require
subsequent anticoagulation therapy.
2. Glenn procedure (BCPS)
The bidirectional cavopulmonary shunt(BCPS) or bidir-
ectional Glenn procedure is an end (superior vena cava) to
side (right pulmonary artery) venous shunt. This is a
palliative procedure that increases oxygen saturation, but
without increasing left ventricular work, and is usually
performed in children with univentricular cardiac physiol-
ogy, as the first stage of the two stage Fontan procedure. The
IVC is unchanged after a Glenn procedure.
The implications with respect to thrombosis are that,
following a Glenn procedure, the SVC blood flows directly
to the lungs without any assistance from the heart. Hence
any reduction in SVC flow, due to thrombus occlusion, will
dramatically reduce pulmonary blood flow. Pulmonary
emboli are of specific concern in that if the pulmonary
vascular resistance is increased, the patient may become
unsuitable for a Fontan completion, which limits long term
survival significantly in the absence of cardiac trans-
plantation. Blood flow from the IVC still bypasses the
lungs, meaning that any thrombus in the lower venous
system can give rise to paradoxical emboli. Collaterals
around central venous thrombosis may interfere with the
ability to complete the Fontan surgery. The threat of being
unable to complete the Fontan may be a justification for
more aggressive antithrombotic therapy (thrombolysis or
surgery) than might otherwise be indicated.
Thrombotic complications following the Glenn shunt are
infrequently reported [19–21]. There appears to be no data
to support the need for routine thromboprophylaxis. How-
ever, once again, the fact that many patients subsequently
proceed to Fontan procedures has led to some suggestions
that thromboprophylaxis is warranted after a Glenn shunt to
reduce the risk of thrombosis in the pulmonary vasculature,
hence increasing the likelihood of successful conversion to a
full Fontan circuit. Current clinical practices vary, and
Fig. 1. Teenage boy with previous BT shunt on the right side, and venous
thrombosis in the left brachial/axillary vein. Note the difference in size of
the arms. There was noticeable reduced hair growth on the right arm. The
boy was left handed.
P. Monagle / Progress in Pediatric Cardiology 21 (2005) 17–21
18
3. include: no anticoagulation, heparin followed by aspirin,
heparin followed by warfarin therapy. There is no evidence
to support a preference for any of these approaches at this
time.
3. Fontan procedure
There are numerous modifications of the Fontan proce-
dure, but the basic principles remain the same. Both the
SVC (usually done in a first stage BCPS) and the IVC are
anastomosed to the pulmonary arteries. Hence the pulmo-
nary blood flow is totally passive, depending on venous
flow mechanisms without any cardiac pump assistance. The
univentricle is then able to function as a left ventricle,
providing systemic blood flow. Post operatively, many
patients have deliberate, limited, right to left interatrial
shunting via a ‘‘fenestration’’. The blood flow in such cases
increases the risk of paradoxical emboli.
The implications with respect to thrombosis following
Fontan surgery are significant. First, the presence of right to
left communication continues the potential for paradoxical
emboli. Second, any pulmonary emboli which increase
pulmonary vascular resistance have an accentuated impact
on pulmonary blood flow, as the pulmonary pressure
cannot be increased to overcome a pressure gradient. The
Fontan circuit makes the diagnosis of pulmonary emboli
particularly difficult. Depending on the attachment of the
SVC and IVC to the pulmonary arteries, isotope may need
to be injected into both an arm and a leg to achieve full
lung perfusion scanning. As for patients with severe
pulmonary hypertension having ventilation/perfusion scans,
the transient obstruction of pulmonary capillaries by the
macro-aggregated isotope labeled albumin may rarely
precipitate a hypoxic episode. Finally, depending on the
exact type of Fontan surgery, the risk of late (many years
later) thrombosis associated with dysrythmias may be
increased.
The incidence of thrombosis after Fontan surgery has not
been determined by prospective trials. Three cross sectional
surveys used transoesophageal echocardiography to assess
the point prevalence of TE following Fontan surgery [22–
24]. The studies reported prevalences of 17, 20 and 33%
respectively. All studies demonstrated an increased sensi-
tivity with transoesophageal compared to transthoracic
echocardiography. These studies highlight the importance
of using the appropriate diagnostic test to determine the
incidence of thrombosis in any population. In cohort studies
which had TE (venous thrombosis, arterial emboli or both)
as a primary outcome measure the duration of follow up
varied considerably. The reported incidence of venous
thrombosis ranged from 3 to 19% and the incidence of
stroke ranged from 3 to 19% [25–32]. Retrospective cohort
studies not primarily directed at TE as an outcome have
reported cumulative risk of venous thrombosis ranging from
0 to 20% [33–45].
The frequency of TE was increased in recent studies
compared to earlier studies, reflecting increased survival,
longer duration of follow up, improved diagnostic tests, or
increased awareness of the potential for thrombosis. The
retrospective nature of the studies, frequent lack of sensitive
diagnostic tests and limited follow up not only account for
variation in reported incidences, but suggest that the
reported frequencies of TE following Fontan surgery are
minimal estimations.
In general, information in the literature on the manage-
ment and outcome of TE post-Fontan is scarce and often
poorly documented. Previous reviews of the literature have
reported that total resolution of thrombosis was achieved in
only 48% of cases. Death occurred in 25% despite
aggressive treatment. Follow up duration for these patients
varied from 1 month to 5 years [23,24,26–29,32,41,42,
46–58].
Given the lack of good data specifically related to
outcome of thrombosis following Fontan surgery, it is
worthwhile considering the outcome of venous thrombosis
and stroke in children with congenital heart disease (CHD)
in general.
The Canadian Childhood Thrombophilia Registry has
provided the largest prospective data base of pediatric
venous TE, with a mean follow up time of 2.36 years. CHD
was the underlying disease process in 75 of the 405 children
(19%) reported with venous TE. The TE associated mortal-
ity in the CHD subgroup was 7%. Morbidity (post-phlebitic
syndrome and TE recurrence) was 23% [59].
The Canadian Stroke Registry identified CHD as the
most common identifiable cause in a cohort of 165 children
with arterial ischaemic stroke. Thirty six percent of children
with stroke had underlying CHD. In the entire stroke
registry cohort, only 22% of children fully recovered. Sixty
six percent had residual neurological defects and/or seizures
[60].
Thus thromboembolic complications in children after
Fontan surgery appear to be frequent and with significant
clinical implications. This has lead to attempts to stratify
STUDY OUTLINE
Patient enrollment
Fontan Procedure
Randomisation immediately post surgery
Heparin / warfarin
Target INR 2-3
Aspirin 5mg/kg/dy
TTE/TOE at 3 months
TTE/TOE at 2 years
Study completion
Monitor for clinical thrombosis,
embolism or bleeding
Fig. 2. Study schema for Fontan A trial, designed to determine the optimal
primary antithrombotic prophylaxis agents following Fontan surgery.
P. Monagle / Progress in Pediatric Cardiology 21 (2005) 17–21 19
4. children according to thromboembolic risk. However, no
clear risk factors have been established yet by well
designed studies. Further, consideration of the role for
primary prophylaxis is the source of considerable ongoing
debate.
The options for primary prophylaxis include routine
prophylactic anticoagulation with warfarin or antiplatelet
agents. All anticoagulants increase the risk of bleeding.
The risks in children after Fontan surgery are unknown.
Clearly patients receiving warfarin will have higher
probability of bleeding complications compared to those
receiving aspirin. Recent Australian data suggests that
with a well coordinated pediatric anticoagulation clinic the
annual risk of major bleeding in children on warfarin can
be reduced to 0.05% per patient year. Warfarin requires
regular monitoring, which can have a significant impact
on family life [61,62]. Recent reports raise the prospect of
warfarin causing reduced bone density in children
although further studies are required to confirm this effect
[63]. At this time there are no convincing data that any
prophylactic antithrombotic regimen is effective in reducing
TE. The current multi centre Australian and Canadian
randomized controlled trial, comparing heparin/warfarin
anticoagulation to aspirin therapy after Fontan surgery (see
Fig. 2 for study schema) will provide the best evidence to
date about the true incidence of post Fontan thrombosis in
patients receiving prophylaxis, as well as the safety and
efficacy of each therapeutic option. Further trials will be
required to delineate the optimal prophylactic therapy. In the
meantime, current recommendations suggest aspirin (5 mg/
kg/day) or therapeutic heparin followed by vitamin K
antagonists to achieve a target INR of 2.5 (range 2 to 3).
The optimal duration of therapy is unknown. Whether
patients with fenestrations require more intensive therapy
until fenestration closure is unknown.
4. Conclusions
Modern cardiac surgery has improved the survival for
many children with congenital heart disease. Thrombosis
has long been recognized as a significant complication,
which is associated with important morbidity and mortality.
Blalock–Taussig shunts, Glenn and Fontan procedures are
arguably the most significant cardiac surgical procedures
which are complicated by thrombosis. Despite this, and
despite the incredible advances in surgical techniques, there
is a frightening lack of good data to support or refute the
role of antithrombotic prophylaxis following these proce-
dures. There is an urgent need for the value and importance
of well designed randomized trials to be understood by
physicians and surgeons involved in the care of children
with congenital heart disease. Case reports, case series, and
retrospective observational studies will not adequately
answer the questions at hand. The current Fontan A study,
despite its limitations, demonstrates the feasibility of
performing multi centre randomized trials in such children.
Unless many such trials are performed in the coming years,
unnecessary adverse outcomes will continue to occur. The
current uncertainty around the optimal primary prophylaxis
regimes should be addressed such that generations of future
children requiring cardiac surgery do so with minimal risk
of thrombosis.
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