CLINICAL AND LABORATORY OBSERVATIONS
Hemolytic Anemia due to Right Ventricular to Pulmonary
Artery Conduit Stenosis
Sudha Rao, MD,* Julie A. Creaden, MSN, APN, CPNP-PC,w
Shunyou Gong, MD, PhD,z Cynthia Rigsby, MD,y
and John M. Costello, MD, MPHw
Summary: Hemolytic anemia is a well-recognized complication in
patients with left-sided mechanical heart valves. It is rare to see
hemolysis with a bioprosthetic valve in the right ventricular outflow
tract. We report a 4-year-old-girl with history of truncus arteriosus
status-post repair who developed hemolytic anemia as a result of a
calcified and obstructed bioprosthetic right ventricular to pulmo-
nary artery–valved conduit. The hemolysis was alleviated by
replacing the obstructed conduit with a larger valved conduit.
Key Words: hemolytic anemia, obstructed conduit, RVOT
(J Pediatr Hematol Oncol 2017;00:000–000)
CASE REPORT
A 4-year-old-girl presented with pallor and a hemolytic ane-
mia. She was born with truncus arteriosus type 1A and underwent
surgical repair at 2 months of age that included atrial and ven-
tricular septal defect closure and placement of a #12 bovine right
ventricular (RV) to pulmonary artery (PA)–valved conduit (Con-
tegra conduit; Medtronic Inc.). She did well for the next 4 years
with no cardiovascular symptoms and adequate energy level. A few
weeks before her current visit, she began to tire more easily. There
was no report of shortness of breath, syncope, diaphoresis, or
cyanosis. There was also no recent report of fevers, vomiting,
diarrhea, or dark urine.
On physical examination, the patient was afebrile, anicteric,
the heart rate was regular, with a normal S1 and normally split S2.
There was no click present and no gallop rhythm. There was a
grade IV/VI harsh systolic murmur present, best heard at the left
upper sternal border. There were good brachial and femoral pulses
palpable without delay. The lungs were clear to auscultation
bilaterally, with upper airway congestion noted, slightly congested
nares and productive cough with no retractions or increased work
of breathing. The abdomen was soft, nontender, and not distended.
The liver edge was palpable just below the right costal margin and
the spleen was not palpable. The extremities were warm to touch
and well perfused. There was no extremity edema present.
Her hemoglobin was noted to have dropped from 111 to 75 g/
L over a period of 3 months. She now had an increased reticulocyte
count of 21.9%, an increased mean corpuscular volume of 98 fl and
an increased serum lactic acid dehydrogenase of 1575 IU/L.
Peripheral blood smear revealed presence of 5% burr cells and 5%
schistocytes together with significant polychromatophilia (Fig. 1A).
Received for publication July 13, 2016; accepted January 26, 2017.
From the Departments of *Pediatrics, Division of Pediatric
Hematology-Oncology-Transplantation; wPediatrics, Division of
Pediatric Cardiology; zPathology and Laboratory Medicine; and
yMedical Imaging Administration, Ann & Robert H. Lurie Child-
ren’s Hospital of Chicago, Northwestern University Feinberg
School of Medicine.
The authors declare no conflict of interest.
Reprints: Sudha Rao, MD, Department of Pediatrics, Division of
Pediatric Hematology-Oncology-Transplantation, Ann & Robert
H. Lurie Children’s Hospital of Chicago, 225 East Chicago Avenue,
Chicago, IL 60611-2605 (e-mail: sudharao1@comcast.net).
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Of interest, the direct antiglobulin test was negative, the total
bilirubin was only mildly elevated to 1.2 mg/dL with direct bilir-
ubin at < 0.2 mg/dL. An echocardiogram was most notable for RV
to PA conduit stenosis. There was turbulent flow seen within the
conduit, with a peak velocity of at least 3.9 m/s (peak gradient,
61 mm Hg), which was increased compared with that seen on prior
studies. There was also mild truncal valve regurgitation which was
unchanged compared with prior studies, and no residual intra-
cardiac shunts.
A cardiac computed tomographic angiogram was done to
further define the anatomy of the RV to PA conduit and the
pulmonary arteries. There was significant conduit calcification seen
with resultant irregularity to the contour of the lumen of the
conduit (Figs. 1B, C). There were peripheral areas of thin mural
nonenhancement that likely represented intimal hyperplasia. The
proximal aspect of the conduit was severely narrowed in compar-
ison with a normal pulmonary valve dimension for age. The
proximal right branch PA was normal in diameter, and the distal
right branch PA was mildly dilated. The left branch PA was
moderately dilated.
In view of the evidence of a severely stenotic, calcified con-
duit, with conduit stenosis and RV hypertension, with hemolysis
presumably secondary to the obstructed conduit, intervention was
thought to be indicated. Options included percutaneously dilating
the RV to PA conduit versus performing a surgical RV to PA
conduit replacement. Surgical intervention was decided upon as the
option with the greatest benefit. A redo median sternotomy was
performed and the right ventricle to PA conduit was replaced with
18 mm Contegra pulmonary bovine-valved conduit.
Histologic section of the original stenotic conduit confirmed
the presence of intimal hyperplasia and calcification (Fig. 1D).
Two weeks after surgery, laboratory tests demonstrated res-
olution of hemolysis. The hemoglobin was stable at 111 g/L and the
reticulocyte count was at 1.4%. There was no evidence of schis-
tocytes or burr cells on the peripheral smear. Three months after
surgery, the hemoglobin was 134 g/L with a normal mean corpus-
cular volume of 79.6 fl. The patient had not been transfused after
the operation.
DISCUSSION
Hemolysis is a well-recognized and potentially serious
complication of left-sided mechanical or bioprosthetic heart
valves. In this setting, the hemolysis is usually attributed to
structural deterioration or paravalvular leak. The reported
rate of significant hemolysis has significantly decreased with
the introduction of improved valve models.1,2
However, hemolytic anemia has been rarely reported
in patients with a bioprosthetic RV to PA-valved conduit.
Suda et al3 reported a 10-year-old-boy who had significant
RV to PA conduit obstruction in whom transcatheter
placement of a stent alleviated the hemolysis and the
hemoglobin normalized over 3 months.
Hemolysis has not been reported in several other large
series of patient with a bioprosthetic RV to PA-valved
conduits. In a prospective study of 60 patients with
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 Rao et al J Pediatr Hematol Oncol  Volume 00, Number 00, ’’ 2017

FIGURE 1. A, Peripheral blood smear before conduit removal (Giemsa and Wright,  1000). Numerous schistocytes (thin arrows), echi-
nocytes (thick filled arrows), and polychromatic cells (thin unfilled arrows) are shown. B, Sagittal reformatted image (A) from the contrast-
enhanced computed tomographic angiogram shows the marked narrowing (between white arrows) of the proximal right ventricle (RV) to
pulmonary artery (PA) conduit. The black arrow shows the peripheral calcification and intimal hyperplasia leading to luminal irregularity.
C, Three-dimensional volume rendered image of the heart and great arteries in an anterior projection (B) shows the marked luminal
irregularity of the right ventricle (RV) to pulmonary artery (PA) conduit. D, Histology of the stenotic conduit (hematoxylin and eosin,  400).
Abundant calcifications (thin arrows) and marked intimal hyperplasia (white arrows) are noted. CO indicates conduit obstruction.

Contegra conduits in the right ventricular outflow tract
(RVOT) who had 133 patient-years of follow-up, there was
no hint of hemolysis.4 In a subsequent prospective multi-
center trial of 165 patients who underwent RVOT recon-
struction with a Contegra conduit with follow-up of 687
patient-years, multiple complications were reported and
hemolysis was not listed as one of them.5 In several more
large retrospective series, hemolysis has not been reported a
complication of bioprosthetic valves and conduits in the
RVOT.6–9
The patient in this case report had a 12 mm valved
Contegra conduit placed in the RVOT at 2 months of age.
Four years later, she demonstrated brisk hemolysis due to
stenosis of the conduit. There was no clinical or labo-
ratory evidence for an alternative cause of hemolysis.
Calcification within the shunt and intimal hyperplasia
were noted on the chest computed tomographic angio-
gram study as well as on the histology of the removed
conduit (Fig. 1D) which most likely caused shearing stress
for the circulating red blood cells. Given that the degree
of stenosis seen in this patient is commonly encountered
in such a clinical setting, we suspect that the extent of
conduit calcification and irregularity was an important
contributor to the hemolysis. Our patient experienced
relatively immediate stabilization of the hemoglobin and
normalization of the reticulocyte count within 2 weeks of
replacing the conduit.
We conclude that hemolysis is a rare complication of
obstructed bioprosthetic RV to PA-valved conduits. Alle-
viation of the obstruction using transcatheter methods or
surgical replacement seems to be effective in afflicted
patients.

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 J Pediatr Hematol Oncol  Volume 00, Number 00, ’’ 2017
REFERENCES
1. Akins CW, Miller C, Turina MI, et al. Guidelines for reporting
morbidity and mortality after cardiac valvular operations. J
Thorac Cardiovasc Surg. 1996;112:708–711.
2. Mecozzi G, Milano AD, De Carlo M, et al. Intravascular
hemolysis in patients with new-generation prosthetic heart valves:
a prospective study. J Thorac Cardiovasc Surg. 2002;123:550–556.
3. Suda K, Matsamura M, Matsumoto M. Alleviation of
hemolysis after the stent implantation into an obstructed extra
cardiac conduit. Int J Cardiol. 2005;99:135–136.
4. Boethig D, Breymann T. Contegra pulmonary valved conduits
cause no relevant hemolysis. J Card Surg. 2004;19:420–425.
5. Breymann T, Blanz U, Wojtalik MA, et al. European Contegra
Multicentre Study: 7 year results after 165 valved bovine jugular
vein graft implantations. Thorac Cardiovasc Surg. 2009;57:257–269.
Copyright r 2017 Wolters Kluwer Health, Inc. All rights reserved.
Copyright r 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Hemolytic Anemia due to RV to PA Conduit Stenosis
6. Sandica E, Boethig D, Blanz U, et al. Bovine jugular veins
versus homografts in the pulmonary position: an analysis across
two centers and 711 patients-conventional comparisons and
time status graphs as a new approach. Thorac Cardiovasc Surg.
2016;64:25–35.
7. Yong MS, Yim D, d’Udekem Y, et al. Medium-term outcomes
of bovine jugular vein graft and homograft conduits in children.
ANZ J Surg. 2015;85:381–385.
8. Sabate Rotes A, Eidem BW, Connolly HM, et al. Long-term
follow-up after pulmonary valve replacement in repaired
tetralogy of Fallot. Am J Cardiol. 2014;114:901–908.
9. Batlivala SP, Emani S, Mayer JE, et al. Pulmonary valve
replacement function in adolescents: a comparison of biopros-
thetic valves and homograft conduits. Ann Thorac Surg.
2012;93:2007–2016.
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