Archna Sharma

Bedangshu Saikia

Neeraj Gupta

Neetu Vashisht

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Exchange transfusion for neonate with haemolytic uremic syndrome

Saikia et al. SpringerPlus  (2016) 5:52 
DOI 10.1186/s40064-016-1667-x
CASE STUDY
Exchange transfusion for neonate 
with haemolytic uremic syndrome
Bedangshu Saikia1*, Neetu Vashisht1, Neeraj Gupta1 and Archna Sharma2
Abstract 
Introduction: Haemolytic uremic syndrome (HUS) is one of the most common causes of acute renal failure in chil-
dren but it is uncommon in newborns. To our knowledge only five cases have been reported so far (probably under-
reported). The known modalities of treatment include transfusion of plasma and plasmapheresis. We report a case of 
neonatal HUS for whom we performed an exchange transfusion to good effect.
Case description: A term vaginally born baby, meconium stained and floppy at birth presented with severe anae-
mia in the first few hours of life. The baby later on developed renal failure and blood picture was suggestive of severe 
thrombocytopenia and microangiopathic haemolytic anaemia. No extra renal manifestations of birth asphyxia were 
noted. A double volume exchange transfusion was performed relatively early and subsequently platelet and haemo-
globin stabilised and renal failure improved.
Discussion and evaluation: The clinical impression in this case was convincing of neonatal HUS, likely attributable 
to birth asphyxia but needs to be differentiated from disseminated intravascular coagulation (DIC) and thrombotic 
thrombocytopenic purpura (TTP). The coagulation profile is usually normal in HUS but it is abnormal in DIC, whereas 
in TTP one would find hyperbilirubinemia, increased creatinine, haemolysis etc. TTP is rare but not very uncommon 
in infancy. Congenital TTP is attributed to an inherent deficiency of ADAMTS-13, which is a vWF-cleaving metallo-
protease. Irrespective of the etiology of HUS in our case, a dramatic response was observed with exchange transfu-
sion. Transfusion of fresh frozen plasma (FFP) and plasmapheresis are known treatment modalities. FFP replaces the 
missing or altered complement factors and plasmapheresis removes antibodies, immune complexes and toxins. An 
exchange transfusion combines both these functions.
Conclusions: In the absence of facilities for plasmapheresis, exchange transfusion is a good alternative.
Keywords: Birth asphyxia, Meconium aspiration, Microangiopathic haemolytic anaemia (MHA), Neonatal HUS
© 2016 Saikia et al. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License 
(http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, 
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and indicate if changes were made.
Introduction
Neonatal haemolytic uremic syndrome (HUS) is char-
acterised by the triad of microangiopathic haemolytic 
anaemia (MHA), thrombocytopenia and renal failure 
(Corrigan and Boineau 2001). It is rare in newborns; to 
be very precise probably under-reported. To our knowl-
edge, only five cases of neonatal HUS have been reported 
to-date; three were found to be associated with birth 
asphyxia (Biran et  al. 2007), one was associated with 
transplacental transmission of E. coli O157 (Ulinski et al. 
2005) and another related to intracellular vitamin B12 
deficiency (Kind et al. 2002).
We describe the case of a neonate with HUS secondary 
to birth asphyxia presenting as severe anaemia, as early 
as 4 h of life. The anaemia was refractory to red cell trans-
fusions. The haematological and renal profile improved 
following a double volume exchange transfusion done 
at 16 h of life. Plasmapheresis and plasma infusions have 
been used previously to treat HUS. Exchange transfusion 
essentially provides plasma exchange besides augmenting 
the haemoglobin levels. Arguably this is the first report of 
neonatal HUS treated with exchange transfusion.
Open Access
*Correspondence:  bedangshu@gmail.com 
1 Department of Pediatrics and Neonatology, St Stephens Hospital,  
Tis Hazari, New Delhi 110054, India
Full list of author information is available at the end of the article
Page 2 of 4Saikia et al. SpringerPlus  (2016) 5:52 
Case description
A three kilogram baby boy was born vaginally at 38 weeks 
of gestation to a primiparous mother. The baby was 
meconium stained and not vigorous at birth. Endotra-
cheal intubation and positive pressure ventilation were 
needed for resuscitation. He was extubated at 3  min of 
life, after establishment of adequate respiratory efforts.
Haemoglobin at birth was 18.3  g/dL and the plate-
let count was 1.62 × 109/L. A blood smear examination 
done at 1 h of life was normal (Table 1). At around 4 h 
of life, marked pallor was noted. Respiratory distress (res-
piratory rate 70/minute), subcostal retractions and fall-
ing saturations necessitated initiation of bubble CPAP. 
CPAP of 8 cm of water and FiO2 of 50 % were needed to 
maintain oxygen saturations above 90  %. Falling blood 
pressure and other markers (clinical and biochemical) 
of hemodynamic compromise prompted fluid resuscita-
tion followed by ionotropes. Dobutamine was started to 
augment the falling cardiac output. Subsequently, oligo-
anuria was also noted to have set in.
The results of the investigations at 4  h are detailed in 
the Table 1. The haemoglobin had fallen to 7.7 g/dL and 
platelets had decreased to 43,000/mm3. Peripheral smear 
showed fragmented RBCs and schistocytes suggestive of 
MHA (Fig. 1). The baby was switched on to intermittent 
positive pressure ventilation at 5 h of life in view of wors-
ening respiratory distress. Chest X-ray did not reveal any 
lung parenchymal abnormality. Packed cells (45 mL) were 
transfused at 6 h of life, followed by a second transfusion 
(45  mL) as the haemoglobin did not rise satisfactorily 
following transfusion of the first aliquot. Haemoglobin 
remained low (6.7 g/dL) even after two transfusions at 7 h 
of life. The reticulocyte count was 7.8 %. Blood urea nitro-
gen was 40.3 mg/dL and serum creatinine was 1.6 mg/dL 
at 14 h of life. Prothrombin time, partial thromboplastin 
time and FDP were normal. There was no haematuria 
and proteinuria or bleeding from peripheral cannulation 
sites. Ultrasound examination of cranium and abdomen 
were normal. The blood group of the baby was compat-
ible with the mother’s and direct Coombs test was nega-
tive. There was no family history of atypical HUS. There 
were no extra-renal manifestations of birth asphyxia.
On account of the falling haemoglobin which contin-
ued despite packed cell transfusions, the evidence of 
red blood cell fragmentocytosis, deranged renal func-
tions and the normal coagulation screen, a diagnosis 
Table 1 Table of investigations
Parameters (in SI units) Age of the index case (in hours, in the first 72 h) and investigations done
1 h of life 4 h of life 7 h of life 14 h of life 29 h of life 53 h of life 65 h of life Day 4 of life
Total leucocyte counts, TLC (per μL) 26,100 12,200 25,200 6500 6700 7500 11,900
Hemoglobin (gm/dL) 18.3 7.7 6.4 12.1 13.1 12.9 12.7
Hematocrit (in %) 57.8 23.1 20 36.4 39.3 39.1 38.4
Platelet count (per μL) 162,000 43,000 64,000 70,000 80,000 89,000 108,000
Reticulocyte count (in %) 5.6 7.8
Direct coomb’s test Negative
Blood urea nitrogen (mg/dL) 12.0 40.3 18.7 16.2 10.6 4.4
Creatinine (mg/dL) 1.3 1.6 1.2 0.8 0.6 0.5
Prothrombin time (s) 14.8
Partial thromboplastin time (s) 28.7
INR (international normalized ratio) 1.05
Sodium (mEq/L) 145.3 137.1 145.0 136.4 138.0 143.3
Potassium (mEq/L) 4.3 4.1 3.84 3.60 5.11 5.0
Serum total calcium (mg/dL) 9.7 6.1 6.1 11.3 7.0 9.7
Serum total bilirubin (mg/dL) 1.72 8.70
Serum indirect bilirubin (mg/dL) 1.36 7.91
Creatinine phosphokinase (U/L) 1414
CK–MB (U/L) 96
pH 7.181 7.153 7.198 7.419
CO2 (mmHg) 43.3 21.4 28 46.3
HCO3 (mmol/L) 15.6 7.2 15.6 29.5
Lactate (mg/dL) 8.7 22.5 6.8 1.5
Schistocytes in peripheral blood smear Present (Fig. 1)
Page 3 of 4Saikia et al. SpringerPlus  (2016) 5:52 
of neonatal HUS was made. 90 mL of fresh plasma was 
transfused. A double volume exchange transfusion with 
whole blood cross-matched with both baby and mother 
was performed using 480  mL of group A Rh positive 
blood. Following the exchange transfusion, haemoglo-
bin increased to 13.1  gm/dL, platelet count increased 
to 80,000/mm3, BUN decreased to 18.7  mg/dL, serum 
creatinine fell to 1.2  mg/dL and urine output improved 
gradually as well. No further blood transfusions or renal 
replacement therapy were needed. The baby was une-
ventfully extubated on day 4 of life and transferred to 
ward on day 5 of life. The baby is now 9 months old and 
doing well in follow up. He has had no significant illness 
or hospitalisation since discharge from our hospital.
Discussion and evaluation
The clinical picture in this case was suggestive of neo-
natal HUS, most likely attributable to birth asphyxia. 
Drastic falls in haemoglobin in absence of bleeding, as 
occurred in our neonate and fragmentocytes seen on the 
smear were suggestive of HUS. Serum haptoglobin levels 
and LDH are used as axillary tools in diagnosing intra-
vascular hemolysis, but they are not reliable in a newborn 
due to inherent hepatic immaturity and these tests were 
not done in our case.
HUS needs to be differentiated from disseminated 
intravascular coagulation (DIC) and thrombotic throm-
bocytopenic purpura (TTP). There are no tests that can 
definitely differentiate HUS from DIC except that the 
coagulation profile is usually normal in HUS but it is 
abnormal in DIC. The fact that the child did not suffer 
any other MHA/TMA episode supports the idea that 
he does not have congenital TTP as the rate of recur-
rence is very high with congenital TTP; more than 60 % 
of patients have their relapses within the first year and 
about 90  % relapses within the first 4  years. (Hovinga 
et al. 2010).
TTP can also present with similar symptomatology 
and associated thrombocytopenia, hyperbilirubine-
mia, increased creatinine, hemolysis etc. (Moake 2002). 
Though rare, TTP is not as uncommon in infancy as 
previously thought. The congenital presentation of TTP 
is attributed to an inherent deficiency of vWF-cleaving 
metalloprotease (ADAMTS-13) (Moake 2002). However, 
measurement of ADAMTS-13 in newborns is highly 
laboratory-dependent and also the fact that it is a costly 
investigation to obtain.
Non-immune thrombocytopenia in association with 
microangiopathic haemolytic anaemia can also occur in 
Kasabach Merritt syndrome and renal vein thrombosis. 
There was no suggestion of these in our neonate.
Three cases of neonatal HUS following asphyxia have 
been reported till date (Biran et al. 2007). They also pre-
sented with a features of anaemia, thrombocytopenia 
and schistocytes on peripheral smear. Renal failure was 
present in all three cases. Two cases were treated with 
peritoneal dialysis while the other showed spontaneous 
improvement in renal parameters. The earliest onset was 
at 12 h. Biran et al. (2007) hypothesised that “endothelial 
damage that occurs in birth asphyxia leads to a vicious 
cycle of consumption of platelets and plasma factors 
involved in hemostasis and fibrinolysis (complement 
factors H/I and ADAMTS13)”. Complement factor H/I 
deficiency is known to cause excessive activation of the 
alternative complement pathway causing injury to the 
capillary endothelial cells and subsequent symptoms of 
HUS (Caprioli et al. 2001). ADAMTS13 is a metallopro-
tease enzyme which is needed to cleave the large mul-
timers of vWF (von Willebrand factor) into smaller inert 
fractions. In the absence of this enzyme, the uncleaved 
large multimers induce platelet adhesion and aggrega-
tion at sites of endothelial injury leading to platelet rich 
thrombi in the end organs (Furlan and Lämmle 2000). 
Besides consumption of these factors, congenital defi-
ciency of ADAMTS can also precipitate HUS. We did not 
investigate for these deficiencies and it is possible that 
these deficiencies coexisted in our case.
Whatever the exact etiology of HUS in this case 
(whether secondary to alternate complement pathway 
activation or paucity of ADAMTS13) it responded dra-
matically to exchange transfusion (Licht et al. 2005). Tra-
ditionally, transfusion of fresh frozen plasma (FFP) and 
plasmapheresis have been used in treatment of HUS irre-
spective of the exact etiopathogenesis (Scully et al. 2012). 
Currently, the monoclonal antibody eculizumab is being 
used in some centres for the treatment of refractory TTP 
(Chapin et al. 2012); Besbas et al. (2013) used this therapy 
Fig. 1 Peripheral smear showing schistocytes classical of microangio-
pathic haemolytic anaemia
Page 4 of 4Saikia et al. SpringerPlus  (2016) 5:52 
successfully to treat an infant with recurrent disease. 
Treatment with eculizumab is expensive and takes time 
for its effects though. FFP acts by replacing the missing or 
altered complement factor H/I or ADAMTS13 enzyme. 
Plasmapheresis removes antibodies (which consume the 
ADAMTS13) as also the immune complexes and toxins 
but it is not useful in the congenital forms of HUS. An 
exchange transfusion combines both these functions of 
removing antibodies and replenishing the deficient or 
altered proteins (Coppo et  al. 2010). In the absence of 
facilities for plasmapheresis, exchange transfusion is a 
good alternative. Exchange transfusions are performed 
in most neonatal units usually in the context of neonatal 
hyperbilirubinemia. Neonatal HUS may be a new indica-
tion for this procedure.
Conclusions
Neonatal HUS is a very rare complication and even rarer 
associated with birth asphyxia. Early differentiation from 
similar presentation and diagnosis is important in terms 
of further planning and outcome. Exchange transfusion 
may be a viable alternative to plasmapheresis in resource 
limited settings.
Authors’ contributions
Evaluation and data collection was carried out by BS, NV with inputs from AS. 
Analysis and interpretation of data was by BS, NV, and NG. Review of literature 
and initial drafting by BS, NV, and NG. All authors contributed to the critical 
review and revision of the manuscript. All authors read and approved the final 
manuscript.
Author details
1 Department of Pediatrics and Neonatology, St Stephens Hospital, Tis Hazari, 
New Delhi 110054, India. 2 Department of Pathology, St Stephens Hospital, Tis 
Hazari, New Delhi 110054, India. 
Acknowledgements
None.
Competing interests
The authors declare that they have no competing interests.
Consent
Parental consent was obtained for presentation of the case in conferences and 
publication in journals.
Received: 10 May 2015   Accepted: 4 January 2016
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Exchange transfusion for neonate with haemolytic uremic syndrome

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