Rhesus isoimmunization_late onset hemolytic

disease of the newborn without Jaundice

ABSTRACT

Rhesus isoimmunization commonly presents with severe anemia associated with

early neonatal jaundice treated with phototherapy and exchange transfusion.
Seldomly, babies who have mild or no symptoms at birth may present later with
severe hemolytic anemia. In this case report, we have described a newborn infant
who had no post-natal jaundice and presented with severe anemia in the second
week of life. This case signifies the importance of regular follow up and close
monitoring of Rh-isoimmunized infants for the first two months for delayed onset
anemia.

Keywords: Anemia, Blood transfusion, Direct coomb’s test, HDN, Jaundice,

Newborn, Phototherapy, Rh isoimmunization

INTRODUCTION:

Hemolytic disease of the newborn (HDN) secondary to rhesus isoimmunization is

caused by the trans-placental channeling of maternal antibodies which are active
against paternal Rh antigens of the infant leading to hemolysis. This hemolysis not
only can cause anemia in the intrauterine period but can also lead to jaundice and
anemia of variable intensity after birth. Sometimes, neonates with mild or no
initial symptoms in the immediate newborn period present with late onset
anemia[1]. In this case report, we present a 14th day old infant born to an Rh-
negative mother who presented with late onset severe anemia in the absence of
jaundice.
CASE REPORTCASE REPORT:

A 14th day old male newborn, weighing 3 kilograms, born of a non

consanguineous marriage to a 25 year old gravid 4 para 3 mother by normal
vaginal delivery, presented to us with severe anemia. There were no significant
events in the antenatal period. The child was born in good condition and there
were no complaints of jaundice, cyanosis, and fits in the immediate post natal
period. On examination, he had severe anemia, tachypnea, tachycardia and
hepatosplenomegaly. On admission, his hemoglobin was 5.8 gm/dl; reticulocyte
count (corrected) 12%, Mean Corpuscular Volume(MCV) 105.3 fl. Peripheral
smear showed polychromasia, dimorphic picture of RBCs, target cells,
acanthocytes and spherocytes. Total serum bilirubin was 0.89 mg/dl; direct
bilirubin – 0.15mg/dl. A full septic work-up was negative. Direct coomb’s test was
strongly positive. Baby’s blood group was O positive; mother’s blood group - O
negative and father’s blood group was O positive. Mother’s indirect coomb’s test
was positive with positive anti-D antibody titers which established the diagnosis
of hemolytic disease of the newborn secondary to Rh-isoimmunisation with anti-D
antibodies. Mother had conceived thrice before this pregnancy; all were
uneventful normal vaginal deliveries. She had declined anti – D prophylaxis in all
pregnancies. All of her children were born healthy with blood group O positive
and no post natal complications were noted in any of them. The infant was given
packed cells transfusion; post transfusion hemoglobin dropped again to 5.5gm/dl.
Again packed cells were transfused on day 17th after which hemoglobin showed
slight improvement to 6.3 gm/dl. Two more packed cells were transfused on day
19 and 22 which showed a dramatic increase in hemoglobin levels. The infant was
finally discharged at day 24 with hemoglobin 13.6gm/dl and negative direct
coomb’s test. Parents were counselled about the nature of illness, implications of
refusing anti – D prophylaxis and high chances of complications in subsequent
pregnancies. Contraception was robustly advised. They were then called for
follow up after 1 week and then monthly for 2 months. On each visit, the child
was found to be thriving well and hemoglobin to be in normal range.
Discussion:
Rhesus isoimmunization is a preventable disease in which Rh-negative mother
develops antibodies against paternal Rh-antigen of fetal red blood cells due to
exposure of fetal blood into mothers circulation through feto-maternal
hemorrhage secondary to abortion, trauma, invasive procedure, post-delivery etc.
This is called sensitization or iso/allo-immunization. Sensitization occurs greatly in
the first pregnancy and is reduced in further pregnancies. It does not usually
affect the first born but can cause hemolytic disease in subsequent newborns.
Prevention of isoimmunization in these Rh-negative pregnant women is achieved
by giving prophylactic dose of Anti-D immunoglobulin which neutralizes the effect
of these iso-antibodies. Failure or a delay in giving prophylaxis may cause
destruction of fetal red blood cells leading to hemolytic disease of the newborn
(HDN). For many years rhesus isoimmunization has been the main cause of
neonatal and perinatal morbidity and mortality but the rate has now been
reduced because of the introduction of anti-d immunoglobulin prophylaxis[2,3].

Rhesus isoimmunisation is responsible for causing varying severity of anemia from

fetal hydrops in utero to mild to severe anemia in the immediate post-natal
period[4]. Recent evidence has shown that these iso-antibodies may continue to
cause destruction for six to 10 weeks postnatally[5].Studies have shown that the
reason might be because of either not undergoing exchange transfusion in the
immediate post natal period or because of progressively improving
reticuloendothelial function in the second week of life[6,7].This increased rate of
hemolysis is not always associated with a rise in serum bilirubin because of
parallel maturation of liver[8].

The case described here illustrate that the baby although being Rh-positive, the
mother being Rh-negative and never receiving any anti-D prophylaxis, did not
develop any complications of hemolytic disease of the newborn in previous
pregnancies possibly because of intact placental barrier which might have
prevented mixing of maternal and fetal RBC’s thus avoiding sensitization. Also, in
our case, the baby developed anemia in second week of life in the absence of
jaundice which is an uncommon yet recognized presentation of HDN. Although,
the baby recovered well with repeated packed red blood cells transfusions, the
duration of hospital stay and need for repeated blood transfusions could have
been prevented by upfront exchange transfusion at the time of admission. The
case described here demonstrate that all infants with HDN due to Rhesus
isoimmunization must be considered to be at risk for late anemia even in the
absence of jaundice or anemia in the immediate post natal period. Sufficient post
discharge scrutiny, including repeat hemoglobin dimensions should be arranged.
Parents should be counselled about the significance of seeking timely medical
attention for the symptoms of anemia.

REFERENCES:

1.Fyfe TM, Ritchey MJ, Taruc C, Crompton D, Galliford B, Perrin R: Appropriate

provision of anti-D prophylaxis to RhD negative pregnant women : a scoping
review.BMC Pregnancy Childbirth. 2014 Dec 10, 14():411.

2. Bowman J: Rh-immunoglobulin: Rh prophylaxis. Best Pract Res Clin Haematol.

2006, 19:27-34.

3. Gollin YG, Copel JA: Management of the Rh-sensitized mother. Clin Perinatol.
1995 Sep, 22(3):545-59.

4. Urbaniak SJ, Greiss MA: RhD haemolytic disease of the fetus and the newborn.
Blood Rev. 2000 Mar, 14(1):44-61.

5.Hayde M, Widness JA, Pollak A, Kohlhauser-Vollmuth C, Vreman HJ, Stevenson

DK: Rhesus isoimmunization: increased hemolysis during early infancy.Pediatr
Res. 1997 May, 41(5):716-21

6 . Fraser ID, Oppe TE, Tovey GH, Webb DA: Post-exchange anaemia in Rh
haemolytic disease. Lancet. 1964, ii:1309–11
7. Ebbesen F, Eur J Pediatr: Late anemia in infants with rhesus haemolytic disease
treated with intensive phototherapy. 1979 Apr 3, 130(4):285-90.

8. Gross S, Shurin SB, Gordon EM. Behrman’s Neonatal-Perinatal Medicine:

Diseases of the Fetus and Infant. 3rd edn. St Louis: Mosby; 1983. The blood and
haematopoietic system.