More information about text formats
Reflecting to the letter of Mark P Tighe, et al. we would like to
report our case with rhesus-haemolytic disease treated with D-penicillamine (DPA) and phototherapy without exchange transfusion:
We recently cared for a term infant boy (blood group B, Rh-positive, weighed 3100 gm) who was born at 37. gestation to a 33-year old, blood group B, Rh-negativ mother. During pregnancy the indirect Coom...
We recently cared for a term infant boy (blood group B, Rh-positive, weighed 3100 gm) who was born at 37. gestation to a 33-year old, blood group B, Rh-negativ mother. During pregnancy the indirect Coombs tests showed: 1 : 16 and 1:32 titres, respectively. The baby was born as an 11.offspring of his mother and appeared jaundice at 10 hours of life and had moderate anaemia. The direct Coombs test was strongly positive (++++) in the cord blood. At 12 hours of age, the bilirubin level was 207 micromol/liter; the haemoglobin value was 119 g/liter. Phototherapy and orally administered D-penicillamine (300 mg/kg per day divided in four doses for 5 days) were started. The clinical characteristics of the infant with Rh-haemolytic disease are shown in Table 1.
His physical growth and developmental processes at 18 months of age revealed no abnormalities of neurodevelopmental maturation, as based on an evaluation of motor developmental milestones, and date obtained by the classic neurologic
examination, and cerebral neuromotor maturational markers. Although this combined therapy of hyperbilirubinaemia has been performed successfully in our case concerning the avoidance of an exchange transfusion in the infant with haemolytic disease, care must be taken not to overlook developing anaemia which may require transfusion. Table 1 showes that the baby's lowest haemoglobin level was 67 g/liter on day 9 and 130 g/liter on day 12, clarifiying the existence of a serious haemolytic process and the efficacy of a single red blood cell transfusion.
According to our calculation the cost of DPA treatment would be about 15 - USD (5 days treatment for a newborn with 3 kg of body weight needs 5x900 mg DPA, i.e. 300 mg/kg daily, in divided doses. That is 4500 mg DPA total). 18 capsules of 250 mg orally administered D-penicillamine costs about 15.3 - USD in the USA. The performance of an exchange transfusion with 600 ml donor blood, however, costs approximately 150 - USD, not to speak about the risk of the exchange itself: 3 death per 1000 procedures and the risk of AIDS and hepatitis from transfusion. Furthermore, without proper treatment about 25% of infants suffering from serious hyperbilirubinaemia are expected to be at risk of neurodevelopmental disorders at 1 year of age in developing countries .
Finally, we would like to emphasize that the combined alternative treatment of rhesus haemolytic disease described herein is a safe, inexpensive and effectice therapy even for the extremely jaundiced African infants.
Table 1. Clinical Date of the Reported Infant
Phth, phtototherapy; Sebi, serum bilirubin;
Hb, haemoglobin; PRBC, packed red blood cell
(1) Mark P Tighe, Alyson O'Donnell, Mary Morgan Bloodless treatment
of infants with rhesus-haemolytic disease Electronic letter (29 November
(2) Wolf MJ, Wolf B, Bijleveld C et al. The predictive value of
developmental testing of extremely jaundiced African infants.
Developmental Medicine& Child Neurology 1998; 40:405-410.
We read with interest the letter discussing bloodless treatment of
infants with haemolytic disease , which highlighted the successful use of
erythropoietin and D-penicillamine. We wish to contribute to the
discussion of the use of erythropoietin
with a case report:
Mrs M (G2 P1), a Jehovah’s Witness, presented at 12 weeks with high
avidity anti-D antibodies (9.5 I.U.), and anti-JKa antib...
Mrs M (G2 P1), a Jehovah’s Witness, presented at 12 weeks with high
avidity anti-D antibodies (9.5 I.U.), and anti-JKa antibody titres of 1
I.U. The role of blood products was discussed with the parents, who wished
to avoid their use. Other treatment options were discussed, including
iron, erythropoietin and minimal phlebotomy. The anti-D antibody level
peaked at 31 weeks at 14.1 I.U. Baby M was born in good condition at 37+5
weeks. The cord bilirubin (SBR) was high, and the Direct Coombs Test (DCT)
was strongly positive. Phototherapy was started and SBR and haemoglobin
(Hb) were monitored with capillary blood gas analysis, with formal
laboratory samples sent daily, to minimise iatrogenic blood loss.
Folic acid (100mcg od), Sytron (2ml bd) and erythropoietin (750 i.u.
subcut. three times a week) were commenced on day 5. At discharge (day 19)
the Hb reached a nadir of 8.6g/dl with no reticulocytes. By 6 weeks the Hb
was 11.8 g/dl, with a reticulocyte count of 18x 109 and the DCT was still
strongly positive. Erythropoietin was discontinued and the Hb and
reticulocyte count remained stable at 3 months.
The rate of SBR rise in the first 12 hours and high antibody titres would
have made exchange transfusion a reasonable option, although Baby M
remained asymptomatic. However adequate fluids and phototherapy
immediately after birth proved sufficient. Further blood loss was reduced
by minimal phlebotomy, and erythropoiesis maximised with folic acid, iron,
and erythropoietin acting in synergy .
Recombinant erythropoietin was ethically acceptable to baby M’s parents
and can reduce transfusions for isoimmune-haemolytic disease (such as ABO
 ) and subsequent anaemia. Elevated endogenous erythropoietin might be
expected in rhesus-haemolytic disease, with recombinant erythropoietin
providing little extra erythropoiesis. However erythropoietin levels
analysed in babies with rhesus-haemolytic disease are unexpectedly low,
with associated bone marrow suppression . In this case, while on
erythropoietin, the Hb continued to rise despite a strongly positive DCT,
(still present postnatally at six weeks) and ceased rising off
erythropoietin. In addition the reticulocyte count improved markedly, and
continued to rise off erythropoietin.
A six-week course of erythropoietin costs about £350, which is
similar to transfusion costs. One unit of leucodepleted, irradiated, CMV
negative blood is £113 , in addition to the cost of exchange equipment.
Rising transfusion costs and limited blood product reserves make
erythropoietin more cost-effective in rhesus-haemolytic disease. In
addition erythropoietin has few side-effects, while 3% of neonates have
transfusion reactions .
Minimal phlebotomy is important in neonatal management to avoid blood
products. Hb and SBR are available by blood gas analysis, and requires
95mcl of blood, compared to 500mcl for serum electrolytes and SBR, and
500mcl for a full blood count. Baby M lost an estimated 24 ml of blood
for tests during his inpatient stay (10.6% of blood volume).
Throughout the antenatal and postnatal period, consistent and regular
communication with the parents maintained a good rapport, and it was
emphasised that all treatment modalities would be explored before
obtaining a specific treatment order for blood products.
We believe that these strategies helped Baby M overcome complicated
maternal antibody isoimmunization without the use of blood products, and
that recombinant erythropoietin is cost-effective, safe and could make up
for a shortfall in endogenous erythropoietin production.
(1). Lakatos L Bloodless treatment of infants with haemolytic disease.
Arch Dis Child 2004; 89-1076.
(2). Bader D. Kugelman A.Weinger-Abend M et al The role of high-dose oral
iron supplementation during erythropoietin therapy for anemia of
prematurity. J Perinatology. 21(4):215-20, 2001 Jun.
(3). Lakatos L. Csathy L. Nemes E. “Bloodless” treatment of a Jehovah’s
Witness infant with ABO hemolytic disease. J Perinatology 19(7); 530-2;
(4). Thorp JA, O’Connor T, Callenbach J et al. Hyporegenerative anemia
associated with intrauterine transfusion in Rhesus Haemolytic disease. Am
J Obs Gynae 1991; 165(1); 79-81.
(5). Figures from Southampton University Pathology Services.