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Year : 2018  |  Volume : 7  |  Issue : 1  |  Page : 48-50

Acute hemoglobin increase after transfusion and immunoglobulin for rhesus hemolytic disease of the newborn

1 Department of Paediatrics, Leeds General Infirmary, Leeds, UK
2 Medical School, University of Nottingham, Nottingham, UK
3 Department of Radiology, Hull and East Yorkshire NHS Trust, Hull, UK
4 Department of Paediatrics, Hull and East Yorkshire NHS Trust, Hull, UK

Date of Web Publication6-Feb-2018

Correspondence Address:
Dr. Hilary Klonin
Hull Royal Infirmary, Anlaby Road, Hull HU3 2JZ, FRCPCH
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcn.JCN_48_17

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We describe two infants with severe hemolytic disease of the fetus and newborn (HDFN) with hepatosplenomegaly treated with intravenous immunoglobulin. Packed red blood cells (PRBC) were transfused resulting in an acute disproportionate increase in hemoglobin with clinical consequences in one case. These cases appear to highlight previously unreported sequelae. We discuss a hypothetical mechanism and suggest that the effect warrants further research as a possible way to decrease the need for and risks of PRBC transfusion in HDFN.

Keywords: Hemoglobin increase, red blood cell transfusion, immunoglobulin, Rhesus Disease

How to cite this article:
Hughes GO, Osman J, Coady AM, Klonin H. Acute hemoglobin increase after transfusion and immunoglobulin for rhesus hemolytic disease of the newborn. J Clin Neonatol 2018;7:48-50

How to cite this URL:
Hughes GO, Osman J, Coady AM, Klonin H. Acute hemoglobin increase after transfusion and immunoglobulin for rhesus hemolytic disease of the newborn. J Clin Neonatol [serial online] 2018 [cited 2022 May 19];7:48-50. Available from: https://www.jcnonweb.com/text.asp?2018/7/1/48/224809

  Introduction Top

The National Institute of Clinical Excellence guidelines state that hemolytic disease of the fetus and newborn (HDFN) can be treated intravenous immunoglobulin (IVIG) to reduce the rise in bilirubin.[1] IVIG may prevent hemolysis by competing with anti-D sensitized neonatal erythrocytes to occupy the Fc receptor sites of the cells of reticuloendothelial system, decreasing the antibody-dependent cellular cytotoxic effects which are the cause of the erythrocyte breakdown.[2],[3]

We used IVIG in two infants with HDFN and hepatosplenomegaly and gave a transfusion of packed red blood cells (PRBC) to treat anemia. Both cases developed much higher hemoglobin (Hb) than anticipated by their clinical condition and transfusion calculations. We believe that this association has not been previously described.

  Case Reports Top

Case 1

A 2390 g male infant with rhesus (Rh) alloimmunization and rising maternal anti-D and anti-C titers was delivered at 34 weeks and 5 days gestation, by elective cesarean section to prevent hydrops fetalis. Serial fetal ultrasound scans showed an enlarged spleen [4] [Figure l] with middle cerebral artery peak systolic velocity (PSV) indicating anemia. The infant had hepatosplenomegaly; the spleen palpable at 7 cm and liver palpable at 5 cm below the rib cage [Figure 2]. He was treated for respiratory distress syndrome (RDS). He received a bolus of 2.5 ml/kg 10% dextrose and commenced on 90 ml/kg/day intravenous fluids. Umbilical cord blood bilirubin was 149 umol/L and direct antiglobulin test (DAT) strongly positive. A diagnosis of HDFN was made. Phototherapy started from birth. Twenty-four milliliters of IVIG was administered over 4 h (0.5 g/kg). Hb was 77 g/L (range 135–215 g/L) and hematocrit was 0.25 (range 0.39–0.63 SI units). He was transfused with 14 ml/kg Rh-negative blood, to increase Hb to no >100 g/L. An hour into the PRBC transfusion, the hematocrit fell to 0.20 but was 0.34 2 h after the transfusion and reached 0.61 4 h later, after completion of IVIG [Figure 3]. Hb 4 h after the end of blood transfusion was 156 g/L. Blood film showed dimorphism, polychromasia, and occasional  Howell-Jolly bodies More Details. Nucleated red cell to white blood cell ratio (NRBC/WBC) increased to 501/100.
Figure 1: Measurement of the fetal spleen length (dotted line) 7.2 cm. Fifth to ninety-fifth centiles are between 3.5 and 5.2 cm at 34-week gestation[4]

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Figure 2: Anteroposterior supine chest X-ray showing hepatosplenomegaly

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Figure 3: Time from birth and rise in hematocrit (percentage) or bilirubin (umol/L) after blood transfusion and intravenous immunoglobulin

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One hour after completion of the PRBC transfusion, he developed acute hemodynamic compromise, responding to supportive treatment. An echocardiogram showed normal cardiac anatomy without fluid overload. Hematocrit and Hb fell over the next 24 h and then stabilized.

Over the next day, he developed signs and symptoms suggestive of necrotizing enterocolitis (NEC) abating after 3 days. The bilirubin decreased. By day 6, hepatosplenomegaly had almost completely resolved. He was discharged on day 14.

All charts and volumes were checked by the local clinical team and transfusion services in conjunction with national services. The hematocrits were directly measured values from the blood gas analyzer (Instrumentation Laboratory, Gem 4000, Warrington). Laboratory values were obtained regularly and corresponded

Case 2

A 2770 g, 34-week gestation female infant was delivered by elective cesarean section to a mother with rising anti-e titers through pregnancy. Due to middle cerebral artery PSV indicating anemia, fetal blood transfusion had been undertaken in the week before delivery. Hepatosplenomegaly was present; liver palpable at 3 cm below the costal margin and a spleen tip present. She was treated for RDS and received 90 ml/kg/day intravenous fluids. The cord blood bilirubin was 80 IU/L and first measured one from the infant, 125umol/L. DAT was strongly positive. A diagnosis of HDFN was made. Phototherapy commenced from birth. Bilirubin continued to rise to 140 umol/L 7 h after birth when 28 ml IVIG (0.5 g/kg) was administered over 4 h. Her first measured Hb was 98 g/L. At 4 h of age, she received a top-up transfusion of 15 ml/kg PRBC aiming to increase her Hb by no more than 30 g/L. Her Hb 3 h after commencement of the PRBC transfusion, shortly after commencement of IVIG was 129 g/L [Figure 4]. However, 4 h after the end of the PRBC transfusion, it reached 155 g/L. Blood film showed polychromasia with highest NRBC/WBC being 97/100. The Hb dropped over the next 38 h to 138 g/L. The bilirubin stabilized. She was discharged on day 13.
Figure 4: Time from birth and rise in hemoglobin (g/L) or bilirubin (umol/L) after blood transfusion and intravenous immunoglobulin

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  Discussion Top

We describe two infants with HDFN who received PRBC transfusions calculated to produce an increase in Hb of 30 g/L or less.[5],[6] The Hb increase should be lessened by the presence of concurrent hemolysis, demonstrated by the initial bilirubin rise, additional fluid bolus diluting the hematocrit,[7] and repeated phlebotomy [8] with the increase in Hb no greater at 7 h posttransfusion than at 1 h.[5] In the first case, the Hb increased by 79 g/L over a 9 h period and in the second by 57 g/L over an 8 h period, as the bilirubin levels stabilized and dropped. It is possible that the early hemodynamic compromise in Case 1 may have resulted from the effect of an acute rise in blood viscosity, given the absence of other demonstrable causes.

We suggest the enlarged liver and spleen, undertaking highly active erythropoiesis, released red cells into the bloodstream, evidenced by the high NRBC/WBC ratio. The anti-D-coated red cells would be protected by the IVIG, from breakdown. This along with the PRBC transfusion caused the unexpected increase in Hb. The timing of the Hb rise after the completion of the IVIG infusion [Figure 3] and [Figure 4] suggests an additive effect to that of the PRBC transfusion,[5] with the release of endogenous red blood cells. The decrease in the rise of bilirubin supports the effectiveness of the IVIG in protecting these from breakdown.

Case 1 had signs and symptoms suggestive of NEC. The association of IVIG administration with NEC shown by Figueras-Aloy et al. may warrant further investigation.[9] It would be interesting to know the rise in Hb in this series to look for parallels with transfusion-associated NEC.[10]

In Case 2, hepatosplenomegaly and Hb rise were less dramatic. Conceivably in utero blood transfusion attenuated hematopoietic upregulation, decreasing the effect.

If IVIG protects red cells released by active hematopoiesis, then a delay or decrease in PRBC transfusion for infants with HDFN and hepatosplenomegaly, receiving IVIG, may allow endogenous erythropoiesis to correct the anemia, decreasing need for PRBC transfusion with attendant risks.[11] This acute Hb increase associated with bilirubin decrease has not previously been reported to our knowledge. Further study is required to see whether this effect is reproducible and useful.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.


We thank Dr. Gaili for kind permission to report his patient, Mark Williams, and Mark Padget, for their thoughtful review of this manuscript and advice on hematological reports and Dr. Nubli Mustapa for his invaluable expertise on the formation of graphs and presentation of mathematical data.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

National Institute of Clinical Excellence Guideline Jaundice in Newborn Babies under 28 days. Available from: https://www.nice.org.uk/guidance/cg98. [Last accessed on 2016 Jul 06].  Back to cited text no. 1
Gottstein R, Cooke RW. Systematic review of intravenous immunoglobulin in haemolytic disease of the newborn. Arch Dis Child Fetal Neonatal Ed 2003;88:F6-10.  Back to cited text no. 2
Freyne B, O'Hare FM, Molloy EJ. Efficacy and safety of intravenous Ig and alterations in haematological parameters of infants with isoimmune haemolytic disease. Arch Dis Child Fetal Neonatal Ed 2012;97:F76-7.  Back to cited text no. 3
Schmidt W, Yarkoni S, Jeanty P, Grannum P, Hobbins JC. Sonographic measurements of the fetal spleen: Clinical implications. J Ultrasound Med 1985;4:667-72.  Back to cited text no. 4
Davies P, Robertson S, Hegde S, Greenwood R, Massey E, Davis P, et al. Calculating the required transfusion volume in children. Transfusion 2007;47:212-6.  Back to cited text no. 5
Morris KP, Naqvi N, Davies P, Smith M, Lee PW. A new formula for blood transfusion volume in the critically ill. Arch Dis Child 2005;90:724-8.  Back to cited text no. 6
Van PY, Riha GM, Cho SD, Underwood SJ, Hamilton GJ, Anderson R, et al. Blood volume analysis can distinguish true anemia from hemodilution in critically ill patients. J Trauma 2011;70:646-51.  Back to cited text no. 7
O'Riordan JM, Fitzgerald J, Smith OP, Bonnar J, Gorman WA, National Blood Users Group, et al. Transfusion of blood components to infants under four months: Review and guidelines. Ir Med J 2007;100 Suppl 1-24:496.  Back to cited text no. 8
Figueras-Aloy J, Rodríguez-Miguélez JM, Iriondo-Sanz M, Salvia-Roiges MD, Botet-Mussons F, Carbonell-Estrany X, et al. Intravenous immunoglobulin and necrotizing enterocolitis in newborns with hemolytic disease. Pediatrics 2010;125:139-44.  Back to cited text no. 9
Paul DA, Mackley A, Novitsky A, Zhao Y, Brooks A, Locke RG, et al. Increased odds of necrotizing enterocolitis after transfusion of red blood cells in premature infants. Pediatrics 2011;127:635-41.  Back to cited text no. 10
Venkatesh V, Khan R, Curley A, New H, Stanworth S. How we decide when a neonate needs a transfusion. Br J Haematol 2013;160:421-33.  Back to cited text no. 11


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

This article has been cited by
1 Hemolytic Disease of the Newborn: A Review of Current Trends and Prospects
Akshay Kiran Myle,Ghanim Hamid Al-Khattabi
Pediatric Health, Medicine and Therapeutics. 2021; Volume 12: 491
[Pubmed] | [DOI]


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