Study on the application value of red blood cell distribution width and platelet distribution width in neonatal exchange transfusion with hyperbilirubinemia

Abstract

Purpose

The study aimed to evaluate the application of Red Blood Cell Distribution Width (RDW) and Platelet Distribution Width (PDW) in the treatment of neonatal exchange transfusion (ET) with hyperbilirubinemia as well as to provide relevant reference materials for clinical diagnosis and treatment.

Patients and methods

This was a retrospective study in a single center. Between January 2011 and December 2020, a total of 198 neonates, who were admitted to Fujian Maternity and Child Health Hospital for hyperbilirubinemia and treated with ET therapy were selected. They were divided into blood group antibody negative (BGAbN) ET (n = 92) and blood group antibody positive (BGAbP) ET (n = 106) groups. We analyzed changes in serum total bilirubin (STB), serum indirect bilirubin (SIB), and platelet count(PLT) before and after ET; The clinical data of the neonates with hyperbilirubinemia were collected, and RDW and PDW were compared in the two groups before ET..

Results

The concentrations of STB, SIB, and platelet count were much higher before ET and decreased significantly after ET; the difference was statistically significant (p<.001); There were significant differences between the two groups in RDW and PDW before ET.

Conclusion

ET therapy is the most timely and effective treatment method for severe hyperbilirubinemia in neonates clinically; RDW and PDW can help determine neonatal hemolysis caused by blood group antibodies.

Keywords:

• Exchange transfusion
• RDW
• PDW
• hyperbilirubinemia

Introduction

Severe neonatal hyperbilirubinemia (SNH) is one of the most frequent reasons for hospitalization or readmission in the first week of life worldwide [1,2]. It develops into bilirubin encephalopathy rapidly and easily [3,4]. The cause of neonatal hyperbilirubinemia is that, on the one hand, the newborn's liver is not fully developed and bilirubin cannot be excreted normally; on the other hand, the combined bilirubin in the intestine is decomposed, resulting in a high proportion of enterohepatic circulation [5]. Severe neonatal hyperbilirubinemia (SNH) is an important cause of neonatal morbidity and mortality, especially in low- and middle-resource developing countries [6]. ET is currently the most rapid and effective method for the clinical treatment of hyperbilirubinemia [7]. The purpose of ET is to exchange a large amount of bilirubin, free antibodies, sensitized red blood cells, etc. in the blood, which helps indirectly connect bilirubin and albumin [8].

The key to the treatment of children with severe hyperbilirubinemia is to reduce the bilirubin level in a timely and effective manner. In the treatment of neonatal severe hyperbilirubinemia caused by blood group antibodies, a compatible ET is used. Newborns with severe hyperbilirubinemia by non-blood group antibodies can be treated with compatible ET or the same type of ET. The operation of neonatal hemolysis test is complicated and time-consuming; the routine blood test is simple and less time-consuming. There are few studies on the application of blood routine to assist in judging neonatal hemolysis. The objective of this study was to evaluate the effect of ET in children with severe hyperbilirubinemia and explore the application value of RDW and PDW used to distinguish whether neonatal hemolysis was related to blood group antibodies.

Materials and methods

Study design

This retrospective study was conducted on all neonates who underwent ET for hyperbilirubinemia. Inclusion criteria were as follows: (a) new-borns admitted to the hospital due to hyperbilirubinemia and treated with ET, (b) meeting the eligibility standards for ET [9], and (c) high bilirubin caused by non-blood-group antibodies-related blood disease.

We divided neonates into BGAbN ET and BGAbP ET treatment groups; compared changes in STB, SIB, PLT, RDW and PDW before and after ET; and retrospectively analyzed the clinical data of the infants.

Patients and equipments

Data on 252 neonatal cases of hyperbilirubinemia ET in the Department of Neonatology, Fujian Maternity and Child Health Hospital, from January 2011 to December 2020 were collected, of which 198 met the inclusion criteria. They were divided into BGAbN ET (n = 92) and BGAbP ET ET (n = 106) treatment groups.

The test instrument used for bilirubin was the Abbott al16200 (Abbott, Chicago, USA). The concentration of platelet count, RDW and PDW were detected using the instrument Sysmex®XN-3000 (Sysmex Corporation, Kobe, Japan). The instrument used for blood type and neonatal hemolysis tests was the WADiana DG-57 (Diagnostic Grifols, Barcelona, Spain).

Blood selection and dosage

New-borns with ABO hemolysis received O-type red blood cells and AB-type fresh frozen plasma; those with Rh hemolysis received red blood cells and plasma with ABO-blood type similar to that of the child and Rh-blood type similar to that of the mother's red blood cells and plasma; and those with hemolytic disease caused by non-blood group antibodies received a homotype of blood composition similar to that of the child. Using the standard of 160–180 ml/kg body weight, we strictly cross-matched blood, basing the amount of ET against the weight of the child.

ET was implemented through the simultaneous transfusion of peripheral arteriovenous double tubes. The scalp vein was selected as the ET route, as per routine, and the radial artery selected as the blood collection route. The total blood exchange volume was 160–180 ml/kg body weight, and the difference between input and output blood volume generally did not exceed 3–5 ml/kg. The speed of ET was maintained at approximately 5 ml/(kg.min), and the treatment time for ET was generally 1.5–2.0 h. For every 100 ml of blood exchanged, 1 ml of 10% calcium gluconate was evenly supplied.

Statistical analysis

All statistical analyses were performed using SPSS Statistics version 25.0 (IBM Corp., Armonk, N.Y., USA). The measurement data are expressed as mean ± standard deviation (i.e. X ± S), using the paired sample t-test and independent sample t-test, chi-squared test for the analysis of normative comparisons. Application of receiver operating characteristic curve (ROC curve) to evaluate the diagnostic value of RDW and PDW, the areas under the curve (AUCs) are provided with their sensitivity, specificity, and 95% confidence intervals (CIs). p-Values less than .05 were considered statistically significant.

Results

In 252 infants, we identified 198 infants who underwent ET for hyperbilirubinemia. Among the included cases, the infants were more likely to be male (60.61%), gestational age was 33–41 weeks, transfusion time ranged from 1 to 12 days, and birth weight was 2.3–3.9 kg. They were divided into BGAbN ET (n = 92) and BGAbP ET (n = 106) treatment groups. There were no differences in gender, gestational age and birth weight between BGAbN ET group and BGAbP ET group, and there were no differences in STB, SIB and PLT levels between the two groups before and after ET. These results were presented in Table 1, Figures 1 and 2.

Table 1. Comparison of gender, gestational age, birthweight before and after BGAbN ET and BGAbP ET groups.

	BGAbN ET	BGAbP ET	p
Gender			1.000
Male	64	56	/
Female	28	50	/
Gestational age (weeks)	38.35 ± 1.82	38.60 ± 1.43	−1.075
Birthweight (kg)	3.11 ± 0.50	3.24 ± 0.42	−1.907

In the BGAbN ET group, changes before and after ET were statistically significant (p < .001). STB (umol/L) decreased from 505.52 ± 92.18 to 275.59 ± 75.10, SIB (umol/L) was from 467.52 ± 86.13 to 258.70 ± 66.26, and the number of platelets (×10^9/L) was from 282.42 ± 110.06 to 96.53 ± 39.29 (Figure 1).

Figure 1. STB, SIB, and PLT before and after ET in the BGAbN ET group. Abbreviations: STB: serum total bilirubin; SIB: serum indirect bilirubin; PLT: platelet count. ***p-Values were considered statistically significant.

In the BGAbP ET group, changes before and after ET were statistically significant (p<.001). STB (umol/L) decreased from 443.84 ± 85.64 to 251.15 ± 64.57, SIB (umol/L) was from 416.78 ± 83.92 to 232.92 ± 59.65, and the number of platelets (×10^9/L) was from 245.06 ± 91.71 to 86.45 ± 40.19 (Figure 2).

Figure 2. STB, SIB, and PLT before and after ET in the BGAbP ET group. Abbreviations: STB: serum total bilirubin; SIB: serum indirect bilirubin; PLT: platelet count. ***p-Values were considered statistically significant.

We compared RDW and PDW between the two groups before ET. RDW had obvious difference between the two groups, the BGAbP ET group was significantly higher than the BGAbN ET group, the difference was statistically significant (p<.001); PDW had obvious difference between the two groups, the BGAbN ET group was significantly higher than the BGAbP ET group, and the difference was statistically significant (p<.05) (Table 2).

Table 2. Comparison of RDW and PDW between the two groups before ET.

	BGAbN ET	BGAbP ET	t	p
RDW	14.54 ± 2.66	18.09 ± 3.03	−8.675	<.001
PDW	11.92 ± 3.58	10.76 ± 1.91	2.897	<.05

RDW and PDW had high sensitivity and specificity in distinguishing whether neonatal hemolysis was related to blood group antibodies, the significantly different factors were evaluated by ROC curve analysis. (Table 3, Figures 3 and 4).

Figure 3. ROC curves of RDW before ET. p<.05 Suggests significantly different.

Figure 4. ROC curves of PDW before ET. p<.05 Suggests significantly different.

Table 3. ROC curves of RDW and PDW before ET.

	AUC	Standard deviation	p	Cutoff	Sensitivity (%)	Specificity (%)
RDW	0.840	0.028	.000	15.65	77.4	79.3
PDW	0.614	0.040	.006	10.25	76.1	47.2

RDW was positively correlated with neonatal hemolysis related to blood group antibodies, r = 0.527, p<.001; and PDW was negatively correlated with blood group antibodies, r = 0.203, p = .004 (Table 4).

Table 4. Comparison of the correlation between RDW, PDW and blood group antibodies in the diagnosis and treatment of neonatal hemolysis.

		Blood group antibody
RDW	r	0.527*
	p	<.001
PDW	r	0.203*
	p	.004

*indicates significant at the 10% level.

Discussion

There are many causes of neonatal hyperbilirubinemia, among which blood group incompatibility between the fetus and the mother is a common cause. Studies have reported an association between ABO incompatibility and severe anemia at birth [10,11]. In contemporary perinatal centers, 15–40% of newborns treated with Rh or ABO hemolytic disease of the newborn (HDN) require at least one exchange transfusion [12]. The degree of decrease in total bilirubin and indirect bilirubin is the most important indicator of the effect of exchange transfusion therapy. Blue light is a common way to treat neonatal hyperbilirubinemia, but the effect of lowering bilirubin levels is limited [13]. Exchange blood therapycan greatly reduce the bilirubin concentration in a short period of time and prevent the occurrence of bilirubin encephalopathy. Moreover, it can exchange immune antibodies and sensitized red blood cells in the body, and then reduces hemolysis [14]. It has been reported that more than half of newborns with severe hyperbilirubinemia receive transfusion therapy [15]. Exchange blood therapy can effectively reduce the aggravate of hemolysis [16].

ET therapy can effectively remove sensitized red blood cells in children, while white blood cells, platelets and plasma are also eliminated during the transfusion process [17]. In our study, ET therapy in the BGAbN group and the BGAbP group has a significant effect on reducing the bilirubin level (p < .001). This result is consistent with previous research results [18]. The cause of neonatal hyperbilirubinemia affects the choice of blood components and the effect of ET, so it is of great significance to quickly identify the cause of neonatal hemolysis.

The main cause of neonatal jaundice is the increase of bilirubin level, which is related to the short life span, rapid production and excessive destruction of neonatal red blood cells. The heterogeneity of red blood cells is manifested in the abnormality of red blood cell size, morphology and negative surface charge. With increased heterogeneity and decreased deformability, the red blood cells will be captured, swallowed and destroyed when the blood flow through the splenic sinus, thereby increasing the level of bilirubin. Red blood cell volume distribution width (RDW) is a parameter that reflects the heterogeneity of red blood cells. It uses a high-precision hematology analyzer, which measures tens of thousands of red blood cells, and obtains the coefficient of variation of red blood cell volume after statistical processing. It is a quantitative indicator of red blood cell heterogeneity, which can accurately and timely reflect the size of red blood cells. In the study by Al-Lawama M, 33% of children had a reduction in platelet count after ET [19]. Another study has reported that as many as 54.6% of children undergoing ET therapy will develop thrombocytopenia [20]. One of the reasons for this result may be related to the input blood components. The blood we used is that in which the components of platelets has been removed, in order to accelerate the speed of blood exchange. The platelets in the blood circulation pool are quickly replaced, and the body is temporarily unable to replenish platelets in time, resulting in a temporary decrease in the number of platelets. Therefore, exchange transfusion therapy has an effect on the number, size and morphology of platelets in the body. Platelet distribution width (PDW) is a parameter that reflects the heterogeneity of platelets. Clinicians should pay attention to the impact of exchange transfusion on platelets, in order to avoid misdiagnosis or missed diagnosis of thrombocytopenia. In some cases, platelet transfusion is necessary to prevent fatal bleeding in vital organs. However, whether exchange blood affects the function of platelets needs further research.

The presence of blood group antibodies may aggravate hemolysis in newborns. We used RDW and PDW to initially explore their application value in early identification. The RDW was much higher in the BGAbP group, while the PDW was much higher in the BGAbN group. According to the comparison of the two groups before ET and the results of the ROC curve, it can be seen that RDW and PDW can effectively be used to identify whether the blood group antibodies were the major cause of neonatal hemolysis.

Although this study has obtained some information regarding the effect of ET on newborns and the application of RDW and PDW in the treatment of neonatal ET with severe hyperbilirubinemia, there are still some shortcomings. This study was limited to two time points, before and after ET i.e., and did not involve the changes in the observation period during ET. In addition, this study did not investigate the long-term effects of ET therapy on neonates.

Conclusion

ET therapy is a quick and effective treatment for severe neonatal hyperbilirubinemia. RDW and PDW can effectively determine the cause of neonatal hemolysis, which is conducive to the diagnosis and treatment of neonatal hemolysis.

Ethical approval

This study was approved by the ethical committee of Fujian Maternity and Child Health Hospital, The study complied with the Declaration of Helsinki.

Acknowledgments

The Authors would like to thank the Blood Transfusion Department, Fujian Maternity and Child Health Hospital for helping to perform part of this work. There is no funding to report.

Disclosure statement

No potential conflict of interest was reported by the author(s).