Are we transfusing right? A retrospective study on appropriateness of pediatric blood transfusions

INTRODUCTION

Blood transfusion practice is proven beyond doubt to benefit individuals in life-threatening situations. More so, the intense level of anxiety to save a life is augmented when a pediatric patient is on the receiving end. Blood transfusions in the pediatric age group are vital, considering their indication and survival. The sole decision to transfuse blood or its components as per indication is of dire importance, as there are pronounced dangers associated with transfusion. It can lead to several unwanted acute and chronic complications and may expose the recipient to infectious agents. The inappropriate use of blood and its components without an absolute indication may expose the patients to unnecessary risk of untoward adverse reactions. Such inappropriate transfusions can significantly contribute to increased demand and can result in a shortage for patients for whom there could be an actual requirement.^[1] Transfusion medicine has evolved as a specialty embracing laboratory and clinical knowledge into the art of transfusion. Transfusion of red blood cells (RBC) and other components has now become one of the relatively common procedures over the past few decades.^[2] Whole blood transfusion, RBCs, and other blood components are generally given to patients for various indications requiring blood transfusion. Fresh frozen plasma (FFP) is the primary source of various coagulation factors required for patients with clotting factor deficiencies.^[3,4] Hence, with the forethought of effectively rationalizing the process, we tried to analyze the trend of blood transfusions and comprehend the absolute necessity and indications and the type of transfusions requested from various departments in our tertiary care hospital and retrospectively inspect and gather survey evidence and publish to humbly educate clinicians on the rational demands of transfusion warranted and to ascertain overall safe transfusion practices. Our study emphasizes the stringent rational use of blood and blood products, improving the standards of transfusion that benefit the overall society by means of reserving the blood store to treat emergencies adequately.

MATERIALS AND METHODS

Our study is of a retrospective type, conducted over 6 months at the regional blood center in a tertiary care hospital. Our study population comprised pediatric patients <18 years of age who had received blood transfusions in the form of whole blood, packed RBCs (PRBCs), FFP, platelets, or cryoprecipitate. Our study adhered to the World Medical Association (WMA) Declaration of Helsinki-Ethical Principles for Medical research involving human subjects (WMA) and was approved by the Institutional Ethical Committee of the institution SMC/IEC/2023/FEB/037. Data were collected retrospectively by thorough scrutiny of blood transfusion request forms. Patient’s record data, including age, sex, diagnosis, indications for transfusion, number, and types of blood components requested, were extracted after double-checking for credibility. Appropriateness of transfusion requests was analyzed with respect to variables such as sex, age of the patient, and the blood component requested. Key points for determining appropriate versus inappropriate blood transfusion in the pediatric age group (<18 years) were based on the latest British Committee for Standards in Haematology (BCSH) and Association for the Advancement of Blood and Biotherapies (AABB) guidelines. Significant and appropriate transfusions in the pediatric population are those where a restrictive threshold is applied, recommending red cell transfusion for hemodynamically stable children when hemoglobin (Hb) is <7 g/dL, with modifications for certain neonatal and illness contexts. Transfusion is also justified in cases of acute blood loss over 15% of total blood volume, symptomatic anemia with clinical evidence of inadequate oxygen delivery, or as part of chronic transfusion programs for conditions such as thalassemia or sickle cell disease. For neonates, age and clinical stability dictate thresholds; for example, Hb <10 g/dL in the 1^st week of life for preterm infants off respiratory support is appropriate. Transfusions outside these parameters, or without clear clinical justification or recent Hb measurement, are considered inappropriate by both BSH and AABB guidelines.^[5,6] The detailed methodology of our study has been depicted in Figure 1.

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Figure 1:

Study methodology flow chart. BCSH: British Committee for Standards in Hematology, AABB: Association for the Advancement of Blood and Biotherapies.

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RESULTS

The present study aimed to comprehensively analyze the pediatric transfusions taking place in our tertiary care center over 6 months. From April to September 2023, a total of 5323 transfusion requests were obtained, among which there were 186 (3.5%) pediatric transfusions. An average of 31 pediatric transfusions took place every month over 6 months. The age of study participants ranged from 1 day to 17 years. The median age of participants was 42 days (interquartile range = 8.24 years), and more than half of the participants hailed from the neonatal age group. Appropriateness of transfusion according to age, gender and blood components requested have been depicted in detail in Table 1. For analysis purposes, we divided the age range into four groups: <1 month, >1 month-1 year, >1 year-5 years, and >5 years up to 18 years. We tried to derive significant and appropriate transfusions that were truly indicated among the total transfusions divided by sex and age-wise distribution that proved to be statistically significant (P = 0.021, P < 0.001), respectively. The most requested blood component was packed RBCs (n = 92, 49.4%), followed by FFP (n = 49, 26.3%), and >70% of the requested transfusions were repeat transfusions for the same participants. Majorly, anemia of various causes (around 60%) was followed by indications in preterm infants. Various other diseases for which transfusion was sought have been depicted in detail in Table 2. We derived a statistical correlate of appropriateness of transfusions based on various diagnoses, and that proved to be statistically significant (P < 0.001). Out of the 186 pediatric transfusion requests, 36 requests (around one-fifth) were found to be inappropriate with respect to the case indication, as per the British Committee for Standards in Hematology and Association for the AABB’s guidelines.

Other parameters, such as case indication and type of transfusion (single or repeat), were also analyzed, and they have been depicted in Table 2.

We analyzed every transfusion request with respect to the blood component requested with standard guidelines, and derived statistical significance for appropriateness.

DISCUSSION

As a part of the team of transfusion medicine, we have been following up on blood transfusions constantly, but an attempt like this to establish the appropriateness of transfusions and audit over the past months renders a greater insight into the logistical challenges of the department, as well as the entire tertiary care hospital, for that matter. Anemia is one of the most common causes for seeking blood and component transfusions worldwide. Our study also finds similar results with maximum cases of anemia stemming from a variety of reasons. In many cases, blood transfusions may be required repeatedly with frequent interval gaps to sustain life in severe cases. Although thalassemia is common in the northwestern belt of our country, in the southern part, we do see many cases of all types of hemolytic anemias also referred from various parts of the country owing to the better medical and treatment facility options available.^[8,9] Our discussion will revolve around the most common diagnoses or indications for which transfusion requests were raised in our tertiary care hospital setting, and comparing the same with global standards or practices and published evidence. Multiple studies, such as those by Mufti et al.,^[10] Zhong et al.,^[11] and Ferraris et al.,^[12] emphasize the importance of transfusion in unprecedented post-operative complications.^[10-12] In a study, from 366 patients who underwent primary palatoplasty repair at an average age of 10.5 months, six were re-admitted to the hospital after discharge following their primary admission with complaints of bleeding from the surgical site; around five required blood transfusions. Bleeding occurred as a delayed complication in 1.6% of cleft palate repair surgeries (1 in 61 operations).^[13] Similarly, in our study, we find that cleft palate and certain other surgical conditions warrant the use of blood component transfusion to stabilize the hemodynamic status of the individuals in the perioperative or postoperative period, which could be a rational approach.

Our study analysis reveals that necrotizing enterocolitis (NEC) is more commonly seen in preterm infants due to their undeveloped gut, as one of the indications for which blood transfusions were administered. One of the randomized controlled studies analyzed the risks associated with mesenteric ischemia and transfusion-related NEC for premature and concluded that NEC in infants was not seen to increase by enteral feeding during RBC transfusion.^[14]

At birth, the Hb level of the fetus is usually higher than the adult Hb level due to the fact that the fetus has to compensate for its decreased partial pressure of oxygen in arterial blood. Then, after birth, Hb level tends to decrease rapidly as the fetal RBCs undergo rapid destruction rather than their replenishment. This rapid destruction causes physiological anemia of infancy, which usually occurs at 1^st month of life. This physiological anemia of infancy is more severe in preterm infants.^[15] A greater degree of anemia occurs in extremely low birth weight neonates (<1000 g), and they warrant RBC transfusions more frequently during their admission.^[16,17]

The important aim of transfusion in neonates is to prevent hypoxia to tissues, which ultimately results in end-organ damage.^[18,19] There are certain landmark trials, such as IOWA, premature infants in need of transfusions, effects of transfusion thresholds on neurocognitive outcomes of extremely low-birth-weight infants, and transfusion of premature infants, which provide evidence regarding RBC transfusion threshold limits in neonates.^[20-23] The understanding of the trials suggests that thresholds for transfusion of critically ill neonates in the 1^st week of life have to be in the range between 11 g/dL and 13 g/dL, and in older infants who are stable without any ventilatory support, the transfusion thresholds have to be in the range between 7 g/dL and 10 g/dL.^[24] The main aim of setting these lower thresholds is to preserve the blood for appropriate patients who were in need of transfusion and also to prevent the neonates from the hazards of transfusion.

Transfusion of blood components in preterm infants for various indications is the most common request for blood transfusion in our retrospective analytical study. We should also realize the fact that PRBC transfusions in preterm infants have been proven to be associated with significant morbidity and complications. Although neonates born in <26 weeks’ gestational age typically require several PRBC transfusions, preterm infants born between 26 and 34 weeks’ gestational age also require PRBC transfusions during their hospital stay for various reasons that are nevertheless potentially preventable. A novel study came up with an interventional qualitative trial that included the implementation of evidence-based threshold limits of transfusion, supporting erythropoiesis in bone marrow, and bringing down laboratory specimen volumes collected by increasing capillary test panels. They concluded that there was no great change in mortality or the rate of NEC in preterm neonates. Improvements witnessed actually had a sustained documentation for 24 months after implementation.^[25] Hence, we could be more vigilant in opting for transfusions, especially in preterm, and thereby avoid the other transfusion-related adverse effects. Platelet transfusions in dengue patients could stand as lifesaving at a count <10,000/cu.mm of blood.^[26] Unfortunately, platelet transfusions are done in less severe cases with not so critical a fall in platelet levels.

One of the cases in our study population had inherited Von Willebrand’s disease, for whom repeated transfusion was done. Numerous studies provide substantial evidence that plasma-derived Von Willebrand factor-containing factor VIII concentrates (pd-VWF/FVIII-C) as the mainstay treatment in Von Willebrand Disease.^[27]

In one of similar kind of study retrospective survey of transfusions was carried out as part of quality assurance and found that out of 520 transfusions over a period with 1218 units of PRBCs rendered to 297 patients (88%) was considered appropriate; of 106 transfusions with 405 units of FFP transfused to 83 patients (90%) was learnt to be appropriate; and of 187 transfusions of 320 units of albumin given to 99 patients (64%) were only proved to be appropriate.^[28] The present study adopted a novel approach in evaluating transfusion practices in the pediatric population at a tertiary care hospital, with reference to established standard guidelines. The clinical implications underscore the critical importance of strict protocol adherence by clinicians before making transfusion requests, as such interventions carry potential risks, including adverse reactions and fluid overload in children. Following our findings, we highlighted the issue of inappropriate transfusions during clinical review meetings and initiated awareness programs across various faculties and departments to reinforce compliance with standard transfusion protocols. Nevertheless, we recognize the inherent limitation of our work, being confined to a single-center study. Moving forward, we aspire to expand this research to a multicenter setting, thereby generating more robust and statistically significant results that encompass a larger patient population. Furthermore, routine implementation of such audit and scrutiny mechanisms in tertiary care teaching hospitals could substantially reduce the burden of inappropriate transfusions.

CONCLUSIONS

In comparison with the standard guidelines, our study highlights the prevalence of inappropriate transfusions carried out in a tertiary care hospital in South India, a developing nation. By means of our study results, we would like to emphasize and educate the medical community as a whole in following and implementing rational adoption of transfusion practices for obligatory diagnostic indications, which entails an adequate reserve of blood products for medical exigencies.