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 Table of Contents  
REVIEW ARTICLE
Year : 2018  |  Volume : 3  |  Issue : 2  |  Page : 98-102

Current practices in pediatric transfusion


Department of Transfusion Medicine, KEM Hospital, Mumbai, Maharashtra, India

Date of Web Publication24-Oct-2018

Correspondence Address:
Dr. Charusmita Modi
Department of Transfusion Medicine, KEM Hospital, Mumbai, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/GJTM.GJTM_10_18

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  Abstract 


The article opens with an account of red cell and platelet transfusion guidelines in fetal and neonatal period. This is followed by a discussion on the special requirements for transfusion in pediatric surgeries and hemostatic disorders. A scheme for the long term transfusion management in thalassemia and sickle cell anemia is summarised. Finally, the complications of transfusion seen in pediatric patients are described.

Keywords: Intrauterine, maternal alloantibodies, pediatric, transfusion


How to cite this article:
Modi C. Current practices in pediatric transfusion. Glob J Transfus Med 2018;3:98-102

How to cite this URL:
Modi C. Current practices in pediatric transfusion. Glob J Transfus Med [serial online] 2018 [cited 2018 Nov 20];3:98-102. Available from: http://www.gjtmonline.com/text.asp?2018/3/2/98/243919




  Introduction Top


Blood transfusion is a frequent procedure in pediatric and neonatal units, especially in the intensive care setting. Transfusion guidelines are evolving in these domains. The present paper explores these recommendations in the setting of a tertiary care center handling a high volume of neonatal and pediatric patients. Requirements of transfusion vary at different developmental stages and each has its unique indications and requirements. Commonly recognized stages are fetal, neonatal, and childhood.


  Fetal Red Cell Transfusions Top


Transfusion in fetal life may be indicated due to fetal red cell destruction which is most commonly due to maternal alloantibodies against red cell antigens (D, c, E, K, Fya, and Jka)[1] Another important cause is Parvovirus B19 infection during pregnancy.[1] Maternal alloantibodies are produced following a previous pregnancy or transfusion. Repetitive exposure to minute amounts of Rh-positive cells, by the sharing of contaminated needles between Rh-negative intravenous drug-abusing women with Rh-positive partners has also been reported to lead to severe Rh sensitization.[2] When the mother is alloimmunized with high-titer anti-D, plasmapheresis associated with infusion of intravenous immunoglobulins, offer an effective antenatal management.[1] Very severe fetal anemia with fetal–placental hydrops may require intrauterine transfusion with packed red cells. The posttransfusion hematocrit should not be more than four times higher than the initial hematocrit, as an abrupt increase in blood viscosity could compromise the cardiovascular system.[1] When an intrauterine transfusion has been given, the infant would require irradiated cellular blood components until 6 months after the expected date of delivery.[3]


  Fetal/neonatal Platelet Transfusions in Alloimmune Thrombocytopenia Top


Fetal platelet transfusions may be indicated for fetal and neonatal alloimmune thrombocytopenia (FNAIT). Transfusion departments have to provide advice relating to the diagnosis of FNAIT, identify the antibodies causing it, and provide appropriate blood components.

FNAIT is most commonly caused by antibodies to human platelet antigen (HPA); anti-HPA1a or 5b.[4] Mothers of Asian ancestry whose newborns have alloimmune thrombocytopenia, most often have antibodies specific for HPA-4 antigens.[2] “Antibody-negative” FNAIT may be caused by low-avidity anti-HPA antibodies which may not be detected in standard assays requiring washing of the target antigen.[4] FNAIT may also occur due to maternal ABO antibodies. Fetuses who express extremely high levels of platelet A1 and B antigens (type 2 high expressers) could be at risk for thrombocytopenia if born to an ABO incompatible mother.[4] FNAIT may present in the first pregnancy and can give rise to intracranial hemorrhage in the prenatal period and tends to be more severe in subsequent pregnancies.[4] The degree of thrombocytopenia in the fetus and the risk of intracranial hemorrhage can be reduced with high-dose intravenous immunoglobulins with or without corticosteroids.[4] For intrauterine transfusion, platelet should be transfused more slowly than red cells because of increased risk of fetal circulatory stasis.[3] A study is upcoming where nonimmunized HPA-1a-negative women will be given anti-HPA-1a antibodies after delivering an HPA-1a-positive child.[5]


  Neonatal Red Cell Transfusions Top


Ill neonates are more likely to receive transfusions than any other patient age group, and red blood cells (RBCs) are the component most often transfused during the neonatal period.[6] RBC replacement is considered for sick neonates when approximately 10% of blood volume has been lost or they have symptomatic anemia.[6] The majority of red cell transfusions to neonates are top-up transfusions of small volumes (15 ml/kg over 4 h) given to replace phlebotomy losses in the context of anemia of prematurity, particularly for preterm very low birth weight neonates.[3] Small-volume aliquots limit donor exposures and prevent circulatory overload in the neonates.[6] Small-volume RBC transfusion aliquots are commonly made with a multiple-pack system. Quad packs are produced from a single unit of whole blood that is diverted into a primary bag with three integrally attached smaller bags.[6]


  Exchange Transfusion in Newborn on the Decline Top


Exchange transfusion (ET) is becoming increasingly uncommon because of the considerable decrease in the incidence of HDFN due to anti-D, the use of intravenous immunoglobulins, and the efficacy of modern phototherapy techniques.[1] The clinical significance of HDFN caused by ABO incompatibility is none to moderate.[2] However, the incidence and severity of hyperbilirubinemia in ABO-incompatible neonates in certain populations may be increased by the presence of a variant UDP glucuronyltransferase gene promoter.[7] For ET, RBCs are resuspended in ABO-compatible thawed fresh frozen plasma (FFP).[6] “Quarantine” plasma or donor-retested plasma is considered a safer component for ET.[1] “Quarantine” plasma is frozen plasma which is released only after the donor is found to be nonreactive for the transfusion transmissible disease markers in his subsequent donation. This subsequent donation period exceeds the window period of the TTI tests.[8] The procedure of ET may alter the medication levels and therefore should be monitored and adjusted appropriately.[2]


  Neonatal Platelet Transfusions Top


Thrombocytopenia in neonates is defined as platelet count <150 × 109/L, similar to that in adults.[2] Most platelet transfusions in preterm and full-term infants are performed to treat platelet counts <50,000/μL in the presence of active bleeding.[6] The infusion of 10 mL/kg of platelet concentrate should be able to raise the blood platelet count to >100 × 109/L in an infant.[2] The desired volume of the concentrate can be transferred to a transfer bag using a sterile connecting device. However, unless the transfer bag is made of plastic suitable for platelet storage, the aliquot should be used as soon as possible.[2] When leukocyte-reduced platelets have been ordered, the ordered dose may need to be adjusted for the loss of platelets during leukocyte-reduction filtration, which may be as high as 20%.[2] Careful monitoring of posttransfusion platelet counts is essential, given the serious consequences of inadequate dosing in thrombocytopenic newborns.[2] When platelets are issued from a single donor platelet unit, the plasma must be ABO compatible with the patient's RBCs, especially in those who have received a hematopoietic progenitor cell transplant (HPCT). When a Group O patient is engrafted major ABO-mismatched HPCT, a unique situation arises. These patients lack tissue and soluble A or B antigen. They develop much more severe hemolysis if they receive blood component containing anti-A or anti-B.[9]

Clinical conditions

Necrotizing enterocolitis (NEC) and purpura fulminans call for special attention from transfusion medicine experts. Infants with NEC frequently develop thrombocytopenia and anemia and may require transfusions.[10] In patients of NEC with T activation, saline-washed RBCs avert the risk of hemolysis induced by anti-T in (normal) donor plasma.[2] Washing a unit of RBCs using 1–2 L of 0.9% sodium chloride will remove approximately 99% of plasma proteins, electrolytes, and antibodies but may result in loss of up to 20% of the red cell mass, depending on the protocol used.[2] “Plasma-containing components” from low-titer anti-T donors may be advisable. This can be determined in the transfusion service. A minor crossmatch using plasma from the component to be transfused is mixed with patient's T-activated red cells. If anti-T present in the donor is low in titer, the crossmatch will be negative or weak and the component may be transfused.[2]

Neonatal purpura fulminans is a hematological emergency characterized by skin necrosis and disseminated intravascular coagulation (DIC) that may progress rapidly to multiorgan failure. It may be the presenting feature of a severe deficiency of either anticoagulant protein C or less commonly protein S. Acquired deficiency of protein C is most often associated with infection with  Neisseria More Details meningitidis and Streptococcus pneumoniae. Rare congenital forms are associated with loss-of-function mutations of protein C or protein S. Early recognition is crucial to reduce morbidity and mortality. The standard treatment for purpura fulminans is transfusion of FFP 10–20 mL/kg every 12 h. FFP replaces the deficient anticoagulant protein.[2],[3]


  Pediatric Red Cell Transfusions Top


In serological testing, pediatric patients are divided between those younger and older than 4 months of age. For infants younger than 4 months, the initial testing must include ABO and D typing of the patient's red cells and screening for unexpected red cell antibodies using either plasma or serum from the infant or mother.[6] The blood group interpretation in a neonate may be influenced by weak antigenic expression, masking of antigenic sites by circulating maternal antibodies, and previous intrauterine or postnatal transfusion.[1] The author supports the policy of confirmation of blood group at 6 months of age, as followed by some centers. For small volume transfusions given for correction of anemia and iatrogenic blood loss, RBCs are given at a hematocrit approximately 70%.[2] For large volume transfusions required for ET, the hematocrit should be approximately 45% to 60%.[6]


  Pediatric Surgeries Top


Pediatric surgeries which have major blood loss and need large volume transfusions are the craniofacial, scoliosis, and cardiac surgeries.[3] For these elective large volume transfusions in infants, group identical units are preferred to minimize the use of O- and D-negative red cells.[3] In the event of massive surgical blood loss, massive transfusion protocol consisting of RBC, FFP, and platelets given in the ratio of 30:30:20 ml/kg (total of 70 ml/kg) in each cycle has been found to be effective in successful management.[11] During massive surgical blood loss, cell salvage reduces the need for allogeneic blood. However, sickle cell disease and conditions characterized by red cell fragility are contraindicated for cell salvage.[3]


  Management of Pediatric Trauma Top


Hemorrhage and traumatic brain injury are the leading causes of death in pediatric trauma patients. Traumatic hemorrhage is associated with traumatic coagulopathy. The massive transfusion protocols designed for its management are based on early component therapy with coagulation factors and minimal use of crystalloids. This transfusion strategy is termed hemostatic resuscitation. Coagulation abnormalities associated with traumatic brain injury show a combination of both hypocoagulable and hypercoagulable states.[11]


  Transfusion in Cardiac Surgeries Top


Before cardiac surgeries, the hemostasis needs special attention. Unfractionated or low molecular weight heparin should be used to bridge the anticoagulation for those children who have been prescribed oral anticoagulation or antiplatelet agents following previous cardiac surgery.[3] Blood for cardiopulmonary bypass must be monitored for its potassium content. Blood with high serum potassium concentrations may be associated with cardiac arrest at the start of cardiopulmonary bypass in small children. Red cells from the donor having a mutation for familial pseudohyperkalemia leak potassium more rapidly at the low temperatures of red cell storage. If the concentration of potassium in a unit of red cells is high, it is possible to wash the red cells in a cell saver before addition to the circuit.[3]


  Disorders of Hemostasis Top


Disorders of hemostasis also necessitate transfusions. The major cause of coagulation laboratory test abnormalities and bleeding in neonatal patients is liver failure from congenital infectious hepatitis, sepsis, congenital hemochromatosis, or other factors.[2] Factors influencing the management of a bleeding disorder are its type, severity, presence of active bleeding, response to pharmacological agent, presence of inhibitors, and available therapeutic agents. Judicious use of pharmacological agents reduces the requirement of blood transfusion, for example, in von Willebrand's disease, antifibrinolytic therapy is an important adjunct in the management of bleeding involving mucous membranes.[2],[12]

In a patient with coagulation factor deficiency and in need of a surgery, a 100% correction of clotting factor is given on the morning of the surgery. The factor level is maintained at >50% to 60% for the next 5–7 days. After that, factor levels can be allowed to decrease to 30%.[2] Transfusion of 10–20 mL/kg of FFP will usually yield a coagulation factor concentration of approximately 30% of normal.[2]


  Management of Disseminated Intravascular Coagulation Top


Another hemostatic disaster is DIC. In infants with severe DIC, mortality can reach up to 80%. An increase in the D-dimer and schistocytes on peripheral smear helps in differentiating DIC from dilutional coagulopathy. Transfusion of FFP is indicated for replacement of clotting as well as inhibitory factors. FFP is transfused at a dose of 10–20 mL/kg and repeated every 6–8 hourly. Cryoprecipitate is transfused at a dose of 10 mL/kg to maintain fibrinogen >100 mg/dL. Platelets are given at a dose of 5–10 mL/kg to maintain platelet count >50,000/mL.[12] Although bleeding is the most frequent complication of DIC, microvascular thrombosis and end-organ dysfunction can be devastating. If evidence of end-organ injury is present, especially encephalopathy and cardiopulmonary dysfunction, a combination of FFP and heparin may be used.[2]


  Transfusion in Thalassemias Top


The decision to initiate lifelong transfusion therapy should be based on definitive diagnosis of an hematological condition. The diagnosis should take into account the molecular defect, the severity of anemia on repeated measurements, the level of ineffective erythropoiesis, and clinical criteria such as failure to thrive or bone changes.[13] In a study, 42% of patients with HbE beta-thalassemia could be reversed from transfusion dependent to nontransfusion dependent without any deleterious medical conditions.[14] Beta-thalassemia intermedia and HbE beta-thalassemia are nontransfusion dependent.[14] HbE beta-thalassemia may show phenotypic instability in the early years of life, where the phenotype changes from mild-to-severe phenotype during the first 15 years of life.[15]

In thalassemic heterozygotes who develop anemia, the possibility of megaloblastic pathogenesis should be pursued even when the RBC indices maintain their microcytic-hypochromic expression. Macrocytosis, the hallmark of uncomplicated megaloblastic anemia, may be absent in individuals with either α- or β-thalassemia.[16] In patients with thalassemia, diagnosing and managing underlying nutritional deficiencies is important and may prevent the need for transfusion.

In the pediatric patients who need chronic transfusions, monitoring growth and development are important outcome measures of efficacy.[3]

Rate of alloimmunization

In patients who begin transfusion after the first few years of life, autoimmune hemolytic anemia and alloimmunization are seen more commonly as compared to those in whom the transfusions are started early. It is also observed that the prevalence of alloantibodies varies among centers and may be related to the homogeneity of the population and strategies for antigen matching.[13]

When to consider splenectomy

For patients of beta-thalassemia major, the transfusion requirement of the patient should be recorded. As the annual transfusion requirements rise above 200 ml/kg/year of pure red cells, splenectomy may be considered.[13]

Cardiac involvement in thalassemia

For investigating the patients of thalassemia major for their cardiac autonomic function, “heart rate variability” (HRV) has been developed. The depressed HRV compared to normal suggests that HRV may be a marker of cardiac sympathovagal imbalance as well as early indicator of cardiac involvement in both thalassemia major and HbE beta-thalassemia.[15]

Prophylaxis for long-term transfusions

All children starting with regular transfusions should be vaccinated against hepatitis B as early as possible.[3] Thalassemic patients may have iron overloading due to chronic blood transfusion, which could lead to impaired immune response toward vaccination.[17] Following the hepatitis B vaccination, serum levels of anti-HBs should be performed. In nonresponders (anti-HBs <10 IU/ml), revaccination is recommended.[17]


  Transfusion in Sickle Cell Anemia Top


The goal of transfusion in patients with sickle cell disease is to reduce the risk of stroke by decreasing the percentage of circulating red cells capable of sickling, while simultaneously avoiding an increase in blood viscosity.[2] Hydroxyurea is effective in decreasing the frequency of pain episodes and in preventing life-threatening neurological events in patients with sickle cell anemia.[18] If a patient with sickle cell disease has been transfused within the last 3 months, genotyping may be performed or a hypotonic wash may be utilized for antigen typing. RBCs from sickle cell patients are resistant to hypotonic washing, whereas RBCs from normal persons (e.g., donors) lyse when subjected to hypotonic conditions.[19] Sickle cell patients who develop red cell alloantibodies are more likely to develop red cell autoantibodies. These patients are susceptible to hyperhemolysis following red cell transfusion, which is also referred to as the sickle cell hemolytic transfusion syndrome. In this condition, transfused sickle cell patients develop severe anemia following transfusion, with hemolysis of transfused as well as autologous red cells.[2] The recent advances in nonmyeloablative transplant may induce sufficient mixed hematopoietic chimerism to treat sickle cell disease-related complications.[2]


  Complications of Transfusion Top


Newborn infants are much less likely than children and adults to experience acute allergic or febrile reactions. They rarely become alloimmunized to red cells because of their immature immune system, but they are more susceptible to developing cytopenias from passively transferred antibodies in blood components.[2] Transfusion of incompatible plasma is more likely to cause acute hemolysis in infants than adults, due to small blood volumes. Fatal hemolytic transfusion reactions have occurred when Group O whole blood was administered to Group A infants, with the mistaken belief that this was acceptable as “universal donor” blood.[2] The most risk-free transfusion is the one that never happens. Hence, it is imperative to consider whether each and every transfusion is truly indicated.[2]

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Girelli G, Antoncecchi S, Casadei AM, Del Vecchio A, Isernia P, Motta M, et al. Recommendations for transfusion therapy in neonatology. Blood Transfus 2015;13:484-97.  Back to cited text no. 1
    
2.
Hillyer CD, Strauss RG, Luban NL. Hand Book of Pediatric Transfusion Medicine. California: Elsevier; 2004.  Back to cited text no. 2
    
3.
New HV, Berryman J, Bolton-Maggs PH, Cantwell C, Chalmers EA, Davies T, et al. Guidelines on transfusion for fetuses, neonates and older children. Br J Haematol 2016;175:784-828.  Back to cited text no. 3
    
4.
Peterson JA, McFarland JG, Curtis BR, Aster RH. Neonatal alloimmune thrombocytopenia: Pathogenesis, diagnosis and management. Br J Haematol 2013;161:3-14.  Back to cited text no. 4
    
5.
Husebekk A, Skogen B, Killie MK, Ahlen T, Tiller H, Eksteen M, et al. Foetal and neonatal alloimmune thrombocytopenia (FNAIT). ISBT Sci Ser 2011;6:261-4.  Back to cited text no. 5
    
6.
Wong E, Punzalan R. Neonatal and Pediatric Transfusion Practice. In: Fung MK, Eder AF, Spitalnik SL, Westhoff CM, editors. Technical Manual. 19th ed. Bethesda: American Association of Blood Banks; 2017.  Back to cited text no. 6
    
7.
Kaplan M, Hammerman C, Renbaum P, Klein G, Levy-Lahad E. Gilbert's syndrome and hyperbilirubinaemia in ABO-incompatible neonates. Lancet 2000;356:652-3.  Back to cited text no. 7
    
8.
Hillyer CD, Silberstein LE, Ness PM, Anderson KC, Roback JD. Blood Banking and Transfusion Medicine-Basic Principles and Practice. 2nd ed. Philadelphia, PA: Churchill Livingstone Elsevier; 2007.  Back to cited text no. 8
    
9.
Harris SB, Josephson CD, Kost CB, Hillyer CD. Nonfatal intravascular hemolysis in a pediatric patient after transfusion of a platelet unit with high-titer anti-A. Transfusion 2007;47:1412-7.  Back to cited text no. 9
    
10.
Maheshwari A. Immunologic and hematological abnormalities in necrotizing enterocolitis. Clin Perinatol 2015;42:567-85.  Back to cited text no. 10
    
11.
Nystrup KB, Stensballe J, Bøttger M, Johansson PI, Ostrowski SR. Transfusion therapy in paediatric trauma patients: A review of the literature. Scand J Trauma Resusc Emerg Med 2015;23:21.  Back to cited text no. 11
    
12.
Hillyer CD, Shaz BH, Zimring JC, Abshire TC. Transfusion Medicine and Hemostasis. Burlington: Elsevier; 2009.  Back to cited text no. 12
    
13.
Cappellini MD, Cohen A, Porter J, Taher A, Viprakasit V. Guidelines for the management of transfusion dependent thalassaemia (TDT). Cyprus: Thalassaemia International Federation; 2014.  Back to cited text no. 13
    
14.
Hossain MS, Raheem E, Sultana TA, Ferdous S, Nahar N, Islam S, et al. Thalassemias in South Asia: Clinical lessons learnt from Bangladesh. Orphanet J Rare Dis 2017;12:93.  Back to cited text no. 14
    
15.
Fucharoen S, Weatherall DJ. The hemoglobin E thalassemias. Cold Spring Harb Perspect Med 2012;2. pii: a011734.  Back to cited text no. 15
    
16.
Mazzone A, Vezzoli M, Ottini E. Masked deficit of B(12) and folic acid in thalassemia. Am J Hematol 2001;67:274.  Back to cited text no. 16
    
17.
Sharifi Z, Milani S, Shooshtari MM. Study on efficacy of hepatitis B immunization in vaccinated beta-thalassemia children in Tehran. Iran J Pediatr 2010;20:211-5.  Back to cited text no. 17
    
18.
Nevitt SJ, Jones AP, Howard J. Hydroxyurea (hydroxycarbamide) for sickle cell disease. Cochrane Database Syst Rev 2017;4:CD002202.  Back to cited text no. 18
    
19.
New York State Council on Human Blood and Transfusion Services. Guidelines for transfusion of Pediatric Patients. New York: New York State Department of Health; 2016.  Back to cited text no. 19
    




 

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  In this article
Abstract
Introduction
Fetal Red Cell T...
Fetal/neonatal P...
Neonatal Red Cel...
Exchange Transfu...
Neonatal Platele...
Pediatric Red Ce...
Pediatric Surgeries
Management of Pe...
Transfusion in C...
Disorders of Hem...
Management of Di...
Transfusion in T...
Transfusion in S...
Complications of...
References

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