Transfusion of Blood Components in Paediatric Age Groups

➡️Introduction

Pediatric transfusion is a complex area of medicine covering a wide age range from intrauterine life to young adults. The prescriber must balance the risks and benefits of transfusion in each age group and be aware of the indications for special components.

Compared to adult practice, there is a relative lack of high-quality research to inform evidence-based guidelines.

The aim of this adapted clinical practice guideline (CPG) is to provide evidence-based recommendations for the transfusion of blood components in the paediatric age group.

➡️Scope

This guideline focuses on any disease or condition requiring red blood cells, platelets, and/or plasma products transfusion(s) to prevent or control anaemia, bleeding, and thrombotic disorders. It Provides an evidence-based document for the appropriate use of blood components, define indications, dosing, and administration of different blood components.

It also covers safe transfusion practice including pre-transfusion testing, handling of blood components, and close monitoring of transfused patients and includes recommendations in special situations (multi-transfused subjects, massive transfusion, and the critically ill).

 

➡️Guideline development process and methods

After reviewing all the inclusion and exclusion criteria and quality appraisal results, the GDG/ GAG recommended using the following source original clinical practice guidelines (CPGs):

1. Guideline on the investigation and management of acute transfusion reactions Prepared by the BCSH Blood Transfusion Task Force. BSH 2012¹

2.  Guidelines on red cell transfusion in sickle cell disease. BSH 2016a^2,3

3.  Guidelines for the use of platelet transfusions. BSH 2016b⁴

4.  Recommendations on Red Blood Cell Transfusion in General Critically Ill Children Based on Heamoglobin and/or Physiologic Thresholds from the Paediatric Critical Care Transfusion and Anaemia Expertise Initiative. TAXI 2018⁵

5.  Clinical practice guidelines use of blood components in newborn. NNF 2020.⁶

6. Guidelines on the use of irradiated blood components. BSH 2020a⁷

7.  Guidelines on Transfusion for Fetuses, Neonates and Older Children. BSH 2016 - addendum 2020b^8,9

8. British Society of Haematology Guidelines on the spectrum of fresh frozen plasma and cryoprecipitate products: their handling and use in various patient groups in the absence of major bleeding. BSH 2018 – addendum 2020^10,11

We conducted Adolopment for these guidelines: (Adoption, Adaptation, and Development)

         -   Adoption for most of the guideline recommendations.

         -    Development of Good Practice Statements

Recommendations and Good Practice Statements (GPS)

This version of the CPG includes recommendations and good practice statements on the following four sub-sections:

A. Transfusion guidelines in the different age groups:

The guideline covers transfusion guidelines for the different blood products in neonates as well as in infants and children.

This guideline emphasis on indications, dosing, and mode of transfusion.

 

B. Recommendation on blood product irradiation:

This section includes recommendations and good practice statements on when and how to irradiate blood products according to different clinical situations.

C. Identification and management of transfusion reactions:

This section handles the diagnosis and lines of management in case of blood product reactions.

We can summarize the guidelines’ recommendations for Transfusion of Blood Components in Pediatric Age Groups in the following:

Transfusion in neonates:

▪️  Decision of transfusion is based on the clinical status. For those not requiring cardiopulmonary support or oxygen supply and condition is stable, packed RBCs transfusion is not usually required unless Hb level is below 7g/dl (GPS).         

▪️ For non-bleeding neonates, platelet transfusions should not be routinely administered if platelet count is ≥ 25 × 109/l (High LOE, Strong recommendation).         

▪️ In neonatal alloimmune thrombocytopenia (FNAIT), maintaining platelet count > 30 x109/l is strongly recommended (High LOE, Weak recommendation).       

▪️ FFP may be of benefit in neonates with clinically significant bleeding or prior to invasive procedures with a risk of significant bleeding, and who have an abnormal coagulation profile (Intermediate LOE, weak recommendation).    

▪️ FFP should be used for the management of severe hereditary protein S deficiency (Intermediate LOE, Strong recommendation).        

▪️FFP transfusion is preferred over cryoprecipitate in the management of disseminated intravascular coagulation (Intermediate LOE, weak recommendation).         

▪️ Prophylactic FFP is not recommended in non-bleeding neonates receiving therapeutic hypothermia and having deranged coagulation parameters (High LOE, Strong recommendation).    

Transfusion in infants, children, and adolescents

▪️  In children with oncologic diagnoses, those who are critically ill or at risk for critical illness, and hemodynamically stable, a Hb concentration of 7– 8 g/dl is suggested as a threshold for RBC transfusion (Intermediate LOE, weak recommendation).         

▪️   A perioperative Hb transfusion threshold of 7 g/dl should be used in stable patients without major co-morbidity or bleeding (High LOE, weak recommendation).         

▪️  Patients with chronic anaemia due to red cell aplasia may require an Hb threshold of 8 g/dl (Intermediate LOE, weak recommendation).

▪️  Transfusion is recommended and may be lifesaving in acute sickle complications such as splenic sequestration, hepatic sequestration, aplastic crisis and severe acute chest syndrome (High LOE, strong recommendation). Transfusion is not recommended in uncomplicated painful crises (High LOE, weak recommendation).

▪️   In severe bleeding, maintain the platelet count above 50 ×109 /l (High LOE, weak recommendation).         

▪️ In patients with multiple traumas, traumatic brain injury or spontaneous intracerebral hemorrhage, maintain the platelet count above 100 ×109 /l (Intermediate LOE, weak recommendation).

▪️ In patients with bleeding that is not considered severe or life-threatening, consider platelet transfusion if the platelet count is below 30 ×109 /l (Intermediate LOE, weak recommendation).    

▪️ In post-transfusion purpura (PTP), intravenous immunoglobulin is the treatment of choice (High LOE, weak recommendation).

▪️  Only use platelet transfusion prior to a procedure or surgery when other treatment has failed and/or the intervention is urgent. Usual threshold counts may be unachievable or unnecessary and individual case review is required (High LOE, weak recommendation),

▪️ In Glanzmann thrombasthenia, consider human leucocyte antigen (HLA)-matched platelets (Intermediate LOE, weak recommendation) where available (GPS) (Intermediate LOE, weak recommendation).      

▪️ Use general haemostatic measures to treat bleeding in patients during treatment with aspirin, P2Y12 antagonists or glycoprotein IIa/IIIb inhibitors. If necessary, consider drug cessation and reversal of the effect of co-prescribed anticoagulants (Intermediate LOE, weak recommendation).

▪️  Use TXA to counteract the effect of anti-platelet agents when a risk/benefit assessment would support this (High LOE, strong recommendation).

▪️ Do not use prophylactic platelet transfusions in patients with autoimmune thrombocytopenia (High LOE, weak recommendation).

▪️ Use a ‘no prophylactic platelet transfusion’ strategy for asymptomatic patients with chronic bone marrow failure (Intermediate LOE, Strong recommendation).    

▪️ Do not give platelet transfusions routinely prior to minor procedures e.g. bone marrow aspirate or trephine biopsy, peripherally inserted central catheters (PICCs), traction removal of tunneled CVCs, cataract surgery (High LOE, weak recommendation).

▪️  Pathogen-reduced plasma may be used for factor replacement in congenital coagulation factor deficiency If virally inactivated specific clotting factors are not available (High LOE, weak recommendation).  

▪️ FFP may be beneficial in children with DIC who have a significant coagulopathy (PT/APTT >1.5 times midpoint of normal range or fibrinogen <1.0 g/l) associated with clinically significant bleeding or prior to invasive procedures (Intermediate LOE, weak recommendation).   

▪️Prophylactic FFP should not be administered to non-bleeding children with minor prolongation of the prothrombin time (Intermediate LOE, Strong recommendation)/ activated partial thromboplastin time or decreased fibrinogen including prior to surgery, although it may be considered for surgery to critical sites (Intermediate LOE, weak recommendation).

▪️ FFP should not be used in the management of inherited factor deficiencies other than in a few exceptional circumstances where specific factor concentrates are not available (High LOE, weak recommendation).        

▪️Urgent plasma exchange with solvent detergent fresh frozen plasma (SD FFP) is indicated for thrombotic thrombocytopenic purpura (TTP) (High LOE, strong recommendation) and some forms of atypical hemolytic uremic sundrome (HUS) (Intermediate LOE, weak recommendation).

➡️Modification of blood components and related Precautions

▪️  Gamma- or X-irradiation of blood components, is the recommended procedure to prevent TA-GvHD (High LOE, strong recommendation).

▪️  Red cells for neonatal exchange blood transfusion (EBT) should be irradiated (High LOE, weak recommendation).      

▪️  Routine irradiation of red cells for transfusion to preterm or term infants (other than for EBT) is not required unless there has been a previous intrauterine transfusion (IUT) (Intermediate LOE, weak recommendation).

▪️  All transfusions of cellular components and fresh plasma from first- or second-degree relatives should be irradiated, even if the patient is immunocompetent. All HLA-selected components should be irradiated even if the patient is immunocompetent (High LOE, strong recommendation).

▪️  All severe congenital T-lymphocyte immunodeficiency syndromes with significant qualitative or quantitative T-lymphocyte deficiency should be considered as indications for irradiation of cellular blood components (High LOE, strong recommendation).          

▪️  There is no indication for irradiation of cellular blood components for infants or children with temporary defects of T-lymphocyte function as the result of a viral infection. There is also no indication for irradiation of cellular blood components for adults or children who are HIV-antibody positive or who have acquired immune deficiency syndrome (AIDS) (High LOE, strong recommendation).    

▪️   All recipients of allogeneic HSCT should receive irradiated blood components from the time of initiation of conditioning chemo/ radiotherapy (High LOE, strong recommendation).

▪️ All patients undergoing autologous stem cell transplant (ASCT) irrespective of underlying diagnosis or indication for this treatment should receive irradiated cellular blood components from initiation of conditioning chemo/radiotherapy until 3 months post-transplant (High LOE, weak recommendation).   

▪️For patients with aplastic anaemia, transfusion of irradiated cellular components is not routinely recommended (High LOE, strong recommendation).  

▪️  All adults and children with Hodgkin Lymphoma at any stage of the disease should have irradiated red cells and platelets indefinitely (Intermediate LOE, weak recommendation).

▪️  All patients treated with purine analogue drugs (fludarabine, cladribine, bendamustine and pentostatin) , should receive irradiated blood components indefinitely (Intermediate LOE, weak recommendation).         

▪️ Treatment of patients with rituximab is not an indication for use of irradiated cellular blood components  (High LOE, strong recommendation).

▪️  Use of irradiated cellular blood components is not indicated for patients undergoing solid organ transplantation (SOT) (High LOE, strong recommendation).         

▪️ For patients with recurrent febrile reactions, it is recommended to use a trial of premedication with oral paracetamol given one hour before the reaction is anticipated. Patients who continue to react should have a trial of washed blood components (Intermediate LOE, weak recommendation).

▪️  Provision of CMV safe blood for transfusion in preterm neonates by using CMV seronegative donors or leukoreduction or a combination of both is strongly recommended (High LOE, weak recommendation).     

▪️ For intrauterine transfusions use of CMV negative and leuco-depleted packed red blood cell is strongly recommended (High LOE, weak recommendation).

➡️Guideline Registration

PREPARE (Practice guideline REgistration for transPAREncy), WHO Collaborating Center for Guideline Implementation and Knowledge Translation, EBM Center, University of Lanzhou, Lanzhou, China. Registration Number: (PREPARE-2022CN444). Link: http://www.guidelines-registry.org/