CONCEPT OF BLOOD COMPONENT THERAPY & PEDIATRIC TRANSFUSION PRACTICES
Dr. Bharat Agarwal *
Consultant Pediatric Hematologist-Oncologist Head, Dept. of Pediatric Hematology-Oncology, B.J.Wadia Hospital for Children, Parel, Mumbai 400012, India *
Blood component therapy refers to the transfusion of the specific part of blood that the patient needs, as opposed to the routine transfusion of Whole Blood. This not only conserves blood resources, since one donated unit can benefit several patients, but also provides the optimal method of transfusing patients who require large amounts of a specific blood component.

During manufacture, the entire blood bag and any integrally attached satellite bags and needles are sterilized. As the entire blood collection system is sterile, disposable and never reused, it is IMPOSSIBLE for a donor to contact hepatitis, AIDS or other transfusion-transmitted diseases by donating blood. The blood collection set is considered to be a closed system, being open only at the tip of the needle used for donor phlebotomy. Once the administration ports of a blood bag are opened, however, the unit is considered to be an open system. According to the AABB standards for Blood Banks and Transfusion Services 1, any blood component prepared in an open system and stored at 4 C has a maximum shelf life of 24 hours because of the risk of bacterial contamination. To prepare components (see Table 1) that have the maximum permitted shelf life, integral satellite bags must be used to ensure maintenance of the closed system. Alternatively, sterile connecting devices are available; these devices permit sterile attachment of separate plastic bags.
Whole Blood
Description of Components:
A unit of Whole Blood contains approximately 450 ml of blood and 63 ml of anticoagulant/ preservative. The hematocrit of a typical unit ranges from 0.36-0.44 (36-44%). Whole Blood is stored in a carefully monitored refrigerator at 1-6 C. The shelf life of Whole Blood is dictated by the percent recovery of the transfused red cells 24 hours after infusion. This value must average> 75%. For this reason, the shelf life of Whole Blood depends on the preservative used in the blood collection bag [the shelf life of CPD (citrate-phosphate-dextrose) blood is 21 days; that of CPD-adenine (CPDA-1) is 35 days]. See Table 2.2, 3-diphosphoglycerate (2,3-DPG), a molecule that facilities the release of oxygen from hemoglobin, decreases during storage and is regenerated after infusion of the blood. (1)

There is little scientific justification for use of "fresh" Whole Blood (i.e., blood collected within the previous 24 hours). Blood less than 24 hours old is rarely available, because of the time required to perform post donation ABO and Rh typing, to screen for the presence of atypical antibodies and to complete required infectious diseases testing. Whole Blood less than 7 days old may be desirable for neonatal exchange transfusions.

Another component, Whole Blood, Modified, is prepared by returning the plasma to the red blood cells after removal of platelets and/or cryoprecipitate.

Indications:
Whole Blood provides both oxygen-carrying capacity and blood volume expansion. The primary indication is for treating patients who are actively bleeding and who have sustained a loss of greater than 25% of their total blood volume. Such a patient may develop hemorrhagic shock. Unless a patient who receives Whole Blood needs volume replacement in addition to oxygen carrying capacity, fluid overloads may occur, especially if rapid infusion is attempted.

Whole Blood stored over 24 hours contains few viable platelets or granulocytes. In addition, levels of Factor V and Factor VIII decrease with storage. To supply platelets or granulocytes, the appropriate cellular components should be used. Fresh Frozen Plasma (FFP) should be given to replace needed labile clotting factors. Levels of stable clotting factors, however, are well maintained in units of Whole Blood.

Contraindications and Precautions:
Whole Blood should not given to patients with chronic anemia who are normovolemic and require only an increase in red cell mass; Red Blood Cells (RBCs) should be used for such patients. Hemolytic transfusion reaction are always a risk with blood transfusion. Transmission of viral infections, such as hepatitis viruses, human immunodeficiency virus (HIV) and cytomegalovirus (CMV), as well as allergic and febrile transfusion reaction are complications that should be considered whenever blood is transfused. (2),(3)

Dose and Administration:
In an adult, one unit of Whole Blood will increase the hemoglobin by about 10 g/L (1g/dL) or the hematocrit by about 0.03-0.04 (3.4%). In pediatric patients, a Whole Blood transfusion of 8 ml/kg will result in an increase in hemoglobin of approximately 10 g/dl). Whole Blood must be administered through a blood filter. The rate of infusion depends on the clinical condition of the patient, but each unit or aliquot should be infused within 4 hours.
Red Blood Cells
Description of Components:
RBCs are prepared from Whole Blood by the removal of 200-250 ml of plasma. They are stored at 1-6 C in a variety of different anticoagulant/preservative solutions. These solutions have varying amounts and/or types of preservative agents (e.g., buffer, dextrose, adenine and mannitol). The resultant RBCs stored in additive solutions (AS) have hematocrits of 0.52-0.60 (52-60%) and a shelf life of 42 days, while RBCs stored in CPDA-1 have hematocrits of 0.70-0.80 (70-80%) and can be stored for 35 days. (1) (4) (5) Storage of RBCs in CPD or CP2D results in hematocrits similar to that of RBCs stored in CPDA-1, but a shelf life of 21 days. Stored RBCs do not contain functional platelets or granulocytes. RBCs and Whole Blood have the same oxygen-carrying capacity because they both contain the same number of red cells.

Indications:
RBCs are indicated for treatment of anemia in normovolemic patients who require only an increase in oxygen-carrying capacity and red blood cell mass. These include patients with chronic anemia due to diseases such as renal failure or malignancy. The transfusion requirements of each patient should be based on clinical status rather than on any predetermined hematocrit or hemoglobin value. A volume of 500 mL of RBCs (2 units) provides twice the increment in hematocrit, as does infusion of an equal volume of Whole Blood. Whole Blood contains 200-250 ml of plasma, which provides an unnecessary volume load to patients who do not require or cannot tolerate excessive volume expansion, such as anemia patients with cardiac failure (especially the very young and the elderly).

Contraindications and Precautions:
Risks associated with RBC infusion are the same as those encountered with Whole Blood, (2) (3) Hypervolemia can also occur with infusion of excessive amounts of RBCs.

Dose and Administration:
RBCs must be transfused through a filter. The higher hematocrit of CPD or CPDA-1 RBCs results in increased viscosity, which may slow the transfusion rate. Fifty to 100 ml of isotonic sodium chloride (0.9% USP) may be used to dilute the CPD or CPDA-1 RBCs to decrease viscosity, but this practice must be balanced against the risk of hypervolemia. The lower hematocrit of the AS RBC units permits more rapid infusion rates. For patients at risk of circulatory overload or for pediatric patients, concern over the additional volume due to the 100 ml of additive solution may warrant concentrating the component by centrifugation or sedimentation. No solutions, other than isotonic saline, and no medications should be added to RBCs.
Washed Red Blood Cells
Description of Component:
RBCs may be washed with sterile saline using machines specially designed for this purpose. The Washed RBCs are suspended in sterile saline, usually at hematocrits of 0.70-0.80 (70-80%) with a volume of approximately 180 ml. Saline washing removes all but traces of plasma (98%), reduces the concentration of leukocytes and removes platelets and cellular debris. Saline washing may be performed at any time during the shelf life of a unit of blood, but since washing is ordinarily performed in an "open" system, the resultant red cell component can be stored for only 24 hours at 1-6 C.

Indications:
The sole indication for Washed RBCs in adults is for transfusion to patients who have had recurrent or severe allergic reactions in whom it may be important to minimize the amount of plasma proteins infused. They may also be used in neonatal or intrauterine transfusion. Until the development of efficient leukocyte-reduction filters, Washed RBCs were frequently ordered to provide "leukocyte-reduced" RBCs, (6) however, using Washed RBCs for this purpose alone is no longer justifiable.

Contraindications and Precautions:
The use of an open-system washing technique limits the shelf life of Washed RBCs to 24 hours following preparation because of the risk of bacterial contamination. (7) Otherwise, the transfusion hazards associated with washed cells are similar to those of packed RBCs. Washed RBCs are capable of transmitting following preparation because of the risk of bacterial contamination. (7) Otherwise, the transfusion hazards associated with washed cells are similar to those of packed RBCs. Washed RBCs are capable of transmitting hepatitis (8) and other infectious disease. As they contain viable leukocytes, Washed RBCs will not prevent graft-vs-host disease (GVHD) or cytomegalovirus infection.

Dost and Administration:
All units must be infused through a blood filter. Use of Washed RBCs provides a smaller red cell mass to the patient because of the loss of some red blood cells during the washing procedure. Thus, patients who are chronically transfused with Washed RBCs may require additional transfusions to achieve an appropriate hematocrit.
Platelets
Description of Components:
Platelets are prepared from individual units of Whole Blood by centrifugation. Each bag should contain at least 5.5 x 10 platelets in sufficient plasma to maintain a pH of greater than 6.0 throughout the storage period (usually 50-70 ml). Platelet concentrates, which are stored in the blood bank for up to 5 days at 20-24 C with constant, gentle agitation, have nearly normal post-transfusion recovery and survival.(9) Alternatively, they may be stored for 48 hours at 1-6 C. They are frequently pooled prior to use.

Indications:
Platelets are indicated for treatment of bleeding due to thrombocytopenia [usually below 50 x 109/L (50,000/µL)] or to the presence of functionally abnormal platelets (thrombocytopathy). (10) Prophylactic transfusion of platelets may be indicated for patients with platelet counts below 15-20 x 109/L (15-20,000/µL) associated with bone marrow hypoplasia due to chemotherapy, tumor invasion or primary aplasia. This number may be safety lowered for some patients. (11) There is no evidence that prophylactic transfusion of platelets is beneficial in massive transfusion (12) or in cardiac surgery. (13)

Contraindications and Precautions:
Platelets transfusion is usually not effective in patients with rapid platelet destruction. These conditions include idiopathic autoimmune thrombocytopenic purpura (ITP), thrombotic thrombocytopenic purpura (TTP) and untreated disseminated intravascular coagulation (DIC). In such patients, platelet transfusion should employed only in the presence of active bleeding and with careful clinical monitoring. Patients with thrombocytopenia due to septicemia or hypersplenism also may fail to benefit from platelet transfusions.
Chills, fever and allergic reactions may occur. Fever should not be treated with antipyretics containing aspirin, as aspirin will inhibit platelet function. Repeated transfusions may lead to alloimmunization to HLA and other antigens and result in the development of a "refractory" state manifested by unresponsiveness to platelet transfusion (see section on Alloimmunization). Due to small amounts of red blood cells in the concentrate, Rh-negative women of childbearing potential, prevention of Rh immunization by the use of Rh immune globulin should be considered. Because of the plasma contain in Platelets, ABO-incompatible Platelets may cause a positive direct antiglobulin test (DAT) and, very rarely, hemolysis. (14) transfusion-transmitted infectious diseases are similar to those with RBCs. Bacterial contamination of Platelets is of special concern because this component is stored at room temperature.

Dose and Administration:
The usual dose for a thrombocytopenic, bleeding adult is 6-10 units of Platelets; for children, it is about 1 unit/10 kg body weight. One unit of Platelets usually increases the platelet count in a 70-kg adult by 5 x 109/L. Repeated failure to achieve hemostasis or the expected increment in platelet count may signify the refractory state. (10) (15) Platelet refractoriness may be associated with antibodies to HLA and other platelet antigen, splenomegaly, DIC. Sepsis, bone marrow transplantation and massive transfusion. The emergence of antibody-mediated platelet destruction is suspected on the basis of the poor clinical response to platelet transfusion and may be supported by calculating the post-transfusion platelet count increment (CI):


(Post-tx plt ct) - (Pre-tx plt ct
CI = ----------------------------------------------------- x BSA
(Platelets transfused x 10 11)
where   Pre-tx plt ct = pretransfusion platelet count
Post-tx plt ct= posttransfusion platelet count
BSA = body surface area in square meters

A CI of> 7.5-10 x 10(9)/L from a sample drawn 10 minutes to 1 hour posttransfusion, or a CI of> 4.5 x 10(9)/L from a sample 18-24 hours posttransfusion are considered acceptable, i.e., not indicative of refractoriness. (16) (17) Ideally, posttransfusion counts are obtained both within 1 hour and after 18 hours: however, the early CI is more informative regarding the presence of platelet antibodies and the refractory state. The 1-hour CI is diminished primarily by antiplatelet antibodies and by splenomegaly, but the 18 to 24 hour CI is also diminished by fever, infection, sepsis, DIC, storage time and other factors. (18) (19) Patients who repeatedly have poor clinical or 1-hour CI responses are said to be refractory to platelet transfusion. Patients who are refractory due to the emergence of antiplatelet alloantibodies are said to be alloimmunized, and usually require HLA-matched platelets (see section on alloimmunization). Platelets must be administered through a filter and pretransfusion red blood cell compatibility testing is not necessary. Concentrates may be pooled before administration or infused individually. Platelets should be transfused within 4 hours after they are pooled. Irradiation of platelets may be indicated to prevent GVHD in immunosuppressed or selected immunodeficient patients.

Platelets, Pheresis
Description of Components:
Platelets, Pheresis are collected from an individual donor during a 2 to 3-hour cytapheresis procedure, and contain more than 3 x 10 (11) platelets. (20) This is equal to 6-8 units of platelets. The volume of plasma in the product varies from 200-400 ml. The number of leukocytes and red blood cells varies with the apheresis technique. Units of Platelets, Pheresis collected by recently developed techniques may be considered leukocyte-reduced.

Indications:
Platelets, Pheresis that have been HLA-matched with the recipient are indicted for patients who are unresponsive to random donor platelets because of HLA alloimmunization. Non HLA-matched platelets, Pheresis are also used in patients who are not refractory, in order to limit exposure to multiple donors. Controversy exists as to whether the use of this component rather than platelets reduces the frequency of alloimmunization in patients requiring long-term transfusion support. In addition, there is no scientific evidence to suggest an advantage in using non-HLA-matched Platelets, Pheresis in patients who are already alloimmunized and/or refractory unless the platelets are cross match-compatible. Neither is it advantageous to use HLA matched Platelets, Pheresis in patients whose refractory state is not due to alloimmunization. (21) In such patients, HLA-MATCHED platelets, Pheresis would not survive longer in vivo than would the random-donor platelets. Physicians treating patients who are refractory to Platelets should consult with the transfusion service director to determine the best therapeutic alternatives (see section on Alloimmunization).

Contraindications and Precautions:
Side effects and hazards are similar to those for platelets.

Dose and Administration:
One unit of Platelets, Pheresis will usually increase the platelet count of a 70-kg adult by 30-60 x 10 (9)/L (30-60,000/µL). See above for discussion of CI. Red blood cell compatibility testing must be performed if the component contains a significant number of red blood cells (>5 ml). Preferably, the donor's plasma should be ABO compatible with the recipient's red blood cells if they are not group-specific. Administration is similar to that for Platelets.
Fresh Frozen Plasma
Description of Components:
Plasma is composed primarily of water, with about 7% protein and 2% carbohydrates and lipids. FFP is prepared from Whole Blood by separating and freezing the plasma within 8 hours of phlebotomy. It may be stored for up to 1-year at 18 C or lower. The volume of a typical unit is 200-250 ml. Under these conditions, loss of Factors V and VIII, the labile clotting factors, is minimal. FFP is used primarily to provide replacement coagulation factors (Table 3). 1 ml of FFP contains approximately one unit of coagulation factor activity.

Indications:
FFP is indicated for use in bleeding patients with multiple coagulation factor deficiencies secondary to liver disease, DIC and the dilutional coagulopathy resulting from massive blood or volume replacement. (51) In general the prothrombin time (PT) or partial thromboplastin time (PTT) ratio (test value/control value) should be at least 1.5 before FFP is used. It is also indicated for patients with congenital factor deficiencies for which there is no coagulation concentrate available, such as deficiencies of Factor V or XI. In the past, FFP was also used for patients with mild congenital and acquired factor deficiencies, including mild hemophilia B (Factor IX deficiency), to reduce the risk of hepatitis with the commercial concentrates than available. However, in recent years the risk of hepatitis associated with commercially available concentrates has been reduced or eliminated by one of several virucidal techniques. (23) FFP is also used along with plasmapheresis in the treatment of TTP and hemolytic uremic syndrome.

Contraindications and Precautions:
FFP should be used merely to provide blood volume expansion, as this exposes patients unnecessarily to the risk of hepatitis and other transfusion-transmitted diseases. Albumin, plasma protein fraction (PPF) or other colloid or crystalloid solutions that do not transmit infection are safer products to use for blood volume expansion. Similarly, FFP should not be used as a source of protein for nutritionally deficient patients. Because clotting factors are present in FFP in approximately normal concentrations of about 1 unit/ml, the posttransfusion increment in coagulations levels is limited, in part, by the patient's to tolerate the infused volume of plasma without developing fluid overload. Accordingly, treatment of severe coagulopathies with FFP is often difficult, and patients with severe coagulation factor deficiencies may need to receive more concentrated preparations if they are available (24) In general, FFP has a risk of infectious disease transmission equal to that of Whole Blood. However, FFP does not transmit certain viruses that are transmitted exclusively through leukocytes, e.g., CMV and human lymphotropic virus type I (HTLV-I). Allergic reactions and transfusion-associated lung injury (TRALI, also referred to as noncardiogenic pulmonary edema) can occur with FFP infusion. (24) (25) A solvent/detergent form of pooled FFP that will reportedly not transmit HIV or hepatitis is currently undergoing trials of safety and efficacy. (26)

Dose and Administration:


The dose of FFP depends on the clinical situation and underlying disease process. Posttransfusion assessment of the patient's coagulation status is important, and monitoring of coagulation function with a PT, PTT or specific factor assays is critical. As with all blood components, FFP must be given through a filter. FFP is thawed at 30-37 C and should be transfused as soon as possible, but it must be transfused within 24 hours if being used as a source of labile coagulation factors. After thawing, storage is at 1-6 C. Compatibility testing is not required but ABO-compatible FFP should be used.
Cryoprecipitated Antihemophilic Factor
Description of Components:
Cryoprecipitated antihemophilic factor (AGF) us a concentrated source of certain plasma proteins. It is prepared by thawing one unit of FFP between 1 and 6 C. After thawing, a white precipitate forms; this is the cryoprecipitate. The supernatant plasma is removed, leaving the cold precipitated protein plus 10-15 ml of plasma in the bag. This material is then refrozen at-18 C or lower within 1 hour and has a shelf life of 1 year. Cryoprecipitate contains concentrated Factor VIII:C (the procoagulant activity), Factor VIII:vWF(von Willebrand factor), fibrinogen and Factor XIII. Each bag of Cryoprecipitated AHF contains approximately 80-120 units of Factor VIII:C, about 250 mg of fibrinogen and about 20-30% of the Factor XIII present in the initial unit. (27) (28) Approximately 40-70% of the vWF present in the initial unit of FFP is recovered in the Cryoprecipitated AHF.

Fibrinogen concentrates are no longer available because of the extremely high incidence of hepatitis associated with fibrinogen prepared from pools of human plasma. Currently, the main source of concentrated fibrinogen is Cryoprecipitated AHF.


Indications:
Cryoprecipitate may be indicted for the treatment of hemophilia A, von Willebrand's disease, congenital or acquired fibrinogen deficiency, Factor XIII deficiency and obstetric complications or other situations associated with consumption of fibrinogen, e.g., DIC. For all forms of von Willebrand's disease, except Type IIB, desmopressin (DDAVP) should be given first as treatment. It has also been reported to be beneficial in treating the bleeding tendency associated with uremia (29); however, as with von Willebrand's disease, the use of desmopressin should be considered as initial therapy, since it is free of the potential infectious complications of cryoprecipitate. (30) Small amounts of cryoprecipitate (sometimes autologous) are also used as fibrinogen source and mixed with thrombin to prepare "fibrin glue" to aid in surgical hemostasis and for other purposes. (31)

Contraindications and Precautions:
Cryoprecipitated AHF should not be used to treat patients with deficiencies of factors other than Factor VIII, fibrinogen, vWF or Factor XIII. ABO-compatible cryoprecipitate should be used whenever possible as small amounts of anti-A and anti-B alloagglutinins are present. In rare instances, infusion of large amounts of ABO-incompatible units of cryoprecipitate can cause hemolysis; a positive DAT can be seen with infusion of smaller doses. The risk of infectious disease transmission, for each unit Cryoprecipitated AHF given, is the same as that for FFP. When large amounts of Cryoprecipitated AHF are used, the patients' fibrinogen level may become markedly elevated and should be monitored, as hyperfibrinogenemia can be associated with an increased risk of thromboembolism.

Dose and Administration:
Prior to infusion, Cryoprecipitated AHF is thawed at 30-37 C. If the cryoprecipitate is pooled, the inside of the bags should be rinsed with a small amount of saline to maximize recovery of Factor VIII. Concentrates are administered through a standard blood filter; no compatibility test is required. If the thawed cryoprecipitate is not used immediately, it may be stored for no more than 6 hours if it is being used as a source of Factor VIII:C or for 4 hours after pooling. For calculation of the dose of Cryoprecipitated AHF.
Pediatric Transfusion Practices
Transfusion in Neonatal Patients:
As the survival of more immature infants has improved, the number of RBC transfusions given in neonatal intensive care units has increased. There are two types of anemia that develop in premature infants. The first occurs early as a result of the multiple blood sampling that is needed for laboratory monitoring of critically ill premature infants whose total blood volume is very small. The second develops a few weeks after birth and is a physiologic decline in hemoglobin concentration (anemia of prematurity) as result of multiple factors, the primary being inadequate production of erythropoietin a response to the degree of anemia. (32) Recombinant EPO is being evaluated for use in the treatment of anemia of prematurity and preliminary studies look promising. (33)

The indications for transfusion in the neonate vary from those in the adult as a result of the infant's physiologic immaturity, small blood volume and inability to tolerate minimal stress. The decision to transfuse is usually based on multiple parameters including calculated blood loss (generally 10% of total blood volume)over a given time period, expected hemoglobin levels and clinical status (dyspnea, apnea, respiratory distress, poor weight gain). There are conflicting data, however, on the usefulness of clinical signs (tachycardia, tachypnea, apnea, etc) in an assessment of the need for RBC transfusions in the premature infants. (32) The transfusion of 10 ml/kg of RBCs over a 2- to 3-hour period should raise the hemoglobin concentration by approximately 30 g/l (3 g/dl).

Neonatal transfusion practices vary greatly. (34) The use of unmodified RBCs is the main type of red cell component used by transfusion services to provide small-volume transfusions for neonatal patients. These transfusion are generally an aliquot from blood units (with the most frequent storage media being CPDA-1) less than 7 days old in order to minimize excess potassium and maximize RBC 2,3-DPG levels. However, it has been estimated that the amount of potassium or metabolic toxin that would be infused in a small-volume transfusion, even from units stored for up to 42 days, would be minimal and unlikely to be clinically significant. (35), (36) Several methods have been developed not only to provide small-volume transfusions with minimal blood wastage, but also to limit donor exposure. (36), (37) These may involve extending the storage period of RBCs for neonatal transfusion. Washed, deglycerolized and leukocyte-reduced (by filtration) red cell components are also used for small-volume neonatal transfusions, but much less frequently than unmodified RBCs. (34)

Infants less than 4 months old rarely produce antibodies against blood group antigens; therefore, standards for pretransfusion serologic testing for these patients are different than those for older infants, children and adults. (7) Prior to any neonatal transfusion, an ABO group. Rh type and antibody screen must be performed. Maternal serum can be used for the latter, since IgG blood group antibodies are passively transferred from mother to infant during gestation. If the initial antibody screen is negative and the RBCs used for transfusion are either group O or ABO identical or compatible with both the mother and child and either the same Rh type as the infant or Rh-, then further typing and compatibility testing can be omitted during the first 4 months of life. If a clinically significant antibody is present, then RBC that do not contain the corresponding antigen should be prepared for transfusion for as long as the antibody persists in the infant's serum. Procedures must be in place to ensure that infant's serum. Procedures must be in place to ensure that infants do not receive transfusion of any blood component that contains a clinically significant unexpected antibody.

In contrast to the large numbers of RBC transfusions given to neonates, relatively few other blood components are transfused. (38) It has been shown that, in general, the primary use of FFP is in the treatment of coagulation disorders. Its use for the sole purpose of treating hypovolemia or to adjust hematocrit values of red cell concentrates for transfusion is not recommended. Platelet transfusion practices have also been shown to be variable, with the most controversial issue being the platelet level at which prophylactic transfusion should be given to sick premature infants. (39) The efficacy of granulocyte transfusions in the septic and neutropenic neonates is still not fully established. (4)

Transfusion in OLDER infants and Children:
The decision to transfuse RBCs or other blood components to older infants and children is based on indications similar to those used for adults, taking into consideration the differences in blood volume, ability to tolerate blood loss and the normal hemoglobin and hematocrit levels for the appropriate age group. In certain chronic anemias' of childhood, there are clinical settings in which RBC transfusions are required to suppress endogenous hemoglobin production. Children with sickle cell anemia who have suffered a cerebrovascular accident or major splenic sequestration and are not candidates for splenectomy may require a chronic RBC transfusion program in order to suppress the production of hemoglobin S. Children with thalassemia Syndromes are given routine RBC transfusions to prevent tissue hypoxia and suppress endogenous erythropoiesis in order to support more normal growth and development. (41)

CMV-Negative Blood:
Premature infants who are born to mothers who are CMV antibody negative or of unknown serologic status and who weight less than 1200g at birth may be at increased risk for morbidity and mortality from transfusion-transmitted CMV. Accordingly, for these or other high risk patients, it is prudent to provide for transfusion cellular blood components that have been selected or processed to reduce the risk of CMV transmission. (42)

Irradiated Blood:
Posttransfusion graft-vs-host disease has been reported in pediatric patients with congenital immunodeficiency associated with severe cellular immune defects, in infants following intrauterine transfusion with or without subsequent exchange transfusion, and in children who are immunosuppressed as a result of chemotherapy or irradiation for various malignancies. Gamma irradiation of cellular blood components is effective in preventing GVHD in patients who are at high risk for developing this complication. (43)

Administration of Blood:
Necessary steps in preparation for blood transfusion are the proper identification of the patient and the proper labeling of the blood sample. After blood collection, the identification systems within and outside the blood bank must be in place to ensure that technical and clerical errors are not made.

At the time of transfusion, the blood component unit with the compatibility tag attached must be compared with the patient's identification bracelet. A complete and careful identification system is essential. No discrepancies in spelling or identification numbers should exist. The patients should remain under direct observation for 5-10 minutes after the infusion begins and must be checked periodically until the transfusion is completed.

Blood Warming:
Transfusion of cold blood at rates exceeding 100 ml/minute has been associated with a high rate of cardiac arrest when compared to rates in a control group receiving warm blood. (43) However, patients receiving blood at a slow rate should not routinely receive warm blood.
Blood warmers are of two types: 1) a coil of plastic tubing placed in a temperature-monitored water bath at no more than 38 C and 2 electrically heated plates in contact with a flat plastic blood bag. Automatic warming devices must have a visible thermometer and should have an audible warning system. Blood must not be warmed above 38 C. (20) Warming the whole unit of blood by immersion in hot water or by the use of microwave blood warmers is not recommended, since hemolysis can result from overheating. (44) The use of blood warmers is generally restricted to:
  1. Adult patients receiving rapid and multiple transfusions (rate over 50 ml/kg/hour).
  2. Exchange transfusions in infants
  3. Children receiving blood in volumes in excess of 15 ml/kg/hour.
  4. Patients with severe paroxysmal nocturnal hemoglobinuria or severe cold agglutinin disease.

Time Limits for Infusing Blood Components:

A unit of blood should not be kept at room temperature for more than a short time because of the risk of bacterial growth. If clinical conditions require an infusion time of greater than 4 hours, the unit should be divided into aliquots and portions kept in the blood bank refrigerator until required. Changing of the blood filter every 4 hours is also recommended. A unit of blood that has been allowed to warm above 10 C, but is not used, cannot be reissued by the transfusion service. Blood must never be stored in unmonitored refrigerators.

Concomitant Use of Intravenous Solutions:
Only normal saline (0.9% USP) may be administered with blood components. Other solutions may be hypotonic (e.g., 5% dextrose in water) and cause hemolysis in vitro or may contain additives such as calcium (Ringer's lactate) that can initiate in-vitro coagulation in citrated blood. (45) To increase infusion rate and decrease viscosity, RBCs may be diluted with normal saline (0.9% USP). Medications should never be added to a unit of blood, for several reasons. One is that some drugs may cause hemolysis due to their excessively high pH. Second, if medication is added to blood and the transfusion is discontinued subsequently because of a transfusion reaction, the dose of prescribed medication infused may not be difficult to decide if any adverse reactions were due to the drug or to the blood.

Filters:
All blood components must be administered through a filter to remove blood clots and other debris. Standard blood filters, with a pore size of about 170 microns, trap large macroaggregates, but not the microaggregates that form progressively in blood after 5 days of storage. These microaggregates can lodge in the pulmonary circulation, but their role in the development of pulmonary toxicity is unproven. (46) Microaggregate blood filters with 20-to 40-micron pores can remove more of this microaggregate debris, but they are not indicated for routine blood transfusions. A lack of benefit of the filters has been shown for patients requiring an average 7 units of blood for elective surgical procedures. (47) The use of microaggregate filters should be restricted and determined by the transfusion committee. Disadvantages of microaggregate filters include the potential for becoming clogged and resistance to rapid blood deliver. Special filters are presently available to provide leukocyte-reduced components.

Transfusion of Platelets and Granulocytes:
Platelets and granulocytes are routinely administered through a component blood administration set. These sets have the standard 170-micron filter but storage tubing, to permit delivery of as much of the component as possible, and no rubber flash ball, which may activate platelets. Pediatric patients requiring platelet or granulocyte transfusions may require concentrates with decreased plasma volumes. In patients with a history of recurrent febrile reactions to these components the severity of symptoms may be premedication with antipyretics other than aspirin. Leukocyte-reduction filters alleviate these reactions in some patients. (48)

Corticosteroids may be helpful in patients with severe reactions. Subcutaneous or intravenous meperidine can control the severe shaking chill reactions sometimes seen with granulocyte or platelet infusions.

Infusion Devices:
Several electronic infusion devices or "blood plumps" are available. These machines are designed to deliver parenteral fluids, including blood components, at flow rates as low as 1 ml/hour. The pump mechanisms vary with different manufactures and include syringe-type pumping systems, peristaltic roller devices and electromechanical pumps, which operate on a positive volumetric displacement principle.

Dome systems require manufacturer-supplied pump cassettes, while others can be used with standard intravenous administration set tubing. Although most pump systems do not induce mechanical hemolysis when used with Whole Blood, gross hemolysis may result when some models are used to administer RBCs. This is attributable to the high shear forces generated with use of high hematocrit RBC concentrates, which are quite viscous. Available data show that the use of the pumps with other blood components, such as Platelets and Granulocytes, is acceptable. (49), (50) If these pumps are to be used to administer units of RBCs or other components, the manufacturer should be consulted regarding the suitability of the instrument for this purpose. In addition leukocyte-reduction filters cannot be used with some syringe-type pump.
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Agarwal B D.. Available From : http://www.pediatriconcall.com/fordoctor/ Conference_abstracts/report.aspx?reportid=279
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