pediatric transfusion therapy: practical considerations

11
Basic and Behavioural Sciences Indian .I Pediatr 199u; ~6 : 3(17-317 Pediatric Transfusion Therapy : Practical Considerations Roshni Kulkarni and Renuka Gera Pediatrics~Human Development, Michigan State University, East Lansing, ,VII, USA Abstract : Over the past decade, safety of blood has increased tremendously because of better donor screening as well as testing of the units for transmissible diseases. Component therapy has allowed more effective and economic use of blood. Whole blood is rarely used; instead. packed red cetfs, p~atefets, and fresh frozen plasma (FFP) are the mos~ cerumen cc~ponefn-; used. These products are further refined using irradiation and m!croaggregate filters and in the case of FFP, viral inactivation. Irradiation prevents transfusion-associated graft versus host dis- ease, whereas microaggregate filters remove leukocytes, decreasing the rates ot alloimmunization, febrile nonhemolytic (FNH) reactions, and cytomegalovirus (CMV) transmis- sion. Autologous donation in older children probably provides the safest blood as far as transmis- sible diseases are concerned. More families request a directed donation and solicit physician help in deciding as well as making arrangements for autologous and/or directed donations. Transfusions of blood and blood components in children are often challenging and require a knowledge of physiologic changes in hemoglobin and blood volumes during different ages. The unique needs of neonates, immunocompromised patients, and patients with congenital hemolytic anemia (sickle cell, thalassemia) mandate that the pediatrician have an appropriate knowledge of transfusion volumes and choice of blood product as well as indications for transfusion. (Indian d Pediatr 1999; 66 : 307-317) Key words : Transfusion; Anemia; Packed red cell, Platelet. Blood transfusions are often life saving and are an integral part of the supportive care in children of all ages with underlying hematologic problems, trauma and those undergoing surgery. Transfusions in the pediatric age group are particularly chal- lenging and carry the risk of reactions, or transmit infectious agents. While many of the indications for transfusion in the pediatric age group are similar to adults, the threshold and volumes for transfusion vary at different ages. Reprint requests : Roshni Kulkarni, M.D., Michigan State University, Pediatrics/Human Development, B401 Clinical Centre, 138 Service Road, East Lansing, MI 48824-1313. E-mail : kulkarnl @ pilot.msu.edu Packed red c~lls (prc), platelets, fresh fru- zen plasma (FFP) are the most comnu)n type of blood products used in any age group and are derived from whole blood. "The red cells is either administered with tile aid ot a filter as leuko-poor red cells or >toted as fro- zen or deglycerolized cells. Ihe platelct rid~ plasma is separated into platelet concen- trate or fresh frozen plasma, the latter can be further separated into cry uprecipitate, single donor plasma or pooled to,, bc proc- essed into plasma derived products such as clotting factor concentrates, albumin, m~- munoglobulins, etc. After colk~ction blood i> routinely tested as per Federal Drug Ad- ministration (FDA) requirement for the fol- lowing : ABe and I) group; hepatitis B st~r-

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Basic and B e h a v i o u r a l Sc iences Indian .I Pediatr 199u; ~6 : 3(17-317

Pediatric Transfusion Therapy : Practical Considerations

Roshni Kulkarni and Renuka Gera

Pediatrics~Human Development, Michigan State University, East Lansing, ,VII, USA

Abstract : Over the past decade, safety of blood has increased tremendously because of better donor screening as well as testing of the units for transmissible diseases. Component therapy has allowed more effective and economic use of blood. Whole blood is rarely used; instead. packed red cetfs, p~atefets, and fresh frozen plasma (FFP) are the mos~ cerumen cc~ponefn-; used. These products are further refined using irradiation and m!croaggregate filters and in the case of FFP, viral inactivation. Irradiation prevents transfusion-associated graft versus host dis- ease, whereas microaggregate filters remove leukocytes, decreasing the rates ot alloimmunization, febrile nonhemolytic (FNH) reactions, and cytomegalovirus (CMV) transmis- sion. Autologous donation in older children probably provides the safest blood as far as transmis- sible diseases are concerned. More families request a directed donation and solicit physician help in deciding as well as making arrangements for autologous and/or directed donations.

Transfusions of blood and blood components in children are often challenging and require a knowledge of physiologic changes in hemoglobin and blood volumes during different ages. The unique needs of neonates, immunocompromised patients, and patients with congenital hemolytic anemia (sickle cell, thalassemia) mandate that the pediatrician have an appropriate knowledge of transfusion volumes and choice of blood product as well as indications for transfusion. (Indian d Pediatr 1999; 66 : 307-317)

Key w o r d s : Transfusion; Anemia; Packed red cell, Platelet.

Blood transfusions are often life saving and are an integral part of the support ive care in chi ldren of all ages with unde r ly ing hemato log ic problems, t rauma and those unde r go ing surgery. Transfus ions in the pediatr ic age g roup are par t icu lar ly chal- lenging and carry the risk of reactions, or transmit infectious agents. While man y of the indicat ions for t ransfus ion in the pediatr ic age g roup are similar to adults , the threshold and volumes for transfusion vary at different ages.

Reprint requests : Roshni Kulkarni, M.D., Michigan State University, Pediatrics/Human Development, B401 Clinical Centre, 138 Service Road, East Lansing, MI 48824-1313. E-mail : kulkarnl @ pilot.msu.edu

Packed red c~lls (prc), platelets, fresh fru- zen plasma (FFP) are the most comnu)n type of b lood p roduc t s used in any age group and are derived from whole blood. "The red cells is either administered with tile aid ot a filter as leuko-poor red cells or >toted as fro- zen or deglycerolized cells. I h e platelct rid~ plasma is separa ted into platelet concen- trate or fresh frozen plasma, the latter can be fur ther separa ted into cry uprecipi tate, single donor plasma or pooled to,, bc proc- essed into plasma derived products such as clott ing factor concentra tes , a lbumin, m~- munoglobulins, etc. After colk~ction blood i> rout ine ly tes ted as per Federal Drug Ad- ministration (FDA) requirement for the fol- lowing : A B e and I) group; hepatitis B st~r-

308 R. KULKARNI AND R. GERA Vol. 66, No. 3, 199 ~)

face antigen (Hbs Ag), human immune defi- ciency virus (HIV)antigen; antibodies to hepatitis B core (HBc), hepatitis C virus (HCV), HIV1, HIV2, human T-cell lympho- tropic viruses, type 1 (HTLV1); and a sero- logic test for syphilis.

Following is a brief description of the various blood components and their shelf life, as well as indications for use. For fur- ther details the reader is referred to the American Association of Blood Banks tech- nical volume 1.

Whole Blood : One unit (500 ml) of whole blood is the amount of blood collected from a single donation. It contains one units of red cells and one unit of plasma in 63 ml of ant icoagulant /preservat ive CPDA-1 (Citrate Phosphate Dextrose Adenine). Citrate prevents coagulation by binding to the calcium (Ca), thereby inhibiting several steps in Ca dependent coagulation path- ways. The shelf life is 35 days when stored at 1-6~ It contains reduced amounts of la- bile clotting factors such as FV and FVIII and has no viable platelets or granulocytes. Reconstituted whole blood (fresh frozen plasma added to prc) is a preferred product over whole blood for simultaneous replace- ment of blood volume and oxygen carrying capacity.

Packed red ceils (PRC) : Packed cells are prepared by removing most of the plasma from one unit (500 ml) of CPDA-1 contain- ing whole blood. A unit of prc has a volume of approximately 300 ml and a hematocrit (Hct) of 80% and hemoglobin (Hgb) of 22-24 g/dl . CPDA-1 prc is preferred in infants and neontates because of the low volume of the anticoagulant and may require addition of 0.9% NaC1 to reduce the viscosity. For neonates and infants (below 4 months of age) who require small volumes of blood, one unit of CPDA-1 prc, as 125 ml aliquots,

is distributed into triple or quad packs (3-4 satellite bags joined to a main bag). Such multiple aliquots from a single donor unit decreases donor exposure.

To enhance red cell survival, and in- crease shelf life to 42 days, 100 ml of addi- tive solution (Adsol | containing dextrose, adenine, mannitol and sodium chloride) is often added to CPDA-1 prc. This lowers the Hct to 50-65% thereby decreasing the vis- cosity, and is the product of choice in older children and adults. Packed cells are com- patible with 0.9% NaC1, 5% albumin and fresh frozen plasma. Glucose containing so- lutions cause sl,.ldging and reduce red cell survival and solutions containing calcium such as Ringer's lactate can cause clot for- mation.

Leukocyte-reduced (LR) red cells : Microaggregate filters remove 98% of con- taminating leukocytes from PRCs. These leukocytes transmit cytomegalovirus (CMV), cause febrile nonhemolytic (FNH) transfusion reaction and are responsible for alloimmunization to HLA antigens. The lat- ter affect post transfusion platelet incre- ments. LR units significantly reduce, if not prevent, transfusion-transmitted CMV (TT- CMV) 2~.

Frozen o1" deglycerolized cells : Glycerol, a cryoprotective and cryopreservative agent, prevents red cell intracellular ice crystal for- mation that causes f reeze/ thaw damage, osmotic stress and denaturation of proteins. Glycerolized red cells have a life span of 10 years. The main indications for freezing red cells are collection of rare blood types and for red cell preservation following autolo- gous donation. Prior to use, the glycerol is removed by an osmotic process (either me- chanical or automated) that uses increasing concentrations of salt, so that the final product contains red ceils suspended in sa-

Vol. 66, No. 3, 1999 PEDIATRIC TRANSFUSION THERAPY 309

line. This process called deglycerolizat ion, removes 98% of lymphocytes . Since the bag of blood is entered for washing with saline, there is a dange r of contaminat ion; there- fore the cells mus t be used within 24 hours of deglycerolization.

Washed red cells : Red cells are washed with normal saline ei ther manua l ly or us- ing a u t o m a t e d cell washers , to r em o v e white cells, platelets and p lasma prote ins such as imrnunoglobul in A (IgA) and com- plement . Washed cells are indicated in (1) IgA def ic ient pa t ien ts who are at r isk for anaphylaxis f rom IgA in the plasma and (2) pat ients wi th pa roxysma l noc tu rna l hemog lob inu r i a in w h o m c o m p l e m e n t in donors" p l a sma causes lysis of recipients complement sensitive red cells. Since prepa- ration of washed cells is in an open system, the p roduc t mus t be used within 24 hours because of danger of contamination.

Indications and volumes for red cell transfu- sions : The main indica t ion for red cell transfusion is to increase the oxygen carry- ing capaci ty of b lood and thereby p reven t or revert tissue hypoxia. Although, there is no a rb i t ra ry level of hernatocr i t that indi- cates a transfusion, a rough guide is given

in table 1. Chi ldren with acute b lood loss may require transfusions to maintain a nor- mal or near no rma l hematocr i t . Signs of acute blood loss (> 25% blood volume) re- sul t ing in shock and ca rd iovascu la r col- lapse are of ten subtle in ch i ldren and in- clude pallor, anxiety, tachypnea, bradycar- d i a / t a c h y c a r d i a , h y p o t en s io n and de- creased capil lary filling. Systolic hypoten- sion, an indicator of shock, varies at differ- ent ages (< 4yrs < 65 m m Hg; 5-8yrs < 75 m m Hg; 9-12 yrs < 85 m m Hg; 13-adults < 95 m m Hg). In severe hemorrhage , central venous pressure (CVP) is usual ly 0-2 m m Hg. Blood and fluids increase CVP to 6-7 m m Hg. at which poin t c i rcula t ion is re- stored 4. The volume for transfusion is based on the formula that 3 rn l / kg prc will raise H b g / d l . In chi ldren with severe anemia and impending hear t failure, a cont inuous infusion of 2 m l / k g / h r of prc can be given until the desired volume is reachedL For pa- tients with hemorrhagic or burn shock, ex- change t ransfus ions or mass ive t ransfu- sions can be administered. Massive transfu- sion is def ined as rep lacement of pat ients blood volume in less than 24 hours or acute admin is t ra t ion of more than half the pa-

TABLE 1. Indications for Packed Red Cell (prc) Transfusions

Age Hb level (g/dl) Hct (%) Clinical situati~n

Newborn-4 mo < 13 40 Severe cardiopulmoncwy disease

< 10 30 Major surgery Moderate cardiopulmonary disease

< 8 25 Symptomatic anemia

7-8 20-25 Prior to surgery

Marrow failure (Aplastic anemia/Leukemia)

Symptomatic anemia

< 13 40 Severe cardiopulmon a ry disease Ventilatory support

Older children

Adolescents

Any age : acute blood loss > 10-15 %

31 {} R. KULKARNI AND R. GERA

TABLE 2. Volumes for Packed Red Cell Transfusions

Vol. 66, No. 3, 1999

Packed red cell transfusion us ing Hb (donor unit Hb 22-24 g/dl) :

TBV x desired Hb - observed Hb 70-75 x Hb diff.

Hb of prc unit 22-24

Usually a Hb difference of 4-5 g/dl is desirable = 3 • 4-5 = 12-15 cc/kg

Packed red cell transfusion us ing Hot, (donor unit Hot 65%) TBV x (Hct desired - Hct observed) 75 • (35-25)

Hct of donor unit 65

Usually a Hct difference of 10-12% is desirable = 12-14 cc/kg

= 1.25 x 10

tient's blood vo lume per hour, and is based on oxygen consumpt ion 6.

Transfusions for chronic anemias in chil- d ren are often based upon the under ly ing cause. Ch i ld ren wi th i ron def ic iency anemia and anemia of p rematur i ty can of- ten tolerate very low levels of Hb and sel- d o m requi re t ransfus ion . Pat ients wi th sickle cell anemia, thalassemia, Diamond- Blackfan anemia, cancer, aplastic anemia, etc. on the other hand, require intermittent or chronic t ransfusion therapy. Such trans- fusions are a lways ordered in m l / k g b o d y weight rather than whole units. A s tandard transfusion of 12-14 m l / k g raises l ib by 2-4 g / d l (table 2) 7. In hemodynamica l ly stable patients, a max imum of 15 m l / k g of prc can be admin i s te red in one t ransfus ion 8. Chil- d ren wi th severe anemia (Hb < 5 g / d l ) should receive prc as a cont inuous infusion (2 m l / k g / h r ) or as mul t ip le in te rmi t ten t t ransfusions of 3-5 m l / k g over 3 hrs wi th several hours in be tween transfusions to al- low cardiovascular stabilization ~,7. A rough guide frequently used for children with se- vere anemia is as follows : wt (in pounds) x Hb (in grams).

In children with adequate venous access, a full vo lume exchange or a par t ia l ex~ change t ransfus ion using prc rapidly cor- rects severe anemia wi thou t changes in b lood vo lume (table 3). Other indicat ions for exchange t ransfusion include neonatal hyperbi l i rubinemia , removal of endotoxin in patients with sepsis, disseminated intra- vascular clotting (remove fibrin split prod- ucts and prov ide procoagulants), respirato- ry distress synd rome , h y p e r a m m o n e m i a , c i rcula t ing ant icoagulants , i m m u n e com- plexes, sickle cell disease 9.

Platelet concentrates : There are two types of platelet concentra tes avai lable namely, r an d o m donor units (RDU) or pooled con- centrates, and apheresis or single donor units (SDU). One RDU is de r ived f rom 1 unit of whole blood, within 8 hours of col- lection, by-cen t r i fuga t ion . It contains at least 5.5 x 101~ platelets per bag or unit and multiple units are combined prior to admin- istration.

Apheresis or SDU platelets are collected using machines that use centrifugal force to separa te b lood into var ious fract ions de- p e n d i n g on the d i f ferent densi t ies of the

Vol. 66, No. 3, !.999 PEDIATRIC TRANSFUSION THERAPY

TAm-~ 3. Volumes for Exchange Transfusions and Partial Exchange Transfusions 7

311

Exchange transfusions

Whole blood (WB) exchange :

Total blood volume x 2 x wt (kg) = cc of WB One volume exchange replaces 75% TBV Two-volume exchange replaces 90%

Partial exchange transfusions for severe anemia

Exchange volume (ml) using Wt. (kg) % TBV x desired Hb rise

Hb = (Hb donor blood - H b )

(initial Hb + desired Hb) Hb W

Exchange volume (ml) using aHct --

Hct w =

Wt. (kg) x TBV x desired Hct rise

(Hct donor blood - Hctw)

(initial Hct + desired Hct)

var ious componen t s . Briefly, b lood f rom a donor is d r a w n either intermit tent ly or con- t inuous ly into a centr i fuge bowl, the com- p o n e n t s s e p a r a t e d and r e m a i n d e r of the b lood is r e t u r n e d to tbe donor . SDU col- lected in this m a n n e r has a vo l um e of 200- 250 ml and contains at least 3 x 10 ~1 pla te- lets p e r bag. One SDU equals app rox i - mate ly 6 RDU and minimizes the number of donor exposures in the recipient.

Platetet concent ra tes are s tored at r oom tempera tu re for a m a x i m u m of 5 days with con t inuous agi ta t ion to p r even t c lumping. Besides platelets, it contains white cells, tu- m o u r necros i s fac tor (TNFct) a n d o ther cy tok ines tha t cause febri le react ions. Leukocyte reduct ion of platelets reduces the risk of a l lo immuniza t ion and refractoriness to platelet t ransfusions 1~

The major indicat ions for platelet t rans- fusions 11 (table 4) are b leeding secondary to dec reased pla te le t p r o d u c t i o n (mal ignan-

cies, aplas t ic anemia , etc.) or qua l i ta t ive platelet disorders. Ptatelef t ransfusions are

TABtE 4. Indications for Platelet Transfusions

Platelet level Clinical situation (cu ram)

< 10,000" Production related thrombocy- topenia Marrow failure (leukemia aplastic anemia)

Prior to lumbar puncture. Brain tumor patients receiving chemo/radiation therapy

Prior to minor surgery/invasive procedure

Prior to major surgery Patients on ventilatory support Clinically unstable neonates

Actively bleeding patients with qualitative platelet defect

< 20,000

< 50,000

< 100,000

Any level

312 R. KULKARNI AND R. GERA Vol. 66, No. 3, 1999

TABLE 5. Platelet Transfusion Volumes

1 unit per m 2 of body surface area raises plate- let count by 10,000

1 unit/kg body weight will increase platelet count to 30,000

Usual volume -- 0.2 units/kg

Single Donor Unit (SDU) platelets 15 ml/kg Practical considerations 8

Infants 2 units Toddlers 3 units Young children 4 units

Preadolescents 6-8 units Adolescents 6-8 units

ineffective when thrombocytopenia is due to increased platelet destruction [e.g., im- mune thrombocytopenic purpura (ITP)]. Prophylactic platelet transfusions are often administered to patients receiving myelotoxic chemotherapy 12, or prior to sur- gery in thrombocytopenic patients 13. In pa- tients with myeloid leukemia, Rebulla et al. ~4 recently lowered the threshold for platelet transfusions from 20 x 109/L to 10 x 109/L resulting in a 21.5% decrease in platelet transfusion without an increase in bleeding complication. Central line place- ment (internal jugular or subclavian line cannulation) has been performed in pro- foundly thombocytopenic patients with minimal complications is. Table 5 gives guidelines for platelet transfusions. For pediatric use, low-volume platelets can be used. However, centrifugation to remove ex- cess plasma from platelet units may cause clumping and affect viability and function.

Fresh frozen plasma (FFP) : FFP is the plasma separated from centrifuged whole blood and stored at - 18 ~ C. One unit of FFP is approximately 200-280 ml and contains 1 uni t /ml activity of each of the coagulation factors and 1-2 m g / m l of fibrinogen. Usu-

ally, 10-15 ml /kg is administered. The ma- jor indications for the use of FFP are defi- .ciencies of hemostatic factors (FXI, XIII, and Vitamin K dependent factors such as II, VII, IX, X and anti-thrombin III proteins C and S) either congenital or secondary to liver disease disseminated intravascular coagu- lation etc. Recently, a solvent detergent (SD) treated pooled FFP 9 has become available for use in the USA. The SD treatment inacti- vates viruses such as HIV, hepatitis B, etc., by dissolving the lipid envelope.

Cryoprecipitate is the precipitated materi- al obtained when FFP is thawed at 1-6 ~ C. One unit or bag of cryoprecipitate is ap- proximately 10-12 ml and contains 100-250 mg of fibrinogen (F), 80-100 units of FVIII, vWF (von Willebrand Factor), FXIII and 20- 40 mg/bag of fibronectin. Fibronectin is an adhesive protein that takes part in clotting as well as in cell binding and migrationlt Since cryoprecipitate is not virally inacti- vated and contains other proteins, it is not recommended for the treatment of hemo- philia and von Willebrand disease. Instead, recombinant factors or immunoaffinity pu- rified virally inactivated plasma derived FVIII or coagulation FIX products are pre- ferred. The major indications of cryoprecipi- tate are treatment of bleeding associated with hypofibrinogenemia, dysfibrinogene- mia, and FXIII deficiency and during sur- gery as a fibrin glue or sealant when used in combination with topical thrombin. For afibrinogenemia or hypofibrinogenemia, with bleeding, one can administer 1 bag of cryoprecipitate/2kg IV followed by 1 bag/ 15 kg dailylL Alternatively, the amount (bags) of cryoprecipitate required can be calculated as (desired F - observed F) x plasma volume [blood volume (ml) x (1.0- Hct)] divided by 250 mg (fibrinogen/bag).

Autologous transfusion and directed dona- tions : Predeposited autologous blood trans-

Vol. 66, No. 3, 1999 PEDIATRIC TRANSFUSION THERAPY 3t3

fusions (PABT) have been administered to infants and children in whom transfusions were expected to be required during an elec- tive operation 1718. Alternatively, a safe vol- ume of blood can be collected just prior to surgery with the intent of transfusing at the completion of surgery 19.

Directed donor blood or platelets are in- tended for a specific recipient. Such dona- tions became popular because of growing awareness of transfusion transmitted dis- eases such as HIV. Blood products from di- rected donors should be irradiated to pre- vent transfusion-associated graft-versus- host disease (TA-GVHD) and subjected to the same testing as is required by FDA for banked blood. Blood from first degree rela- tives is discouraged for patients who are potential candidates for allogenic bone marrow transplant. Transfusion may sensi- tize the patient and interfere with the trans- plant. In cases of neonates with alloim- mune thrombocytopenia, washed maternal platelets (to remove plasma-containing al- loantibodies) can be administered.

Granulocyte transfusion : The precise role of granulocyte transfusion in pediatrics is unclear. The main indication for granulo- cyte transfusion is neonatal bacterial sepsis associated with neutropenia. Controversy exists regarding the neutrophil level at which to transfuse and efficacy when com- pared to other forms of therapy such as in- travenous immunoglobulin (IVIG) and re- combinant granulocyte colony-stimulating factor (rG-CSF). Granulocytes are collected by apheresis and the recommended dose is 1-2 x 109 WBC/kg body weight 9.

Special Considerations in Pediatric Trans- fusion Therapy

Irradiated blood : The main indication of

irrdiated blood (packed cells, platelets and granulocytes) is the prevention of TA- GVHD in immune-suppressed patients. Gamma radiation to a dose of 25 Gray (2500 rads or 2500 cGy) inactivates immuno-competent lymphocytes without damaging platelets and red cells. Irradia- tion is also recommended when the donor is a blood relative of the recipient since shared HLA haplotype allows donor lymphocytes to escape immune-surveil- lance and cause TA-GVHD 1

Transfusion transmitted cytomegalovirus (TT-CMV) : CMV, a herpesvirus transmitted by leukocytes, accounts for significant mor- bidity and mortality in immuno-compro- mised recipients. It causes post perfusion mononucleosis, hepatitis, pneumonitis, gastroenteritis, etc. The prevalence of CMV seropositive persons, as determined by the presence of antibody, ranges from 40-70% in the USA 2~ The rate of seroconversion fol- lowing use of CMV seronegative blood is equivalent to leukocyte reduction (LR) blood (1-4% versus < 2.5%). LR units (packed cells and platelets) with a residual leukocyte count of 5 x 106 can significantly reduce, if not prevent, post-transfusion CMV in high-risk neonates and transplant recipients. CMV safe blood (CMV negative or LR) is indicated in low birth weight in- fants, transplant patients and HIV infected seronegative patients 3.

Transfusions in neonates and infants : Re x placement of cumulative blood loss for lab- oratory studies accounts for the majority of neonatal transfusions 21 with an average of 8-10 donor exposures per neonate. The de- cision to transfuse neonates is often arbi- trary and based either on Hct alone or on other clinical parameters such as apnea or bradycardia or poor weight gain. Perhaps oxygen delivery rather than Hb concentra-

314 R. KULKARNI AND R. GERA vol. ~6, No. 3, 1999

tion may be a better indicator of transfu- sion. To date there is little information eval- uating oxygen deliveryL Currently, clinical trials with recombinant erythropoietin are under way for treatment of physiologic ane- mia of infancy. Erythropoietin at doses of > 600 u / k g / w k started at an average of 21 days of life improved reticulocyte counts and Hb levels and reduced the number of infants that required late transfusion. How- ever, it did nothing for the bulk of infants who were transfused before that age 22.

Transfusions in sickle cell anemia : Transfu- sions (either simple or partial or full ex- change) in sickle cell anemia are indicated for CNS infarction, aplastic crises, hypoxia due to acute chest syndrome, exacerbation of severe anemia causing cardiovascular in- sufficiency, sequestration crises (splenic, hepatic or pulmonary). Other indications include, prior to high-risk procedures such as general anesthesia, surgery (ENT, ab- dominal or thoracic or other major surger- ies), or angiograms using hyperosmolar dye. The purpose of transfusion therapy in life threatening situations is rapid replace- ment of sickle Hb with donor normal Hb A. Care must be taken not to exceed a Hct of 35% so as to avoid hyperviscosity :3. Partial exchange transfusion removing 0.8% of pa- tients blood volume (6cc/kg) and replacing with prc (12cc/kg) often suffices 23. Alterna- tively for adolescents and adults, one can phlebotomize 500 cc of whole blood, infuse 300 cc saline, phlebotomize another 500 cc of whole blood and infuse 4-5 units of packed ceUs 24.

Chronic transfusion therapy in sickle cell anemia, on the other hand, is intended to suppress erythropoiesis. In most cases, simple transfusions given at 3-4 week inter- vals suffice. To prevent iron overload, chelation therapy with desferrioxamine is

recommended for patients with serum ferritin above 2000 ~ g / m F ~, although iv DFO can be given at the time of prc transfu- sion when the serum ferritin is 500-1000 ]ag/ml. Indications for chronic transfusion therapy include stroke prevention, chronic heart failure, complicated pregnancy, pro- longed hematuria, recurrent priapism and unremitting vaso-occlusive crises. In a re- cent Stroke Prevention Trial 2~' (STOP) of 130 children ages 6-12 years, only 1/63 had stroke in the chronic transfusion group compared to 10/67 receiving standard care. These results led to early termination of the trial. Transcranial Doppler detected t in 12 children at risk for stroke.

Transfusion therapy in thalassemia : Thalassemias are congenital anemias caused by deficiency of beta or alpha chains affecting Hb synthesis: Transfusions are a mainstay of the treatment of thalassemia and are initiated when the Hb falls below 7 g/dl . Since alloimmunization to minor blood group antigens occurs in 20- 30% of patients, prior to initiation of trans- fusion programme, a complete blood typing should be obtained. Besides improving tis- sue oxygenation, transfusions suppress in- effective erythropoiesis as well as iron ab- sorption from the gut. Clinical benefits in- clude normal growth and development and activity. Hypertransfusion programs main- tain pre-transfusion Hb between 8-9 g/dl . The goal is normal growth and develop- ment. The goal of the supertransfusion (Hb between 11-12 g/dl) programme is to de- crease gastrointestinal iron absorption :7. Transfusion interval to maintain pre-trans- fusion Fib varies from 3-5 weeks. Chelation therapy with DFO is recommended for iron overloaded patients.

Transfusions is pediatric oncology patient~ : Transfusion of irradiated and LR or CMV

!7ol. 66, No. 3, 1999 PEDIATRIC TRANSFUSION TIqERAP'~'

TABLE 6. Adverse Effects of Blood Transfusion

315

Non infectious complications Infectious complications Metabolic complications

Hemolysis Febrile non-hemolytic Circulatory overload TRALI (Transfusion-related acute lung injury) TAGVHD (Transfusion associated graft-versus-host disease) Urticaria Anaphylaxis (IgA deficiency) Immune-suppression Hypothermia Embolism, (air/clot) Platelet refractoriness

"viral infections 2e TTHIV 1:493,000 transfusions HBV 1 : 63,000 transfusions HTL V1, 1 : 641,000 transfusions HCV 1 : 103,000 transfusions CMV Parvovirus Epstein Barr Virus (EBV) Colorado Tick Fever Creutzfeldt-Jakob Disease Parasitic Diseases Malaria/Fitaria Babesia Chagas disease Toxoplasmosis Bacterial infections

Citrate toxicity Hyper/hypokalemia Coagulopa H~y .Iron overload

negative red cells and platelets are often an integral par t of m a n a g e m e n t in pedia t r ic oncology pa t ien ts 2s. Prc t ransfus ions and platelet t ransfus ions are ind ica ted when the Hb is be low 7-8 g / d l and platelet counts are < 10,000/cumin. The threshold for t ransfus ion is h igher for pat ients with brain tumors , and pat ients undergoing ra- diation therapy, surgery or procedures and also for those r equ i r ing ven t i l a to ry sup- ports 27. HLA matched or leuko-poor plate- lets are used for platelet refractoriness and FNH that of ten occur fo l lowing mul t ip le transfusions.

Adverse effects of transfusion : Blood car- ries the risk of non-infectious, infectious as well as metabol ic compl ica t ions (table 6). Careful dono r selection, p re - t rans fus ion screening and use of autologous blood can

significantly reduce these complications. It is beyond the scope of this article to discuss in detail all the complications. The reader is referred to excellent books and articles on this topic1,1'2L

C o n c l u s i o n

Recent advances in donor screening and blood testing have made blood transfusion safer than in the past decade. C o m p o n e n t therapy has allowed for more effective and economic ut i l izat ion of blood. I r radia t ion and leukocyte reduction of packed cells and platelets has decreased side effects such as TA-GVHD and FNH reactions m recipients. For congenital hemolyt ic anemias such as sickle cell anemias and thalassemias one mus t be aware of the consequences of

316 R. KULKARNI AND R. GERA Vol. 66, No. 3, 1999

chronic t r ans fus ion therapy.

REFERENCES

1. Blood and Components . In : Vengelen- Tyler V (ed) Technical Manual, 12 edn. Bethesda, The American Association of Blood Banks. 1996; 135-157.

2. Luban NL. Management of pediatric transfusions. Vox Song 1994; 67 : 229-233.

3. Leukocyte reduct ion for the prevention of Transfusion-Transmitted Cytomegalo- virus (TT-CMV). Association Bulletin 97-2. American Association of Blood Banks. 1997.

4. Kevy SV, Gorlin JB. Red cell transfusion. In : Nathan, DG and Orkin SH (eds.). Nathan and Oski's Hematology of Infancy and Childhood,'5 edn. Philadelphia. WB Saun- ders 1998; 1784-1801.

5. Jayabose S, Tugal O, Ruddy R et al. Transfusion therapy for severe anemia. Am ] Pediatr Hematot Oncot 1993; 15 : 324- 327.

6. Donaldson MD, Seaman MI, Park GR. Massive Blood Transfusion. Brit J Anaesth 1992; 69 : 621-630.

7. Breiter SN and Luban NLC. Appendix : Transfusion Formulas. In : Kasprisin DO and Luban NLC {eds). Pediatric Transfu- sion Medicine Volume II. CRC Press, 1987; 177-189.

8. Buchanan GR. Hematologic support ive care of the pediatric cancer patient. In : Pizzo PA and Poplack DG (eds.). Princi- ples and Practice of Pediatric Oncology, 3 edn. Lippincott Raven 1997; 1051-1068.

9. Manno-CS. What ' s new in transfusion medicine ? Pediatr Clin N A m e r 1996; 43 : 793-808.

10, Leukocyte reduction and ultraviolet B ir- riation of platelets to prevent alloimmu- nization and refractoriness to platelet transfusions. The Trial to Reduce Alloim- munization to Platelets Study Group. N. Engl J Med 1997; 337 : 1861-1969.

11. Strauss RG. Blood and blood component transfusions. In : Behrman RE, KIiegman

RM and Arvin AM (eds.). Nelsons Text Book of Pediatrics. 15 ed. WB Saunders, 1996; 1417-142l.

12. Gaydos LA, Frierich EJ, Mantel N, et al. The quantitative relation between platelet count and hemorrhage in patients with acute leukemia. N Engl [ Med 1962; 266 : 905,

13. Practice Guidelines for blood component therapy : A report by the American Soci- ety of Anesthesiologists Task Force on Blood Component Therapy. A nesthesiolo- gy 1996; 84 : 732-747.

14. Rebulla P, Finazzi G, Marangoni F et r A multicentre randomized study of the threshold for prophylactic platelet trans- fusions in adults with acute myeloid leukemia. Gruppo ltaliano Malattie Ema- tologiche Maligne dell' Adulto. N E~t<l ] Med 1997; 337 : 1870-1875.

15. Barrera R, Mina B, Huang Yc t aI. Acute complications of central liile placement in profoundly thrombocytopenic cancer pa- tients. Cancer 1996; 78:2025-2030.

16. Ratnoff OD. Some therapeutic agents in- fluencing hemostasis. In : Cloman RW, Hirsh J, Marded VJ, Salzman EW (ed~). Hemostasis and ThTwubosis. Be~sic Prillciplcs and Clinical Practice. 1994; 1104-1133.

17. Kemmotsu H, Joe K, Nakamura H et aL Predeposited autologous blood transfu- sion for surgery in infants and children. ] Pediatr Surg 1995; 30 : 659-661.

18. Mayer MN, de Montalembert M, Audat F et al. Autologous blood donation for elec- tive surgery in children weighing 8-25 kg. Vas-San$1996; 70 : 224-228.

19. Means LJ, Ferrari LR, Fisher QA et al. Evaluation and preparati~m of pediatric patients undergoing anesthesia. Section on anesthesiology. Pediatrics 1996; 98 : 502-508.

20. Luban NLC. Cytomegak~virus. In : An- derson KJ, Ness PM (eds). 5cie~t!fic Basis of TransyqLsion Medicine. lmplicatioH tot CIi~t- ical Practice. Philadelphia : WB Saunders 1994.

2t. Strauss RG. Transfusiota ttnerapy in

Vol. 66, No. 3, 1999 PEDIATRIC TRANSFUSION THERAPY 317

Neonates. Am J Dis Child 1991; 145 : 904- 911.

22. Doyle-JJ. The role of erythropoietin in the anemia of prematurity. Semin-Perinatol 1997; 21 : 20-27.

23. Vichinsky E, Lubin BH. Suggested guide- lines for the treatment of children with sickle cell anemia. Hematol Oncol Clin North Am 1987; 1 : 483-501.

24. Porter JB, Herhns ER. Transfusion and exchange transfusion in sickle cell anemias with particular reference to iron metabolism. Acta Hematol 1987; 78 : 198.

25. Embury SH. Sickle cell disease. In : Hoffman R, Benz EJ, Shattil SJ et at. (eds.). Hematology Basic Principles and Practice, 2nd edn. Churchill Livingstone 1995; 611- 647.

26. Adams RJ, McKie VC, Hsu Le t al. Pre- vention of first stroke by transfusions in

children with sickle cell anemia and ab- normal results on transcranial doppler ultrasonography. N Etlgl ] Med 1998; 339 : 5-11.

27. Schwartz E, Benz EJ, Forget BG. Tha- lassemia syndromes. In : Hoffman R, Benz. EJ. Shattil SJ (eds). H,'motology Basic Principles and Practice 2 edJl Churchill Liv- ingstone 1995; 586-610.

28. Barnard DR, Feusner ]H, Wolff LJ. Blood component therpay. In : Ablin AR (ed). Supportive Care of Children with Cancer : Current Therapy and Guidelines fronl the Children's Cancer Group, 2 edn. Baltimore : The Johns Hopkins University Press. 1997; 37-46.

29. Schreiber GB, Busch MP, Kleinman SH et al. The risk of transfusion-transmitted viral infections. N EnRl ] Med 1996; 334 : 1685-1690.

C O U G H COLD PRODUCTS CONTRAINDICA TED I N CHILDREN

I. Cough suppressants such as codeine

2. Oral antihistamine drugs such as promethazine. High doses of antihistamines can sedate a child and may make feeding difficult. These drugs are used for hay fever (allergic rhinitis) but should not be used for common cold.

3. Medicated nose drops or sprays containing ephedrine.

4. Nasal decongestants-al though they can produce short-term relief they can cause rebound congestion of the nose which can interfere with breathing and feeding.

5. Tropical antiseptics and anaesthetics. Antiseptics (cetylpyridinium, domiphen) and local anaesthetics (benzocaine, dyclonine) are sometimes applied topically to relieve sore throat pain.

They are available as oral lozenges but also as aerosols, gels or solutions.

Abstracted from: Health Dialogue, Issue No. 14, Sept 1998; pp 5