Contents
28.1 Introduction . . . 414
28.2 Blood Screening Guidelines . . . 414
28.2.1 Blood Product Processing . . . 415
28.3 Transfusion Complications . . . 416
28.3.1 Hemolytic Reactions . . . 416
28.3.2 Nonhemolytic Reactions . . . 416
28.3.3 Allergic Reactions . . . 417
28.3.4 Graft Versus Host Disease (GvHD) . . . 417
28.3.5 Fluid Overload . . . 418
28.3.6 Transfusion-acquired Infections . . . 418
28.3.6.1 Bacterial Infections . . . 418
28.3.6.2 Cytomegalovirus (CMV) . . . 418
28.4 Erythrocyte Transfusion . . . 419
28.4.1 Erythrocyte Transfusion Options . . . 419
28.4.2 Special Transfusion Considerations . . . . 420
28.4.2.1 Partial Exchange Transfusion . . . 420
28.4.2.2 Specific Risks of Erythrocyte Transfusion . . . . 420
28.5 Platelet Transfusion Options . . . 420
28.5.1 Procurement and Storage . . . 421
28.5.2 Transfusion Guidelines . . . 421
28.5.3 Dosing Recommendations . . . 421
28.5.4 Infusion Guidelines . . . 421
28.5.5 Platelet-specific Transfusion Risks . . . 421
28.5.6 Platelet Alloimmunization . . . 421
28.5.7 Treatment Options . . . 421
Blood Transfusion Therapy Elizabeth Kassner 28.6 Granulocyte Transfusion . . . 421
28.6.1 Indications . . . 422
28.6.2 Dosing Guidelines . . . 422
28.6.3 Specific Risks . . . 422
28.7 Albumin . . . 422
28.7.1 Volume . . . 422
28.7.2 Transfusion . . . 422
28.8 Fresh Frozen Plasma (FFP) . . . 422
28.8.1 Indications . . . 422
28.8.2 Volume . . . 422
28.8.3 Transfusion . . . 422
28.9 Cryoprecipitate . . . 423
28.9.1 Indications . . . 423
28.9.2 Volume . . . 423
28.9.3 Transfusion . . . 423
28.10 Intravenous Immunoglobulin (IVIG) . . . 423
28.10.1 Indications . . . 423
28.10.2 Volume . . . 423
28.10.3 Side Effects . . . 423
28.11 Recombinant Human (rHu) Erythropoietin Alpha . . . 423
28.12 Palliative Care Issues for Transfusion Therapy . . 423
28.12.1 Erythrocyte Transfusion . . . 423
28.12.2 Platelet Transfusion . . . 423
References . . . 424
Bibliography . . . 424
28.1 Introduction
Blood transfusion is an essential part of modern health care. Used correctly, it can save life and im- prove health. However, as with any therapeutic inter- vention, it may result in acute or delayed complica- tions and carries the risk of transmission of infec- tious agents, such as human immunodeficiency virus (HIV), hepatitis viruses, syphilis, and Chagas disease.
It is also expensive and uses a scarce human resource.
The decision to transfuse blood or blood products must be based on a careful assessment of clinical and laboratory indications that a transfusion is necessary to save the individual’s life or prevent significant morbidity (Tables 28.1, 28.2, 28.3).
Children with malignancy or who are undergoing immunosuppressive treatment often experience myelosuppression that requires the necessary, and sometimes emergent, transfusion of blood products.
28.2 Blood Screening Guidelines
The differences in human blood are due to the pres- ence or absence of certain protein molecules called antigens and antibodies. The antigens are located on the surface of the red blood cells (RBCs), and the an- tibodies are in the blood plasma. Individuals have different types and combinations of these molecules.
There are more than 20 genetically-determined blood group systems known today, but the AB0 and Rh systems are the most important ones used for blood transfusions. Not all blood groups are compat- ible with each other. Mixing incompatible blood groups leads to blood clumping or agglutination, which is dangerous for blood recipients.
For a blood transfusion to be successful, AB0 and Rh blood groups must be compatible between the donor blood and the patient blood (Table 28.4). If they are not, the RBCs from the donated blood will agglutinate. The agglutinated red cells can clog blood vessels and stop the circulation of the blood to vari- ous parts of the body. The agglutinated RBCs also he- molyze.
Table 28.1. Age-appropriate blood volumes (adapted from Lanzkowsky, 1999)
Age Total blood volume (ml/kg)
Newborn 82–86
1–3 years 74–81
4–6 years 80–85
7–9 years 86–88
10–15 years 83–88
16–18 years 90
Table 28.2. Disease and treatment transfusion guidelines based on hemoglobin (Rogers et al., 2002; Norville and Bryant, 2002)
Indication Hemoglobin
Prior to a course of chemotherapy
a<8 g/l Receiving radiation therapy
b<10 g/l Recovering from therapy-induced <7–8 g/l bone marrow suppression and low reticulo-
cyte count Signs and symptoms of anemia <10 g/l Active bleeding <8 g/l or acute
blood loss of
>10 % total blood volume
If child is asymptomatic, hold transfusion during known chemotherapy or radiation therapy-induced myelosuppres- sion
a
Unless child is beginning an intensive course of therapy with an existing low hemoglobin (8–10 g/dl), even if asymp- tomatic
b
During radiation therapy, hemoglobin should be main-
tained above 6–7 g/dl for optimal oxygen-carrying capacity
28.2.1 Blood Product Processing
Processing of blood products may include:
▬ Addition of:
1. Citrate-phosphate dextrose adenine (CPDA-1) Anticoagulant: binds to calcium, inhibiting co- agulation pathways
2. ADSOL (dextrose, adenine, mannitol, sodium chloride)
Enhances red cell survival
Each unit contains approximately 350–380 ml, with a hematocrit of 75–80% if preserved with CPDA-1 and 55–60% if preserved with ADSOL (Kulkarnis and
Gera, 1999; Norville and Bryant, 2002; Rogers et al., 2002)
▬ Washed cells: uses normal saline to remove white blood cells (WBCs), platelets, and plasma proteins
▬ Leukocyte depletion (leukopore filtration): allows for greater percentage of leukocyte removal than washed or frozen platelets (99.5% versus 90%, respectively). This will prevent alloimmunization to human leukocyte antigens (HLA), cytome- galovirus (CMV) transmission, immune suppres- sion, and nonhemolytic febrile reactions, and will possibly decrease the incidence of graft versus host (GvHD) disease. The recommended Food
Table 28.3. Disease/treatment specific transfusion guidelines (Norville and Bryant, 2002; Rogers et al., 2002)
Disease/treatment Platelet count
Leukemia 10,000–20,000/mm
3Brain tumor <30,000/mm
3Requiring lumbar puncture <20,000/mm
3Requiring bone marrow aspirate/biopsy <5,000 /mm
3Requiring surgery >50,000/mm
3>100,00/mm
3for surgery of eye or brain Requiring intramuscular injection >20,000/mm
3Presence of bleeding 60,000/mm
3(with normal prothrombin, partial thromboplastin, and fibrinogen level)
Child on therapy, with platelet recovery Platelet count <5,000/ul anticipated to be >1–2 days
Febrile patient with acute illness <20,000/mm
3Table 28.4. Blood type compatibility
Blood group Antigens Antibodies Can give blood to Can receive blood from
AB A and B None AB AB, A, B, 0
A A B A and AB A and 0
B B A B and AB B and 0
0 None A and B AB, A, B, 0 0
Type and screen requested when likelihood of transfusion is low Type and crossmatch: Required for every PRBC transfusion Includes ABO, Rh crossmatching and antibody screen Includes ABO and Rh typing and antibody screen
Good for 72 hours; may use sample for type and crossmatch Antibody identification performed for positive antibody screen
and Drug Administration guidelines allow 5¥10
6leukocytes per unit of blood or platelets (Rogers et al., 2002) Indications for leukocyte-reduced blood products include chronic transfusions, patients receiving chemotherapy, and bone marrow trans- plant candidates.
▬ Irradiation of blood products: This causes deple- tion of lymphocytes. Graft versus host disease (GVHD) occurs when donor lymphocytes engraft in a susceptible recipient. These donor lympho- cytes proliferate and damage target organs, espe- cially the bone marrow, skin, liver, and gastroin- testinal tract, which ultimately can be fatal. The disease initially was recognized as a complication of intrauterine transfusion and transfusion to re- cipients of allogeneic marrow transplant in pa- tients who had received total body irradiation.
If irradiated blood products are recommended, (Table 28.5), the irradiation dose is 1,500–2,500 cGy to the midplane with at least 1,500 cGy in the field without resultant cellular damage (Kulkarnis and Gera, 1999; Rogers et al., 2002; Wuest, 1996). Irra- diation of red blood cells decreases the storage time to 28 days.
28.3 Transfusion Complications 28.3.1 Hemolytic Reactions
Hemolytic transfusion reactions (HTR) typically oc- cur when immunologic incompatibility between transfused donor RBCs and recipient alloantibodies produces accelerated destruction of transfused cells.
Transfusion of ABO-incompatible RBCs to a recipi- ent with the corresponding preformed antibodies is the most common etiology. Complement-mediated intravascular hemolysis is associated with acute he- molytic transfusion reactions (AHTR) and extravas- cular RBC destruction with delayed hemolytic trans- fusion reactions (DHTR). AHTR are the most severe and are a medical emergency requiring rapid identi- fication of the event, discontinuation of the trans- fusion, hydration, and intensive patient monitoring.
The risk of hemolytic reactions from transfusions is approximately 1:25,000, with the risk of fatal he- molytic reactions approximately 1:160,000. AHTR are most often caused by ABO incompatibility be- tween patient and donor during red cell transfusion.
The signs and symptoms of ATHR will usually ap- pear within the first 5–15 minutes after the transfu- sion is started, but can happen at any time during the transfusion. They generally consist of
▬ Temperature increase >1 °C or 2 °F
▬ Hemoglobinuria
▬ Chills
▬ Hypotension
▬ Severe low back pain or chest pain
▬ Anuria
▬ Nausea and vomiting
▬ Dyspnea, wheezing
▬ Anxiety, impending sense of doom
▬ Diaphoresis
▬ Generalized bleeding
▬ Disseminated intravascular coagulation (DIC) Laboratory findings include hemoglobinemia, hemo- globinuria, and decreased haptoglobin.
Table 28.5. Indications for irradiated blood products in pedi- atric hematology/oncology patients
Generally accepted indications Bone marrow transplant recipients Patients with Hodgkin’s disease or non-Hodgkin’s lymphoma
Patients with certain solid tumors including neuroblastoma and glioblastoma
Patients receiving HLA-matched components or components from biological relatives Indications under review
Patients with certain hematologic malignancies such as acute leukemia
Patients receiving crossmatched compatible platelets No established indications
Most patients receiving chemotherapy
Patients with aplastic anemia not receiving
immunosuppressive therapy
Treatment consists of the following:
▬ Stop transfusion
▬ Administer diphenhydramine (1 mg/kg PO or IV;
maximum 50 mg/dose) and Paracetamol/acetamin- ophen (15 mg/kg PO; maximum 1,000 mg/dose) In contrast to RBC transfusion – in which ABO in- compatibility has potentially lethal implications – ABO matching has historically been considered less critical for platelet transfusion. Nonetheless, platelets bear ABO blood group antigens, and the plasma con- tained in platelet concentrates results in passive transfer of anti-A or anti-B antibodies (Heal et al., 1989)
28.3.2 Nonhemolytic Reactions
Nonhemolytic reactions are certainly more common than hemolytic reactions (30% rate of occurrence – 10% PRBC, 20% platelets) (Norville and Bryant, 2002) These reactions occur more often in children receiving frequent transfusions and begin shortly after the transfusion is started. They result from al- loantibodies in the patient’s plasma that react to HLA or other antigens on leukocytes or tumor necrosis factor, interleukin-1, -6, -8, and other cytokines.
Symptoms include:
▬ Chills
▬ Fever (rise of 1 °C in 24-hour period)
▬ Urticaria
▬ Rigors
▬ Headache
▬ Nausea
Treatment consists of the following:
▬ Stop transfusion
▬ Administer diphenhydramine (1 mg/kg PO or IV;
maximum 50 mg/dose) and acetaminophen (15 mg/
kg PO; maximum 1,000 mg/dose)
▬ Consider premedicating future transfusion with diphenhydramine (0.5–1mg/kg; maximum 50 mg PO or IV) and acetaminophen (10–15 mg/kg PO);
Solu-Cortef 1–2 mg/kg IVP may also be given pri- or to transfusion in children with repeated trans- fusion reactions)
▬ Platelet transfusion may be restarted. However, if patient has a second reaction, the transfusion must be discontinued
28.3.3 Allergic Reactions
Allergens found in plasma may cause allergic trans- fusion reactions. If the recipient is sensitive to these, antibodies will be produced.
Clinical signs include:
▬ Skin erythema
▬ Pruritis
▬ Swollen lips
▬ Vomiting
▬ Hypotension
▬ Wheezing
▬ Laryngeal edema
▬ Anxiety
▬ Irritability
▬ Progression to anaphylaxis
Management aims to stop the allergic process. Anti- histamine can be administered. In the absence of fever the infusion can continue/restart. Recurrent al- lergic reactions indicate the routine use of antihista- mine with the possible addition of a steroid. Howev- er, if bronchospasm or life-threatening symptoms occur the infusion must be discontinued and the re- action treated.
28.3.4 Graft Versus Host Disease (GvHD) GvHD occurs when transfused lymphocytes are not recognized by the immunocompromised patient, re- sulting in engraftment of transfused cells that mount an attack against the host. Blood-relative donors with similar HLA haplotypes may increase the risk of oc- currence.
Symptoms may occur up to 30 days after transfu- sion and include
▬ Erythematous maculopapular dermatitis
▬ High fever
▬ Liver dysfunction
▬ Severe gastrointestinal symptoms (anorexia, diar- rhea, vomiting)
▬ Pancytopenia
Prevention should be attempted and includes the fol- lowing:
▬ Avoid donations from blood relatives
▬ Administer only irradiated blood components
28.3.5 Fluid Overload
Fluid overload may occur during blood product transfusion if the transfusion is administered too rapidly or the wrong volume is infused.
Symptoms include:
▬ Dyspnea
▬ Cough
▬ Tachycardia
▬ Hypertension
▬ Edema
▬ Headache
Treatment consists of the following:
▬ Stop transfusion
▬ Administer oxygen
▬ Diuretics (furosemide 1–2 mg/kg dose IV)
28.3.6 Transfusion-acquired Infections 28.3.6.1 Bacterial Infections
Transfusion-transmitted bacterial reaction has been identified as the most common and severe infectious complication associated with transfusion. Approxi- mately 57% of all transfusion-transmitted infections and 16% of transfusion-related deaths have been as- sociated with bacterial contamination. It has been es- timated that 1 in 38,500 units of red cells, 1 in 3,300 units of random donor platelets, and 1 in 2,000 units of apheresis platelets are contaminated with bacteria (Blajchman, 1999).
Blood components may be contaminated with bacteria throughout many stages of preparation, in- cluding blood collection, processing, pooling, and transfusion. Bacteria may enter into blood compo- nents through several sources: donors’ bacteremia, exposure to donor skin bacteria by venipuncture, and contaminated bags and environment in blood banks or hospitals.
The bacteria implicated in bacterial reactions as- sociated with red cells are typically Gram-negative bacilli such as Yersinia enterocolitica and Pseudo- monas fluorescens. In contrast, bacteria implicated in reactions associated with platelets are mostly Gram- positive species such as Staphylococcus and Strepto- coccus. The clinical severity of transfusion-transmit- ted bacterial reactions depends largely on the type and load of bacteria involved as well as the recipient’s condition. Gram-negative agents usually produce en- dotoxins and cause severe reactions, whereas Gram- positive agents often cause minor reactions. The load of bacteria is determined by the storage time. Platelet units that are stored over 3 days and red cell units that are stored over 21 days are strongly associated with an increased risk of bacterial reactions. In addi- tion, age and underlying diseases in recipients may also play an important role in determining the sever- ity of a bacterial reaction.
Symptoms include:
▬ Fever
▬ Chills, rigors
▬ Hypotension
Treatment consists of the following:
▬ Obtain cultures and treat with antibiotics as ap- propriate
▬ Treat with acetaminophen (15 mg/kg PO; maxi- mum dose 1,000 mg) and meperidine (0.5–1 mg/
kg) for rigors
▬ Consider pre-medicating future transfusion with diphenhydramine (0.5–1mg/kg, maximum 50 mg, PO or IV) and acetaminophen (10–15 mg/kg PO)
▬ Prestorage filtration may decrease febrile reac- tions
28.3.6.2 Cytomegalovirus (CMV) (See section 16.4.3 in chapter 16)
Infection with cytomegalovirus (CMV) is common
and often lasts for a lifetime. The prevalence of CMV
antibodies increases with age, and approximately
50–80% of the adult population are infected with the
virus. The acute infection is usually asymptomatic,
particularly in immunocompetent individuals. How-
ever, CMV infection may result in severe outcomes in immunocompromised or immunodeficient individu- als, including those receiving bone marrow or solid organ transplants.
The prevalence of CMV antibodies among blood donors is 35–50%. Prevention of transfusion-trans- mitted CMV infection in high-risk recipients is criti- cal.
▬ Use CMV-seronegative blood products for CMV- negative patients
▬ Use leukocyte-depleting filters capable of >3 log removal of white blood cells if only CMV-positive blood products are available
28.4 Erythrocyte Transfusion
Erythrocytes originate from pluripotent stem cells, which undergo proliferation, differentiation, and maturation. Iron and chemical growth factors stimu- late the process of erythropoiesis. Erythrocyte values vary with age until 12 years,, and thereafter according to gender (Table 28.6). Iron, ferritin, and bilirubin values vary until age 15 years, and thereafter accord- ing to gender (Table 28.7). The lifespan of erythro- cytes in serum is approximately 90–120 days; there- fore, signs or symptoms of treatment-associated ane- mia may not be observed for 4–6 weeks after the myelosuppressive therapy has been administered.
Table 28.6. Normal hematocrit, hemoglobin, and reticulocyte values for age (Lankowsky, 1999; Schwartz, 2000)
Age Hematocrit (%)
aHemoglobin (g/dl) Reticulocyte
Cord blood 51–55 13.5–20 3.2–5
2 weeks 50–51 12.5–20 0.5–1
3 months 35–36 9.5–14.5 0.7–1
6 months–6 years 36–37 10.5–14 1
7–12 years 38–40 11–16 1
Adult male 43–47 13–18 1
Adult female 41–42 12–16 1
a