TRANSFUSION THERAPY

PRINCIPLES OF TRANSFUSION THERAPY

Because of the potentially life-threatening consequences of blood type ABO

incompatibility and disease transmission through blood products, transfusion
therapy is limited to occasions when it is absolutely necessary and stringent
screening techniques are used before transfusion begins. Blood product
procurement, storage, preparation, and testing are regulated by the Food and Drug
Administration, the American Association of Blood Banks, and the Joint Commission
on Accreditation of Healthcare Organizations.

Blood Compatibility

Antigens

• The surface membrane of the red blood cell (RBC) is characterized by

glycoproteins known as antigens.
• More than 400 different antigens have been identified on the RBC membrane.
• There are fewer than a dozen clinically significant antigens, and of these, only
two antigenic systems (ABO and Rh) require routine prospective matching
before the transfusion.
• The ABO blood group system is clinically the most significant because A and
B antigens elicit the strongest immune response.
• The presence or absence of A and B antigens on the RBC membrane
determines the person's ABO group (see Table 27-1). The ability to make A or
B antigens is inherited.
• Antibody formation without specific exposure to antigen is unique to the ABO
system. Antibody directed against the missing antigens is produced by age 3
months in neonates.

TABLE 27-1 Blood Group Antigens and Antibodies of ABO System

BLOOD ANTIBODY ANTIBODY IN APPROXIMATE FREQUENCY OF
GROUP ON RBC PLASMA OCCURRENCE IN POPULATION
A A anti-B 45%
B B anti-A 8%
AB A and B none 3%
O none anti-A and anti- 44%
B

Antibodies
• Antibodies (or immunoglobulins) are proteins produced by B lymphocytes;
they consist of two light and two heavy chains that form a Y shape.
• Antibodies generally have a high degree of specificity, and interact only with
the antigen that stimulated their production.
• The five classes of immunoglobulins are determined by differences in their
heavy chains: immunoglobulin (Ig) G, IgA, IgM, IgD, IgE.
• The interaction of antibodies and antigens triggers an immune response, the
humoral immune response.
• Antibodies against the A and B antigens are large IgM molecules. When they
interact with and coat the A and B antigens on the RBC surface, the
antibody/RBC complexes clump together (agglutinate).
• Antibody/RBC complexes also activate the complement cascade, resulting in
the release of numerous active substances and RBC lysis. The large
antibody/RBC complexes also become trapped in capillaries, where they may
cause thrombotic
complications to vital organs, and in the reticuloendothelial system, where
they are removed from circulation by the spleen.
• The extent of the humoral response elicited by anti-A and anti-B interaction
with A and B antigens depends on the quantity of antibody and antigen.
Page | 2

Other Red Blood Cell Antigens

• Non-ABO RBC antigen-antibody reactions usually do not produce powerful

immediate hemolytic reactions, but several have clinical significance.
• After A and B, D is the most immunogenic antigen. It is part of the Rhesus
system, which includes C, D, and E antigens.
○ D (Rh)-negative people do not develop anti-D without specific
exposure, but have a high incidence of antibody development
(alloimmunization) after exposure to D.
○ Two common methods of sensitization to these RBC antigens are by
transfusion or fetomaternal hemorrhage during pregnancy and
delivery.
○ Anti-D can complicate future transfusions and pregnancies. For the D
(Rh)-negative person, exposure to D should be avoided by the use of
Rh-negative blood products. In the case of Rh-negative mother and Rh-
positive fetus, prophylaxis for exposure to D uses Rh immunoglobulin
(RhoGAM), which will prevent anti-D formation.
○ Exposure to RBC antigens from other antigenic systems (such as Lewis,
Kidd, or Duffy) may also cause alloimmunization, which becomes
clinically significant in people who receive multiple blood products
during long periods.

Blood Transfusion Options

Autologous Transfusion

• Before elective procedures, the patient may donate blood to be set aside for
later transfusion. Patients may donate one unit every 3 to 4 days up to 3 days
prior to surgery provided hemoglobin greater than 11 g/dL.
• Autologous RBCs can also be salvaged during some surgical procedures or
after trauma-induced hemorrhage by use of automated cell-saver devices or
by manual suction equipment.
• Autologous blood products must be clearly labeled and identified.
• Autologous transfusion eliminates the risks of alloimmunization, immune-
mediated transfusion reactions, and transmission of disease, making it the
safest transfusion choice.

NURSING ALERT

Patients who do not meet standard criteria for blood donation may still be eligible to
donate autologous blood before elective surgeries. The nurse should encourage
suitable candidates to

consider this underused option.

Homologous Transfusion

• With this most common option, volunteer donors' blood products are
assigned to patients randomly.
• Before donation, volunteer donors receive information about the process,
potential adverse effects, tests that will be performed on donated blood,
postdonation instructions, and education regarding risk for human
immunodeficiency virus (HIV) infection and signs and symptoms.
• Donors are screened against eligibility criteria designed to protect donor and
recipient (see Table 27-2).

TABLE 27-2 General Blood Donor Eligibility Criteria

Age 17 years
Weight Minimum 110 lb (49.9 kg)
Page | 3

Vital signs Afebrile, normotensive, pulse 50-100, blood pressure < 180/100 mm Hg
Hemoglobi 12.5 g/dL
n
History Travel, exposures, and past illnesses or events may defer or disallow
blood donation. Examples: travel to malarial areas, living in areas
exposed to bovine spongiform encephalopathy, blood transfusion or
tattoo within 12 months, recent surgery or pregnancy, corneal
transplant, history of hepatitis or unexplained jaundice, history or most
cancers, history of behaviors at high risk for human immunodeficiency
virus.
Immunizati Recent attenuated and live vaccines generally result in deferral.
ons
Illnesses A variety of current illnesses may defer or disallow blood donation.
Examples: clotting disorders, sickle cell disease, systemic lupus
erythematosus, multiple sclerosis, Lyme disease.

Directed Transfusion

• In directed transfusion, blood products are donated by a person for

transfusion to a specified recipient.
• This option may be used in certain circumstances (eg, a parent who provides
sole transfusion support for a child), but in general, no evidence exists that
directed donation reduces transfusion risks.

Blood Product Screening

Serologic Testing

• Routine laboratory testing is performed to assess the compatibility of a

particular blood product with the recipient before release of the blood product
from the blood bank. (See Table 27-3, page 964.)

○ ABO group and Rh type: determines the presence of A, B, and D

antigens on the surface of the patient's RBCs.
○ Direct Coombs' test: determines the antibody attached to the patient's
RBCs.
○ Crossmatch (compatibility test): detects agglutination of donor RBCs
caused by antibodies in the patient's serum.
○ Indirect Coombs' test: identifies lower molecular weight antibodies
(IgG) directed against blood group antigens.

TABLE 27-3 ABO and Rh Compatibility Chart

This chart identifies ABO and Rh compatibility when transfusing whole blood, red
blood cells, and plasma. Components suspended in plasma, such as platelets and
cryoprecipitate, usually follow plasma compatibility rules if the total volume
exceeds 120 mL for an adult patient.
WHOLE BLOOD
Donor
Recipie Rh Rh
A B O AB
nt positive negative
[check
A
mark]
[check
B
mark]
[check
O
mark]
[check
AB
mark]
Rh [check [check
positive mark] mark]
Page | 4

Rh [check
negative mark]

RED BLOOD CELLS

Donor
Recipie Rh Rh
A B O AB
nt positive negative
[check [check
A
mark] mark]
[check [check
B
mark] mark]
[check
O
mark]
[check [check [check [check
AB
mark] mark] mark] mark]
Rh [check [check
positive mark] mark]
Rh [check
negative mark]

PLASMA
Donor
Recipie Rh Rh
A B O AB
nt positive negative
[check [check
A
mark] mark]
[check [check
B
mark] mark]
[check [check [check [check
O
mark] mark] mark] mark]
[check
AB
mark]
Rh [check [check
positive mark] mark]
Rh [check [check
negative mark] mark]

Screening for Infectious Diseases

• Routine laboratory testing is performed to identify antigens or antibodies in

donor blood that may indicate prior exposure to specific blood-borne
diseases.
• Such testing supplements other principles of donation designed to decrease
the risk of disease transmission via blood products, including the use of
volunteer donors, the exclusion of high-risk populations, and the screening of
donors via health and social history.
• Through the use of donor screening and blood testing the risk of infections
transmitted with donated blood is < 1%.
• Specific conditions screened for include:
○ Hepatitis: tests for the presence of hepatitis B core and surface
antibodies and hepatitis C viral titer.
○ HIV-1 and HIV-2: tests for prior exposure to the virus.
 All blood products in the United States have been screened since
the test first became available in 1985. Current tests include
testing for antibodies with enzyme-linked immunosorbent assay
or enzyme immunoassay, or antigen with the P24 test. Nucleic
acid testing is becoming more widely used and provides a
mechanism to look for the presence of HIV-1 and HIV-2 before
antibody formation.
Page | 5

 Because antibody to the virus is not produced until at least 6

weeks after exposure, donor screening and exclusion of high-risk
groups (eg, homosexual men, I.V. drug abusers, prostitutes, and
sexual partners of high-risk people) remain important parts of
preventing transmission of HIV via blood products.
 A low risk of HIV transmission (estimated to be 1/100,000 units
of blood) remains.
○ Cytomegalovirus (CMV): tests for the antibody against CMV.
 Approximately 50% to 75% of blood donors have been exposed
to CMV and 10% to 20% carry CMV virus in white blood cells
(WBCs).
 Patients with impaired immune function (eg, bone marrow and
organ transplant recipients, premature babies) are at risk for
CMV infection from transfused blood.
○ Syphilis: tests for the presence of antibody against the spirochete.
○ Bacteria: contamination of blood products with bacteria may occur
during and after collection of blood. This risk is managed by
maintenance of sterile technique during phlebotomy and blood
processing procedures, correct storage techniques, visual inspection of
blood products, and limitation on shelf life.
○ Other infections that may be transmitted via blood transfusions include
human T-cell lymphoma virus
(HTLV) 1 and 2, malaria, babesiosis, Chagas' disease, and yersinia.
Although the risk appears remote, variant Creutzfeldt-Jacob disease
can be transmitted via blood transfusions, which has led to restrictions
on donation by individuals who have lived in areas with bovine
spongiform encephalopathy or “mad cow” disease.

ADMINISTRATION OF WHOLE BLOOD AND BLOOD COMPONENTS

Whole blood and blood components are administered to increase the amount of
oxygen being delivered to the tissues and organs, to prevent or stop bleeding
because of platelet defects or because of deficiencies or coagulation abnormalities,
and to combat infection caused by decreased or defective WBCs or antibodies. (See
Procedure Guidelines 27-1, page 966, and Standards of Care Guidelines)

General Considerations

• A unit of whole blood is usually separated into its various component parts
shortly after collection.
• Less than 3% of the blood collected nationwide is transfused as whole blood.
○ The use of blood components conserves the limited supply of blood,
provides optimal therapeutic benefit, and reduces the risk of
circulatory overload.
○ Due to the risks, blood components should be administered only with
informed consent and meticulous identification procedures.

Whole Blood

Description

• Consists of RBCs, plasma, plasma proteins, and approximately 60 mL

anticoagulant/preservative solution in a total volume of approximately 500
mL.
• Indications include acute, massive blood loss of greater than 1,000 mL,
requiring the oxygen-carrying properties of RBCs and the volume expansion
provided by plasma. In general, even acute loss of as much as one-third of a
patient's total blood volume (1,000 to 1,200 mL) can be safely and rapidly
replaced with crystalline or colloidal solutions.
Nursing and Patient Care Considerations
Page | 6

• For rapid infusions of large volumes of whole blood, additional steps may be
taken to deliver product rapidly and safely.
○ A small-pore (20 to 40 µm) filter may be used to remove
microaggregates (platelets, WBCs) that have been identified in the
lungs of massively transfused patients.
○ An approved blood warmer may be indicated to prevent hypothermia
and cardiac arrhythmias associated with the rapid infusion of
refrigerated solutions.
○ Electromechanical infusion devices to deliver blood at high flow rates
can hemolyze RBCs and should be used with caution.
• Observe closely for the most common acute complication associated with
whole blood transfusion—circulatory overload (rise in venous pressure,
distended neck veins, dyspnea, cough, crackles at bases of lungs).

STANDARDS OF CARE GUIDELINES

BLOOD TRANSFUSION

When administering whole blood or blood components, ensure the following:

• Follow up on results of complete blood count and report to health care
provider so appropriate blood product can be ordered based on patient's
condition.
• Contact the blood bank with health care provider's order and ensure timely
delivery of blood product.
• Establish a patent I.V. line with compatible I.V. fluid.
• Use appropriate administration setup, filter, warmer, etc.
• Obtain baseline vital signs.
• Make sure proper blood product is given to the right patient.
• Transfuse at prescribed rate during prescribed time, as tolerated by patient.
• Observe for acute reactions–allergic, febrile, septic, hemolytic, air
embolism, and circulatory overload–by assessing vital signs, breath
sounds, edema, flushing, urticaria, vomiting, headache, back pain.
• Notify patient's health care provider or available house officer if signs of
reaction or other abnormality arise.
• Be aware of delayed reactions and educate patient on risk and what to look
for: hemolytic, iron overload, graft-versus-host disease, hepatitis, and other
infectious diseases.

Footnote
This information should serve as a general guideline only. Each patient situation
presents a unique set of clinical factors and requires nursing judgment to guide
care, which may include additional or alternative measures and approaches.

Packed RBCs

Description

• Consist primarily of RBCs, a small amount of plasma, and approximately 100

mL anticoagulant/preservative solution in a total volume of approximately
250 to 300 mL/unit.
• Packed RBCs are typically contaminated with WBCs that may increase the risk
of minor transfusion reactions and alloimmunization. For patients who receive
multiple blood products during a specific period (eg, patients with leukemia or
aplastic anemia), packed RBCs may be further manipulated to remove WBCs
by washing or freezing the product in the blood bank or by the use of small-
pore (20 to 40 µm) leukoreduction filters during administration.
• Indications include restoration or maintenance of adequate organ
oxygenation with minimal expansion of blood volume.
Page | 7

• Dosage: average adult dose administered is 2 units; pediatric doses are

generally calculated as 5 to 15 mL/kg.

PROCEDURE GUIDELINES 27-1

ADMINISTERING BLOOD AND BLOOD COMPONENTS EQUIPMENT

• Tourniquet
• Iodine-containing skin antiseptic
• Needle or venous catheter
• Y-type blood infusion set
• 170-µ filter
• Normal saline
• Blood product as described

PROCEDURE

Nursing Action Rationale

Preparatory phase
1 Inform the patient of the 1 Instruct the patient to report unusual
. procedure, blood product to be . symptoms immediately.
given, approximate length of
time, and desired outcome.
2 Obtain and record baseline vital 2 If the patient's clinical status permits, delay
. signs. . transfusion if baseline temperature is greater
than 101.7° F (38.7°C).
3 Prepare infusion site. Select a 3 Antecubital veins are not recommended for
. large vein that allows patient . lengthy infusions. Prolonged restriction of arm
some degree of mobility. Start movement is uncomfortable and inconvenient
the prescribed I.V. infusion. for the patient. In the event of an acute
reaction, the I.V. catheter should be
maintained with normal saline.
DRUG ALERT Crystalloid solutions other than 0.9% saline and all medications are
incompatible with blood products.
They may cause agglutination or hemolysis.
4 Obtain blood product from blood 4 Platelets are normally cloudy. If the transfusion
. bank. Inspect for abnormal color, . cannot begin immediately, return product to
cloudiness, clots, and excess air. blood bank. Blood out of proper storage
Read instructions on the product (above 50° F [10° C]) for more than 30
label regarding storage and minutes cannot be reissued. Never store blood
infusion. Check expiration date. in unauthorized refrigerators, such as those on
the nursing unit.
5 Verify patient identification. 5 The majority of acute fatal transfusion
. . reactions are caused by clerical errors. Patient
a Ask the patient to state his or and product verification is the single most
. her full name and compare with important function of the nurse. It is strongly
name on the wrist band. If the recommended that two qualified individuals
patient is unable to state his or perform this task. Do not proceed with the
her name, verify identity with transfusion if there is a discrepancy. Contact
an individual familiar with the the blood bank immediately.
patient.
b Compare the name and ID
. number on the wristband with
the bag tag, transfusion form,
and medical order.
c.Confirm ABO and Rh
compatibility by comparing the
bag label, bag tag, medical
record, and transfusion form.
d Check bag labels for expiration
Page | 8

. date and satisfactory serologic

testing.

Performance phase
1 Start infusion slowly (ie, 2 1 Institutional policy may vary regarding flow
. mL/minute). Remain at bedside . rates and patient monitoring. Signs of a severe
15-30 minutes. If there are no transfusion reaction (ie, acute hemolytic,
signs of adverse effect, increase anaphylactic) are usually manifested during
flow to the prescribed rate. infusion of the initial 50-100 mL.
2 Observe the patient closely and 2 Acute reactions may occur at any time during
. check vital signs at least hourly . the transfusion
until 1 hour after transfusion.
Report signs of adverse effect to
health care provider immediately.
3 Record the following information 3 Facts relating to the transfusion should be
. on the patient's chart: . charted exactly.
a Time and names of persons
. starting and ending the
transfusion.
b Names of individuals verifying
. patient ID.
c.Unique product identification c. It must be possible to trace each transfusion
number. product to the original blood donor.
d Product and volume infused.
.
e Immediate response–for
. example, “no apparent
reaction.”

Nursing and Patient Care Considerations

• Infuse at the prescribed rate. Generally, a unit can be given to an adult in 90

to 120 minutes. Pediatric patients are usually transfused at a rate of 2 to 5
mL/kg per hour.
• To reduce the risk of bacterial contamination and sepsis, RBCs must be
transfused within 4 hours of leaving the blood bank.
• Observe closely (particularly during first 15 to 30 minutes) for the most
common acute complications associated with packed RBCs, allergic and
febrile transfusion reactions. Signs and symptoms of the more serious, but
rare, hemolytic transfusion reaction are usually manifested during infusion of
the first 50 mL.

Platelet Concentrates

Description

• Consist of platelets suspended in plasma. Products vary according to the

number of units (each unit is a minimum of 5.5×1010 platelets) and the
volume of plasma (50 to 400 mL).
• Platelets may be obtained by centrifuging multiple units of whole blood and
expressing off the platelet-rich plasma (multiple-donor platelets) or from a
single volunteer platelet donor using automated cell separation techniques
(apheresis). The use of single donor products decreases the number of donor
exposures, thus decreasing the risk of alloimmunization and transfusion-
transmitted disease.
Page | 9

• Patients may become alloimmunized to human leukocyte antigens (HLAs)

through exposure to multiple platelet products. Apheresis products from HLA-
matched platelet donors may be necessary. However, HLA-matched
transfusions are commonly difficult to obtain because of the many possible
HLA combinations in the population.
• Indications include prevention or resolution of hemorrhage in patients with
thrombocytopenia or platelet dysfunction.
• Platelet transfusions are generally contraindicated in heparin-induced
thrombocytopenia, where they may precipitate arterial thrombosis, and in
thrombotic thrombocytopenic purpura where they may worsen this
autoimmune destruction of platelets.
• Dosage: average dose is generally 1 unit of platelets for each 10 kg of body
weight; however, patients who are actively bleeding or undergoing surgical
procedures may require more.

Nursing and Patient Care Considerations

• Infuse at the rate prescribed. Generally, the infusion can be completed within
20 to 60 minutes, depending on total volume.
• Observe closely for the most common acute complications associated with
platelet transfusions, allergic and febrile transfusion reactions.
• Bacterial contamination of platelets, usually skin commensals from the
donor's arm, occurs in 4 to 10 per 10,000 units and limits the shelf life of
platelet products.

Plasma (Fresh or Fresh-Frozen)

Description

• Consists of water (91%), plasma proteins including essential clotting factors

(7%), and carbohydrates (2%). Each unit is the volume removed from a unit
of whole blood (200 to 250 mL).
• May be stored in a liquid state or frozen within 6 hours of collection.
• Indications include treatment of blood loss or blood clotting disorders related
to liver disease and failure, disseminated intravascular coagulation (DIC),
over-anticoagulation with warfarin (Coumadin), all congenital or acquired
clotting factor deficiencies, and dilutional coagulopathy resulting from
massive blood replacement. Storage in liquid state results in the loss of labile
clotting factors V and VIII, so that only plasma that has been fresh frozen can
be used to treat factor V and VIII deficiencies.
• Dosage: depends on the clinical situation and assessment of prothrombin
time, partial thromboplastin time, or specific factor assays.

Nursing and Patient Care Considerations

• Infuse at the rate prescribed. Generally, the infusion can be completed within
15 to 30 minutes, depending on total volume.
• Observe closely for the most common acute complication associated with
plasma infusion, volume overload.

Cryoprecipitate

Description

• Consists of certain clotting factors suspended in 10 to 20 mL plasma. Each

unit contains approximately 80 to 120 units of factor VIII (antihemophilic and
von Willebrand factors), 250 mg fibrinogen, and 20% to 30% of the factor XIII
present in a unit of whole blood.
• Indications include correction of deficiencies of factor VIII (ie, hemophilia A
and von Willebrand's disease), factor XIII, and fibrinogen (ie, DIC).
P a g e | 10

• Dosage: adult dosage is generally 10 units, which may be repeated every 8 to

12 hours until the deficiency is corrected or until hemostasis is achieved.
Nursing and Patient Care Considerations
Infuse at the rate prescribed. Generally, the infusion can be completed within 3 to
15 minutes.

Fractionated Plasma Products

Description

• Various highly concentrated plasma protein products are commercially

prepared by pooling thousands of single plasma units and by extracting the
desired protein. Most techniques involve heat or chemical treatments, which
eliminate the risk of transmitting blood-borne viruses, such as hepatitis B and
HIV.
• Colloid solutions provide volume expansion in situations where crystalloid
solutions are not adequate, such as therapeutic
plasma exchange, shock, and massive hemorrhage. They may also be used in
the treatment of acute liver failure, burns, and hemolytic disease of the
newborn.
○ Albumin is available as a 5% solution, which is oncotically equivalent to
plasma, and as a concentrated 25% solution.
○ Plasma protein fraction (PPF) is available as a 5% solution. Rapid
infusion of PPF has been associated with hypotension.
○ Albumin and PPF are pasteurized and carry no risk of viral disease.
They do not contain preservatives and should be used immediately
after opening.
• Immune serum globulins (ISGs) are concentrated aqueous solutions of
gamma globulin that contain high titers of antibody.
○ Must be administered by deep I.M. injection.
○ Nonspecific ISG is prepared from random donor plasma and is used to
increase gamma globulin levels and to enhance general immune
response in mild inherited or acquired immune disorders such as
hypogammaglobulinemia.
○ Specific ISG is prepared from donors who have high antibody titers to
known antigens and is used to treat specific disorders or conditions.
Hepatitis B immunoglobulin, varicella zoster immunoglobulin, and Rh
immunoglobulin are examples of specific ISGs.
○ ISGs carry no risk of hepatitis B, HIV, or other blood-borne infections.
○ Problems associated with use include pain at the injection site,
limitations on volume administered, loss of IgG into extravascular
tissue, or by degradation at the injection site.
• I.V. immunoglobulins (IVIGs) are aqueous solutions of immunoglobulins at a
higher concentration and are given in larger volumes than ISGs.
○ Like ISGs, they may be nonspecific or specific.
○ Indications include chronic replacement therapy in patients with
congenital or acquired immunodeficiency syndromes, acute
autoimmune disorders such as immune thrombocytopenic purpura,
and the treatment of chronic lymphocytic leukemia. Also, there are
numerous investigational uses, such as Guillain-Barré syndrome,
myasthenia gravis, rheumatoid arthritis, and viral infections, such as
CMV, adenovirus, and influenza. IVIGs may also be used to treat
platelet alloimmunization.
○ IVIGs do not appear to transmit HIV, but have been reported to
transmit hepatitis C.
○ Administration of IVIG should be closely monitored because of the
possibility of anaphylactic reactions. Dosage and rate of infusion
depend on the manufacturer's formulation.
• Factor VIII concentrate is a lyophilized concentrate used to treat moderate to
severe hemophilia A and severe von Willebrand's disease.
P a g e | 11

• Factor IX concentrate is a lyophilized concentrate used to treat factor IX

deficiency (Christmas disease).

Nursing and Patient Care Considerations

• These products may be distributed by the pharmacy rather than by the blood
bank.
• Check order and product insert to ensure proper dosage and administration
route.

Granulocyte Concentrates

Description

• Consist of a minimum of 1 ×; 1010 granulocytes, variable amounts of

lymphocytes (usually less than 10% of the total number of WBCs), 6 to 10
units of platelets, 30 to 50 mL RBCs, and 200 to 400 mL plasma.
• Obtained via apheresis, generally of multiple donors.
• Indications include treatment of life-threatening bacterial or fungal infection
unresponsive to other therapy in a patient with severe neutropenia.
• Dosage: generally 1 unit daily for approximately 5 to 10 days, discontinuing if
no therapeutic response.

Nursing and Patient Care Considerations

• Product must be ABO compatible and, if possible, Rh compatible because of

the high erythrocyte content.
• Transfuse granulocytes as soon as they are available. WBCs have a short
survival time, and therapeutic benefit is directly related to dose and viability.
• Premedicate per order to prevent adverse effects, generally with
antihistamine and acetaminophen. Steroids may also be required.
• Begin the transfusion slowly and increase to the rate prescribed and as
tolerated. The recommended length of infusion is 1 to 2 hours.
• Observe the patient closely throughout the transfusion for signs and
symptoms of febrile, allergic, and anaphylactic reactions, which may be
severe. Have emergency medications and equipment readily available.
• Agitate the bag approximately every 15 minutes to prevent granulocytes
from clumping at the bottom of the bag.
• Do not administer amphotericin products immediately before or after
granulocyte transfusion because pulmonary insufficiency has been reported
with concurrent administration of amphotericin and granulocytes. Many
institutions recommend a 4-hour gap to avoid this risk.

Modified Blood Products

Purpose

• To reduce the risk of specific transfusion-related complications, blood

products may receive further processing or treatment.
○ Leukocytes are removed from blood products through filtration,
washing, and freezing to reduce the risk of febrile, nonhemolytic
transfusion reactions, and alloimmunization to HLA.
○ Function and proliferation of donor lymphocytes are inhibited by
irradiation, to decrease the risk of posttransfusion graft-versus-host
disease (GVHD) in immunocompromised patients.

Methods

• Filtration
P a g e | 12

○ Standard filters (170 µm) effectively remove gross fibrin clots.

○ Microaggregate filters (approximately 40 µm) remove microscopic
aggregates of fibrin, platelets, and leukocytes that accumulate in RBC
products during storage. Their use is recommended during rapid,
massive transfusion of whole blood or packed RBCs to prevent
pulmonary complications. They reduce the risk of CMV transmission
and may also decrease the incidence of febrile transfusion reactions by
removing many of the leukocytes present.
○ Special leukocyte-depletion filters have been developed for use with
platelet products that remove 80% to 95% of leukocytes and that
retain 80% of the platelets. These filters also reduce the risk of CMV
transmission.
○ A product may be filtered before release from the blood bank, but more
commonly is released with the appropriate filter that must be attached
to the standard infusion set at the bedside per manufacturer's or blood
bank's instructions.

• Washing
○ Washing RBCs or platelets with a normal saline solution removes 80%
to 95% of the WBCs and virtually all of the plasma to reduce the
incidence of febrile, nonhemolytic transfusion reactions.
○ Washing requires an additional hour of processing time, and the shelf
life of the product is reduced to 24 hours after this additional
manipulation.

• Freezing
○ RBCs can be frozen within 7 days of blood collection, and then remain
viable for 7 to 10 years.
○ Removal of the hypertonic freezing preservative (glycerol) before
transfusion eliminates all of the plasma and 99% of WBCs.
○ Thawing and deglycerolization of RBCs requires an additional 90
minutes of preparation time and reduces shelf life to 24 hours after this
additional manipulation.
○ Freezing is also an effective method of storing rare blood types and
autologous RBCs.

• Irradiation
○ Exposure of blood products to a measured amount of gamma
irradiation inhibits lymphocyte function and proliferation without
damaging RBCs, platelets, or granulocytes. This eliminates the ability
of transfused lymphocytes to engraft in the immunocompromised
transfusion recipient and the accompanying risk of posttransfusion
GVHD.
○ Patients at risk for posttransfusion GVHD include bone marrow and
peripheral stem cell transplant recipients, premature neonates, and
patients with congenital immunodeficiency disorders, Hodgkin's and
non-Hodgkin's lymphomas, and HIV.

TRANSFUSION REACTIONS

Every transfusion of blood components can result in an adverse effect. Reactions

can be placed into two general categories: acute and delayed.
Acute Reactions
• Acute reactions may occur during the infusion or within minutes to hours
after the blood product has been infused.
• Acute reactions include allergic, febrile, septic, and hemolytic reactions, air
embolism, and circulatory overload. Patients who also receive multiple blood
products within a short time frame may also be at risk for hyperkalemia,
hypocalcemia, and hypothermia.
P a g e | 13

• Because reactions may exhibit similar clinical manifestations, every symptom

should be considered potentially serious and the transfusion should be
discontinued until the cause is determined.
• When a reaction is suspected, the health care provider should be notified
immediately and blood bags with tubing from all products recently transfused
should be returned to the blood bank for evaluation.
• The following samples should also be obtained if an acute reaction is
suspected.
○ A clotted blood sample to examine serum for hemoglobin and confirm
RBC group and type.
○ An anticoagulated blood sample for a direct Coombs' test to determine
the presence of antibody on the RBCs.
○ The first voided urine sample to test for hemoglobinuria.
• Precautions must be taken to avoid the hemolysis of RBCs during
venipuncture and sample collection because this could lead to invalid test
results. Whenever possible, blood samples should be drawn from a fresh
venipuncture and not from existing needles or catheters.
• If the only symptoms are those resulting from a mild allergic reaction (eg,
urticaria), extensive evaluation may not be necessary. In the event of a
severe reaction (eg, hypotension, tachypnea), more tests may be required to
determine the cause of the reaction.
• Causes, clinical manifestations, management, and prevention of acute
reactions are summarized in Table 27-4, pages 970 and 971.

TABLE 27-4 Acute Reactions to Blood Transfusion

ACUTE
REACTI CLINICAL
ON CAUSE MANIFESTATIONS MANAGEMENT PREVENTION
Allergic Sensitivity to • Flushing • Stop • Before
plasma protein • Itching, rash transfusion transfusion,
or donor • Urticaria, immediately ask patient
antibody, which hives . Keep vein about past
reacts with open (KVO) reactions. If
• Asthmatic
recipient with normal patient has
wheezing
antigen. saline. history of
• Laryngeal
Notify anaphylaxis,
edema
health care alert health
• Anaphylaxis
provider care provider,
and blood have
bank. emergency
• Give drugs
antihistami available, and
ne as remain at
directed bedside for
(diphenhydr the first 30
amine). minutes.
• Observe for
anaphylaxis
–prepare
epinephrine
if
respiratory
distress is
severe.
• If hives are
the only
clinical
manifestati
on, the
transfusion
P a g e | 14

can
sometimes
continue at
a slower
rate.
• Send blood
samples
and blood
bags to
blood bank.
Collect
urine
samples for
testing.
Febrile, Hypersensitivit • Sudden chills • Stop • Give
nonhemo y to donor and fever transfusion antipyretic
lytic white blood • Headache immediatel (acet-
cells, platelets, • Flushing y and KVO aminophen or
or plasma with normal aspirin)
• Anxiety
proteins. saline. before
Notify transfusion
health care as directed.
provider • Leukocyte-
and blood poor blood
bank. products may
• Send blood be
samples recommende
and blood d for future
bags to transfusions.
blood bank.
Collect
urine
samples for
testing.
• Check
temperatur
e ½ hour
after chill
and as
indicated
thereafter.
• Give
antipyretics
as
prescribedâ
€“treat
symptomati
cally.
Septic Transfusion of • Rapid onset • Stop • Do not permit
reactions blood or of chills transfusion blood to
components • High fever immediatel stand at room
contaminated • Vomiting, y and KVO temperature
with bacteria. diarrhea with normal longer than
• Marked saline. necessary.
hypotension Notify Warm
health care temperatures
provider promote
and blood bacterial
bank. growth.
• Obtain • Inspect blood
P a g e | 15

cultures of for gas

patient's bubbles,
blood and clotting, or
return abnormal
blood bags color before
with transfusion
administrati • Complete
on set to infusions
blood bank within 4
for culture. hours.
• Treat Change
septicemia administratio
as n set after 4
directed– hours of use.
antibiotics,
I.V. fluids,
vasopressor
s, steroids.
Circulato Fluid • Rise in • Stop • Concentrated
ry administered at venous transfusion blood
overload a rate or pressure and KVO products
volume greater • Distended with normal should be
than the neck veins saline. given
circulatory • Dyspnea Notify whenever
system can health care positive.
• Cough
accommodate. provider. • Transfuse at a
• Crackles at
Increased blood • Place rate within
in pulmonary base of lungs
patient the
vessels and upright with circulatory
decreased lung feet in reserve of the
compliance. dependent patient.
position. • Monitor
• Administer central
prescribed venous
diuretics, pressure of
oxygen, patient with
morphine, heart
and disease.
aminophylli
ne.
Hemolyti Infusion of • Chills; fever • Stop • Meticulously
c incompatible • Lower back transfusion verify patient
reaction blood products: pain immediatel identification
• Antibodi • Feeling of y–KVO –from
es in head with 0.9% sample
recipient' fullness; saline. collection to
s plasma flushing • Notify product
attach to • Oppressive health care infusion.
transfuse feeling provider • Begin
d red and blood infusion
• Tachycardia,
blood bank. slowly and
tachypnea
cells • Treat shock, observe
• Hypotension,
(RBCs), if present closely for 30
hemolyzi vascular
• Draw minutes–co
ng the collapse
testing nsequences
cells • Hemoglobinu
samples, are in
either in ria, proportion to
hemoglobine collect
circulatio urine the amount
n or in mia of
sample.
the • Bleeding incompatible
• Maintain
reticuloe • Acute renal
P a g e | 16

ndothelia failure blood blood

l system. pressure transfused.
• Antibodi with I.V.
es in colloid
donor solutions.
plasma Give
attach to diuretics as
recipient prescribed
RBCs, to maintain
causing urine flow,
hemolysi glomerular
s (may filtration,
result and renal
from blood flow.
infusion • Insert
of indwelling
incompat catheter to
ible monitor
plasmaâ hourly urine
€“less output.
severe Patient may
than require
incompat dialysis if
ible renal failure
RBCs). occurs.

Delayed Reactions

• Delayed reactions occur days to years after the transfusion.

• Delayed reactions include delayed hemolytic reactions, iron overload
(hemosiderosis), GVHD, infectious diseases (eg, hepatitis B, hepatitis C, CMV,
Epstein-Barr virus, malaria, HIV, HTLV).
• Symptoms of a delayed reaction can vary from mild to severe. Diagnosis may
be complicated by the long incubation period between transfusion and
reaction and the complexity of diagnostic tests.
• Causes, clinical manifestations, management, and prevention of delayed
reactions are summarized in Table 27-5, pages 971 and 972.

TABLE 27-5 Delayed Reactions To Transfusion Therapy

DELAYED CLINICAL
REACTION CAUSE MANIFESTATIONS MANAGEMENT PREVENTION
Delayed The • Fever • Generally, no • The
hemolytic destruction • Mild jaundice acute crossma
reaction of transfused • Decreased treatment is tch
red blood hematocrit required, but blood
cells by hemolysis may sample
antibody not be severe should
detectable enough to be
during cause shock drawn
crossmatch, and renal within 3
but formed failure. If this days of
rapidly after occurs, blood
transfusion. manage as transfus
Rapid outlined under ion.
production acute Antibod
may occur hemolytic y
because of reactions. formatio
antigen n may
exposure occur
P a g e | 17

during within
previous 90 days
transfusions of
or pregnancy. transfus
ion or
pregnan
cy.
Iron Deposition of • Diabetes • Treat –
overload iron in the • Decreased symptomaticall
(hemosidero heart, thyroid y.
sis) endocrine function • Deferoxamine
organs, liver, • Arrhythmias (Desferal),
spleen, skin, which chelates
• Heart failure
and other and removes
and other
major organs accumulated
symptoms
as a result of iron through
related to
multiple, the kidneys;
major organ
long-term administered
failure
transfusions I.V., I.M., or S.C.
(aplastic
anemia,
thalassemia).
Graft- Engraftment • Erythematous • Immunosuppre • Transfus
versus-host of skin rash ssion with e with
disease lymphocytes • Liver function corticosteroids, irradiate
in the bone test cyclosporine A. d blood
marrow of abnormalities • Symptomatic product
immunosupp • Profuse, management s.
ressed watery of pruritus,
patients, diarrhea pain
setting up an • Fluid and
immune electrolyte
response of replacement
the graft for diarrhea
against the
host.
Infectious
disease
Hepatitis B Hepatitis B • Elevated liver • Usually • Screen
virus enzymes resolves blood
transmitted (ALT/AST) spontaneously donors,
from blood • Anorexia, within 4-6 tempor
donor to malaise weeks. Can arily
recipient via • Nausea and result in rejectin
infected vomiting permanent g those
blood liver damage. who
• Fever
products. Treat may
• Dark urine
symptomaticall have
• Jaundice
y. had
contact
with the
virus.
Those
with a
history
of
hepatiti
s after
age 11
are
perman
P a g e | 18

ently
deferre
d;
pretest
all
blood
product
s (EIA).
Hepatitis C Hepatitis C • Similar to • Symptoms • Pretest
(formerly virus serum B usually mild. all
non-A, non- transmitted hepatitis, but Interferon and blood
B hepatitis) from blood symptoms are ribavirin may donors
donor to usually less be used to (ALT,
recipient via severe. treat chronic anti-
infected Chronic liver liver disease. HBc
blood disease and antibod
products. cirrhosis may y, anti-
develop. hepatiti
sC
antibod
y).
Epstein-Barr Transmitted • Fever • Rest and • Questio
virus, through • Fatigue supportive n
cytomegalo infected • Hepatomegal management. prospec
virus, blood y tive
malaria products. blood
• Splenomegaly
donors
regardin
g colds,
flu,
foreign
travel.
Acquired Human • Night sweats • Combination • Test
immunodefi immunodefici • Unexplained antiretroviral each
ciency ency virus weight loss therapy. donor
syndrome (HIV) • Lymphadenop for HIV
(AIDS) transmitted athy antibody
from blood .
• Pneumocystis
donor to • Reject
pneumonia
recipient via prospec
• Kaposi's
infected tive
blood sarcoma
high-
products. • Diarrhea
risk
donors:
males
who
have
had sex
with
another
male
since
1977;
users of
self-
injected
I.V.
drugs;
male or
female
partners
P a g e | 19

of
prostitut
es;
hemoph
iliacs or
their
sexual
partners
; sexual
partners
of those
with
AIDS or
high
risk for
AIDS;
immigra
nts from
Haiti or
sub-
Saharan
Africa.
Human T- HTLV-1 • Signs of • HTLV-1-infected • Screen
lymphotropi transmitted neuromuscula individuals all
c virus type from blood r disease have a low risk prospec
1 (HTLV-1) donor to • Signs of T-cell of developing tive
associated recipient via leukemia disease blood
myelopathy blood (3%–5%). donors
and tropical products. Incubation for anti-
spastic period 10-20 HTLV-1
paraparesis years. antibody
(HAM/TSP) • Should disease .
Adult T-cell occur, treat
leukemia symptomaticall
y.
Syphilis Spirochetemi • Presence of • Penicillin • Test
a caused by chancre therapy blood
Treponema • Regional before
pallidum. lymphadenop transfus
Incubation 4- athy ion
18 weeks. • Generalized (rapid
rash plasma
reagin).
Organis
m will
not
remain
viable in
blood
stored
24-48
hours at
39.2°
F (4°
C).

BLOOD AND MARROW STEM CELL TRANSPLANTATION

P a g e | 20

Blood and marrow stem cell transplantation are potentially lifesaving treatments
with application in many malignant and nonmalignant disorders. Several decades of
research have advanced this technology from an experimental treatment of last
resort to the preferred method of intervention for selected diseases. Although the
basic procedures are now well established, this field continues to grow rapidly
through ongoing research in areas such as nonmyeloablative (“mini”)
allogeneic transplants, the application of biologic response modifiers to modulate
the immune response, and the use of donor lymphocyte infusions to prevent or
treat posttransplant relapse.

PRINCIPLES OF BLOOD AND MARROW STEM CELL TRANSPLANTATION

Types of Stem Cell Transplant

The type of transplant selected is contingent on factors, such as the underlying

disorder, the availability of a histocompatible (HLA-matched) donor, and the clinical
condition of the patient. Stem cells may come from the patient (autologous), and
identical twin (syngeneic) or another donor (allogeneic). Stem cells are found in
bone marrow, in peripheral blood (especially if the patient is treated to increase the
numbers of circulating stem cells), and in umbilical cord blood.

Autologous Bone Marrow Transplantation

• Bone marrow is removed from the patient during an operative harvesting
procedure, frozen, and reinfused after the patient has undergone high-dose
chemotherapy and possibly radiotherapy.
• Advantages: readily available, usually lower morbidity and mortality than
allogeneic bone marrow transplantation (BMT).
• Disadvantages: operative procedure, marrow must be disease free, sufficient
quantity of cellular marrow must be aspirable, in most cases has higher rate
of relapse than allogeneic bone marrow transplantation.

Syngeneic Bone Marrow Transplantation

• Bone marrow is removed from an identical twin during an operative
harvesting procedure and infused into the patient, who has undergone high-
dose chemotherapy and possibly radiotherapy.
• Advantages: patient's marrow does not need to be harvestable (eg, aplastic
anemia, myelofibrosis), generally lower morbidity and mortality than
allogeneic BMT.
• Disadvantages: higher relapse rate than in allogeneic BMT.

Allogeneic Bone Marrow Transplantation

• Bone marrow is removed from a donor who is most commonly a sibling or
other close relative (related) but may be a volunteer donor (unrelated).
○ Identical HLA phenotypes are preferred. HLA mismatches require
additional immunosuppression and are associated with higher
morbidity and mortality.
○ Bone marrow is removed during an operative harvesting procedure and
infused into the patient, who has undergone high-dose chemotherapy
and possibly radiotherapy.
○ Allogeneic bone marrow may be treated in various ways before
infusion, including removing RBCs if ABO incompatible and removing T
lymphocytes to reduce the risk of GVHD.
• Advantages: patient's marrow does not need to be harvestable (eg, aplastic
anemia, myelofibrosis, genetic disorders), lowest rate of relapse.
• Disadvantages: risk for GVHD, generally higher morbidity and early mortality
than other types of BMT. Unrelated and HLA-mismatched transplants have
higher risk of GVHD and infectious complications, and risk of graft rejection or
failure.
P a g e | 21

Autologous or Allogeneic Peripheral Blood Stem Cell Transplantation

Although hematopoietic stem cells are primarily found in the bone marrow, they can
also be found in the peripheral circulation in smaller numbers.
• Most peripheral blood stem cell transplantations are autologous.
• Peripheral blood stem cells are collected using one or more apheresis
procedures after the patient or donor has been treated to increase the
number of circulating stem cells by methods such as timed administration of
chemotherapy and growth factors. The cells are frozen and stored, and later
reinfused into the patient after high-dose chemotherapy and possibly
radiotherapy.
• Advantages: patient's marrow does not need to be harvestable (as in
hypocellular or tumor-contaminated bone marrow); there is no operative risk
to the patient or donor. Peripheral blood stem cell transplantation has a low
risk of morbidity and mortality and eliminates lengthy hospital stays. The
product may be used alone or in conjunction with autologous or allogeneic
bone marrow.
• Disadvantages: for allogeneic donors, the long-term risks of boosting healthy
bone marrow production with growth factors, and in some cases
chemotherapy, are not yet known.
Umbilical Cord Blood Stem Cell Transplantation
• Umbilical cord blood is rich in stem cells, and may be stored at birth for later
autologous use, related allogeneic use, or unrelated allogeneic use.
• Advantages: may provide lifesaving allogeneic stem cells from new sibling to
older child, no risk to the donor.
• Disadvantages: may have higher risk of graft failure than other types of
transplants; number of stem cells may be insufficient for older patients.

Nonmyeloablative or “Mini” Transplants

• Conventional conditioning for blood and marrow stem cell transplants
requires high doses of chemotherapy and radiotherapy to destroy existing
bone marrow cells. This results in significant morbidity and mortality,
particularly in certain patient populations (eg, elderly patients, those with
poor organ function).
• Prior research has demonstrated that under certain conditions individuals can
exist with bone marrow stem cells from two sources (self and allogeneic
donor)—a state known as mixed chimerism. These changes in the immune
system appear to enhance the antitumor immune response.
• The goals of nonmyeloablative conditioning regimens are to prevent graft
rejection and promote mixed chimerism. The preparative regimen uses
combinations of such agents as cyclophosphamide (Cytoxan), fludarabine
(Fludara), antithymocyte globulin (ATG), and irradiation. Allogeneic bone
marrow or peripheral blood stem cells are then infused.
• Donor lymphocytes are usually given at intervals following transplant to
further enhance the immune antitumor effect.
• Advantages: patients otherwise ineligible for allogeneic transplant due to
age, comorbid conditions, or organ function are more likely to tolerate the
less-toxic preparative regimen. Patients do not usually experience significant
neutropenia, thrombocytopenia, anemia, and accompanying complications.
Outpatient transplants are usually feasible.
• Disadvantages: this remains a new treatment approach and there is not
enough data yet to determine whether it is as effective and safe as
conventional allogeneic transplants. The incidence of acute and chronic
GVHD and the extent of treatment-related mortality appear to be as high, but
the population treated with minitransplants is also older and at higher risk for
complications.

The Human Leukocyte Antigen System and Transplantation

• The immune-mediated recognition of the differences in HLA antigens is the
first step in the rejection of a transplanted organ or graft or in GVHD.
P a g e | 22

• The HLA antigens are complex proteins expressed on the surface of all
nucleated cells (A, B, C antigens) or cells of the immune system (D antigens).
○ More than a hundred different antigens have been identified.
○ Antigens are classified according to the locations on chromosome 6,
which encodes them.
○ A person's genetically inherited mixture of antigens expressed on cell
surfaces is the phenotype or tissue type of that person.
• Although considerably more complex, determination of HLA type is similar to
that of ABO testing.
○ Lymphocytes are mixed with antibody directed against known HLA
antigens. Lymphocytes will survive if the antigen is absent and will be
inactivated if it is present. This method identifies HLA-A, -B, and -C
antigens.
○ Donor and recipient lymphocytes are mixed and cultured together. This
test, the mixed lymphocyte culture, identifies HLA-D antigens. Survival
of both sources of cells indicates compatibility.
○ New techniques for determining a person's genetic HLA code use DNA
probes. These tests are highly accurate, but their use remains limited
because of the specialized techniques and high cost.
• Siblings have a 1-in-4 chance of having identical sets of HLA antigens. With a
decreasing national birthrate, however, only 35% of people in the United
States can anticipate having an HLA-identical sibling.
• Because of the complexity of the HLA system, unrelated people have less
than a 1-in-5,000 chance of having identical HLA types. The National Bone
Marrow Donor Registry, which was established in 1987, maintains a
computerized list of potential HLA-typed bone marrow donors and provides
assistance to patients who seek an unrelated donor. Information on becoming
a volunteer bone marrow donor or on initiating a computerized search for a
donor can be obtained by calling the National Marrow Donor Program (see
Box 27-1, page 952, for additional resources for patients undergoing blood
and marrow stem cell transplantation).

Indications
• If an HLA-matched related donor is available, allogeneic bone marrow
transplantation is generally considered the treatment of choice in certain
disorders, including:
○ Severe aplastic anemia.
○ Inherited immunodeficiency disorders, such as severe combined
immunodeficiency disease and Wiskott-Aldrich syndrome.
○ Allogeneic bone marrow transplantation has also been used with
varying success in the treatment of other genetic disorders (eg,
thalassemia, sickle cell disease).
• Allogeneic, syngeneic, and autologous bone marrow transplantation are also
widely applied in other malignancies, where success rates depend largely on
factors such as the age of the patient, current disease status, the extent of
prior treatment, and coexisting morbidity.
• Autologous peripheral blood stem cell transplantation is used in the
treatment of solid tumors such as Ewing's sarcoma and in the treatment of
leukemias and lymphomas. Allogeneic peripheral blood transplantation is
generally used in the treatment of leukemias.
• Diseases and disorders treated with this technology are summarized in Box
27-1.

BOX 27-1 INDICATIONS FOR BONE MARROW TRANSPLANTATION

ALLOGENEIC
Nonmalignant
• Aplastic anemia
• Myelofibrosis
• Wiskott-Aldrich syndrome
P a g e | 23

• Thalassemia
• Severe combined immunodeficiency diseases
• Mucopolysaccharidoses
• Sickle cell disease
Malignant
• Acute myeloid leukemia
• Acute lymphocytic leukemia
• Hodgkin's lymphoma
• Non-Hodgkin's lymphoma
• Myelofibrosis
• Multiple myeloma
• Selected solid tumors
Autologous
• Acute myeloid leukemia
• Acute lymphocytic leukemia
• Hodgkin's lymphoma
• Non-Hodgkin's lymphoma
• Multiple myeloma
• Selected solid tumors

HARVESTING OF BONE MARROW AND PERIPHERAL BLOOD STEM CELLS

Evaluation of Recipient
• Eligibility criteria include age (generally younger than age 55 for allogeneic,
younger than age 65 for autologous and syngeneic bone marrow
transplantation, and younger than age 70 for peripheral blood stem cell
transplantation) and availability of suitable stem cell source.
• Before undergoing transplantation, an extensive workup ensures that the
patient's disease is treatable with stem cells and that the patient has no
limitations that will increase the risk of mortality.
• Specific criteria may vary among transplant centers and treatment protocols,
but generally include:
○ Disease-specific evaluation of severity and extent of current disease
manifestations.
○ Adequate cardiac function: generally left ventricular ejection fraction
greater than 45%.
○ Adequate pulmonary function: generally, forced expiratory capacity
and forced vital capacity greater than 50%.
○ Adequate renal function: generally, creatinine less than 2 mg/dL.
○ Adequate hepatic function: generally, bilirubin less than 2 mg/dL.
○ No active infections (including HIV).
○ No coexisting severe or uncontrolled medical conditions.

Evaluation of Blood and Marrow Donors

• Because bone marrow donation for allogeneic or syngeneic BMT is an elective
procedure with no benefit to the donor, great care is taken to ensure that the
potential donor is fit for surgery and understands the potential risks.
Autologous bone marrow donors must generally meet the same criteria.
Evaluation includes:
○ Thorough medical history and physical examination
○ Chest X-ray
○ Electrocardiogram
○ Laboratory evaluation (complete blood count [CBC], chemistry profile,
testing for CMV, hepatitis B and C, HIV, HTLV, and syphilis, ABO and Rh
determination, coagulation studies).
• Informed consent including potential donor complications must be obtained.
• Relatively common complications include:
○ Bruising.
P a g e | 24

○ Pain at aspiration sites.

○ Mild bleeding.
• Rare complications include:
○ Adverse effects of anesthesia (general, spinal, or epidural).
○ Infection of aspiration sites.
○ Persistent pain.
○ Transient neuropathies.
• Because of the significant loss of blood volume and RBCs during the harvest
procedure, donors are advised to give one or two units of autologous blood 1
to 3 weeks before surgery, which may be reinfused during marrow collection
if needed.
• Evaluation of donors for peripheral blood stem cell transplantation is similar,
but less stringent. The apheresis procedure is similar to donating platelets.

Stem Cell Collection Procedure

Bone Marrow Harvest (Autologous, Syngeneic, or Allogeneic)

• Performed under epidural, spinal, or general anesthesia under sterile
conditions in operating room.
• An aspiration needle is used to puncture the skin and puncture the iliac crest
multiple times without exiting the skin, removing marrow in 2- to 5-mL
aliquots (samples).
• Marrow is drawn up into heparinized syringes and filtered to remove fibrin
clots and other debris.
• Marrow may be infused immediately, treated and infused, or frozen in a
preservative solution containing dimethyl sulfoxide (DMSO) until needed.
• Bone marrow donation is a relatively safe operative procedure with few
serious complications.

Postharvest Care of the Bone Marrow Donor

• Procedure is generally done as same-day care, with discharge after recovery
from anesthesia.
• Observe for potential complications (bleeding, hypotension caused by fluid
loss).
• Instruct patient to resume normal activities gradually during the week after
donation.
• Instruct patient to keep aspiration sites clean and dry and observe for signs
of infection (redness, swelling, warmth or discharge at sites, fever, malaise).
• Provide adequate analgesia and instruct patient about pain management.
• Arrange follow-up appointment with primary care provider in 2 to 3 weeks for
a CBC.

Harvesting of Peripheral Blood Stem Cells

• Involves donor preparation by “priming” hematopoietic system with
timed chemotherapy and sequential growth factors to increase number of
circulating stem cells.
• Large-bore central catheter suitable for apheresis procedures is inserted.
• One to ten apheresis procedures may be needed to collect sufficient numbers
of suitable cells.
• Cells are frozen in a preservative solution that contains DMSO until needed.
• Acute complications of apheresis include citrate toxicity, which may be
managed by increasing dietary calcium intake 2 to 3 days before procedure
and by using calcium-based antacids during procedure. Blood calcium levels
are carefully monitored throughout the procedure and I.V. calcium given as
needed.

PREPARATION AND PERFORMANCE OF THE TRANSPLANT

Preparation of Recipient
P a g e | 25

• A long-term central catheter is inserted for multiple I.V. treatments, including

blood products, total parenteral nutrition, and blood-drawing.

• High-dose chemotherapy or radiotherapy is administered to:

○ Destroy residual tumor cells.
○ Suppress immune response against new stem cells.
○ Create space within donor marrow for new stem cells.

• Symptoms immediately associated with high-dose chemotherapy or

radiotherapy regimens used in blood and marrow stem cell transplantation
may include:
○ Severe nausea and vomiting (with most regimens).
○ Cardiomyopathy, hemorrhagic cystitis (with cyclophosphamide
[Cytoxan]).
○ Seizures (with busulfan [Myleran]).
○ Fever, generalized erythema, parotitis (with total body irradiation).

Infusion of Bone Marrow or Peripheral Blood Stem Cells

TABLE 27-6 Infusion Guidelines for Bone Marrow or Peripheral Blood Stem
Cells
TYPE OF PROCESSING POTENTIAL
STEM PRIOR TO ADVERSE NURSING
CELLS INFUSION VOLUME EFFECTS CONSIDERATIONS
ABO- Filtered to 500–2,0 Volume overload, Emergency medications
compatible remove large 00 mL allergic reactions, available, close
untreated particles pulmonary monitoring
allogeneic compromise (fat
bone emboli, cell
marrow aggregates)
ABO- Removal of red 200–60 Allergic reactions,Prehydrate to ensure
incompatibleblood cells and 0 mL intravascular adequate renal perfusion
bone plasma hemolysis (rare) and alkaline urine,
marrow emergency medications
available, close
monitoring
Autologous Filtered and 100–50 Related to DMSO: Emergency medications
bone frozen with 0 mL Histamine- available, close
marrow dimethyl release reaction monitoring, cardiac
sulfoxide (DMSO) (flushing, chest monitoring recommended
as preservative, tightness,
thawed in warm abdominal
water bath cramping,
immediately nausea), cardiac
prior to infusion arrhythmias,
anaphylaxis
Peripheral Frozen with 100–1,0 Related to DMSO: Administer as tolerated
blood stem DMSO as 00 mL Histamine- (may be high volume and
cells preservative, release reaction DMSO content),
thawed in warm (flushing, chest premedicate with
water bath tightness, antihistamine and
immediately abdominal antiemetic, emergency
prior to infusion. cramping, medications available,
nausea), cardiac close monitoring, cardiac
arrhythmias, monitoring recommended
anaphylaxis

NURSING ALERT
Unlike all other blood products administered to transplant recipients, stem cells
P a g e | 26

should never be irradiated. In addition, infusion pumps and filters should be avoided
because they may remove or damage stem cells.

Posttransplant Care

General Considerations
• Significant complications that require specialized medical and nursing care
may occur during the first few weeks and months after blood and marrow
stem cell transplantation.
○ Risk is highest in mismatched unrelated allogeneic BMT.
○ Followed by matched unrelated and mismatched related allogeneic
BMT.
○ Followed by matched related allogeneic BMT.
○ Followed by syngeneic BMT.
○ Followed by autologous BMT.
○ Followed by autologous peripheral blood stem cell transplantation.

• Nursing care is aimed at early identification and treatment of problems, and

includes:
○ Comprehensive physical and psychosocial assessment.
○ Immediate notification of health care provider of any abnormal
assessment parameters found.
○ Early recognition and intervention for life-threatening complications,
such as sepsis, respiratory failure, GI bleeding, renal and hepatic
failure, and veno-occlusive disease.
○ Prevention of infection.
○ Prevention of bleeding.
○ Expert symptom management of problems that may occur after blood
and marrow stem cell transplantation, such as nausea, vomiting, pain,
fatigue, anxiety, and delirium.

Hematopoietic Complications
• Blood and marrow stem cell transplant patients, particularly allogeneic
recipients, are at risk for life-threatening bacterial, viral, and fungal infections
because of their profound immunosuppression.
○ Transplant patients are usually cared for in a protective environment,
which ranges from single HEPA-filtered rooms to strict laminar airflow
and isolation in sterile environment.
○ In an ambulatory or home setting, the patient and family must pay
strict attention to methods of preventing infection, including wearing
high-filtration masks, hand washing, safe food handling, and avoidance
of crowded areas and exposure to illnesses.
○ Blood and marrow stem cell recipients are at high risk for nosocomial
blood stream infections related to long-term central venous catheters,
neutropenia, and immunosuppression. Strict adherence to an
evidence-based procedure for insertion and management of central
venous catheters is essential in this population.
○ Additional preventive interventions vary widely and include elaborate
disinfection procedures; modified or sterile diets; prophylactic
antibiotics, antivirals, and antifungals; surveillance cultures.

• The megakaryocyte is generally the last cell produced by new stem cells, and
platelet counts may take months to return to normal.
○ Blood and marrow stem cell transplant patients require frequent
assessment for signs and symptoms of overt or covert bleeding,
protection from injury, and support with platelet products.

• Anemia is a common complication caused by loss of RBCs through aging,

destruction, bleeding, and routine phlebotomy. Blood and marrow stem cell
transplant patients require frequent RBC transfusions.
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GI Complications
• Mucositis may develop because of high-dose chemotherapy and radiation
therapy that destroy rapidly dividing cells, including cells lining the mouth,
esophagus, and GI tract. Management includes meticulous oral hygiene, local
and systemic analgesia, and antimicrobial therapy.
• Nausea and vomiting may arise from multiple causes, including high-dose
chemotherapy, infection, GI bleeding, acute GVHD, and medications.
Management includes pharmacologic and nonpharmacologic interventions,
replacement of fluids and electrolytes, and support of nutritional
requirements.
• Diarrhea may have multiple causes, including high-dose chemotherapy,
infection, GI bleeding, GVHD, and medications. Management includes
cautious use of antidiarrheals, replacement of fluids and electrolytes, support
of nutritional requirements, protection of perirectal skin from excoriation.

Renal and Genitourinary Complications

• Renal failure may arise from multiple causes, including drug toxicity,
infection, and ischemia. Management includes maintenance of fluid and
electrolyte balance, monitoring of drug levels, and hemodialysis or
continuous venovenous hemodialysis.
• Hemorrhagic cystitis may occur as a result of high-dose cyclophosphamide
(Cytoxan) or with certain viral infections, such as adenovirus and BK virus.
Management includes hydration, blood product support, continuous bladder
irrigation, and rare invasive procedures, such as instillation of alum or
formalin, or surgery.

Hepatic Complications
Veno-occlusive disease (VOD) may occur as a result of damage to the liver from
high-dose chemotherapy and radiation therapy; incidence is approximately 20%.
• Signs and symptoms include hepatomegaly (generally painful), bilirubinemia,
weight gain.
• May progress to hepatic encephalopathy, coagulopathies, coma and death in
up to 50% of patients with veno-occlusive disease.
• Management is generally aimed at preventing further damage and at treating
symptoms. The antithrombotic and thrombolytic agent defibrotide may be
administered for severe VOD; however, the risk of bleeding is high with the
administration of this agent.

Pulmonary Complications
• Life-threatening pulmonary infections in stem cell recipients include bacterial
pneumonias, fungal infections, including aspergillosis, viral infections such as
CMV (especially in allogeneic recipients), RSV and, less commonly,
Pneumocystis carinii pneumonia (PCP), legionnaires' disease, toxoplasmosis,
and tuberculosis.
○ Preventive measures include hand hygiene, encouragement of
exercise, deep breathing, and coughing; administration of CMV-
screened and/or leuko-reduced blood products, high-dose acyclovir
(Zovirax) or ganciclovir (Cytovene),
and IVIG for allogeneic BMT patients at high risk for CMV; prophylactic
co-trimoxazole (Bactrim) for patients at risk for PCP. Staff, patient, and
family education regarding risk factors and transmission of these
infectious agents may help prevent primary and nosocomial infections.
○ Supportive care if symptomatic includes pulmonary hygiene, oxygen
therapy, and mechanical ventilation.

• Noninfectious pulmonary disease includes idiopathic pneumonitis, diffuse

alveolar hemorrhage, pulmonary fibrosis, and bronchiolitis obliterans.

Graft-Versus-Host Disease
P a g e | 28

• Acute GVHD occurs in 40% to 60% of allogeneic recipients even with HLA
matching, generally within first 3 months after transplant as a manifestation
of the immune response of activated donor T lymphocytes against the
recipient's cells and organs.
○ Primarily affects the skin, liver, and GI tract; may also affect
conjunctivae and lungs.
○ Severity ranges from mild and self-limited erythematous rash to
widespread blistering of skin, profuse watery diarrhea, and liver failure.
○ Prophylaxis generally includes immunosuppression with such
medications as cyclosporine (Neoral), tacrolimus (FK506), and
methotrexate (Trexall); may also include T-cell depletion of bone
marrow.
○ Treatment generally includes increased doses of routine
immunosuppressive drugs and additional drugs, such as
corticosteroids, antithymocyte globulin, and monoclonal antibodies.

• Chronic GVHD occurs in approximately 20% of long-term survivors; usually

appears within first year after allogeneic blood and marrow stem cell
transplant.
○ It has many similarities to autoimmune disorders such as scleroderma.
○ It affects the skin, mouth, salivary glands, eyes, musculoskeletal
system, liver, esophagus, GI tract, and vagina.
○ Treatment generally consists of corticosteroids and other
immunosuppressive drugs, such as mycophenolate (CellCept) and
thalidomide (Thalomid).
○ Immune system frequently suppressed beyond the effects of
medications; patient is at risk for infections, particularly from
encapsulated bacteria, and should receive prophylaxis with suitable
antibiotic such as penicillin.

Long-Term Sequelae and Survivorship Issues

• Long-term, disease-free survival varies from 5% to 10% for patients with
resistant, aggressive leukemias or lymphomas to 75% to 80% for aplastic
anemia.

• Long-term complications of blood and marrow stem cell transplantation

include:
○ Relapse of original disease.
○ Secondary malignancy.
○ Sterility.
○ Endocrine dysfunction, including reduced levels of human growth
hormone, estrogens and testosterone.
○ Cataracts (risk increased with radiation therapy, corticosteroids).
○ Chronic GVHD (allogeneic).
○ Aseptic necrosis (risk increased with corticosteroids).
○ Encephalopathy (risk increased with cranial irradiation and intrathecal
chemotherapy).

• Survivorship issues after this intensive and potentially life-threatening

treatment include:
○ Feelings of isolation, guilt, and loss.
○ Altered family dynamics.
○ Delayed puberty, decreased libido, early menopause, and other
physical problems that have an impact on sexual relationships.
○ Readjustment to school or work setting.
○ Financial burden of blood and marrow stem cell transplantation (cost of
transplant in the United States in 1999 ranged from approximately
$30,000 for an uncomplicated outpatient peripheral blood stem cell
transplantation to a minimum of $150,000 for an unrelated allogeneic
BMT).
P a g e | 29

○ Chronic health problems and fatigue.

○ Difficulty obtaining adequate health insurance.

• Despite the complex issues blood and marrow stem cell transplant survivors
face as they return to the task of living, several quality-of-life studies have
demonstrated that the majority rate their quality of life highly, would choose
to undergo transplant again, and frequently state that their experiences have
added new dimensions of meaning and purpose to their lives.