Volume 1, Number 1
Release date: December, 2007 - Expiration date: December 2008
Estimated time to complete activity: 1.0 hours
Educational credits: 1.0 contact hours
Click here
for a Printer friendly file.
Lillian M. Nail, PhD, RN, FAAN
Oregon Health & Science University School of Nursing, Portland
Anemia is a common side effect of cancer and cancer therapy,
affecting up to 90% of patients (Knight, Wade, & Balducci, 2004;
Loney & Chernecky, 2000). Anemic patients with cancer may experience
debilitating fatigue, impaired cognitive function, reduced tolerance
to treatment, and decreased survival (Ludwig & Strasser,
2001; Caro, Salas, Ward, & Goss, 2001; Figure 1). Nurses play a
pivotal role in identifying early signs of anemia and intervening
promptly to prevent further system compromise and impairment to
quality of life (QOL; Loney & Chernecky, 2000).
Risk factors for anemia include a history of blood transfusion
during the past 6 months, history of prior myelosuppressive therapy,
bone marrow transplant, history of radiotherapy to more than 20%
of the body, older age, low baseline hemoglobin level, and the
myelosuppressive potential of the patient’s cytotoxic therapy as
determined by the type, intensity, and duration (National
Comprehensive Cancer Network, 2007). As a result of the current
emphasis on dose-dense and high-dose chemotherapy, and
improved survival, the incidence of anemia is on the rise. This trend will likely continue unless there is a shift away from the use of
myelosuppressive therapies.
Mechanisms of anemia in patients with cancer include decreased
red blood cell (RBC) production, increased RBC destruction, and
blood loss. Causes of decreased RBC production include treatmentinduced
bone marrow suppression, impaired erythropoietic response,
nutritional deficiencies, anemia of chronic disease, tumor infiltration
of the bone marrow, RBC aplasia, hemophagocytic syndrome, and
megaloblastic anemia. Examples of RBC destruction include
hemolytic processes that can occur with hemodialysis or autoimmune
hemolytic anemia. Bleeding from the tumor or from surgery are the
most common causes of blood loss in patients with cancer (Cella,
Dobrez, & Glaspy, 2003; Knight et al., 2004; Langer, Choy, Glaspy,
& Colowick, 2002; Loney & Chernecky, 2000). Table 1 lists the current
National Cancer Institute (NCI) and World Health Organization
(WHO) criteria for identifying the different grades of anemia.
Table 2 details the standard laboratory work-up used to establish the
underlying cause of most anemias. Hemoglobin and hematocrit are the
standard measurements for every patient. Hemoglobin is the molecule
that carries oxygen, and hematocrit determines the RBC mass. The
normal hemoglobin concentration varies but is usually in the range of
12 g/dL to 16 g/dL for women and 14 g/dL to 17 g/dL for men. Normal
hematocrit values for women and men are 36% to 48% and 42% to
52%, respectively.
The RBC indices, which include mean corpuscular volume (MCV),
mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin
concentration (MCHC), and red cell distribution width (RDW), define
the size and hemoglobin content of the RBCs. Microcytic RBCs characterize
iron-deficiency anemia, normal RBC size is an indication of anemia
of chronic disease, and macrocytic RBCs are present in anemias
caused by folate deficiency or vitamin B12 deficiency. Normal MCV values
for adults range from 82 g/dL to 98 g/dL. An increased MCH is suggestive
of macrocytic anemia, whereas a decreased MCH is associated
with microcytic anemia. Normal values for adults range from 26 pg to
34 pg. MCHC is characterized as hypochromic, normochromic, or
hyperchromic, and is typically decreased in cancer-related anemia.
Normal values for adults range from 31 g/dL to 37 g/dL. RDW describes
the variation in RBC size, helping to further characterize an anemia. For
example, anemia of chronic disease is identified by a normal MCV and
a normal RDW, whereas iron deficiency is characterized by a low MCV
and a high RDW. Normal values for adults range from 11.5%
to 14.5%.
The reticulocyte count is an important measure of how effective
the bone marrow is in producing new RBCs. Measuring the reticulocyte
counts helps one to distinguish excess blood loss from inadequate
RBC production. A low reticulocyte count indicates the marrow
has a decreased production of RBCs despite an anemic state. A
high reticulocyte count signifies that increased RBC production is
occurring as the marrow attempts to replace the loss of prematurely
destroyed RBCs. Normal reticulocyte values are 0.5% to 1.5% for
men and 0.5% to 2.5% for women. (Cancer Therapy Evaluation Program, 2003)
NCI = National Cancer Institute; WHO = World Health Organization; LLN = lower limit of normal; WNL = within normal limits.
Iron studies are an integral part of evaluating all types of anemias, particularly
those related to cancer, because nearly all anemic patients with cancer
require iron supplementation during treatment for their anemia. Ferritin,
transferrin, total iron-binding capacity, and serum iron measure different
aspects of the most important building blocks for RBCs. These values
define the body’s iron stores and its ability to accumulate and transfer iron
to the marrow. Serum B12 and folate are the vitamins most closely associated
with RBC production. Serum ferritin and transferrin iron saturation are
the most common tests used to evaluate iron status. Normal ferritin values
for men are 18 ng/mL to 270 ng/mL and 18 ng/mL to 160 ng/mL for
women. Normal transferrin values for adults are 200 mg/dL to 400 mg/dL.
Effective management of cancer-related anemia is critical because
of the potential negative impact on patients’ quality of life, functional
status, and survival. Although increasing hemoglobin levels and
enhancing patient quality of life are important goals, the primary goal
of erythropoietic-stimulating agent (ESA) therapy is to reduce the
need for transfusion.
Hemoglobin Level
The rationale for boosting hemoglobin levels is obvious, both in
terms of patient well-being and the implication that low hemoglobin
levels predict decreased survival. This implication rests largely on the
relationship between tissue oxygenation status and the resistance of
tumors to treatment, which has been demonstrated in multiple studies.
Hypoxia, or deficient tissue oxygenation, increases the resistance of
tumors to treatment; optimum hemoglobin levels increase tissue oxygenation
and the effectiveness of treatment. Numerous studies suggest
that radiotherapy, chemotherapy, and combined-treatment outcomes
are improved in patients with higher hemoglobin levels (Littlewood,
2001). Furthermore, five studies from Spain, Italy, Japan, China, and
the United States have shown a strong correlation between hemoglobin
levels and prognosis (Valencia, Alonso, Esco, Lopez-Mata, &
Mendez, 2006; Di Maio et al., 2006; Aoe et al., 2005; Winter et al.,
2004; Chua, Sham, & Choy, 2004). A review of the literature indicates
that tissue oxygenation is highest when hemoglobin levels are between
12 g/dL and 14 g/dL for women and between 13 g/dL and 15 g/dL for
men. Above those levels, blood viscosity increases, flow slows, and
oxygenation begins to decline (Vaupel, Mayer, & Hockel, 2006).
Quality of Life
Although the importance of anemia in the overall cancer symptom
complex remains a subject of debate (Munch, Zhang, Willey, Palmer,
& Bruera, 2005; Wisloff, Gulbrandsen, Hjorth, Lenhoff, & Fayers,
2005), several studies have demonstrated that treating anemia may
significantly improve a patient’s QOL (Apolone, 2004), with the
greatest improvement occurring as hemoglobin levels reach between
11 g/dL and 12 g/dL (Cortesi et al., 2005; Ludwig et al., 2004;
Varlotto & Stevenson, 2005). A systematic review of the literature
from 1980 to 2001 included 16 studies of people with cancer yielding
10,695 subjects. These studies demonstrated a consistent positive
relationship between the amount of increase in hematocrit and
improvement in QOL (Ross et al., 2003).
Transfusion
Decreasing the need for transfusion has become an important topic
of discussion as a number of bloodless medicine centers have emerged
across the country. Transfusions provide less-than-ideal results and are
time-consuming and expensive, with the cost of administering an outpatient
blood transfusion to a patient with cancer being approximately
$938 per unit transfused (Crémieux, Barnett, Anderson, & Slavin, 2000).
The physiological limitations of stored blood are well documented
(Carson, 2002; Corwin et al., 1999). RBCs change shape during storage
by Day 21, resulting in decreased ability to distribute oxygen,
reduced elasticity, and potential for microcirculatory occlusion
(Hovav, Yedgar, Manny, & Barshtein, 1999). Transfusion has not been
shown to increase oxygen uptake in patients with sepsis, and increased
blood age has been associated with greater risk of death and pneumonia
(Carson, 2002; Wagner, 2004). Despite the latter observation, most
blood is administered to patients after 21 days of storage. Although
there are noted benefits of transfusion, including an immediate
increase in hemoglobin concentration, relief of hypoxia symptoms, and
volume replacement, clinical studies have shown inconsistencies in
increased oxygen delivery and oxygen consumption among patients
receiving transfusions (Madjdpour & Spahn, 2005).
Transfusion risks include viral infections (i.e., hepatitis B and C,
HIV, human T-lymphotropic virus (HTLV), cytomegalovirus, Chagas disease, human herpes virus 8, malaria, syphilis, typhoid fever, typhus,
West Nile virus, and avian influenza), bacterial infections, hemolytic
transfusion reactions, transfusion-related acute lung injury (TRALI), and
mistransfusion (Madjdpour & Spahn, 2005; Pomper, Wu, & Snyder,
2003; Table 3). Immediate hemolytic reactions and TRALI, which occur
in critically-ill patients receiving multiple transfusions, may be fatal.
Transfusions may also cause delayed hemolysis (Brooks, 2005). Patients
are typically concerned about the possible risk of infection through
transfusion, especially with HIV. Currently, there are 10 tests
conducted on each unit of blood for infectious diseases: hepatitis B surface
antigen, antibodies to the hepatitis B core, antibodies to hepatitis C virus,
antibodies to HIV types 1 and 2, HIV p24 antigen, antibodies to HTLV,
types 1 and 2, syphilis, and nucleic acid amplification testing, which
detects genetic material of viruses (American Association of Blood
Banks, 2007).
Infection risks vary with the country from which the blood is derived.
There are rough data on infection risks associated with blood transfusions
in developing countries. Malaria is present in an estimated 1 in 3
units of blood and HIV in 1 in 50 units. Chagas disease is present in an
estimated 1 in 133 units of blood. There are no reliable data on bacterial
infections. In developed countries, the risk of transfusion-related
infections is substantially diminished but not absent. HIV is present in
1 in every 1.9 million units of blood and hepatitis B and C are present
in 1 in every 205,000 and 1.8 million units, respectively. Bacterial
infections are present in 1 in every 38,565 units of blood. Pooled blood
products such as clotting factor carry a higher risk of infection because
they comprise blood from multiple patients, thereby increasing the risk
that a pooled blood product may carry a disease (Madjdpour & Spahn,
2005; Shorr & Jackson, 2005).
There is evidence to suggest that transfusions may suppress immune
function, further increasing the risk of infection, and promote cancer
growth through immune suppression, angiogenesis, and by facilitating the metastasis of tumor cells (Shorr & Jackson, 2005; Madjdpour &
Spahn, 2005). The relationship between cancer recurrence and blood
transfusion has been studied, with early research reporting a correlation
between blood transfusion, prognostic factors, and colorectal cancer
recurrence (Jenkins, O’Neill, & Morran, 2007). However, definitive
studies evaluating the relationship between transfusion and cancer outcomes
have yet to be conducted (Heiss, 2000).
In developed countries, immunologic reactions are the most commonly
cited transfusion-related problems. Although much attention has
been paid to assuring the quality and safety of the blood supply, the
complex transfusion chain within hospitals allows opportunities for
errors at a number of critical points in the process that may lead to
avoidable fatalities and morbidities (Stainsby, Russell, Cohen, &
Lilleyman, 2005). One study showed that in approximately half of
incorrect blood component transfusion events, there were multiple
errors in the transfusion process (Stainsby et al., 2005), and that approximately
70% of errors occurred clinically, the most frequent being failure
to perform a pretransfusion bedside check. Laboratory errors accounted
for approximately 30% of transfusion-related errors (Stainsby et al.,
2005), the largest proportion of which has been shown to occur between
the time the blood unit is released from the laboratory and administered
to a patient.
To date, literature suggests that most errors in blood transfusion do
not occur within the transfusion medicine service and are primarily
related to identification problems (Brooks, 2005). Common errors
include specimen mislabeling, improper patient identification and
patient monitoring, and drawing a type and cross on the wrong
patient. Other potential errors include ordering a transfusion for the
wrong patient, omitting informed consent, hanging a unit of blood
with an incompatible intravenous solution, and not hanging the unit of
blood within the required timeframe or infusing it either too slowly or
quickly (Henneman et al., 2007).
Built-in process controls are essential to the safe administration of
blood transfusions and some have already been implemented at various
institutions across the United States. For example, Bloodloc™ is a
mechanical barrier system that requires a code located on the patient’s
wristband to be entered to unlock a bag containing the unit of blood. Bar
code patient identification systems are also used (Brooks, 2005;
Henneman et al., 2007).
|
