I sucked out the section of this article/teaching tool for nurses that I found helpful.
"Anemia is a very common sign of an underlying disease that is often discovered on a routine complete blood count (CBC) in an asymptomatic patient. The incidence of anemia increases with age, affecting up to 44% of men 85 years of age and older. 1 The increased prevalence of anemia with age is generally related to incidence of cancer or bleeding from anti-inflammatory agents such as aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs).
In the United States, anemia affects 4% of men and 8% of women; values are higher for women during their reproductive years due to menstruation. 2 Other industrialized regions such as Europe and Canada have similar anemia rates, but undeveloped countries, because of greater incidences of hemoglobinopathies, infections, and nutritional deficiencies tend to have rates of anemia two to five times greater. 2
Anemia is defined as a decrease in red blood cell (RBC) mass. 3 However, direct measurement of RBC mass is expensive and time consuming. Because of the impracticality of measuring RBC mass, anemia is measured via an RBC count, hemoglobin (Hb) concentration, and hematocrit (Hct) concentration. Since these values are concentrations only, and not absolute measurements, they should be regarded with caution and always in context with the patient’s overall fluid volume status since either dehydration or overhydration can appreciably affect the concentration values. 3
Pathophysiology
Red blood cells, along with white blood cells and platelets, are manufactured in the liver and spleen of a fetus. After birth, cell formation takes over in the bone marrow. New cells, erythroid precursors, are released from the bone marrow to become reticulocytes in circulation. 2 Reticulocytes are matured into RBCs in approximately 24 hours by reticulin. After 120 days, RBCs die and release Hb into the circulation for transport to the liver and spleen where Hb is ultimately broken down. Globulin, the protein base of Hb, is broken down into amino acids that the body can use. Iron is stored in the liver and spleen for future use. The remainder of the Hb molecule, mostly heme, is converted into bilirubin to be excreted in the urine or in the stool.
The Hb contained within the RBCs is made up of heme and globulin. There are four binding sites on the RBC for Hb to bind with. When Hb is bound at all four sites and is carrying oxygen, the RBC is considered fully saturated. When an RBC is fully saturated, it contains approximately 300 molecules of Hb. Oxygen bound to Hb eventually leaves to enter cells where oxygen is needed. Oxyhemoglobin (oxygen bound to Hb) saturation is normally near 100% when measured in arterial blood but decreases to approximately 60% in venous blood after oxygen has left the Hb and gone into the cells.
Etiology
The etiology of anemia depends on the underlying problem or disease that produced the anemia. The causes of anemias can be divided into those resulting from heredity, nutritional deficiencies, blood loss, immunologic and idiopathic, exogenous (medications/chemicals), chronic diseases, infections, and neoplasms. 2 Worldwide, the most common type of anemia is iron deficiency anemia (microcytic) and the second most common is anemia of chronic disease (normocytic).
Anemia can be characterized by changes in the amount or characteristics of Hb present within the RBC and/or by a change in size of the circulating RBCs. At least 100 types of abnormal Hb have been identified. Anemia may also result from a malfunction in RBC or Hb production, an increase in RBC loss, or abnormal lysis of RBCs brought on by categories of causes listed in the previous paragraph. Anemias related to the quality of the cells include microcytic (RBC too small), macrocytic (RBC too large), normocytic (normal size), hypochromic (Hb concentration too low), hyperchromic (Hb concentration too high), normochromic (Hb concentration normal), and combinations of RBC size and Hb concentration (see Table : “Types of Anemia by Mean Corpuscular Volume”). Quantity anemias occur when the destruction of the RBC, through loss or lysis, occurs earlier than the 120-day life expectancy of the cell. 4 In normocytic anemias of chronic disease, the bone marrow either has inadequate production or utilization of erythropoietin to produce RBCs, along with a slightly shortened lifespan of the RBC. 1
Types of Anemia by Mean Corpuscular Volume
Worldwide, the most common causes of blood loss include gastrointestinal bleeding or menstrual loss. Generally, in the United States, the most common causes of iron deficiency anemia are also due to gastrointestinal bleeding and menstrual loss. 5 Many times, bleeding from these areas are occult or not noticed until the Hb becomes dangerously low. Occasionally, iron and blood loss may be due to hemolysis from artificial heart valves or other break down, gastrectomy or other upper-gastrointestinal tract surgery that changes iron absorption, or disease such as celiac sprue). 3 In the United States, approximately 25% to 35% of anemias are related to iron deficiency. 6
If the RBC lifespan is shortened to less than 40 days, the patient has a hemolytic disorder that may be manifested by an increased production of RBCs, increased destruction of RBCs, or both. An increased production is characterized by an increased reticulocyte production; increased destruction of RBCs is characterized by an increase of indirect bilirubinemia. 2 Hemolytic disorders can be inherited or acquired and can be caused by an internal problem with the RBC itself (intracorpuscular defect), or from an external source that shortens the lifespan of the cell (extracor-puscular defect). 2 Careful examination of the peripheral blood smear can help to determine the type of hemolytic disorder. Hereditary hemolytic disorders include spherocytosis, hemoglobinopathies (such as sickle cell), thalassemias, congenital dyserythropoietic anemias (abnormalities of RBC precursors in the bone marrow), and RBC enzymatic deficiencies such as glucose 6-phosphate dehydrogenase (G6PD). 2 The most common hereditary disorder, occurring in 10% to 14% of the African American population, is G6PD deficiency. This number may actually be higher since the disease entity is not borne out until the patient receives an oxidant medication leading to a mild-to-moderate hemolytic anemia, although exposure to oxidant medications can lead to death from hemolysis. In the Mediterranean culture, Caucasian patients can develop chronic hemolytic anemia due to G6PD deficiency without exposure to oxidant medications. Approximately 8% of African Americans carry the sickle cell gene, and approximately 1 in 625 births results in sickle cell disease. 7 In the United States, the most common sickle cell Hb variant is homozygous hemoglobin S disease. 7
Presentation: Signs and Symptoms
(You could look like this:
)
Signs and symptoms of anemia are dependent upon the degree of severity as measured by the RBC, Hb, and Hct, and the etiology of the anemia. The severity of the anemia will lead to signs and symptoms associated with low-oxygen states due to a decreased Hb and therefore, decreased oxygen-carrying capacity. Symptoms may include fatigue, palpitations, chest pain, and shortness-of-breath with exertion. 8 However, patients with pernicious anemia can remain asymptomatic with an Hb of 6 g/dL, whereas someone with iron deficiency anemia may be symptomatic with an Hb of 11 g/dL.
History of the patient with anemia should focus not on the anemia but what may have led to it. Family history is important because Hb abnormalities may be uncovered. The patient’s past medical history should be explored for previous jaundice, gallbladder disease, liver disease, renal disease, bleeding disorders, malabsorption disorders, previous splenectomy, previous history of anemia, and any known abnormal Hb history. The patient’s occupation and hobbies, such as gardening and crafts, are also important to uncover any possible toxicity. Inquire about the patient’s use of all medications and supplements, including prescription and over-the-counter medications, herbs, vitamins, minerals, hair dyes, and any other supplements.
The gastrointestinal tract can also offer information regarding anemia. Black, tarry stools are often associated with gastrointestinal bleeding. If the stool is associated with steatorrhea, it usually floats, has to be flushed numerous times in order to evacuate all stool from the toilet bowl, or oil is noted on the surface of the toilet bowl water, then malabsorption syndromes such as celiac sprue may be a problem.
Dark urine may be associated with liver or renal disease, or with hemolytic syndromes. Menstrual history is important in females to document suspected blood loss. Menses cycle, duration, and flow are important factors as well as pregnancy history.
Cold intolerance may accompany immune system dysfunction problems such as hypothyroidism and systemic lupus erythematosus. Bleeding and hemolytic disorders may lead to purpura, ecchymoses, and petechiae. Bleeding and hemolytic disorders may be a result of infection, trauma, cancers, or collagen vascular disease.
Dietary history is also important since it may uncover nutritional deficiencies or malabsorption problems. Often, iron deficiency may lead to pagophagia (frequently chewing ice). Patients with vitamin B 12 deficiency may experience premature graying of the hair, loss of proprioception, a burning sensation in the tongue, and peripheral neuropathies. If folate is deficient, the tongue may be sore and the patient may also experience cheilosis and steatorrhea. Patients with pernicious anemia also experience paresthesias.
During physical examination there are numerous other dermatological manifestations exhibited besides purpura, ecchymosis, or petechiae; most notably, pallor. However, depending on the cause of the anemia, the nurse practitioner may also observe icterus, spider nevi, and angiomas. Nail defects, such as koilonychia (spooned-shaped), may also be noted. In a patient with thyroid disease, there may be hair coassness, loss of the lateral third of the eyebrows, and facial puffiness or edema. Look for generalized edema as well. Bilateral edema usually indicates problems with the cardiac, renal, or hepatic systems; unilateral edema may indicate cancer or deep vein thrombosis. 2,4
The nervous system should be examined for intactness of the cranial nerves and reflexes as well as proprioception and loss of peripheral sensation. Dementia, a positive Babinski sign, and positive Romberg sign may be noted with B 12 deficiency. The conjunctivae and oral mucus membranes are examined for pallor.
The lymphatic system is palpated for the presence of splenomegaly as well as for signs of infection or cancer. 9 While examining the abdomen, check liver size, which may indicate hepatic dysfunction. Examination of the abdomen also includes a rectal examination and checking for occult blood. In females, a pelvic examination should also be performed. 3
Sickle Cell Disease
In patients with sickle cell disease, vasoocclusive crisis is the most common problem. A crisis will occur suddenly either idiopathically or in response to infection or abrupt change in temperature, including room temperature. 7 Pain affects the joints, bones, and abdomen in most cases and may be accompanied by fever, fatigue, and leukocytosis. 7 Crises may occur as often as six or more times a year or very infrequently; some patients only experience chronic joint pain. Acute chest syndrome can mimic pneumonia as evidenced by pulmonary infiltrates on chest x-ray, leukocytosis, chest pain, and fever; however, fat embolization usually caused by bone marrow infarction within the ribs is most likely the true etiology. 7 Without aggressive and prompt treatment, adult respiratory distress syndrome can ensue. 7
Numerous other problems and symptoms may present in patients with sickle cell disease including autosplenectomy, stroke, cardiomegaly, pulmonary hypertension, renal failure, skin ulcerations, spontaneous abortion, and priapism. 7
FIGURE. Examples of Red Blood Cells in Various Anemias
Diagnostic Data
Initial data should include height, weight, and vital signs. If the patient is complaining of dizziness, orthostatic vital signs should also be obtained to help assess intravascular volume, which will influence interpretation of the Hb and Hct. Weight loss may indicate infection, malabsorption syndromes, or malignancy. Orthostatic vital signs may indicate the same but with the addition of possible blood loss. The presence of fever may indicate infection or malignancy.
If the patient is complaining of chest pain, an electrocardiogram and cardiac enzymes are indicated to rule out an acute cardiac process such as myocardial infarction. A chest x-ray may show cardiac enlargement from longstanding anemia and would rule out any other pulmonary or cardiac problem.
Laboratory Tests
The World Health Organization defines anemia as an Hb of less than 12.5 g/dL in an adult. 18 The first laboratory test to order is a CBC. When anemia is confirmed by a lower-than-normal RBC, Hb, and Hct, look at the mean corpuscle volume (MCV) to determine if the anemia is microcytic (MCV
< 84) or macrocytic (MCV > 96). 2 To determine “color,” look at the mean corpuscle Hb concentration (MCHC). If the MCHC is
< 31, hypochromia exists. If the MCHC is > 36, the value is probably due to spherocytes. 10 To determine if the anemia is normocytic and normochromic, multiply the RBC value by three and the Hb value by three. Normally, the RBC value multiplied by three should equal the Hb value, and the Hb value times three should equal the Hct. Patients whose CBC shows pancytopenia may have decreased RBC production as the cause of their anemia. In pancytopenia, aplastic anemia is generally responsible. 2
If the initial CBC determines the patient has a microcytic, hypochromic anemia, check for iron and look for a source of bleeding, usually gastrointestinal or gynecological. 2 Laboratory tests include a serum iron level, total iron binding capacity(TIBC), and serum ferritin level. 2,4 In iron deficiency anemia, the serum ferritin level is often the first to change and is noted by a decreased level. 4 A ferritin level of less than 20 mcg/L is diagnostic of iron deficiency anemia. 11 If the ferritin level is greater than 20 mcg/L, measuring a transferrin receptor level can confirm iron deficiency anemia. 8,12 If the transferrin receptor level is elevated, the patient has iron deficiency anemia since most iron is delivered to nonintestinal cells bound to transferrin. 3 If the transferrin receptor level is normal, the patient has anemia of chronic disease, which comprises approximately 25% to 35% of all anemias in the United States. 11
In iron deficiency anemia, the serum iron level is also decreased and the TIBC is increased. 3,4 In other microcytic, hypochromic anemias such as thalassemias and lead poisoning, no change may be noted in these markers (see Table : “Laboratory Tests associated with Anemia Workup”). No matter the outcome of these markers, it is still necessary to search for the reason for the iron deficiency anemia or other microcytic anemia through bone marrow aspiration and peripheral blood smear.
Laboratory Tests associated with Anemia Workup 1,2,4,6,13,14
If the MCV is increased and a macrocytic anemia is suspected, then serum vitamin B 12 and folic acid levels are obtained. In the United States, approximately 10% of anemias are related to either vitamin B 12 or folate deficiency. 11
Additional Testing
Schilling’s test determines if a patient can absorb vitamin B 12 properly. During the test, intramuscular vitamin B 12 is administered after a fast in a dose large enough to saturate the plasma transport proteins. Radiolabeled B 12 is then given orally. Urine is collected for 24 hours. More than 8% of the radiolabeled oral B 12 should be recovered in the urine if there is no malabsorption problem. If less than 3% of the radiolabeled oral B 12 is excreted, the patient is considered unable to absorb oral B 12 , probably due to a decrease in intrinsic factor. The test is repeated with the addition of oral intrinsic factor. During the second part, if a low excretion of radiolabeled B 12 still occurs then megaloblastic anemia, not a loss of intrinsic factor, is the reason for malabsorption of B 12 and the resultant anemia. 4
If by the MCV and the MCHC the anemia is found to be normocytic normochromic, then one of three conditions exists and needs to be investigated. These are blood loss, hemolysis, and decreased RBC production. 2
Additional blood work may include the Coombs test to distinguish between hereditary and acquired hemolytic disorders. The Coombs test will be positive in acquired hemolytic disorders that are autoimmune in nature. Another study to determine if the hemolytic disorder is hereditary or acquired is a donor cell chromium survival study. Labeled RBCs from a compatible blood donor without anemia problems or disorders are instilled into the patient. The labeled RBCs will have a normal lifespan if the hemolytic disorder is inherited and a shortened lifespan if the disorder is acquired. 2,11
Besides a chest x-ray, additional imaging studies may be needed to confirm splenomegaly or to rule out cancer. If gastrointestinal bleeding is suspected, an esophago-gastroduodenal (EGD) endoscopy, colonoscopy, or both, may be performed.
A bone marrow aspirate or biopsy may be indicated to help determine the reason for the anemia. Drugs and chemical or other toxic exposure may cause the bone marrow to become aplastic or hypoplastic. Pancytopenia may also be apparent. Some toxins known to suppress bone marrow production of RBCs include assnic, benzene, radiation, and chemotherapy agents. Other medications that may cause bone marrow suppression include antibiotics or other antimicrobials, anticonvulsants, and antihistamines. Infections such as viral hepatitis can also lead to bone marrow suppression. In aplastic anemia, approximately 80% of cases are acquired; the remaining are inherited. Of the acquired cases, most are probably related to idiopathic autoimmune disease. 15
Treatment
Treatment of anemia depends on the cause. Because anemia is a symptom of a problem, the major treatment will correct the underlying problem or disease state that led to the anemia.
Blood Loss
In the case of blood loss, replacing blood as soon as possible will help to correct the anemia. However, blood replacement should be reserved for patients who are symptomatic and show evidence of active bleeding in order to minimize complications associated with blood products. 2
In acute blood loss, the Hct is not reliable because plasma volume is also lost. The Hct can continue to fall until plasma volume is replaced over the next 24 to 48 hours. 2 A patient who experiences acute blood loss but who has adequate iron stores will show an increased MCV (approximately 120 mm 3 ) at 1 week with macrocytes on a blood smear because reticulocytes and young RBCs are larger in numbers and volume than normal. However, if the patient’s iron stores are depleted by the blood loss, the new RBCs will be microcytic and hypochromic, showing an iron deficiency anemia. Iron stores are depleted after approximately 1 to 2 liters of blood are lost, which equals 500 to 1,000 mg of iron loss. 3 Even with iron replacement, full turnaround will not be evident until the smaller cells leave circulation in approximately 120 days; therefore, oral iron replacement should be continued for 3 to 4 months after resolution of the anemia. 3 Because of the risk of anaphylaxis with parenteral iron administration, most circumstances can be handled with oral replacement. 3 Financially and medically, ferrous iron salts are the most effective replacement product. 3 The most commonly utilized ferrous iron salt is ferrous sulfate. The usual adult dose is 325 mg three times a day with meals, which delivers 60 mg of elemental iron. 3 It is important to note that once iron deficiency anemia is resolved by removal of the cause and replacement of iron, iron replacement therapy should be stopped. If not, excess iron intake may occur and is potentially an important factor in the development of coronary artery disease, cerebrovascular disease, certain cancers, osteoporosis, and certain neurodegenerative disorders due to the free radical formation from iron metabolism. 3
Once iron deficiency is resolved by removal of the cause and replacement of iron, iron replacement therapy should stop.
Vitamin B 12 or Folate Deficiencies
Anemia caused by deficiencies of vitamin B 12 and/or folate are reversed by replenishing these deficiencies and correcting the cause of these deficiencies, such as alcohol abuse or proton pump inhibitor intake. Generally, if the patient did not show a deficiency of intrinsic factor or a malabsorption problem on a Schilling test, oral vitamin B 12 should be utilized. 3 Parenteral B 12 offers no advantage over oral products and may not be covered by insurance without documentation of a positive Schilling’s test.
Replacement can be similar in oral or parenteral routes and begins with 800 to 1,000 mcg daily for the first 1 to 2 weeks, followed by up to 1,000 mcg per week until the Hb, Hct, and vitamin B 12 levels have normalized. Serum homocysteine or urinary methylmalonic acid levels may actually reflect vitamin B 12 deficiency more accurately than serum B 12 levels. Maintenance can include monthly injections of up to 1,000 mcg or weekly use of 500 mcg of cyanocobalamin nasal gel (Nascobal)."
I sucked out the section of this article/teaching tool for nurses that I found helpful.
"Anemia is a very common sign of an underlying disease that is often discovered on a routine complete blood count (CBC) in an asymptomatic patient. The incidence of anemia increases with age, affecting up to 44% of men 85 years of age and older. 1 The increased prevalence of anemia with age is generally related to incidence of cancer or bleeding from anti-inflammatory agents such as aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs).
In the United States, anemia affects 4% of men and 8% of women; values are higher for women during their reproductive years due to menstruation. 2 Other industrialized regions such as Europe and Canada have similar anemia rates, but undeveloped countries, because of greater incidences of hemoglobinopathies, infections, and nutritional deficiencies tend to have rates of anemia two to five times greater. 2
Anemia is defined as a decrease in red blood cell (RBC) mass. 3 However, direct measurement of RBC mass is expensive and time consuming. Because of the impracticality of measuring RBC mass, anemia is measured via an RBC count, hemoglobin (Hb) concentration, and hematocrit (Hct) concentration. Since these values are concentrations only, and not absolute measurements, they should be regarded with caution and always in context with the patient’s overall fluid volume status since either dehydration or overhydration can appreciably affect the concentration values. 3
Pathophysiology
Red blood cells, along with white blood cells and platelets, are manufactured in the liver and spleen of a fetus. After birth, cell formation takes over in the bone marrow. New cells, erythroid precursors, are released from the bone marrow to become reticulocytes in circulation. 2 Reticulocytes are matured into RBCs in approximately 24 hours by reticulin. After 120 days, RBCs die and release Hb into the circulation for transport to the liver and spleen where Hb is ultimately broken down. Globulin, the protein base of Hb, is broken down into amino acids that the body can use. Iron is stored in the liver and spleen for future use. The remainder of the Hb molecule, mostly heme, is converted into bilirubin to be excreted in the urine or in the stool.
The Hb contained within the RBCs is made up of heme and globulin. There are four binding sites on the RBC for Hb to bind with. When Hb is bound at all four sites and is carrying oxygen, the RBC is considered fully saturated. When an RBC is fully saturated, it contains approximately 300 molecules of Hb. Oxygen bound to Hb eventually leaves to enter cells where oxygen is needed. Oxyhemoglobin (oxygen bound to Hb) saturation is normally near 100% when measured in arterial blood but decreases to approximately 60% in venous blood after oxygen has left the Hb and gone into the cells.
Etiology
The etiology of anemia depends on the underlying problem or disease that produced the anemia. The causes of anemias can be divided into those resulting from heredity, nutritional deficiencies, blood loss, immunologic and idiopathic, exogenous (medications/chemicals), chronic diseases, infections, and neoplasms. 2 Worldwide, the most common type of anemia is iron deficiency anemia (microcytic) and the second most common is anemia of chronic disease (normocytic).
Anemia can be characterized by changes in the amount or characteristics of Hb present within the RBC and/or by a change in size of the circulating RBCs. At least 100 types of abnormal Hb have been identified. Anemia may also result from a malfunction in RBC or Hb production, an increase in RBC loss, or abnormal lysis of RBCs brought on by categories of causes listed in the previous paragraph. Anemias related to the quality of the cells include microcytic (RBC too small), macrocytic (RBC too large), normocytic (normal size), hypochromic (Hb concentration too low), hyperchromic (Hb concentration too high), normochromic (Hb concentration normal), and combinations of RBC size and Hb concentration (see Table : “Types of Anemia by Mean Corpuscular Volume”). Quantity anemias occur when the destruction of the RBC, through loss or lysis, occurs earlier than the 120-day life expectancy of the cell. 4 In normocytic anemias of chronic disease, the bone marrow either has inadequate production or utilization of erythropoietin to produce RBCs, along with a slightly shortened lifespan of the RBC. 1
Types of Anemia by Mean Corpuscular Volume
Worldwide, the most common causes of blood loss include gastrointestinal bleeding or menstrual loss. Generally, in the United States, the most common causes of iron deficiency anemia are also due to gastrointestinal bleeding and menstrual loss. 5 Many times, bleeding from these areas are occult or not noticed until the Hb becomes dangerously low. Occasionally, iron and blood loss may be due to hemolysis from artificial heart valves or other break down, gastrectomy or other upper-gastrointestinal tract surgery that changes iron absorption, or disease such as celiac sprue). 3 In the United States, approximately 25% to 35% of anemias are related to iron deficiency. 6
If the RBC lifespan is shortened to less than 40 days, the patient has a hemolytic disorder that may be manifested by an increased production of RBCs, increased destruction of RBCs, or both. An increased production is characterized by an increased reticulocyte production; increased destruction of RBCs is characterized by an increase of indirect bilirubinemia. 2 Hemolytic disorders can be inherited or acquired and can be caused by an internal problem with the RBC itself (intracorpuscular defect), or from an external source that shortens the lifespan of the cell (extracor-puscular defect). 2 Careful examination of the peripheral blood smear can help to determine the type of hemolytic disorder. Hereditary hemolytic disorders include spherocytosis, hemoglobinopathies (such as sickle cell), thalassemias, congenital dyserythropoietic anemias (abnormalities of RBC precursors in the bone marrow), and RBC enzymatic deficiencies such as glucose 6-phosphate dehydrogenase (G6PD). 2 The most common hereditary disorder, occurring in 10% to 14% of the African American population, is G6PD deficiency. This number may actually be higher since the disease entity is not borne out until the patient receives an oxidant medication leading to a mild-to-moderate hemolytic anemia, although exposure to oxidant medications can lead to death from hemolysis. In the Mediterranean culture, Caucasian patients can develop chronic hemolytic anemia due to G6PD deficiency without exposure to oxidant medications. Approximately 8% of African Americans carry the sickle cell gene, and approximately 1 in 625 births results in sickle cell disease. 7 In the United States, the most common sickle cell Hb variant is homozygous hemoglobin S disease. 7
Presentation: Signs and Symptoms
(You could look like this:
)
Signs and symptoms of anemia are dependent upon the degree of severity as measured by the RBC, Hb, and Hct, and the etiology of the anemia. The severity of the anemia will lead to signs and symptoms associated with low-oxygen states due to a decreased Hb and therefore, decreased oxygen-carrying capacity. Symptoms may include fatigue, palpitations, chest pain, and shortness-of-breath with exertion. 8 However, patients with pernicious anemia can remain asymptomatic with an Hb of 6 g/dL, whereas someone with iron deficiency anemia may be symptomatic with an Hb of 11 g/dL.
History of the patient with anemia should focus not on the anemia but what may have led to it. Family history is important because Hb abnormalities may be uncovered. The patient’s past medical history should be explored for previous jaundice, gallbladder disease, liver disease, renal disease, bleeding disorders, malabsorption disorders, previous splenectomy, previous history of anemia, and any known abnormal Hb history. The patient’s occupation and hobbies, such as gardening and crafts, are also important to uncover any possible toxicity. Inquire about the patient’s use of all medications and supplements, including prescription and over-the-counter medications, herbs, vitamins, minerals, hair dyes, and any other supplements.
The gastrointestinal tract can also offer information regarding anemia. Black, tarry stools are often associated with gastrointestinal bleeding. If the stool is associated with steatorrhea, it usually floats, has to be flushed numerous times in order to evacuate all stool from the toilet bowl, or oil is noted on the surface of the toilet bowl water, then malabsorption syndromes such as celiac sprue may be a problem.
Dark urine may be associated with liver or renal disease, or with hemolytic syndromes. Menstrual history is important in females to document suspected blood loss. Menses cycle, duration, and flow are important factors as well as pregnancy history.
Cold intolerance may accompany immune system dysfunction problems such as hypothyroidism and systemic lupus erythematosus. Bleeding and hemolytic disorders may lead to purpura, ecchymoses, and petechiae. Bleeding and hemolytic disorders may be a result of infection, trauma, cancers, or collagen vascular disease.
Dietary history is also important since it may uncover nutritional deficiencies or malabsorption problems. Often, iron deficiency may lead to pagophagia (frequently chewing ice). Patients with vitamin B 12 deficiency may experience premature graying of the hair, loss of proprioception, a burning sensation in the tongue, and peripheral neuropathies. If folate is deficient, the tongue may be sore and the patient may also experience cheilosis and steatorrhea. Patients with pernicious anemia also experience paresthesias.
During physical examination there are numerous other dermatological manifestations exhibited besides purpura, ecchymosis, or petechiae; most notably, pallor. However, depending on the cause of the anemia, the nurse practitioner may also observe icterus, spider nevi, and angiomas. Nail defects, such as koilonychia (spooned-shaped), may also be noted. In a patient with thyroid disease, there may be hair coassness, loss of the lateral third of the eyebrows, and facial puffiness or edema. Look for generalized edema as well. Bilateral edema usually indicates problems with the cardiac, renal, or hepatic systems; unilateral edema may indicate cancer or deep vein thrombosis. 2,4
The nervous system should be examined for intactness of the cranial nerves and reflexes as well as proprioception and loss of peripheral sensation. Dementia, a positive Babinski sign, and positive Romberg sign may be noted with B 12 deficiency. The conjunctivae and oral mucus membranes are examined for pallor.
The lymphatic system is palpated for the presence of splenomegaly as well as for signs of infection or cancer. 9 While examining the abdomen, check liver size, which may indicate hepatic dysfunction. Examination of the abdomen also includes a rectal examination and checking for occult blood. In females, a pelvic examination should also be performed. 3
Sickle Cell Disease
In patients with sickle cell disease, vasoocclusive crisis is the most common problem. A crisis will occur suddenly either idiopathically or in response to infection or abrupt change in temperature, including room temperature. 7 Pain affects the joints, bones, and abdomen in most cases and may be accompanied by fever, fatigue, and leukocytosis. 7 Crises may occur as often as six or more times a year or very infrequently; some patients only experience chronic joint pain. Acute chest syndrome can mimic pneumonia as evidenced by pulmonary infiltrates on chest x-ray, leukocytosis, chest pain, and fever; however, fat embolization usually caused by bone marrow infarction within the ribs is most likely the true etiology. 7 Without aggressive and prompt treatment, adult respiratory distress syndrome can ensue. 7
Numerous other problems and symptoms may present in patients with sickle cell disease including autosplenectomy, stroke, cardiomegaly, pulmonary hypertension, renal failure, skin ulcerations, spontaneous abortion, and priapism. 7
FIGURE. Examples of Red Blood Cells in Various Anemias
Diagnostic Data
Initial data should include height, weight, and vital signs. If the patient is complaining of dizziness, orthostatic vital signs should also be obtained to help assess intravascular volume, which will influence interpretation of the Hb and Hct. Weight loss may indicate infection, malabsorption syndromes, or malignancy. Orthostatic vital signs may indicate the same but with the addition of possible blood loss. The presence of fever may indicate infection or malignancy.
If the patient is complaining of chest pain, an electrocardiogram and cardiac enzymes are indicated to rule out an acute cardiac process such as myocardial infarction. A chest x-ray may show cardiac enlargement from longstanding anemia and would rule out any other pulmonary or cardiac problem.
Laboratory Tests
The World Health Organization defines anemia as an Hb of less than 12.5 g/dL in an adult. 18 The first laboratory test to order is a CBC. When anemia is confirmed by a lower-than-normal RBC, Hb, and Hct, look at the mean corpuscle volume (MCV) to determine if the anemia is microcytic (MCV < 84) or macrocytic (MCV > 96). 2 To determine “color,” look at the mean corpuscle Hb concentration (MCHC). If the MCHC is < 31, hypochromia exists. If the MCHC is > 36, the value is probably due to spherocytes. 10 To determine if the anemia is normocytic and normochromic, multiply the RBC value by three and the Hb value by three. Normally, the RBC value multiplied by three should equal the Hb value, and the Hb value times three should equal the Hct. Patients whose CBC shows pancytopenia may have decreased RBC production as the cause of their anemia. In pancytopenia, aplastic anemia is generally responsible. 2
If the initial CBC determines the patient has a microcytic, hypochromic anemia, check for iron and look for a source of bleeding, usually gastrointestinal or gynecological. 2 Laboratory tests include a serum iron level, total iron binding capacity(TIBC), and serum ferritin level. 2,4 In iron deficiency anemia, the serum ferritin level is often the first to change and is noted by a decreased level. 4 A ferritin level of less than 20 mcg/L is diagnostic of iron deficiency anemia. 11 If the ferritin level is greater than 20 mcg/L, measuring a transferrin receptor level can confirm iron deficiency anemia. 8,12 If the transferrin receptor level is elevated, the patient has iron deficiency anemia since most iron is delivered to nonintestinal cells bound to transferrin. 3 If the transferrin receptor level is normal, the patient has anemia of chronic disease, which comprises approximately 25% to 35% of all anemias in the United States. 11
In iron deficiency anemia, the serum iron level is also decreased and the TIBC is increased. 3,4 In other microcytic, hypochromic anemias such as thalassemias and lead poisoning, no change may be noted in these markers (see Table : “Laboratory Tests associated with Anemia Workup”). No matter the outcome of these markers, it is still necessary to search for the reason for the iron deficiency anemia or other microcytic anemia through bone marrow aspiration and peripheral blood smear.
Laboratory Tests associated with Anemia Workup 1,2,4,6,13,14
If the MCV is increased and a macrocytic anemia is suspected, then serum vitamin B 12 and folic acid levels are obtained. In the United States, approximately 10% of anemias are related to either vitamin B 12 or folate deficiency. 11
Additional Testing
Schilling’s test determines if a patient can absorb vitamin B 12 properly. During the test, intramuscular vitamin B 12 is administered after a fast in a dose large enough to saturate the plasma transport proteins. Radiolabeled B 12 is then given orally. Urine is collected for 24 hours. More than 8% of the radiolabeled oral B 12 should be recovered in the urine if there is no malabsorption problem. If less than 3% of the radiolabeled oral B 12 is excreted, the patient is considered unable to absorb oral B 12 , probably due to a decrease in intrinsic factor. The test is repeated with the addition of oral intrinsic factor. During the second part, if a low excretion of radiolabeled B 12 still occurs then megaloblastic anemia, not a loss of intrinsic factor, is the reason for malabsorption of B 12 and the resultant anemia. 4
If by the MCV and the MCHC the anemia is found to be normocytic normochromic, then one of three conditions exists and needs to be investigated. These are blood loss, hemolysis, and decreased RBC production. 2
Additional blood work may include the Coombs test to distinguish between hereditary and acquired hemolytic disorders. The Coombs test will be positive in acquired hemolytic disorders that are autoimmune in nature. Another study to determine if the hemolytic disorder is hereditary or acquired is a donor cell chromium survival study. Labeled RBCs from a compatible blood donor without anemia problems or disorders are instilled into the patient. The labeled RBCs will have a normal lifespan if the hemolytic disorder is inherited and a shortened lifespan if the disorder is acquired. 2,11
Besides a chest x-ray, additional imaging studies may be needed to confirm splenomegaly or to rule out cancer. If gastrointestinal bleeding is suspected, an esophago-gastroduodenal (EGD) endoscopy, colonoscopy, or both, may be performed.
A bone marrow aspirate or biopsy may be indicated to help determine the reason for the anemia. Drugs and chemical or other toxic exposure may cause the bone marrow to become aplastic or hypoplastic. Pancytopenia may also be apparent. Some toxins known to suppress bone marrow production of RBCs include assnic, benzene, radiation, and chemotherapy agents. Other medications that may cause bone marrow suppression include antibiotics or other antimicrobials, anticonvulsants, and antihistamines. Infections such as viral hepatitis can also lead to bone marrow suppression. In aplastic anemia, approximately 80% of cases are acquired; the remaining are inherited. Of the acquired cases, most are probably related to idiopathic autoimmune disease. 15
Treatment
Treatment of anemia depends on the cause. Because anemia is a symptom of a problem, the major treatment will correct the underlying problem or disease state that led to the anemia.
Blood Loss
In the case of blood loss, replacing blood as soon as possible will help to correct the anemia. However, blood replacement should be reserved for patients who are symptomatic and show evidence of active bleeding in order to minimize complications associated with blood products. 2
In acute blood loss, the Hct is not reliable because plasma volume is also lost. The Hct can continue to fall until plasma volume is replaced over the next 24 to 48 hours. 2 A patient who experiences acute blood loss but who has adequate iron stores will show an increased MCV (approximately 120 mm 3 ) at 1 week with macrocytes on a blood smear because reticulocytes and young RBCs are larger in numbers and volume than normal. However, if the patient’s iron stores are depleted by the blood loss, the new RBCs will be microcytic and hypochromic, showing an iron deficiency anemia. Iron stores are depleted after approximately 1 to 2 liters of blood are lost, which equals 500 to 1,000 mg of iron loss. 3 Even with iron replacement, full turnaround will not be evident until the smaller cells leave circulation in approximately 120 days; therefore, oral iron replacement should be continued for 3 to 4 months after resolution of the anemia. 3 Because of the risk of anaphylaxis with parenteral iron administration, most circumstances can be handled with oral replacement. 3 Financially and medically, ferrous iron salts are the most effective replacement product. 3 The most commonly utilized ferrous iron salt is ferrous sulfate. The usual adult dose is 325 mg three times a day with meals, which delivers 60 mg of elemental iron. 3 It is important to note that once iron deficiency anemia is resolved by removal of the cause and replacement of iron, iron replacement therapy should be stopped. If not, excess iron intake may occur and is potentially an important factor in the development of coronary artery disease, cerebrovascular disease, certain cancers, osteoporosis, and certain neurodegenerative disorders due to the free radical formation from iron metabolism. 3
Once iron deficiency is resolved by removal of the cause and replacement of iron, iron replacement therapy should stop.
Vitamin B 12 or Folate Deficiencies
Anemia caused by deficiencies of vitamin B 12 and/or folate are reversed by replenishing these deficiencies and correcting the cause of these deficiencies, such as alcohol abuse or proton pump inhibitor intake. Generally, if the patient did not show a deficiency of intrinsic factor or a malabsorption problem on a Schilling test, oral vitamin B 12 should be utilized. 3 Parenteral B 12 offers no advantage over oral products and may not be covered by insurance without documentation of a positive Schilling’s test.
Replacement can be similar in oral or parenteral routes and begins with 800 to 1,000 mcg daily for the first 1 to 2 weeks, followed by up to 1,000 mcg per week until the Hb, Hct, and vitamin B 12 levels have normalized. Serum homocysteine or urinary methylmalonic acid levels may actually reflect vitamin B 12 deficiency more accurately than serum B 12 levels. Maintenance can include monthly injections of up to 1,000 mcg or weekly use of 500 mcg of cyanocobalamin nasal gel (Nascobal)."