Diagnosing, Classifying, and Managing Anemia in Adults Nursing CE Course

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Anemia: Diagnosing, Classifying, and Managing Anemia in Adults

Disclosure Statement

This module provides a comprehensive overview of anemia in adults, focusing on classification, common etiologies, and a systematic approach to diagnosis and evidence-based management.

Upon completion of this module, learners will be able to:

• describe the epidemiology of anemia among adults in the United States
• explain the pathophysiological mechanisms contributing to anemia and common signs, symptoms, and risk factors associated with various types of anemia
• identify appropriate diagnostic tests and interpret laboratory findings to classify anemia
• discuss common anemia subtypes and their corresponding clinical management

Background

Anemia is a significant global public health issue. Defined as a reduction in the number or quality of circulating red blood cells (RBCs) or hemoglobin (Hb), anemia impairs the blood’s oxygen-carrying capacity, often resulting in fatigue, weakness, and impaired cognitive function (World Health Organization [WHO], 2024). Hb levels below 13 g/dL in adult males and 12 g/dL in nonpregnant adult females are commonly used diagnostic thresholds, although these values can be influenced by factors such as age, altitude, pregnancy, hydration status, and underlying health conditions (Means & Brodsky, 2024; Rogers, 2024; WHO, 2024). Anemia can result from a wide range of conditions, including acute blood loss, impaired erythropoiesis, hemolysis, or a combination of factors. It is not a stand-alone disease but a manifestation of underlying pathology. Due to its complex etiology, a systematic, evidence-based approach to diagnosis and management is essential for improving patient outcomes (Auerbach & DeLoughery, 2025; Barcellini, 2024).

Epidemiology

Anemia affects diverse populations, with recent data underscoring its disproportionate impact on patients assigned female at birth, children, and older adults. According to the Global Burden of Disease (GBD) Anaemia Collaborators (2023), an estimated 1.92 billion people—approximately 24.3% of the global population—were affected by anemia in 2021; the burden remains especially high in low- and middle-income countries. Roughly 30% of females of reproductive age (15–49 years) are affected by anemia, and nearly 40% of pregnant patients are anemic (WHO, 2025). Although its prevalence has declined since 1990, the absolute number of individuals affected continues to rise due to population growth. In the United States, data from the National Health and Nutrition Examination Survey (NHANES) between August 2021 and August 2023 revealed that anemia was notably higher among females (13.0%) compared to males (5.5%) and highest among non-Hispanic Black individuals (22.0%), followed by Asian (11.8%), Hispanic (10.9%), and non-Hispanic White individuals (6.1%). Socioeconomic disparities were also evident, with anemia affecting 14.1% of individuals living below 130% of the federal poverty level, compared to 5.7% among those at or above 350% (Centers for Disease Control and Prevention [CDC], 2024a).

Anemia affects 12.5% of adults aged 60 and older (CDC, 2024a). Older adults often present with multifactorial etiologies, including chronic kidney disease (CKD), inflammatory disorders, nutritional deficiencies, and bone marrow suppression. The presence of anemia in older adults is strongly associated with frailty, impaired functional status, increased risk of hospitalization, and higher all-cause mortality (Rodriguez-Gutierrez et al., 2023). Iron-deficiency anemia (IDA) continues to be the most common subtype, accounting for approximately 50% of all anemia cases worldwide, with disproportionately higher rates among adolescent females, menstruating and pregnant patients, and individuals experiencing food insecurity (WHO, 2024, 2025). A recent study by Tawfik and colleagues (2024) revealed that IDA affects about 15% of the US adult general population. Despite ongoing public health efforts, IDA remains underdiagnosed and undertreated, particularly in communities with limited health care access.

Anemia-related mortality has also persisted in recent years. In 2022, anemia was listed as the underlying cause of over 6,000 deaths in the United States, equating to a mortality rate of 1.8 per 100,000 population (CDC, 2024a). Mortality risk is heightened in patients with comorbidities, especially cardiovascular disease and CKD. These data underscore the need for targeted screening, particularly in high-risk groups, and for evidence-based interventions that address the biological and social determinants of anemia. Nurses play a critical role in assessing risk, identifying early symptoms, interpreting laboratory values, and implementing guideline-based interventions to manage anemia effectively (Auerbach & DeLoughery, 2025; Rogers, 2024).

Pathophysiology

A foundational understanding of hematopoiesis, erythropoiesis, and Hb function is essential to grasp the pathophysiologic mechanisms underlying anemia. Blood is comprised of plasma (e.g., liquid matrix) and cellular elements. Plasma, composed predominantly of water, serves as a transport medium for nutrients, proteins, hormones, and metabolic waste. The cellular elements include leukocytes (white blood cells [WBCs]), thrombocytes (platelets), and erythrocytes (RBCs). While WBCs are integral to the immune system, and platelets facilitate hemostasis (e.g., blood clotting), RBCs are responsible for oxygen delivery to tissue via Hb (Rogers, 2024; Turner et al., 2023).

Mature RBCs are biconcave-shaped discs and serve critical functions in gas exchange and Hb transport. Each RBC contains hundreds of millions of Hb molecules and is capable of reversibly binding to oxygen. RBCs circulate for approximately 120 days before being removed from circulation by macrophages in the spleen and liver through a process called extravascular hemolysis. Hemolysis refers to premature RBC destruction and can occur due to membrane defects, enzymatic deficiencies, autoantibodies, or mechanical stress—accelerated RBC loss without adequate compensatory production results in anemia. Hematocrit (Hct) and Hb levels are key diagnostic indicators representing the volume of RBCs in blood and the oxygen-carrying protein concentration, respectively. Table 1 classifies the severity of anemia among adults based on Hb levels (Barcellini, 2024; Rodriguez-Gutierrez et al., 2023; Turner et al., 2023; WHO, 2024).

Table 1

Anemia Severity Based on WHO 2024 Guidelines

(WHO, 2024)

Hematopoiesis

Hematopoiesis refers to the continuous production of blood cells from multipotent hematopoietic stem cells, primarily within the bone marrow. This ongoing process produces WBCs, platelets, and RBCs in response to physiologic demand. Hematopoiesis occurs in the liver and spleen of a fetus, but after birth, it occurs primarily in the bone marrow. In pathologic states, extramedullary hematopoiesis may resume in organs such as the spleen or liver and is often indicative of severe marrow dysfunction or myeloproliferative disease (Hoffman & Benz, 2022). Hematopoiesis is tightly regulated by a cascade of cytokines and growth factors, including stem cell factor, interleukins, and granulocyte-macrophage colony-stimulating factor (GM-CSF). These mediators guide stem cell proliferation and lineage-specific differentiation. The rate of hematopoiesis is modulated according to the body’s needs; for example, in cases of acute hemorrhage or hemolysis, erythropoietic activity may surge rapidly to replace depleted RBCs. In contrast, chronic inflammatory states or marrow suppression due to chemotherapy or infection may lead to inadequate hematopoiesis over time (Means & Brodsky, 2024; Rodriguez-Gutierrez et al., 2023; Rogers, 2024).

Erythropoiesis

Erythropoiesis is the specific process of RBC production and is regulated predominantly by erythropoietin (EPO), a hormone synthesized in the kidneys in response to hypoxia. When oxygen delivery to tissues is impaired due to anemia, high altitude, or cardiovascular disease, EPO production increases. EPO promotes differentiation and maturation of erythroid progenitor cells in the bone marrow, signaling reticulocytosis, the increased production and release of reticulocytes (immature RBCs) into the bloodstream. Reticulocytes mature into functional erythrocytes within 24 to 48 hours (Auerbach & DeLoughery, 2025; National Heart, Lung, and Blood Institute [NHLBI], 2022d).

Under healthy conditions, approximately 1% of circulating RBCs are reticulocytes. An elevated reticulocyte count in the setting of anemia typically indicates a compensatory marrow response. Conversely, a low reticulocyte index suggests impaired erythropoiesis and may result from deficiencies in essential nutrients (i.e., iron, vitamin B12, folate), CKD, marrow infiltration, or exposure to myelotoxic agents. The efficiency of erythropoiesis depends on several critical cofactors. Adequate supplies of iron are necessary for Hb synthesis, while vitamin B12 and folate are essential for DNA replication and erythroblast proliferation. Disruption in any of these components—due to malabsorption, dietary insufficiency, chronic inflammation, or medication effects—can hinder RBC production and manifest as various subtypes of anemia (Barcellini, 2024; Rodriguez-Gutierrez et al., 2023).

Etiology

Anemia is a multifactorial condition and can be broadly categorized into three main etiologic mechanisms: blood loss, decreased RBC production, and increased RBC destruction (Auerbach & DeLoughery, 2025; Rogers, 2024).

Blood Loss

Blood loss can be acute or chronic. Acute blood loss, such as from trauma or surgery, can rapidly reduce circulating blood volume and Hb levels. To compensate for reduced blood volume during hemorrhage, the interstitial fluid in cells diffuses into the intravascular space; this expands plasma to maintain adequate blood volume, increasing venous return, preload, and stroke volume. These mechanisms increase cardiac output to maintain sufficient oxygen delivery to tissues and organs. The increased fluid decreases the blood’s viscosity (thickness) and causes mass dilution of RBCs, resulting in anemia. In cases of severe bleeding or in situations where timely and adequate intervention is lacking, the cardiac compensatory mechanisms eventually fail, leading to congestive heart failure (CHF). The resulting tissue hypoxia leads to compensatory mechanisms of the pulmonary system, inducing an increased rate and depth of respiration, tachycardia, and related clinical sequelae. When more than 30% of the blood volume is acutely lost, most individuals cannot compensate via the usual mechanisms and often have signs of hypovolemia, including postural hypotension and tachycardia. If the blood volume loss is greater than 40%, hypovolemic shock symptoms develop, including confusion, diaphoresis, hypotension, tachycardia, and dyspnea. These patients have significant deficits in vital organ perfusion, develop hypoxia, and require immediate volume replacement to avoid fatal outcomes (Auerbach & DeLoughery, 2025; Rogers, 2024).

Chronic blood loss, often due to gastrointestinal bleeding (GIB), cancer, or menorrhagia (heavy menstruation), is a leading cause of anemia in adults. Chronic blood loss gradually leads to anemia if it occurs more rapidly than the body can restore or replace the loss or if accelerated erythropoiesis depletes the body’s iron stores (Auerbach & DeLoughery, 2025; Rogers, 2024).

Deficient Erythropoiesis

Deficient erythropoiesis (decreased RBC production) or hyperproliferative anemia can occur in response to nutritional deficiencies (iron, vitamin b12, folate), chronic inflammation, bone marrow disorders (caused by cancer such as lymphoma), stem cell dysfunction, or renal failure. In CKD, reduced EPO production directly impairs RBC generation. Inflammatory cytokines also block erythropoiesis and disrupt iron metabolism, contributing to chronic disease anemia. Deficient erythropoiesis is typically identified by reticulocytopenia, a reduced number of reticulocytes observed on peripheral blood smears (Khan & Jialal, 2023; Means & Brodsky, 2024; Rogers, 2024).

Hemolysis

Hemolytic anemia occurs when RBCs are destroyed faster than they are produced. Hemolysis can occur in response to intrinsic (inherited) abnormalities of the RBCs or extrinsic (acquired) factors. Inherited causes of hemolytic anemia include defects in the RBC membranes, enzymatic pathways, or Hb synthesis, such as in thalassemia and sickle cell disease. Acquired causes of hemolytic anemia are usually immunologic, such as RBC destruction due to autoantibodies (immune-mediated hemolysis from blood transfusion reactions), allergic reactions (drug-induced hemolytic anemia), infection/inflammatory responses (bacterial infections, disseminated intravascular coagulation [DIC]), or exposure to toxic drugs or chemicals. These conditions lead to the premature destruction of RBCs, overwhelming the bone marrow’s capacity to compensate. Hemolysis can occur within the blood vessels or lymphoid tissues that filter the blood, such as the spleen and liver, resulting in splenomegaly or enlargement of the spleen. RBCs are destroyed at a more rapid rate when the spleen is enlarged. The body attempts to compensate for premature RBC destruction by increasing levels of EPO. Diagnostic evaluation typically reveals elevated lactate dehydrogenase (LDH), decreased haptoglobin, increased indirect bilirubin, and elevated reticulocyte count (Barcellini, 2024; Killeen et al., 2025; Means & Brodsky, 2024; NHLBI, 2022a).

Clinical Presentation

Anemia causes a wide spectrum of symptoms depending on several variables, including the underlying cause, the severity of Hb reduction, and the presence of coexisting medical conditions. While anemia is frequently asymptomatic in its early stages, especially if it develops gradually, it often becomes clinically apparent as oxygen delivery to tissues declines and compensatory mechanisms are overwhelmed. In the early phases, anemia may be identified through routine blood work, which may show decreased Hb or Hct levels before any physical symptoms arise; this is especially true in chronic disease states where anemia may be mild or progress slowly. As the condition worsens, tissue hypoxia becomes more pronounced, leading to a range of clinical manifestations. Common symptoms of anemia include fatigue, generalized weakness, lightheadedness, dizziness, headache, and cold intolerance. In moderate to severe anemia, symptoms may escalate to include chest discomfort, syncope, or heart failure—particularly in patients with preexisting cardiovascular disease. Patients typically describe deep, sighing respirations, a sensation of racing heartbeat, or chest heaviness—all signs that reflect compensatory mechanisms to low oxygen levels. Symptoms are usually more pronounced in those with low cardiopulmonary reserve, acute blood loss, or rapidly developing anemia, in contrast to chronic, slowly progressing anemia, which the body can partially compensate for over time. Cognitive impairment, difficulty concentrating, and irritability may also be observed, particularly among older adults or those with coexisting neurologic conditions (Ignatavicius et al., 2023; Killeen et al., 2025; Means & Brodsky, 2024; Rogers, 2024).

A thorough patient history is necessary. Important domains to explore include dietary intake—particularly of iron, folate, and vitamin B12—menstrual history in premenopausal females, gastrointestinal symptoms (e.g., melena, hematochezia, changes in stool color), history of chronic disease (e.g., renal disease, autoimmune disorders), medication use, and family history of hematologic or hereditary disorders. The history-taking should also include details about recent trauma, episodes of acute bleeding, or symptoms suggestive of occult blood loss. Specific symptom patterns may provide clues to the underlying type of anemia. For example, patients with iron deficiency may experience pica (e.g., cravings for nonfood substances such as dirt, ice, or clay), while those with vitamin B12 deficiency may report paresthesias, unsteady gait, or numbness due to demyelinating neuropathy (Means & Brodsky, 2024; Rogers, 2024).

Physical examination findings are variable and can range from unremarkable to strikingly abnormal, depending on the severity and chronicity of anemia. Among the most reliable signs is pallor, best observed in the conjunctivae, oral mucosa, nail beds, and palms. Pallor becomes more prominent as Hb falls below 8 g/dL but may be subtle in moderate anemia. Cardiovascular findings are often evident. Tachycardia is common due to increased cardiac output as a compensatory response to anemia. A systolic flow murmur, frequently described as a hemic murmur, may be present due to turbulent flow over heart valves in the setting of increased circulation. In patients with underlying ischemic heart disease, this increased demand may provoke anginal symptoms or even precipitate acute coronary syndromes (Ignatavicius et al., 2023; Means & Brodsky, 2024; Rogers, 2024).

The skin and mucosal surfaces can provide additional diagnostic clues. In iron deficiency, koilonychia and glossitis may be observed. Koilonychia refers to nails that are concave or scooped out, curving inward at the tips, and often described as “spoon-shaped nails.” Glossitis denotes inflammation of the tongue, frequently evidenced by swelling, redness or purple color, and a smooth, shiny appearance. Angular cheilitis, characterized by painful cracks at the corners of the mouth, is another classic sign. Vitamin B12 deficiency may manifest as a beefy red tongue, along with neurologic signs such as diminished proprioception, impaired vibration sense, and positive Romberg sign. A positive Romberg sign indicates sensory ataxia as the cause of postural imbalance. Findings such as jaundice and scleral icterus suggest hemolytic anemia, where RBC destruction leads to elevated bilirubin levels and reticuloendothelial system (RES) activation. The RES is responsible for eradicating damaged RBCs from circulation. In aplastic anemia or marrow infiltration syndromes, physical findings may include petechiae, purpura, or ecchymoses as a manifestation of underlying thrombocytopenia. Hepatosplenomegaly may be evident on abdominal exams, particularly in cases of chronic hemolysis or marrow infiltration. In trauma patients, abdominal distension may signify internal bleeding or splenic rupture (Barcellini, 2024; Ignatavicius et al., 2023; Killeen et al., 2025; Rogers, 2024).

In advanced or systemic cases, additional findings may include cachexia, thinning of scalp hair, spider nevi, or palmar erythema, especially in cases of infiltrative bone marrow diseases, chronic liver disease, or malignancies (Auerbach & DeLoughery, 2025). Nurses must perform a detailed neurologic assessment, especially in patients presenting with symptoms such as numbness, balance difficulty, or confusion. Neurologic changes are most often observed in megaloblastic anemias, but severe anemia of any type may impact cerebral perfusion and result in similar findings (Ignatavicius et al., 2023; Rogers, 2024).

Diagnostic Tests

When anemia is suspected based on patient symptoms or initial laboratory results, a structured diagnostic approach is essential to determine the underlying cause. A complete evaluation typically begins with a comprehensive panel of blood tests, each offering insights into various etiologies of anemia. The combination of laboratory values, patient history, and clinical findings guides the differential diagnosis and helps clinicians formulate an appropriate management plan. The initial laboratory assessment often includes a complete blood count (CBC), RBC indices, reticulocyte count, peripheral blood smear, iron studies, vitamin levels, and, when indicated, bone marrow examination (Ignatavicius et al., 2023; Rogers, 2024). Refer to Table 2 for the typical reference ranges for these tests, based primarily on current guidelines from the American Board of Internal Medicine (ABIM).

Table 2

Common Laboratory Tests with Reference Ranges in Anemia Evaluation

(ABIM, 2025)

Detailed Analysis of Key Diagnostic Parameters

RBC Indices and Morphologic Classification

The CBC is foundational in anemia evaluation. It quantifies the main components in the blood and provides information about RBC morphology and Hb content. Hb and Hct are interrelated, typically maintaining a 1:3 ratio (e.g., an Hb of 12 g/dL corresponds to an Hct of approximately 36%). However, hydration status can distort Hct readings; dehydration may falsely elevate Hct, whereas overhydration may reduce it. Mean corpuscular hemoglobin (MCH) reflects the average amount of Hb within each RBC, representing how much oxygen-carrying protein is present. Since Hb provides the RBCs with their characteristic red color, the suffix “-chromic” is used. Therefore, an RBC with a normal MCH value has a typical red color and is called “normochromic,” whereas an RBC with a low MCH has a pale red color and is called “hypochromic.” High MCH denotes “hyperchromic” cells, indicating the RBCs contain more Hb than usual. Mean corpuscular hemoglobin concentration (MCHC) measures the average concentration of Hb based on the RBC volume. Variations in MCH and MCHC values can indicate defects in Hb synthesis. The RBC distribution width (RDW) measures variability in RBC size, helping identify mixed anemias or early stages of deficiencies such as IDA. A wide variation in RBC size leads to an elevated RDW, indicating the cells were produced under varying conditions. Minor variations in cell size are expected, so the RDW is considered increased only when it is greater than 15% (Longo, 2017; Rogers, 2024).

Evaluation of the peripheral smear under a microscope may reveal abnormalities in cell morphology. Anemias are morphologically classified as microcytic, normocytic, and macrocytic as follows (Longo, 2017; Means & Brodsky, 2024; Yilmaz & Shaikh, 2023):

• Microcytic anemia is characterized by small RBCs (mean corpuscular volume [MCV] <80 fL), often hypochromic. Common causes include IDA, thalassemia, chronic disease, and lead poisoning.
• Normocytic anemia reveals cells that are of normal size but may be decreased in number. Etiologies include acute blood loss, early-stage IDA, chronic diseases, renal insufficiency, bone marrow suppression, and endocrine disorders.
• Macrocytic anemia is evidenced by RBCs, which are larger than normal (MCV >100 fL) and often due to impaired DNA synthesis. Macrocytic anemia includes vitamin B12 or folate deficiency (megaloblastic anemia), alcohol-related bone marrow suppression, hypothyroidism, and myelodysplastic syndromes.

Reticulocyte Count and Production Index

              Since reticulocytes are immature RBCs released from the bone marrow, the reticulocyte count reflects the bone marrow’s response to anemia. An elevated reticulocyte count implies active erythropoiesis, typically due to hemolysis or acute blood loss. In contrast, a low count suggests inadequate bone marrow response or suppression from marrow failure, nutritional deficiencies, or chronic disease. The reticulocyte production index (RPI) more accurately measures the bone marrow’s response to anemia by calculating the rate at which it produces RBCs. The RPI divides the total Hct by a normal Hct and multiplies by the percentage of total RBCs. An RPI greater than 3 indicates a robust marrow response, whereas a score of less than 2 indicates significant inadequate activity and compensation (Means & Brodsky, 2024; Rogers, 2024).

Iron Studies

                Iron panels offer essential insight into iron availability and storage. The serum iron level reflects circulating iron but fluctuates based on recent intake, limiting its diagnostic value. Ferritin is a protein that stores iron, so serum ferritin is the best indicator of iron storage. A ferritin level of less than 30 ng/mL is highly suggestive of IDA and often precedes changes in serum iron or RBC morphology. However, ferritin also acts as an acute-phase reactant and can be falsely elevated in inflammation or liver disease, masking underlying deficiency. Transferrin is a protein made by the liver that transports iron. Total iron-binding capacity (TIBC) indirectly assesses transferrin availability. When iron is depleted, transferrin synthesis increases, raising TIBC. Conversely, inflammation can reduce transferrin production. Transferrin saturation (TSAT) is the percentage of iron bound to transferrin, calculated by dividing the serum iron level by TIBC. TSAT values below 19% indicate IDA, whereas values over 50% indicate iron overload (Longo, 2017; Means & Brodsky, 2024; Rogers, 2024).

Folate and Vitamin B12

Folate (folic acid) is an essential vitamin for erythrocyte production and maturation and comes solely from dietary intake. Both folate and vitamin B12 are necessary for DNA synthesis and RBC maturation. Deficiencies in either can result in macrocytic anemia, often combined with neurologic symptoms in B12 deficiency. Folate levels less than 3 ng/mL are considered deficient, but folate status may be falsely normalized after recent dietary intake (24 to 48 hours). Vitamin B12 deficiency is typically defined as levels under 200 pg/mL; however, values between 200–300 pg/mL may warrant further confirmatory testing with methylmalonic acid or homocysteine levels (Longo, 2017; Means & Brodsky, 2024; NHLBI, 2022c; Rogers, 2024).

Bone Marrow Evaluation

In refractory or unexplained anemias, when the initial workup is inconclusive or bone marrow pathology is suspected, a bone marrow aspiration and biopsy may be necessary. A bone marrow biopsy can provide direct evidence of erythropoietic activity, marrow cellularity, and potential malignant infiltration. Subsequent investigations depend on abnormalities identified in the primary laboratory workup and the clinical presentation. For instance, if GIB is suspected, a fecal occult blood test (FOBT or stool guaiac) may be ordered. A positive guaiac test suggests GIB as a possible source of chronic blood loss. Similarly, if hemolysis or splenic pathology is suspected, imaging such as abdominal ultrasound can assess for splenomegaly (ABIM, 2025; Chaparro & Suchdev, 2019; Means & Brodsky, 2024).

Integrating Laboratory Findings with Clinical Presentation

Ultimately, the diagnosis of anemia involves integrating laboratory results with patient history and clinical presentation. For instance, a low MCV with low serum ferritin supports IDA, whereas a high MCV with low vitamin B12 or folate suggests megaloblastic anemia. Further, a normal CBC but positive guaiac test may indicate GI bleeding as a source of occult blood loss. When used appropriately, laboratory tests are diagnostic tools that enable clinicians to classify anemia, identify underlying causes, and guide timely, evidence-based treatment interventions accurately (Longo, 2017; Ignatavicius et al., 2023).

Clinical Management of Common Anemias

As outlined previously, anemia can be categorized into several subtypes based on etiology, RBC morphology, and pathophysiologic mechanisms. Understanding the distinct features of each type is essential for accurate diagnosis and management. This section will discuss the seven primary subtypes of anemia and their clinical management strategies.

Iron-Deficiency Anemia

IDA arises when iron levels are insufficient to support adequate Hb production and erythropoiesis. This condition is typically identified through laboratory findings of microcytic, hypochromic RBCs on peripheral smear and decreased serum ferritin levels. Iron is essential not only for Hb production but also for several key metabolic and cellular functions. Although iron is recycled within the body, sustained iron loss or inadequate intake over time can deplete iron reserves and impair RBC production. In the United States, common causes include menorrhagia and GIB caused by gastritis, peptic ulcers, or colorectal cancer. Female patients of reproductive age are particularly vulnerable due to menstrual iron losses, and those experiencing menorrhagia lose an estimated 16 mg or more of iron per cycle. The risk is further elevated in adolescent females, who face dual challenges of menstrual blood loss and rapid growth, and among socioeconomically disadvantaged populations, particularly African American patients and those living in urban areas. During pregnancy, iron demands significantly increase to support fetal development and expand maternal blood volume. Most individuals require 1,000 to 1,200 mg of additional iron throughout pregnancy, yet many begin gestation with low or depleted iron stores. Typically, 27 mg of elemental iron daily through prenatal vitamins is recommended. Without sufficient supplementation, pregnant individuals are at increased risk for IDA, which is associated with adverse outcomes, including preterm birth, low birth weight, and intrauterine growth restriction (Auerbach & Landy, 2025; Garzon et al., 2020; Rogers, 2024).

Beyond blood loss, IDA can also result from inadequate dietary intake or malabsorption. Iron absorption occurs primarily in the duodenum, and conditions that impair duodenal function—such as Helicobacter pylori (H. Pylori) infection, inflammatory bowel disease, or postbariatric surgery—can significantly reduce iron uptake. Patients who have undergone gastric bypass are at higher risk, with IDA prevalence in this group estimated between 25% and 50%. Clinically, IDA tends to develop gradually, with early symptoms including generalized weakness, fatigue, and dyspnea on exertion. As anemia progresses, patients may experience brittle or ridged nails, pallor of the skin and mucous membranes, and angular stomatitis. In advanced cases, glossitis, pica, and paresthesia may emerge (Auerbach & DeLoughery, 2025; Means & Brodsky, 2024; Rogers, 2024).

Management of IDA

Effective treatment of IDA begins with identifying and addressing the underlying cause. Iron replacement therapy is the cornerstone of management and can be delivered orally or intravenously, depending on the patient’s clinical status, tolerance, and response to treatment.

Dietary and Oral Iron Supplementation. The recommended daily iron intake is approximately 8 mg for adult males and 18 mg for premenopausal females. Iron is found in two dietary forms: heme iron, present in animal-based foods such as red meat, poultry, and fish, and nonheme iron, found in plant-based sources like leafy greens, legumes, and iron-fortified cereals. Heme iron is more bioavailable, with up to 30% absorption, compared to 2%–10% absorption for nonheme sources. Individuals following vegetarian or vegan diets may require supplementation to meet iron needs, as it is difficult to achieve adequate intake from nonheme sources alone (National Institutes of Health [NIH], 2024a).

When oral iron replacement is indicated, ferrous sulfate is commonly prescribed due to its affordability, effectiveness, and relatively high absorption rate. The standard dose for adults ranges from 100 to 200 mg of elemental iron per day, usually divided into two or three doses. Oral iron therapy is considered the first-line approach for treating mild to moderate anemia and is safe during pregnancy. Most patients notice symptomatic improvement, such as reduced fatigue and breathlessness, within a few weeks. However, full replenishment of iron stores typically takes 3 to 6 months, even after Hb normalizes. Monitoring serum ferritin levels every 3–4 weeks can help determine when iron therapy can be discontinued. A ferritin level above 50 ng/mL generally reflects sufficient repletion of iron stores (Auerbach & DeLoughery, 2025; Rogers, 2024).

Patients must be advised to take oral iron on an empty stomach to enhance absorption. However, gastrointestinal side effects such as nausea, constipation, dark stools, or metallic taste are common. Vitamin C (ascorbic acid), either in supplement form or via citrus fruits, can enhance iron absorption when taken concurrently. To minimize absorption issues, patients should avoid antacids, calcium supplements, and caffeine within two hours of iron administration. Drug interactions are also important to consider. Oral iron can interfere with the effectiveness of certain medications, including fluoroquinolones (ciprofloxacin [Cipro], levofloxacin [Levaquin]), tetracyclines (doxycycline [Vibramycin]), angiotensin-converting enzyme (ACE) inhibitors (lisinopril [Zestril], ramipril [Altace]), and levothyroxine (Synthroid). To reduce interaction risk, a six-hour separation window is often recommended between iron supplements and these medications (Auerbach & DeLoughery, 2025; Brant, 2020; NIH, 2024a; Rogers, 2024).

Intravenous (IV) Iron Therapy. IV iron is indicated for patients who cannot tolerate oral therapy, have malabsorption syndromes, or present with severe anemia requiring rapid correction, especially in settings such as CKD. It is often preferred for dialysis patients or those needing urgent Hb restoration. Common IV formulations include the following (Cohen & Powers, 2024):

• iron sucrose (Venofer)
• sodium ferric gluconate (Ferrlecit)
• ferumoxytol (Feraheme)
• ferric carboxymaltose (Injectafer)

Newer IV formulations have significantly reduced the risk of hypersensitivity reactions that were previously associated with high-molecular-weight iron dextrans (DexFerrum, INFeD). Despite the lower risk, patients must still be closely monitored during and following iron infusions for signs of reactions, such as flushing, myalgia, back pain, and chest discomfort. If symptoms occur, infusions should be paused and resumed at a slower rate once symptoms resolve and the patient is stable. Routine premedication with antihistamines is discouraged, as it may cause hypotension or tachycardia (Auerbach & DeLoughery, 2025; Brant, 2020).

Blood Transfusions. For patients with severe anemia—regardless of the subtype—packed red blood cell (PRBC) transfusions may be necessary, particularly when symptoms such as chest pain, dyspnea, or heart failure are present. PRBC transfusion provides immediate symptom relief as it improves the oxygen-carrying capacity of the RBCs. Each unit of PRBCs delivers approximately 200 mg of iron, bypassing gastrointestinal absorption altogether. However, transfusions are typically reserved for acute management and are not a substitute for iron repletion unless indicated by clinical urgency (Ignatavicius et al., 2023; Rogers, 2024).

Megaloblastic Anemias (Pernicious Anemia and Folate Deficiency)

Megaloblastic anemias are macrocytic anemias characterized by the presence of large, structurally abnormal, immature RBCs—referred to as megaloblasts—in the bone marrow. These abnormalities result from impaired DNA synthesis, most commonly due to deficiencies in vitamin B12 (cobalamin) or folate. Vitamin B12 deficiency, frequently caused by pernicious anemia, results from the loss of intrinsic factor, a glycoprotein produced by gastric parietal cells that is essential for B12 absorption in the terminal ileum. Since vitamin B12 is necessary for DNA synthesis and neurologic function, its deficiency affects both hematologic and neurologic systems. Expected laboratory findings in pernicious anemia include low Hb and/or Hct, high MCV, low reticulocyte count, low vitamin B12 level, and a usually normal or elevated folate level. These are often accompanied by an elevated LDH secondary to ineffective erythropoiesis and an elevated indirect bilirubin level from hemolysis of immature RBCs in the bone marrow. Symptoms may be subtle and nonspecific in the early stages but can progress to fatigue, anorexia, glossitis, weight loss, and neuropsychiatric disturbances. Neurologic manifestations are often described as “stocking-glove” paresthesia, gait instability, and even cognitive impairment or dementia in severe cases. On exam, patients may present with a smooth, beefy red tongue, jaundiced or pale skin, and signs of ataxia. The average age at diagnosis is around 60, as the condition typically evolves slowly over many years (Means & Brodsky, 2024; NHLBI, 2022c; Rogers, 2024).

Folate deficiency also leads to impaired DNA synthesis but typically does not cause neurologic symptoms. Folate, a water-soluble B vitamin, is required for RBC maturation and replication. Expected laboratory findings in folate-deficiency anemia include low Hb and/or Hct, high MCV, low reticulocyte count, low folate, normal vitamin B12 level, and elevated LDH. Dietary sources are the sole means of acquiring folate, and deficiencies are commonly linked to inadequate intake, chronic alcohol use disorder (AUD), or malabsorptive conditions such as celiac disease. Increased requirements during pregnancy, lactation, or rapid growth periods can further exacerbate deficiency risk. Folate-deficiency anemia during pregnancy is associated with teratogenic effects, including neural tube defects, which prompted the fortification of grain products in the United States with folic acid. Clinical manifestations mirror those of vitamin B12 deficiency, with fatigue and glossitis being common, but without neurologic deficits. Unique features may include severe cheilitis, oral ulcers, gastrointestinal symptoms such as flatulence, diarrhea, and swallowing difficulties (Khan & Jialal, 2023; Means & Brodsky, 2024; NHLBI, 2022c; Rogers, 2024).

Management of Pernicious Anemia

Treatment of pernicious anemia centers on the prompt replacement of vitamin B12 to correct the deficiency and prevent the progression of hematologic and neurologic symptoms. Although both oral and intramuscular (IM) formulations of vitamin B12 are available, IM administration is generally preferred and more effective, especially in cases involving malabsorption, as it ensures more reliable absorption compared to oral supplements. In healthy individuals, only a small fraction of an oral dose (i.e., approximately 10 mcg of a 500 mcg tablet) is absorbed, making injectable therapy more effective for repletion (NIH, 2024b).

Cyanocobalamin, a synthetic form of vitamin B12, is commonly used and administered via the IM route. Treatment protocols vary slightly, but a standard initial regimen includes 1,000 mcg IM daily for 6 to 7 days, followed by weekly doses for several weeks, then monthly maintenance injections. Some clinical pathways may begin with less frequent dosing, depending on patient response and comorbidities. Patients typically experience reticulocytosis within 5 to 7 days of initiating treatment, and improved Hb levels within several weeks. Complete resolution of anemia generally occurs within two months. While hematologic symptoms tend to improve quickly, neurologic complications such as peripheral neuropathy or cognitive changes may persist or only partially resolve, particularly if treatment is delayed (NIH, 2024b; Rogers, 2024).

Since folate deficiency can coexist with vitamin B12 deficiency, concurrent folic acid supplementation is recommended to support RBC production and prevent the masking of macrocytic anemia. Additionally, patients undergoing treatment for severe B12 deficiency should be monitored for hypokalemia, a common side effect during the early recovery phase due to a shift of potassium into regenerating cells. Mild hypokalemia can typically be managed with oral potassium supplementation. Importantly, pernicious anemia is a chronic condition resulting from intrinsic factor deficiency and cannot be cured. As such, lifelong maintenance therapy is required. Most patients will need monthly IM injections of 1,000 mcg of cyanocobalamin to maintain adequate vitamin B12 levels and prevent recurrence (NIH, 2024b; Rogers, 2024).

Management of Folate-Deficiency Anemia

Effective treatment of folate-deficiency anemia involves both nutritional counseling and pharmacologic supplementation. Individuals of childbearing potential are encouraged to consume a folate-rich diet and take at least 0.4 mg (400 mcg) of supplemental folic acid daily, particularly to reduce the risk of neural tube defects should an unplanned pregnancy occur. For patients who are pregnant, a daily prenatal vitamin containing 600–800 mcg of folic acid is recommended to meet the increased demands of fetal development. Patients who cannot tolerate prenatal multivitamins due to nausea or other side effects should take stand-alone folic acid supplements (1 mg daily) and increase dietary intake of folate-rich foods, including leafy greens, legumes, citrus fruits, and fortified cereals. In individuals at higher risk, such as those who have undergone bariatric surgery, have malabsorption disorders, or AUD, higher doses of folic acid (1–5 mg/day) may be required to correct or prevent deficiency. People with AUD, in particular, may benefit from the upper range of dosing, as chronic alcohol consumption impairs both absorption and hepatic storage of folate (Khan & Jialal, 2023; Rogers, 2024).

Treatment response to folic acid supplementation is typically rapid and predictable. A rise in reticulocyte count is usually observed within 7 to 10 days, indicating effective erythropoiesis. Hct levels tend to improve by 4–5% per week, with normalization expected within one month in most patients. Dietary counseling should reinforce the importance of compliance with daily supplementation and nutrient-dense food choices to sustain folate levels over time. If left untreated, folate deficiency may lead to neuropsychiatric complications, including depression, cognitive decline, insomnia, and, in severe cases, psychosis. Although these manifestations are less common than those with vitamin B12 deficiency, they can significantly impair quality of life and may not fully resolve even after the folate deficiency is corrected. Therefore, early diagnosis and adherence to therapy are critical for symptom resolution and long-term neurologic health (Khan & Jialal, 2023; Rogers, 2024).

Anemia of Chronic Disease

Anemia of chronic disease (ACD), also known as anemia of inflammation, is the second most common type of anemia worldwide. It is often observed in individuals with chronic infections, autoimmune diseases, cancer, and CKD. ACD is mediated primarily by an inflammatory response in which cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) disrupt normal iron metabolism, impair EPO production, and inhibit bone marrow responsiveness to EPO. These combined processes suppress erythropoiesis and lead to anemia. Laboratory findings typically include normocytic or mildly microcytic anemia, a low reticulocyte count, and reduced serum iron concentrations. However, unlike IDA, ferritin levels are usually normal or elevated due to its role as an acute-phase reactant. Further, TIBC may also be decreased, reflecting suppressed capacity for iron transport. These laboratory features help distinguish ACD from other causes of microcytic anemia (Means & Brodsky, 2024; Rogers, 2024; Wicinski et al., 2020).

ACD is particularly prevalent in patients undergoing cancer treatment. In these cases, anemia may result from a combination of inflammation, chemotherapy-induced bone marrow suppression, and nutritional deficits. While RBC destruction continues at normal or accelerated rates, impaired marrow function limits the development of new erythrocytes. This imbalance contributes significantly to fatigue and diminished functional capacity in cancer patients. ACD is also common in CHF and is associated with a poorer prognosis. Patients with both anemia and CHF tend to experience exacerbated symptoms, reduced exercise tolerance, and higher hospitalization and mortality rates. CKD frequently coexists with CHF and further compounds anemia risk. Shared risk factors, such as aging, hypertension, elevated BMI, and physical deconditioning, contribute to overlapping pathophysiology in these patients. Key drivers of anemia in this population include chronic inflammation, hemodilution, iron dysregulation, and reduced renal EPO synthesis (Means & Brodsky, 2024; Rogers, 2024; Wicinski et al., 2020).

In patients with CKD, especially those on dialysis, the kidney’s ability to produce EPO declines significantly once the glomerular filtration rate (GFR) falls below 30–40 mL/min/1.73 m². Although initial hypoxia from reduced cardiac output or renal perfusion may transiently stimulate EPO release, the failing kidneys ultimately cannot sustain adequate levels. Without sufficient EPO, erythroid precursors in the bone marrow cannot proliferate effectively, resulting in chronic anemia that typically progresses over time (Means & Brodsky, 2024; Rogers, 2024; Wicinski et al., 2020).

Management of ACD

The primary approach to managing ACD is to address and treat the underlying condition contributing to inflammation or chronic illness. Correction of the root cause often leads to gradual improvement in Hb levels (Rogers, 2024; Wicinski et al., 2020).

Erythropoiesis-stimulating agents (ESAs). In specific cases, such as anemia related to CKD, antiretroviral therapy, or chemotherapy, ESAs such as epoetin alfa (Procrit) or darbepoetin alfa (Aranesp) may be indicated when anemia is symptomatic or significantly impairs quality of life. These agents mimic the action of natural EPO by stimulating RBC production in the bone marrow. ESAs are administered subcutaneously and are often combined with IV iron to optimize response, especially in CKD. Iron status should be closely evaluated before and during ESA treatment. Even with adequate total body iron, many patients with ACD develop functional iron deficiency, where iron is sequestered and unavailable for erythropoiesis. In such cases, IV iron is preferred over oral supplementation to enhance ESA responsiveness and improve outcomes (Means & Brodsky, 2024; Rogers, 2024; Wicinski et al., 2020).

Although ESAs are effective in increasing Hb levels and reducing the need for PRBC transfusions, they carry significant risks, particularly at higher doses. Some common side effects include increased blood pressure, headache, dizziness, joint and muscle pain, and rash (Means & Brodsky, 2024; Rogers, 2024; Wicinski et al., 2020). Clinical trials and postmarketing data have shown that ESAs are associated with increased risk of thrombosis, hypertension, stroke, and potential tumor progression in cancer patients. Due to these concerns, the US Food & Drug Administration (FDA) previously required a Risk Evaluation and Mitigation Strategy (REMS) for ESAs to ensure patients and prescribers were fully informed of the risks. Although the REMS program requirement was lifted in 2017, careful risk-benefit discussions and ongoing monitoring remain an essential component of ESA therapy (FDA, 2017).

Aplastic Anemia

Aplastic anemia is a rare but life-threatening disorder characterized by bone marrow failure, resulting in pancytopenia, a deficiency of RBCs, WBCs, and platelets. The underlying mechanism involves damage to the hematopoietic stem cells, leading to a marked reduction in the production of all blood cell lines. This condition may occur idiopathically or be triggered by identifiable causes, such as exposure to ionizing radiation, cytotoxic medications, environmental toxins, viral infections, or autoimmune processes. Although uncommon, with an estimated incidence of 2 to 5 cases per million people annually, aplastic anemia carries significant morbidity and mortality. It presents most frequently in adolescents and young adults (15–25 years) and older adults over 60 years. Clinical onset can be abrupt or insidious and depends on the degree and pattern of blood cell suppression. Common presenting features include fatigue, pallor, dyspnea, and recurrent infections or fevers due to immunosuppression. Easy bruising, petechiae, mucosal bleeding, and prolonged bleeding times often reflect underlying thrombocytopenia. Unlike other marrow disorders, splenomegaly and neurologic deficits are typically absent. Initial laboratory findings normally reveal pancytopenia, often in the setting of low reticulocyte count from reduced marrow activity. A definitive diagnosis of aplastic anemia requires bone marrow biopsy, which will reveal a hypocellular marrow with replacement by fatty tissue and minimal hematopoietic activity (Ignatavicius et al., 2023; Kulasekararaj et al., 2024; Rogers, 2024).

Management of Aplastic Anemia

The management of aplastic anemia has evolved significantly in recent years, with treatment strategies tailored to disease severity, patient age, comorbidities, eligibility for transplant, and donor availability. The primary therapeutic approaches include hematopoietic stem cell transplantation (HSCT), immunosuppressive therapy (IST), and supportive care measures. For younger patients, particularly those under 40 years of age with severe or very severe aplastic anemia and an available human leukocyte antigen (HLA)–matched sibling donor, allogeneic HSCT is considered the first-line treatment due to its curative potential and favorable long-term outcomes. Advancements in transplantation techniques, including the use of haploidentical donors and improved conditioning regimens, have expanded the applicability of HSCT to a broader patient population (Kulasekararaj et al., 2024; Piekarska et al., 2024).

In cases where HSCT is not feasible, IST remains the standard initial therapy. The goal of IST is to suppress the autoimmune-mediated destruction of hematopoietic stem and progenitor cells in the bone marrow, thereby allowing recovery of blood cell production. IST typically achieves hematologic response in 60%–70% of patients within 3 to 6 months. Long-term follow-up is essential, as some patients may relapse. Horse-derived antithymocyte globulin (ATG) is the preferred IST agent due to its superior efficacy. It is made from antibodies derived from a horse that is specifically engineered to target and reduce the number of T-lymphocytes in the body. T-lymphocytes are believed to play a central role in the immune attack on the bone marrow. Cyclosporine A (CsA) is another cornerstone of IST as it suppresses T-cell activation and cytokine production. It is administered orally or intravenously for at least 6 months. The addition of eltrombopag (Promacta), a thrombopoietin receptor agonist, to IST has further improved hematologic responses and overall survival rates (Kulasekararaj et al., 2024; Piekarska et al., 2024). Eltrombopag (Promacta) stimulates the proliferation of hematopoietic stem and progenitor cells, enhancing trilineage hematopoiesis (RBCs, WBCs, and platelets; Zhang et al., 2024). While on IST, patients require close monitoring of renal function, blood pressure, liver enzymes, and blood counts. Common side effects include serum sickness (with ATG), nephrotoxicity and hypertension (with Cyclosporine A [CsA]), and hepatotoxicity or thrombosis risk (with eltrombopag [Promacta]). Infrequently, splenectomy (surgical removal of the spleen) may be necessary for some patients (Kulasekararaj et al., 2024).

Supportive care is an integral component of aplastic anemia management, addressing complications such as anemia, bleeding, and infections. Transfusion support with leukocyte-depleted and irradiated blood products is essential to minimize alloimmunization and transfusion-related complications. The potential for iron overload resulting from repeated transfusions necessitates regular monitoring of serum ferritin levels and the use of iron chelation therapy if indicated. Prophylactic antimicrobials and prompt treatment of infections are critical, given the immunocompromised state of these patients (Kulasekararaj et al., 2024; Piekarska et al., 2024; Rogers, 2024; Urbanowicz et al., 2021).

For more information, refer to the NursingCE course on Hematopoietic Cell Transplantation.

Hemolytic Anemias (Sickle Cell Disease and Thalassemia)

Hemolytic anemias are characterized by premature destruction of RBCs, which can be hereditary or acquired. Hereditary forms include sickle cell disease (SCD) and thalassemia, while acquired forms involve autoimmune hemolytic anemia, infections, or mechanical damage. SCD is the most common inherited blood disorder in the United States, affecting an estimated 100,000 individuals. The condition predominantly affects people of African descent, occurring in approximately 1 in 365 births among non-Hispanic Black individuals. Among Hispanic populations, the incidence is lower, approximately 1 in 16,300 births. SCD is an autosomal-recessive genetic disorder, so an additional 1 in 13 non-Hispanic Black infants are born with sickle cell trait, meaning they carry one copy of the defective gene but do not have the full disease. As part of universal newborn screening programs, all infants in the United States are tested for SCD at birth. In prenatal settings, the disease can be detected through genetic testing of amniotic fluid or placental tissue (Ashorobi et al., 2023; Bender & Carlberg, 2025; CDC, 2024b).

SCD affects the RBCs and changes the Hb structure, causing it to become defective and misshaped. The disease alters the normal hemoglobin A (HbA) molecule, with two alpha and beta amino acid chains, to the abnormal hemoglobin S (HbS) molecule, composed of abnormal beta chains. In SCD, RBCs are rigid and crescent-shaped, resembling a “sickle” or “C-shape,” making them less flexible and prone to getting caught in small blood vessels. The abnormal cell shape and rigidity lead to vascular occlusion and tissue ischemia, while the premature destruction of sickled RBCs contributes to chronic hemolytic anemia. In chronic hemolytic anemia, the Hb and Hct levels may be low-to-normal depending on the rate of RBC destruction versus bone marrow compensation. Other expected laboratory findings include elevated reticulocyte and RDW and normal or increased MCV. Both LDH and indirect bilirubin are typically elevated. Clinical manifestations are diverse and can begin in infancy, often by 6 months of age. Common symptoms include jaundice, fatigue, shortness of breath, delayed growth, and recurrent pain episodes. Patients frequently report pain that mimics arthritis, often in the joints, limbs, or abdomen. Neuropathic pain and chronic fatigue are also frequent concerns (Bender & Carlberg, 2025; NHLBI, 2024).

A hallmark of the disease is the vaso-occlusive crisis (VOC), a painful episode resulting from sickled cells obstructing blood flow. VOCs may be triggered by dehydration, infection, emotional stress, cold exposure, or other physiologic stressors. These episodes can vary widely in frequency from weekly to once a year and may last several hours to days. More severe complications can include organ damage, acute chest syndrome, priapism, pulmonary hypertension, stroke, or even multisystem organ failure in advanced cases. Over time, the cumulative effects of chronic hemolysis and repeated VOCs increase the risk of life-threatening complications, including sepsis, thromboembolic events, and progressive organ dysfunction. Therefore, early identification and lifelong management are critical for improving outcomes and quality of life for individuals living with SCD (Ashorobi et al., 2023; Bender & Carlberg, 2025; Ignatavicius et al., 2023; Rogers, 2024).

Management of SCD

Timely diagnosis of SCD is essential in order to initiate preventive care and reduce complications. A cornerstone of long-term SCD management includes educating patients and caregivers about how to avoid triggers of VOCs, such as dehydration, infections, and extreme temperatures. Hydroxyurea (Hydrea) is the mainstay treatment option for the chronic management of SCD as it increases fetal hemoglobin (HbF), reducing sickling episodes. HbF is called fetal hemoglobin because newborn babies have it, and when individuals with SCD have higher HbF levels, the RBCs are less likely to cause symptoms. Hydroxyurea (Hydrea) suppresses DNA synthesis, increasing RBC water content and altering their adhesion to the vascular endothelium. This makes the RBCs more flexible, thereby reducing pain and the need for blood transfusions to manage acute issues such as acute chest syndrome. Clinical studies have shown that hydroxyurea (Hydrea) can reduce the incidence of VOC crises by approximately 50%. Common side effects include bone marrow suppression (e.g., neutropenia), nausea, thinning hair, elevated liver enzymes, and potential infertility (American Society of Hematology, n.d.; Ashorobi et al., 2023; Bender & Carlberg, 2025).

Another therapeutic option approved in 2019 is voxelotor (Oxbryta), an oral agent that binds to HbS, decreasing polymerization, and increasing oxygen affinity; this helps prevent the sickling of RBCs. Voxelotor (Oxbryta) is approved for use in patients aged four years and older, with weight-based dosing for pediatric populations and a standard adult dose of 1500 mg once daily. In patients with Class C hepatic impairment, the dose should be reduced to 1000 mg. Adverse effects may include headache, gastrointestinal symptoms (such as nausea, vomiting, and abdominal pain), fever, and hypersensitivity reactions. Rare but serious events like pulmonary embolism have also been reported (Ashorobi et al., 2023; Bender & Carlberg, 2025).

Management of acute VOC episodes typically involves supportive care, including aggressive intravenous hydration, anti-inflammatory therapy, and opioids for severe pain. Although opioids are not generally recommended for chronic pain management due to risks of dependency, they remain the standard of care for acute sickle cell crises, given their effectiveness in rapidly alleviating intense pain. For patients with severe or refractory disease, such as those experiencing complications such as stroke, recurrent VOCs, nephropathy, or retinopathy, HSCT may be considered. Currently, HSCT is the only established cure for SCD; however, due to the potential for serious complications, including graft-versus-host disease (GVHD) and transplant-related mortality, it is typically reserved for patients with high disease burden and a suitable donor match (Ashorobi et al., 2023; Bender & Carlberg, 2025).

Thalassemia

Thalassemia is an inherited blood disorder in which the body produces an inadequate amount of normal Hb. Expected laboratory findings include low Hb and/or Hct, very low MCV (typically <70 fL), low MCH, and normal or mildly elevated RDW; also common are high or normal RBC and reticulocyte counts. Since the condition is caused by a defect in two major proteins that make up normal Hb—alpha-globin and beta-globin—the two major types of thalassemia are named after the defects within these proteins. Alpha-thalassemia results from deletions or mutations in the genes that code for the alpha-globin protein. It is most common in individuals of Southeast Asian, Middle Eastern, and African descent. The severity of the condition depends on how many genes are affected. It presents with two clinically relevant forms: hemoglobin Bart hydrops fetalis (Hb Bart) syndrome, caused by the deletion or inactivation of all four alpha-globin genes, and hemoglobin H (HbH) disease, most frequently caused by the deletion or inactivation of three alpha-globin genes. Hb Bart syndrome is the most severe form, leading to profound anemia, generalized edema, and heart failure in utero. It is typically fatal before or shortly after birth. HbH usually presents within the initial years of life, although milder cases may develop in adulthood. Most commonly, HbH disease presents with splenomegaly, mild jaundice, and bone changes. Infections or exposure to oxidant medications may result in acute episodes of hemolysis. They may also experience gallstones due to chronic hemolysis (Langer, 2024; Tamary & Dgany, 2024).

Beta-thalassemia results from mutations that impair or eliminate the production of beta-globin chains and are inherited in an autosomal-recessive manner. It is more prevalent among individuals from the Mediterranean, Middle Eastern, South Asian, and North African regions. There are three major types of beta-thalassemia: minor, intermedia, and major. Beta-thalassemia minor (or trait) typically involves a mutation in one beta-globin gene, and affected individuals are usually asymptomatic, with only mild microcytic anemia. Beta-thalassemia intermedia presents later in childhood or adolescence and is associated with moderate anemia that may not require regular transfusions. The most severe form, beta-thalassemia major (also known as Cooley’s anemia), manifests within the first two years of life. Affected children develop severe microcytic, hypochromic anemia, along with clinical features such as growth delay, hepatosplenomegaly, jaundice, and bone marrow expansion, which may result in characteristic facial bone deformities. Additional complications include delayed puberty, dark urine from ongoing hemolysis, and cardiac enlargement due to chronic anemia. These patients require lifelong blood transfusions (referred to as transfusion-dependent thalassemia [TDT]), which, over time, can lead to iron overload, a potentially life-threatening complication if not properly managed with iron chelation therapy (Farmakis et al., 2022; Langer, 2024; Means & Brodsky, 2024; NHLBI, 2022b).

Diagnostic evaluation often includes Hb electrophoresis to identify abnormal hb patterns, and peripheral blood smears typically reveal features such as target cells, nucleated RBCs, microcytosis, and anisopoikilocytosis. Reduced HbA and elevated levels of HbF or HbA2 are common findings in beta-thalassemia major. Genetic testing may be used to confirm the diagnosis and guide family counseling (Farmakis et al., 2022; Langer, 2024; Tamary & Dgany, 2024).

Management of Thalassemia

The clinical management of thalassemia has advanced considerably over the past several years, not only emphasizing the prevention of complications but also targeting the underlying pathophysiology. While supportive care such as transfusions and chelation remain the standard of treatment, HSCT is currently the only curative option. However, access to transplantation depends on disease severity, donor availability, and patient eligibility. Management strategies for alpha- and beta-thalassemia differ according to the severity of the disease, whether the patient has TDT, and which globin chain is affected. For alpha-thalassemia, minor forms typically do not require treatment as most individuals are asymptomatic, but genetic counseling should be considered in patients who desire biologic children. HbH causes moderate to severe hemolytic anemia and requires regular monitoring with periodic CBC and iron studies. Folic acid supplementation is usually recommended to support erythropoiesis, and PRBC transfusions may be needed periodically (Baird et al., 2022; Tamary & Dgany, 2024).

In some cases, splenectomy may be considered if it contributes to significant hemolysis or the need for repeated PRBC transfusions. Patients with HbH should avoid sulfa drugs and fava beans due to the risk of hemolysis. For Hb Bart syndrome, intrauterine transfusions may be considered in certain cases if diagnosed early in pregnancy, but the benefit is limited. Prenatal diagnosis and counseling are essential. While HSCT is theoretically curative, it is rarely feasible in Hb Bart syndrome due to the early onset of the disease (Baird et al., 2022; Tamary & Dgany, 2024).

Beta-thalassemia minor typically does not require treatment as most individuals are asymptomatic, with mild anemia. However, like alpha-thalassemia minor, patients should consider genetic counseling, particularly if their partner is also a carrier. The management of beta-thalassemia intermedia is individualized. Folic acid supplementation may be offered to support RBC production, and occasional PRBC transfusions may be required, especially during illness or pregnancy. Patients should be monitored for complications such as iron overload, bone deformities, and leg ulcers. Iron chelation therapy may be necessary, even without frequent transfusions, due to increased intestinal absorption of iron. Beta-thalassemia major requires lifelong management. Affected individuals typically require regular PRBC transfusions to maintain Hb levels and prevent complications. TDT requires the most comprehensive, long-term treatment as chronic PRBC transfusions remain the standard of care, aiming to sustain pretransfusion Hb levels between 9 and 10.5 g/dL. However, repeated PRBC transfusions typically result in progressive iron overload, a significant contributor to long-term morbidity. When overloaded, iron accumulates in vital organs such as the liver, heart, and endocrine glands, increasing the risk of hepatic fibrosis, cardiomyopathy, and diabetes mellitus if not properly managed. Iron chelation therapy is essential in patients with TDT (Baird et al., 2022; Farmakis et al., 2022; Langer, 2024; NHLBI, 2022b).

Iron chelation therapy maintains iron levels within a safe range by balancing iron accumulation with effective iron elimination. This balance helps prevent long-term organ damage caused by chronic iron overload. In patients who already have significant iron accumulation, chelation is used to reduce excess iron stored in tissues and organs. Chelation therapy should be initiated in patients with thalassemia after receiving 10 to 20 RBC transfusions plus any one of the following (Farmakis et al., 2022; Kwiatkowski et al., 2024):

• ferritin level of 1000 ng/mL on two consecutive tests
• liver iron concentration ³5 mg/g dry weight
• cardiac magnetic resonance imaging (MRI) <20 milliseconds

Three primary chelating agents are used, each with different formulations and administration routes (Farmakis et al., 2022; Kwiatkowski et al., 2024):

• Deferasirox (Exjade) remains a widely used first-line option due to its once-daily oral dosing and efficacy in removing both hepatic and cardiac iron buildup. It is available in dissolvable and film-coated tablets. Adverse effects include retinopathy, skin rash, renal toxicity (e.g., increased creatinine, proximal renal tubular dysfunction, proteinuria), elevated transaminases, and gastrointestinal effects, such as bleeding and ulcers.
• Deferiprone (Ferriprox) is available in tablet and liquid form and is typically administered two or three times daily. Adverse effects include neutropenia, gastrointestinal upset, elevated transaminases, arthralgias, and zinc deficiency.
• Deferoxamine (DFOA), an older therapy used since the 1970s, is administered parenterally via subcutaneous route or IV infusion. It remains the preferred agent for young children and is still endorsed as a first-line option by organizations such as the Thalassaemia International Federation (TIF).

While each agent is effective when taken as prescribed, no single therapy is universally superior. Treatment choice often depends on patient age, adherence potential, side effect profiles, and access to medications. Despite some differences across guidelines, expert consensus generally supports flexible, individualized approaches to chelation therapy in thalassemia care. Regular monitoring through serum ferritin, MRI of the heart and liver, and liver function tests are critical to adjust chelation regimens and minimize toxicity (Kwiatkowski et al., 2024).

In severe cases, HSCT is an alternative to traditional PRBC transfusion and chelation therapy and remains the only widely established cure for the disease. Outcomes are most favorable in younger patients with matched sibling donors; however, risks such as GVHD, transplant-related mortality, and limited donor availability restrict its use. For patients lacking a suitable donor or in settings where HSCT is not feasible, emerging drugs and gene therapies offer transformative alternatives (Farmakis et al., 2022). A major development in thalassemia treatment was the approval of luspatercept (Reblozyl), an erythroid maturation agent. Luspatercept (Reblozyl) enhances late-stage erythroid differentiation by inhibiting activin receptor type IIB ligands, improving Hb levels, and significantly reducing transfusion burden in adults with TDT. The BELIEVE trial, a phase 3, randomized, double-blind, placebo-controlled study, evaluated the efficacy and safety of luspatercept (Reblozyl) in adults with transfusion-dependent β-thalassemia. Conducted across 65 sites in 15 countries, the trial enrolled 336 patients who were randomly assigned in a 2:1 ratio to receive either luspatercept (Reblozyl) or placebo, in addition to best supportive care, over a minimum of 48 weeks. Findings revealed that over 20% of luspatercept (Reblozyl)-treated patients achieved at least a 33% reduction in transfusion burden, leading to its approval by the FDA in 2019 (Cappellini et al., 2020; FDA, 2019).

Gene therapy has also evolved from experimental treatment to regulatory approval over recent years. Betibeglogene autotemcel (Zynteglo) is an autologous gene therapy that delivers a functional beta-globin gene into a patient’s hematopoietic stem cells using a lentiviral vector. In 2022, the FDA approved betibeglogene autotemcel (Zynteglo) for patients with beta-thalassemia who require recurrent PRBC transfusions. Clinical trials have shown encouraging results, with patients achieving durable transfusion independence and improved quality of life (Asghar et al., 2022; Oikonomopoulou & Goussetis, 2021; Farmakis et al., 2022).

Supportive care plays an essential role in thalassemia management. Routine surveillance for endocrine dysfunction, osteoporosis, cardiac complications, and psychosocial effects is necessary across the lifespan. Immunizations, especially against hepatitis B, influenza, and pneumococcus, are strongly recommended. Multidisciplinary care teams, including hematologists, cardiologists, endocrinologists, fertility specialists, and nutritionists, are crucial in optimizing long-term outcomes (NHLBI, 2022b).

Conclusion

Anemia is a common and complex condition observed across various health care settings, with each subtype presenting distinct pathophysiologic mechanisms, clinical features, and management strategies. Providing high-quality nursing care requires a tailored approach that begins with early recognition of symptoms, comprehensive health assessments, and accurate interpretation of laboratory results. Nurses are essential in facilitating timely diagnoses, guiding patients through often multifaceted treatment plans, and ensuring adherence to therapies such as oral or IV iron, ESAs, or nutritional interventions. Beyond administering treatment, nurses provide patient education, dispelling misconceptions, promoting iron-rich diets, and reinforcing lifestyle modifications that support recovery. Nurses are also instrumental in identifying and mitigating barriers to care, such as limited access to medications, follow-up appointments, or financial constraints. Continuous monitoring for therapeutic effectiveness and potential adverse effects ensures both patient safety and optimal outcomes. By staying current with evolving guidelines and treatment innovations, nurses are empowered to advocate for evidence-based interventions and deliver compassionate, personalized care. Positioned at the forefront of patient interaction, nurses are uniquely equipped to improve outcomes, prevent complications, and enhance the overall quality of life for individuals affected by anemia (Brant, 2020; Ignatavicius et al., 2023).

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