Anemia Laboratory Diagnosis: A Comprehensive Guide

Introduction

Anemia, characterized by a reduction in circulating red blood cells or hemoglobin concentration, is a prevalent clinical sign encountered in both inpatient and outpatient settings. Often underestimated and inadequately managed, anemia is not a standalone diagnosis but rather an indicator of an underlying pathological process necessitating thorough investigation to determine its root cause. This condition leads to decreased oxygen delivery to tissues, potentially exacerbating existing comorbidities. Despite its clinical significance, discrepancies persist in the formal definition of anemia and established screening protocols [1][2][3]. Effective Anemia Laboratory Diagnosis is therefore crucial for identifying the etiology and guiding appropriate patient management.

Patients with anemia may present with a wide range of symptoms, including fatigue, weakness, lightheadedness, headaches, pallor, jaundice, tachycardia, palpitations, chest pain, dyspnea, cold extremities, and claudication. The variability in these signs and symptoms underscores the importance of objective laboratory testing for definitive diagnosis and classification.

While anemia is fundamentally defined by a decrease in red blood cell count or hemoglobin, the specific hemoglobin thresholds vary based on factors such as gender, ethnicity, and age. Furthermore, guidelines for routine anemia screening across different patient populations remain inconsistent. Similarly, the thresholds for initiating treatment and the therapeutic goals are subject to variations depending on medical specialties and individual patient conditions [4][5][6]. This article provides a comprehensive overview of anemia laboratory diagnosis, focusing on the key tests, interpretation of results, and their clinical significance in identifying the underlying causes of anemia.

In 2010, the World Health Organization (WHO) established anemia diagnostic criteria based on hemoglobin levels: less than 12 g/dl for premenopausal women and less than 13 g/dl for postmenopausal women and men of all ages. However, these standards have been debated, with some proposing alternative thresholds based on race, gender, and age, citing limitations in the WHO data. For instance, one study suggested anemia thresholds of less than 13.7 g/dl for white men (20-60 years), 13.2 g/dl for white men (over 60 years), and 12.2 g/dl for white women of all ages. Although racial differences in hemoglobin levels were acknowledged, specific standards for diagnosing anemia in Black populations were not proposed. Despite these discussions, the WHO standards remain widely used for consistency in the majority of current literature.

Discrepancies also exist regarding anemia screening recommendations. For example, the US Preventive Services Task Force (USPTF) concluded insufficient evidence to support routine iron deficiency anemia screening in asymptomatic children aged 6 to 24 months. In contrast, the American Academy of Family Practice advocates for universal anemia screening at 12 months, including hemoglobin measurement and assessment of iron deficiency risk factors [7][1][8]. Similar inconsistencies are observed in screening recommendations for pregnant women. While the USPTF found insufficient evidence to recommend routine screening for iron deficiency anemia in asymptomatic pregnant women, the American College of Obstetrics and Gynecology recommends screening all pregnant women for anemia and treating if necessary. Currently, there are no routine anemia screening recommendations for non-pregnant, healthy adults. Given these varied approaches to screening, accurate and timely anemia laboratory diagnosis becomes even more critical when anemia is clinically suspected or identified.

Etiology and Classification of Anemia

Anemia arises from three fundamental processes, each with diverse underlying etiologies:

1. Decreased Red Blood Cell (RBC) Production: Given the limited lifespan of RBCs (90-120 days), continuous hematopoiesis is essential to maintain RBC mass. Any disruption to this process can lead to a net deficit in RBC production, resulting in anemia.
2. Increased RBC Destruction: Processes that accelerate RBC destruction or significantly shorten their lifespan, outpacing the bone marrow’s capacity to compensate, will cause anemia. This is also known as hemolytic anemia.
3. Blood Loss: Blood loss, whether acute or chronic, macroscopic or microscopic, if exceeding the rate of hematopoiesis, will inevitably lead to anemia.

These broad categories encompass numerous specific causative etiologies, including:

1. Frank Blood Loss: Trauma or bleeding from various organ systems, such as otolaryngological, gastrointestinal, genitourinary, or gynecological sources.
2. Nutritional Deficiencies: Lack of essential nutrients for hematopoiesis, including iron, vitamin B-12, folate, or generalized malnutrition. Iron deficiency is the most common cause of anemia worldwide.
3. Chronic Diseases and Inflammation: Chronic conditions such as hepatic or renal disease, cancer, chronic infections, and collagen vascular diseases can suppress RBC production or increase destruction. Anemia of chronic disease is a common type of anemia, especially in hospitalized patients.
4. Genetic Disorders: Inherited conditions like thalassemias, hemoglobinopathies (e.g., sickle cell anemia), and glycolytic enzyme abnormalities. Rarer genetic syndromes include Fanconi anemia, abetalipoproteinemia, and hereditary xerocytosis.
5. Infections: Bacterial, viral, and protozoan infections. Malaria is a significant global infectious cause of anemia, particularly in endemic regions.
6. Drug and Chemical Exposures: Certain medications and chemical toxins can induce bone marrow suppression, leading to anemia.
7. Primary Bone Marrow Failure: Conditions causing idiopathic bone marrow suppression or aplastic anemia.
8. Autoimmune Disorders: Autoimmune hemolytic anemia, where the body’s immune system attacks and destroys RBCs.

Epidemiological data on anemia prevalence are complex due to variations in diagnostic criteria across regions, particularly between the United States and the WHO criteria used globally. Demographic, genetic, and geographic factors also contribute to variations in anemia prevalence. Estimates suggest that anemia prevalence is statistically similar in the United States, Canada, and Northern Europe, affecting approximately 4% of males and 8% of females. However, data from other parts of the world are less comprehensive, but available estimates suggest a 2 to 5 times higher anemia frequency worldwide compared to these regions [9][10][11].

Regions with higher anemia rates often correlate with:

1. Areas with higher prevalence of hemoglobinopathies like sickle cell disease, such as regions in Africa, India, and the Mediterranean basin.
2. Regions where thalassemia is more common, particularly the Mediterranean basin.
3. Areas with endemic malaria or other protozoal illnesses, leading to higher rates of anemia of chronic disease.
4. Impoverished areas with increased risk of nutritional anemias due to dietary deficiencies.

Anemia laboratory diagnosis plays a crucial role in differentiating these various etiologies and guiding appropriate treatment strategies.

Pathophysiology

Red Blood Cells (RBCs)

RBCs originate in the bone marrow as reticulocytes, which contain ribosomal RNA (rRNA). Over approximately 24 hours, reticulocytes mature into adult RBCs. The reticulocyte count is a valuable laboratory test to assess the bone marrow’s response to anemia by measuring its RBC production capacity. Each RBC contains two alpha and two beta globin chains, along with heme moieties that reversibly bind oxygen. While genetic variations in globin chain structure are common, most are clinically insignificant. However, variants like sickle cell disease and thalassemia, affecting alpha and beta chains, are major causes of anemia. Furthermore, genetic defects in the RBC membrane, metabolism, and morphology can also lead to anemia. Laboratory diagnosis often includes examining RBC indices and morphology to identify these abnormalities.

Bone Marrow

The bone marrow requires about 21 days to produce reticulocytes from pluripotent stem cells and release them into circulation. Erythropoietin (EPO), primarily produced by the kidneys, is the primary stimulus for RBC production. EPO initiates and sustains the differentiation of pluripotent stem cells into proerythroblasts, a process taking approximately 10 to 15 days. The subsequent stage, lasting 3-4 days, is iron-dependent, where iron is incorporated into the proerythroblast to form heme, completing reticulocyte maturation.

Significant bone marrow pathologies causing anemia include:

• Substrate Deficiencies: Lack of iron, vitamin B12, or folate, essential for healthy reticulocyte production. Laboratory diagnosis includes assessing these nutrient levels.
• Bone Marrow Suppression: Direct suppression of bone marrow function due to medications, toxins, infections, or radiation exposure. Laboratory diagnosis may involve bone marrow biopsy in certain cases.
• Bone Marrow Replacement: Displacement of bone marrow by neoplasms (e.g., leukemia, lymphoma) or fibrosis (myelofibrosis). Bone marrow analysis is crucial for laboratory diagnosis in these conditions.

Kidney

The kidneys play a dual role in anemia pathophysiology. First, they produce approximately 90% of EPO, stimulating RBC production in the bone marrow. Impaired EPO production, often seen in chronic kidney disease, leads to anemia. Laboratory diagnosis includes assessing renal function (serum creatinine) as part of the anemia workup, especially in normocytic anemia. Second, in acute anemia due to blood loss, hypotension triggers stretch receptors, signaling the brain via the glossopharyngeal and vagus nerves. This initiates a cascade of responses, including antidiuretic hormone (ADH) release, leading to water reabsorption by the kidneys and decreased renal perfusion. Reduced renal perfusion activates the renin-angiotensin system, increasing vascular tone and aldosterone release, ultimately increasing intravascular volume.

Central Nervous System (CNS)

The medulla, cerebral cortex, and pituitary gland coordinate the body’s response to acute blood loss anemia and associated volume changes. They increase sympathetic tone and secrete ADH to maintain hemodynamic stability.

Acuity of Anemia Onset

The body’s response to anemia differs significantly based on the rapidity of onset. Acute anemia, caused by rapid blood loss or hemolysis, triggers CNS-directed and renal-mediated compensatory mechanisms to maintain volume and perfusion. The American College of Surgeons’ Advanced Trauma Life Support (ATLS) protocols categorize hemorrhage severity based on blood volume loss and physiological response:

• Class I Hemorrhage: Up to 15% blood volume loss, typically no significant vital sign changes, and no intervention needed.
• Class II Hemorrhage: 15-30% blood volume loss, potentially causing tachycardia, reduced pulse pressure, and peripheral vasoconstriction. Crystalloid volume replacement is usually sufficient, and blood transfusion is generally not required.
• Class III Hemorrhage: 30-40% blood volume loss, resulting in hypotension, tachycardia, and shock. Crystalloid resuscitation and blood transfusion are necessary.
• Class IV Hemorrhage: >40% blood volume loss, exceeding compensatory mechanisms, and life-threatening without rapid, aggressive resuscitation with blood products, crystalloids, and pressors.

Conversely, in chronic, slowly progressive anemia, even very low hemoglobin levels may be tolerated as blood volume is relatively preserved despite reduced RBC mass. Management strategies, including blood product transfusion and anemia-specific therapies like RBC substrates or erythropoietin, are tailored to the specific case and underlying cause, which are determined through anemia laboratory diagnosis.

Key Laboratory Tests for Anemia Diagnosis

A comprehensive panel of laboratory tests is essential for accurate anemia laboratory diagnosis. These tests help classify the anemia, narrow down the differential diagnoses, and identify the underlying etiology. Imaging studies may also be pertinent in certain cases.

1. Complete Blood Count (CBC): The cornerstone of anemia laboratory diagnosis.

   • Hemoglobin (Hb): Measures the concentration of hemoglobin in the blood, the primary oxygen-carrying molecule in RBCs. Low hemoglobin is the defining feature of anemia.
   • Hematocrit (Hct): The percentage of blood volume composed of RBCs. Reduced hematocrit also indicates anemia.
   • Red Blood Cell Count (RBC Count): The number of red blood cells per unit volume of blood.
   • Mean Corpuscular Volume (MCV): Average volume of a single RBC. Classifies anemia as:
     • Microcytic Anemia: MCV below normal range (typically <80 fL). Suggests impaired hemoglobin synthesis, often due to iron deficiency, thalassemia, or sideroblastic anemia.
     • Normocytic Anemia: MCV within the normal range (typically 80-100 fL). Seen in early iron deficiency, anemia of chronic disease, acute blood loss, aplastic anemia, and hemolytic anemias.
     • Macrocytic Anemia: MCV above normal range (typically >100 fL). Suggests impaired DNA synthesis, often due to vitamin B12 or folate deficiency, myelodysplastic syndromes, or liver disease.
   • Mean Corpuscular Hemoglobin (MCH): Average amount of hemoglobin in a single RBC.
   • Mean Corpuscular Hemoglobin Concentration (MCHC): Average concentration of hemoglobin in a given volume of packed RBCs. Helps classify anemia as:
     • Hypochromic Anemia: Low MCHC. Typically seen in iron deficiency anemia and thalassemia.
     • Normochromic Anemia: Normal MCHC.
     • Hyperchromic Anemia: High MCHC (less common, seen in spherocytosis).
   • Red Cell Distribution Width (RDW): Measure of the variation in RBC size (anisocytosis). Elevated RDW is often an early indicator of iron deficiency anemia.

2. Reticulocyte Count: Assesses bone marrow erythropoietic activity.

   • Absolute Reticulocyte Count: Actual number of reticulocytes per microliter of blood.
   • Reticulocyte Percentage: Percentage of reticulocytes among total RBCs.
   • Corrected Reticulocyte Count (or Reticulocyte Production Index – RPI): Corrects for anemia severity and RBC lifespan to provide a more accurate assessment of bone marrow response.
   • Elevated Reticulocyte Count (Hyperproliferative Anemia): Indicates increased RBC production in response to anemia, suggesting blood loss or hemolysis.
   • Low Reticulocyte Count (Hypoproliferative Anemia): Indicates decreased RBC production, suggesting bone marrow disorders, nutritional deficiencies, or anemia of chronic disease.

3. Iron Profile (Iron Studies): Evaluates iron status, crucial for diagnosing iron deficiency anemia.

   • Serum Iron: Measures the amount of iron circulating in the blood, bound to transferrin. Levels fluctuate diurnally and are not a direct measure of iron stores.
   • Ferritin: Reflects the body’s iron stores. Low ferritin is highly specific for iron deficiency. However, ferritin is an acute phase reactant and can be elevated in inflammation, masking iron deficiency in some cases (anemia of chronic disease).
   • Total Iron-Binding Capacity (TIBC): Measures the total amount of transferrin in the blood, indirectly reflecting the availability of binding sites for iron. TIBC is typically elevated in iron deficiency anemia.
   • Transferrin Saturation: The percentage of transferrin saturated with iron (Serum Iron / TIBC x 100). Low transferrin saturation (<20%) is suggestive of iron deficiency.

4. Peripheral Blood Smear: Microscopic examination of RBC morphology. Provides valuable clues about the type and cause of anemia.

   • RBC Morphology: Evaluates RBC size, shape, color (chromia), and inclusions. Helps identify:
     • Microcytes: Small RBCs (iron deficiency, thalassemia).
     • Macrocytes: Large RBCs (vitamin B12/folate deficiency, liver disease).
     • Spherocytes: Spherical RBCs (hereditary spherocytosis, autoimmune hemolytic anemia).
     • Sickle Cells: Crescent-shaped RBCs (sickle cell anemia).
     • Target Cells: RBCs with a central spot of hemoglobin (thalassemia, liver disease).
     • Schistocytes (Helmet Cells): Fragmented RBCs (microangiopathic hemolytic anemia).
     • Tear Drop Cells (Dacrocytes): Teardrop-shaped RBCs (myelofibrosis, thalassemia).
     • Polychromasia: Bluish-tinged RBCs, indicating reticulocytes (increased RBC production).
     • Inclusions: Howell-Jolly bodies (DNA remnants), Pappenheimer bodies (iron granules), Basophilic stippling (RNA remnants).
   • White Blood Cell (WBC) and Platelet Morphology and Count: Evaluated concurrently to assess for other hematological abnormalities.

5. Vitamin B-12 and Folate Levels: Essential for diagnosing macrocytic anemias due to vitamin deficiencies.

   • Serum Vitamin B-12 Level: Measures vitamin B-12 concentration in the blood. Low levels indicate vitamin B-12 deficiency.
   • Serum Folate Level (Red Blood Cell Folate): Measures folate concentration in the blood or RBCs. Low levels indicate folate deficiency. RBC folate is a more accurate reflection of long-term folate status.
   • Methylmalonic Acid (MMA) and Homocysteine: Metabolic markers that are elevated in vitamin B-12 deficiency and, to a lesser extent, folate deficiency. MMA is more specific for vitamin B-12 deficiency, while homocysteine can be elevated in both vitamin B-12 and folate deficiency.

6. Hemolysis Profile: Evaluates for evidence of increased RBC destruction (hemolysis).

   • Lactate Dehydrogenase (LDH): Enzyme released from damaged cells, including RBCs. Elevated LDH can indicate hemolysis, but is non-specific.
   • Haptoglobin: Protein that binds free hemoglobin released from lysed RBCs. Low haptoglobin is a sensitive indicator of intravascular hemolysis.
   • Indirect Bilirubin (Unconjugated Bilirubin): Product of heme breakdown. Elevated indirect bilirubin can result from increased RBC breakdown, but also liver dysfunction.
   • Direct Antiglobulin Test (DAT) or Coombs Test: Detects antibodies or complement proteins on the surface of RBCs, indicating autoimmune hemolytic anemia.
   • Peripheral Blood Smear: May show spherocytes, schistocytes, polychromasia in hemolytic anemias.

7. Hemoglobin Electrophoresis: Identifies abnormal hemoglobin variants, crucial for diagnosing hemoglobinopathies like thalassemia and sickle cell anemia.

   • Separates different types of hemoglobin based on their electrophoretic mobility.
   • Detects abnormal hemoglobin variants (HbS in sickle cell anemia, HbC, HbE) and quantifies different hemoglobin fractions (HbA, HbA2, HbF).
   • Helpful in diagnosing and classifying thalassemias by assessing the proportions of different hemoglobin chains.

8. Bone Marrow Aspiration and Biopsy: More invasive procedure, usually performed when the cause of anemia is unclear after initial anemia laboratory diagnosis or when bone marrow disorders are suspected. Hematology consultation is essential.

   • Bone Marrow Aspirate: Liquid marrow sample examined microscopically. Evaluates cellularity, maturation of blood cell precursors, presence of abnormal cells (e.g., blasts in leukemia, metastatic cells).
   • Bone Marrow Biopsy: Core biopsy sample provides information about bone marrow architecture, cellularity, fibrosis, and infiltrates.
   • Indicated in unexplained cytopenias, suspected myelodysplastic syndromes, aplastic anemia, leukemia, lymphoma, myeloma, and metastatic cancer.

9. Other Relevant Tests: Depending on the clinical context and initial anemia laboratory diagnosis findings, additional tests may be ordered:

   • Serum Creatinine and Blood Urea Nitrogen (BUN): Assess renal function, important in anemia of chronic kidney disease.
   • Thyroid Function Tests (TSH, Free T4): Hypothyroidism can cause anemia.
   • Liver Function Tests (LFTs): Liver disease can contribute to anemia.
   • Coagulation Studies (PT/INR, aPTT): Evaluate for bleeding disorders in cases of blood loss anemia.
   • Stool Occult Blood Test (FOBT) or Fecal Immunochemical Test (FIT): Screen for gastrointestinal bleeding in iron deficiency anemia.
   • Urinalysis: Detect hematuria in cases of genitourinary bleeding.
   • Erythropoietin Level: May be measured in specific situations, such as suspected polycythemia or anemia of chronic kidney disease.
   • Flow Cytometry and Cytogenetic Studies on Bone Marrow: Used to further characterize hematologic malignancies and myelodysplastic syndromes.

Interpreting Laboratory Results and Differential Diagnosis

Interpreting anemia laboratory diagnosis results requires a systematic approach, integrating clinical history, physical examination findings, and laboratory data. The initial step is to classify the anemia based on MCV: microcytic, normocytic, or macrocytic.

1. Microcytic Anemia (Low MCV): Primarily consider disorders of hemoglobin synthesis.

• Iron Deficiency Anemia (IDA): Most common cause globally. Laboratory diagnosis typically shows:
  • Low MCV, MCH, MCHC (hypochromic, microcytic anemia).
  • Low ferritin, low serum iron, high TIBC, low transferrin saturation.
  • Elevated RDW.
  • Peripheral smear may show microcytes, hypochromia, and anisocytosis.
• Thalassemia: Genetic disorders affecting globin chain synthesis. Laboratory diagnosis:
  • Low MCV, often disproportionately low compared to the degree of anemia.
  • Normal or elevated RBC count for the degree of anemia.
  • Normal or slightly elevated ferritin.
  • Hemoglobin electrophoresis is diagnostic, revealing abnormal hemoglobin ratios (e.g., increased HbA2 in beta-thalassemia trait, HbF in beta-thalassemia major).
  • Peripheral smear may show microcytes, target cells, basophilic stippling.
• Sideroblastic Anemia: Impaired iron incorporation into heme. Laboratory diagnosis:
  • Microcytic or normocytic anemia.
  • Elevated serum iron and ferritin, normal or low TIBC, high transferrin saturation.
  • Peripheral smear may show dimorphic RBC population, Pappenheimer bodies (iron granules).
  • Bone marrow aspirate shows ring sideroblasts (iron-laden mitochondria around the nucleus of erythroblasts).
• Anemia of Chronic Disease (in some cases): Can be microcytic or normocytic.

2. Macrocytic Anemia (High MCV): Primarily consider impaired DNA synthesis.

• Vitamin B-12 Deficiency (Cobalamin Deficiency): Laboratory diagnosis:
  • High MCV (macrocytic anemia).
  • Low serum vitamin B-12 level.
  • Elevated MMA and homocysteine levels (MMA more specific for B-12 deficiency).
  • Peripheral smear may show macro-ovalocytes, hypersegmented neutrophils.
• Folate Deficiency: Laboratory diagnosis:
  • High MCV (macrocytic anemia).
  • Low serum or RBC folate level.
  • Elevated homocysteine (MMA is normal).
  • Peripheral smear similar to B-12 deficiency but neurological symptoms are less common.
• Myelodysplastic Syndromes (MDS): Clonal bone marrow disorders. Laboratory diagnosis:
  • Macrocytic or normocytic anemia.
  • Dysplasia in one or more cell lines in bone marrow (erythroid, myeloid, megakaryocytic).
  • Bone marrow aspiration and biopsy are essential for diagnosis.
• Liver Disease: Macrocytosis is common in liver disease, often due to increased RBC membrane lipids.
• Hypothyroidism: Can cause mild macrocytic anemia.
• Alcohol Abuse: Another common cause of macrocytosis.
• Drugs: Certain medications (e.g., methotrexate, hydroxyurea) can cause macrocytosis.

3. Normocytic Anemia (Normal MCV): Broad differential diagnosis. Further classified based on reticulocyte count.

• Normocytic Anemia with Low Reticulocyte Count (Hypoproliferative): Indicates decreased RBC production.
  • Anemia of Chronic Disease (ACD): Most common cause of normocytic anemia. Laboratory diagnosis:
    • Normocytic or microcytic anemia.
    • Normal or low serum iron, low TIBC, normal or elevated ferritin (reflecting inflammation).
    • Reticulocyte count is usually low or inappropriately normal.
  • Aplastic Anemia: Bone marrow failure. Laboratory diagnosis:
    • Pancytopenia (anemia, leukopenia, thrombocytopenia).
    • Low reticulocyte count.
    • Bone marrow aspirate and biopsy show hypocellular marrow.
  • Chronic Kidney Disease (CKD): Reduced EPO production. Laboratory diagnosis:
    • Normocytic anemia.
    • Elevated serum creatinine and BUN.
    • Low erythropoietin level (may be measured).
  • Early Iron Deficiency Anemia: Before MCV falls.
  • Mixed Nutritional Deficiencies: e.g., combined iron and folate deficiency can result in normocytic anemia.
  • Bone Marrow Infiltration: e.g., by cancer or granulomatous disease.
• Normocytic Anemia with High Reticulocyte Count (Hyperproliferative): Indicates increased RBC destruction or blood loss.
  • Hemolytic Anemias: Increased RBC destruction. Laboratory diagnosis:
    • Normocytic anemia.
    • Elevated reticulocyte count.
    • Elevated LDH, low haptoglobin, elevated indirect bilirubin.
    • Positive DAT in autoimmune hemolytic anemia.
    • Peripheral smear may show spherocytes, schistocytes, bite cells, depending on the type of hemolysis.
  • Acute Blood Loss: If recent and significant blood loss. Initially, anemia may be normocytic with a rising reticulocyte count after a few days.

Critical Findings: Severely low hemoglobin levels (<7 g/dL), especially in acute anemia, may be life-threatening and require immediate intervention, including blood transfusion. Signs of active bleeding, severe hemolysis, or bone marrow failure also warrant urgent evaluation and management.

Clinical Significance and Management Implications

Anemia laboratory diagnosis is paramount for effective patient care. Anemia is not merely a hematological abnormality but a significant clinical sign that warrants thorough investigation to identify the underlying etiology. Accurate anemia laboratory diagnosis is crucial for:

• Determining the Cause of Anemia: Guiding targeted therapy and addressing the root cause, not just the symptom of anemia.
• Assessing Anemia Severity: Guiding transfusion decisions and monitoring treatment response.
• Identifying Underlying Systemic Diseases: Anemia can be the presenting sign of various conditions, including chronic diseases, malignancies, and nutritional deficiencies.
• Prognosis and Risk Stratification: Certain types of anemia, such as those associated with myelodysplastic syndromes or chronic kidney disease, can have prognostic implications.

Management strategies are tailored to the specific cause of anemia identified through anemia laboratory diagnosis:

• Iron Deficiency Anemia: Iron supplementation (oral or intravenous).
• Vitamin B-12 or Folate Deficiency: Vitamin replacement therapy (oral or intramuscular B-12, oral folate).
• Anemia of Chronic Disease: Addressing the underlying chronic condition. Erythropoiesis-stimulating agents (ESAs) may be used in certain cases, such as anemia of chronic kidney disease or cancer-related anemia, but with careful consideration of risks and benefits.
• Hemolytic Anemias: Management depends on the cause, ranging from corticosteroids or immunosuppressants in autoimmune hemolytic anemia to splenectomy in hereditary spherocytosis, and avoidance of triggers in G6PD deficiency.
• Thalassemia: Management varies from supportive care (transfusions, iron chelation) in severe thalassemia major to no specific treatment in thalassemia trait.
• Aplastic Anemia: Immunosuppressive therapy, bone marrow transplantation.
• Anemia due to Blood Loss: Stopping the bleeding, blood transfusion, and addressing the underlying cause of bleeding.

The decision to transfuse red blood cells should be based on the patient’s clinical condition, not solely on hemoglobin levels. Transfusion triggers and goals should be individualized. The American Academy of Family Medicine (AAFP) position statement, consistent with updated Cochrane reviews, supports a restrictive transfusion strategy, generally aiming to maintain hemoglobin levels above 7 g/dL in non-cardiac patients, unless there are specific indications for a higher threshold (e.g., acute coronary syndrome, symptomatic anemia unresponsive to other therapies).

Enhancing Healthcare Team Outcomes

The diagnosis and management of anemia require an interprofessional team approach. Effective communication and collaboration among physicians, nurses, laboratory professionals, and pharmacists are essential to ensure accurate anemia laboratory diagnosis, appropriate treatment, and optimal patient outcomes. Healthcare team members should be vigilant in recognizing anemia as a potential sign of underlying disease and initiate timely and appropriate anemia laboratory diagnosis workup. Hematology consultation should be sought in complex or unclear cases. By working collaboratively, the healthcare team can optimize the diagnosis and management of anemia, improving patient outcomes and quality of life.

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Disclosure: Andrew Freeman declares no relevant financial relationships with ineligible companies.

Disclosure: Maitreyee Rai declares no relevant financial relationships with ineligible companies.

Disclosure: Donald Morando declares no relevant financial relationships with ineligible companies.