CMS200 - Week 12

Anemia Overview

• Anemia is defined as having a lower than normal level of healthy red blood cells or hemoglobin.
• Low hemoglobin, low hematocrit, and low RBC count on CBC tests indicate anemia.
• Anemia in adult males: Hemoglobin <130 g/L (13 g/dL), Hematocrit <41%.
• Anemia in non-pregnant adult females: Hemoglobin <120 g/L (12 g/dL), Hematocrit <36%.

Learning Outcomes

• Understand the prevalence, significance, and causes of anemia in various populations (adults, older adults, high-risk groups).
• Recognize the importance of personal and family history, physical exams, and lab tests in diagnosing anemia.
• Categorize anemias by RBC size and etiology (e.g., microcytic, normocytic, macrocytic).
• Analyze the role of poor diet, vitamin deficiencies, gastrointestinal issues, and bleeding in anemia development.
• Differentiate anemia types like iron-deficiency, megaloblastic, pernicious, hemolytic, and non-nutritional using lab results and clinical signs.
• Evaluate the significance of classifying anemia types and identifying treatable causes for appropriate management.
• Investigate complications and prognosis of anemia types and the impact of early recognition and intervention on patient outcomes.
• Design strategies to use interprofessional collaboration and screening recommendations in assessing anemia.
• Apply knowledge of lab evaluations like hemoglobin, hematocrit, reticulocyte counts, and iron, vitamin B12, and folate status.
• Assess the importance of evaluating additional cytopenias, assessing for blood loss, and considering factors like age, race, and sex when diagnosing anemia.

Complete Blood Count (CBC) with Differential

• Red Blood Cell (RBC) Count: Number of RBCs per volume of blood.
• Hemoglobin (Hb): Amount of oxygen-carrying protein in blood.
• Hematocrit (Hct): Percentage of whole blood occupied by packed RBCs.
• Mean Corpuscular Volume (MCV): Average size of RBCs.
• Mean Corpuscular Hemoglobin (MCH): Amount of oxygen-carrying Hb inside RBCs.
• Mean Corpuscular Hemoglobin Concentration (MCHC): Average concentration of Hb inside RBCs.
• Red Cell Distribution Width (RDW): Measurement of variance in RBC size.
• White Blood Cell (WBC) Count: Number of WBCs per volume of blood.
• Various cell types (neutrophils, lymphocytes, monocytes, eosinophils, basophils) are part of a complete blood count with differential

Anemia: General Symptoms

• Anemia symptoms arise from decreased oxygen delivery to tissues.
• Common symptoms include fatigue, tachycardia, palpitations, and dyspnea on exertion.

Diagnosing Anemia with Pallor

• Physical exam findings like pallor can aid in anemia diagnosis.
• Key findings include conjunctival rim pallor, palmar crease pallor, and palmar pallor. They have the highest likelihood ratios for anemia (LR+).

Anemia: Most Reliable Signs

• Conjunctival rim pallor, palmar crease pallor, and palmar pallor are considered most reliable signs in diagnosing anemia.

Anemia: Development

• Anemia can result from decreased RBC production (reticulocytopenia) or increased RBC destruction/loss (reticulocytosis).

Categorizing Anemia by Etiology

• Decreased RBC production can be caused by issues with hemoglobin synthesis (iron deficiency, thalassemia), DNA synthesis (megaloblastic anemia), or stem cell lesions (aplastic anemia).
• Increased RBC destruction or loss (reticulocytosis) can stem from acute blood loss, intrinsic or extrinsic hemolysis (membrane or hemoglobin lesions).

Diagnostic Approach to Anemia

• Diagnosing anemia involves excluding acute blood loss, determining the general mechanism, and identifying the specific cause of RBC underproduction or hemolysis.
• Tools like flowcharts might aid in this process (e.g., figures in Smith's approach to the patient with anemia).

Anemia Due to Acute Blood Loss

• Symptoms include hematemesis, melena, hematochezia, hematuria, menorrhagia, hemoptysis.
• Signs include hypotension and tachycardia.

Brainstorming Activity

• Essential questions to ask patients experiencing anemia symptoms include those related to possible acute blood loss symptoms and risk factors (e.g., gastrointestinal issues, bleeding).
• Risk factors for acute blood loss may include certain medical conditions or procedures.

Anemia: Assess the Reticulocyte Count

• Reticulocyte count measures the percentage of circulating reticulocytes (immature RBCs) in blood.
• Normal reticulocyte count ranges from 0.5 to 1.5%.
• Low or normal count suggests underproduction anemia, while high count signifies hemolysis or marrow response to blood loss.

Anemia: Classify by RPI

• Reticulocyte Production Index (RPI): Corrects reticulocyte count to assess RBC production rate considering the degree of anemia.
• RPI is calculated and used to classify anemia as hypoproliferative (RPI<2.0) or hyperproliferative (RPI >2.0).

Anemia: Classify by MCV

• Mean corpuscular volume (MCV) measures average red blood cell (RBC) size.
• Normocytic anemia (normal MCV) denotes RBCs within a normal size range (80-100 fL).
• Macrocytic anemia (MCV > 100 fL) implies larger-than-normal RBCs, potentially due to impaired DNA synthesis (megaloblastic) or other factors (non-megaloblastic).
• Microcytic anemia (MCV < 80 fL) suggests smaller-than-normal RBCs. Different types are based on cell categorization (e.g., iron deficiency, thalassemia).

Categorizing Anemia by MCV

• This section details anemias categorized by MCV (mean corpuscular volume), differentiating between microcytic, normocytic, and macrocytic types and relevant causes.

Quick Review

• Non-megaloblastic macrocytic anemia can be attributed to liver disease or hypothyroidism.
• Consider demographics and risk factors for conditions leading to liver disease and hypothyroidism.
• Evaluate related signs and symptoms (e.g., fatigue).
• Consider important diagnostic tests (e.g., blood tests)

Caveats of Using MCV

• MCV isn't specific for anemia diagnosis.
• Consider other red blood cell indices (e.g., MCH, MCHC) for a complete picture.
• RDW is not a reliable indicator.

Iron Deficiency Anemia

• Most common cause of anemia globally.
• Prevalence varies by demographic groups (men <50 compared to menstruating women).
• Anemia often involves chronic blood loss as a cause (e.g., GI bleeds, heavy menstruation).

Iron Deficiency Anemia: Causes

• Chronic blood loss (e.g., gastrointestinal bleeds, heavy periods).
• Impaired iron absorption due to dietary causes, medical conditions (e.g., gastritis, celiac disease), or increased demand (e.g., pregnancy).

Iron Deficiency Anemia: Populations at Risk

• Premenopausal women, menstruating women, non-breastfed preschoolers on cows' milk, vegans/vegetarians, those in low-income families.
• Chronic blood loss can result in iron deficiency anemia.

Iron Deficiency Anemia: Specific Signs and Symptoms

• Pica/pagophagia (craving for non-nutritive substances), restless legs, glossitis (sore tongue), cheilitis (inflammation of mouth corners), brittle nails, koilonychia (spooning of nails), and esophageal webs.

Iron Deficiency Anemia: Tests

• Reduced serum ferritin, transferrin saturation, and serum iron levels.
• Elevated total iron-binding capacity assists with diagnosis and assessment of iron stores.
• Lab tests like fecal occult blood tests might reveal sources of gastrointestinal bleeding.

Iron Deficiency Anemia: Tests - Serum Transferrin Receptor-Ferritin Index

• Useful in differentiating iron deficiency from other causes of anemia with mid-range ferritin.
• Index >1.5 suggests iron deficiency, while <1.5 points away from it to other causes.

Iron Deficiency Anemia: Management

• Treat the underlying cause (e.g., gastrointestinal bleeding, hormonal issues).
• Use oral iron or IV iron replacement therapy.

B12 Deficiency Anemia

• Causes megaloblastic anemia due to impaired DNA synthesis and decreased RBC production.
• B12 deficiency is linked to certain risk factors (dietary habits, certain diseases, aging).
• Neurologic symptoms (e.g., paresthesias, sensory loss, ataxia).

B12 Deficiency Anemia: Causes

• Food-cobalamin malabsorption, atrophic gastritis, lack of intrinsic factor, gastrectomy, pernicious anemia, vegan diet.
• Other malabsorptive causes are less common (e.g., ileum disorders, bacterial overgrowth, drug interactions).

B12 Deficiency Anemia: Pernicious Anemia

• Autoimmune-mediated condition where the immune system attacks intrinsic factor.
• Pernicious anemia is more common in older adults.
• Genetic predisposition and possibly infections contribute to the prevalence.

B12 Deficiency Anemia: Tests

• Low serum vitamin B12 and elevated homocysteine and methylmalonic acid levels help differentiate from other conditions and identify B12 deficiency.

B12 Deficiency Anemia: Management

• Treatment involves replenishing B12 intake through dietary adjustments, oral supplements, or injections as needed.

Folate Deficiency Anemia

• Folate deficiency causes megaloblastic anemia, and leads to less-common RBC production.
• Common causes include alcohol abuse, pregnancy, and drug use (e.g., methotrexate).
• Tests include low serum folate levels and elevated homocysteine levels (not specific).

Differential Diagnosis: Non-Nutritional Anemias

• Anemia resulting from non-nutritional causes includes conditions like anemia of renal disease, anemia of chronic disease, thalassemia, and myelodysplastic syndrome.
• Different characteristics differentiate the different types of anemia including testing (e.g., abnormal blood tests).

Comparing Iron Stores in Anemias

• Comparison between anemia causes and their correlated ferritin, total iron-binding capacity (TIBC), and marrow iron levels.

Anemia of Renal Disease

• Kidney disease leads to reduced erythropoietin production, causing anemia.
• The resulting anemia is often normocytic normochromic with hypoproliferative features, possible microcytosis, and a range of associated abnormalities.
• Low serum iron and serum transferrin receptor indexes can contribute to the underlying pathology and anemia severity.

Anemia of Chronic Disease

• Second most prevalent anemia after iron deficiency anemia, associated with infection, inflammation, and malignancy.
• Often presents with a mild, normocytic, normochromic nature.
• The condition can evolve with time, potentially becoming microcytic hypochromic. The blood smear shows little abnormalities. Iron stores typically stay normal/high, differing from iron deficiency and potentially other cases.

DDx: Iron Deficiency Anemia and Anemia of Chronic Disease

• This section presents a table contrasting clinical parameter findings between iron deficiency anemia and chronic disease anemia including CRP levels, hemoglobin levels, and transferrin saturation.

Anemia of Chronic Disease - Further Considerations

• Tests like liver and kidney functions are necessary for further differentiation from other underlying issues.
• Elevated inflammatory markers and the underlying chronic disease itself should be prioritized for treatment.

Sample Case (73-year-old man)

• Describes a clinical scenario with symptoms like fatigue, shortness of breath, abdominal pain, and darker stools.
• 24-hour diet recall provides details of the patient's recent meals.

Case Study Discussion Questions

• Questions related to differential diagnoses, follow-up questions, additional physical exams, and lab tests for the sample case are presented.

Anemia Workup Flowchart

• Flowcharts guide the diagnostic process, suggesting tests based on serum ferritin levels (low, mid-range, elevated) and GFR.

Thalassemia

• Inherited hemoglobin disorders resulting in reduced RBC production.
• Includes alpha and beta thalassemia, characterized by unbalanced globin chain synthesis.
• Prevalence and severity are linked to the specific genetic mutations.

Thalassemia: Severity (a- and ß-thalassemia)

• Describes the varying degrees of severity between the different subtypes of thalassemia based on the number of defective genes. The severity ranges from asymptomatic to potentially lethal in utero.

Thalassemia: Presentation

• Severity ranges from mild to severe, involving various symptoms, growth disturbances, bone issues (e.g., osteoporosis), and possible splenomegaly (especially in more severe forms).

Diagnosing Thalassemia

• Focuses on the diagnostic approach for thalassemias: family history, blood tests (CBC, peripheral blood smear, hemoglobin electrophoresis), and genetic testing.

Myelodysplastic Syndrome (MDS)

• Characterized by hyperplastic bone marrow with failure and precursor blood cell abnormalities, potentially transforming into acute leukemia over time.
• Various subtypes exist, each with unique presentations likely to affect patients in varying ways

Myelodysplastic Syndrome: Risks for Development

• Increased risk with aging. The risk factors associated with prior cancers and therapies (e.g., chemo/radiation) increase with age.

Myelodysplastic Syndrome: Classification

• Detailed description of five subtypes of MDS, varying in their composition of disease, and possible transformation into leukemia.

Myelodysplastic Syndrome: Timing and Clinical Course

• Emphasis on the potential progression and transformation of MDS to acute leukemia. Several timeframes vary depending on the specific subtype and patient characteristics.

Myelodysplastic Syndrome: Presentation

• Symptoms may include megaloblastic or microcytic anemia and pancytopenia (reduced blood cell count) along with potential abnormalities in blood smears that will be evident by laboratory tests .

Hemolytic Anemia

• Anemia caused by increased destruction of red blood cells.
• Several ways to classify hemolytic anemia including acute vs. chronic disease, immune vs. non-immune mediated, intravascular vs. extravascular, inherited vs. acquired, and intracorpuscular vs. extracorpuscular.
• Different types of hemolytic anemia include inherited and acquired forms, and may involve extravascular or intravascular hemolysis.

Hemolytic Anemia: Inherited vs. Acquired

• Explains the distinctions between inherited (e.g., enzymatic deficiencies, hemoglobinopathies) and acquired (e.g., immune-mediated disorders) etiologies of hemolytic anemia.

Hemolytic Anemia: Extravascular vs. Intravascular

• Discusses whether hemolysis occurs outside or inside blood vessels (extravascular or intravascular).
• Different mechanisms and resultant effects influence patient presentation with anemia and associated effects.

Hemolytic Anemia: Signs and Symptoms

• General anemia symptoms (e.g., fatigue, weakness) are common.
• Hemolysis may cause jaundice.
• Some symptoms may appear with specific types of hemolysis and thus may be helpful to diagnose the underlying problem.

Hemolytic Anemia: Tests

• Explains tests utilized in identifying hemolytic anemia such as elevated reticulocytes, LDH, and bilirubin, possible abnormalities in blood smears, and the presence of agglutinins in blood.

Hemolytic Anemia: Management

• Emphasizes the interprofessional approach in treating hemolytic anemias requiring expertise from various healthcare specialists involving the patient's care.

Anemia: General Complications (Untreated/Undiagnosed)

• Untreated or undiagnosed anemia has a variety of possible complications across different ages and medical situations - from pregnant women having problems in labor, to complications affecting elderly people.

Anemia: Interprofessional Management

• Discusses the need for collaboration between various medical specialists to effectively manage anemia, including gastroenterologists, nephrologists, hematologists, gynecologists, and cardiologists (depending on cause and associated conditions).

Case Studies

• A few cases are highlighted to illustrate analysis of blood smears by comparing normal smears with those from patients with anemia.
• The discussion questions pertain to recognizing differences, determining the type of anemia, interpreting CBC results, and considering additional tests.