Anemia and Red Blood Cell Assessment

Anemia Classification and Approach

• Anemia is defined as a decrease in red blood cell (RBC) mass, characterized by a decreased RBC count, hemoglobin, hematocrit (HCT), and packed cell volume (PCV).

Self-Study Questions

• Red blood cells (RBCs) are produced in the bone marrow.
• Erythropoietin stimulates RBC production.
• The primary function of RBCs is to carry oxygen to tissues.
• A decrease in RBC mass is called anemia.
• An increase in RBC mass is not anemia.
• Commonly reported RBC parameters on a complete blood count (CBC) include mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), and red cell distribution width (RDW).
• MCV, MCHC, and RDW are used for classification of anemias; they indicate the size and hemoglobin content of red blood cells; abnormal values often help indicate the underlying cause of anemia.
• Reticulocytes are immature red blood cells.
• Reticulocyte counts and morphology are used to determine if the bone marrow is responding to the anemia or not.
• Mammals, birds, reptiles, and amphibians have different types of red blood cells.

Learning Objectives

• Recognize and classify anemia based on bone marrow response and the underlying mechanism
• Discuss the pathophysiology and pathogenesis of blood loss and hemolytic anemias and how to differentiate them clinically and through a CBC
• Identify non-regenerative anemia using available data, construct species-appropriate differential diagnoses, and discuss pathogenesis and clinical findings

Lecture Overview

• Anemia is a clinical syndrome characterized by a decrease in RBC mass and reduced oxygen-carrying capacity of the blood.
• Anemia is classified based on red blood cell indices (MCV, MCHC), bone marrow response (reticulocytes), and the underlying cause (blood loss, destruction/hemolysis, decreased production).
• Regenerative anemia follows blood loss or hemolysis (RBC destruction) and shows a reactive bone marrow response.
• Non-regenerative anemia follows decreased RBC production and shows an inadequate bone marrow response.

Anemia: Definition

• Anemia is characterized by a decrease in the concentration of circulating red blood cells (RBCs), hemoglobin(Hgb), and packed cell volume (PCV) or hematocrit (HCT).

Erythrogram (CBC Data Example)

• A sample case study presents data with RBC, HGB, HCT, MCV, MCH, MCHC, RDW, Platelets, and WBC counts along with a differential. The result reflects a healthy or deficient animal.
• Additional microscopic findings like the presence or absence of polychromasia, a condition indicating increased immature red blood cell numbers.
• The information provided in the case study can help in the diagnosis and treatment of anemia in the respective animal.

Anemia: Clinical Consequences

• Reduction in oxygen-carrying capacity of the blood—hypoxemia—leads to potential oxygen-deprived tissue damage.
• Clinical signs of anemia include lethargy, exercise intolerance, and other signs depending on severity, rate of onset, and underlying cause.

Anemia—Clinical Diagnostic Approach

• A physical exam assesses physiological signs like pale mucous membranes, weakness, tachycardia (fast heart rate), bounding pulse, and/or heart murmurs, respiratory effort, blood loss signs, organomegaly, lymphadenopathy, and parasites to aid in cause diagnosis.
• Blood loss with or without coagulopathy is determined.
• Signs of internal or external trauma may be present to determine underlying cause diagnosis.

Anemia—Laboratory Diagnostic Approach

• A minimum database (MDB) includes a complete blood count (CBC), chemistry profile, urinalysis.
• CBC parameters are measured to document and assess anemia severity, and evaluate for bone marrow response.
• Chemistry profile (bloodwork) assists in identifying underlying diseases and provides clues to the potential cause.
• Urinalysis helps in the complete evaluation of the renal system.

Anemia—Diagnostic Approach

• Additional tests for anemia diagnosis can include fecal exams for parasites, Coombs' testing for immune-mediated hemolysis, coagulation tests (bleeding disorders), imaging, PCRs for infectious agents (hemoparasites), bone marrow examination (severe non-regenerative anemia, pancytopenia), and biopsy/aspirates (neoplasia, infection, inflammation).

Anemia Classification

• Anemia is classified based on bone marrow response (regenerative vs. non-regenerative), RBC indices (MCV, MCHC, RDW), and the underlying mechanism (blood loss, hemolysis, or decreased RBC production).

Anemia Classification: Big Picture

• Regenerative anemia is characterized by an elevated reticulocyte count and polychromasia (immature RBCs), indicating a responsive bone marrow.
• Non-regenerative anemia has a decreased or absent reticulocyte count and shows inadequate bone marrow response.
• Species variation in reticulocyte response needs to be accounted for.

Review

• Review the Foundation 2a RBC lecture 1 & 2 for more details.

Classification by Bone Marrow Response

• Use reticulocyte count and polychromasia to assess bone marrow response in classifying anemia; distinguish between regenerative and non-regenerative forms of anemias.

Reticulocytes

• High counts indicate regenerative bone marrow responses to anemia.
• Mild cases may show no significant increase.
• Species variation in normal reticulocyte values needs to be considered.

What About nRBCs?

• Nucleated red blood cells (nRBCs) are usually metarubricytes, can indicate severe or abnormally high regenerative response.
• Correct the WBC count if the value goes above a critical threshold.
• nRBCs can be misleading in automated cell counts as they have nuclei like white blood cells (WBCs).

Anemia Classification Using RBC Indices

• Primarily based on MCV and MCHC.
• Microcytic/hypochromic: small, pale RBCs, often associated with iron deficiency.
• Normocytic/normochromic: normal size and hemoglobin content of RBCs, common in various conditions including inflammation and/or CKD.
• Macrocytic/normochromic: large RBCs with normal hemoglobin content, associated with certain regeneration and specific regenerative pathologies.

Classification of Anemia: RBC Indices, Summary

• The classifications using RBC indices, combined with bone marrow responses and other tests, provide more context to help determine the best treatment plan.

Classification by General Mechanism

• Includes blood loss, RBC destruction (hemolysis), and decreased RBC production.

Classification of Anemia by Mechanism

• Hemorrhage, Blood loss: internal/external, regenerative anemia.
• Hemolysis: intra/extravascular, regenerative anemia.
• Decreased production: non-regenerative anemia, typically normocytic, normochromic.

RBC Destruction in Health

• Physiologic removal of a percentage of old or damaged RBCs (extravascular hemolysis) is critical.
• Pathologic causes of hemolysis and premature destruction of RBCs can result in anemias.

RBC Destruction in Health (Detailed)

• Phagocytized RBCs are broken down into components.
• Hemoglobin is converted to unconjugated bilirubin and transported to the liver, where it's conjugated and then excreted into bile.
• Pathologic premature destruction of RBCs can lead to various types and causes of hemolysis.

Premature RBC Destruction Leading to Hemolytic Anemia

• Extravascular hemolysis: unconjugated bilirubin is produced from the macrophages than the liver can handle—causing a build-up of unconjugated bilirubin in the blood, leading to high total bilirubin values.
• Intravascular hemolysis: the free hemoglobin is released into the circulation, taken up by macrophages, and converted to bilirubin; most of the hemoglobin is filtered through the kidneys.

Regenerative Anemias

• Table: Bone marrow response, plasma/serum protein, hemoglobinemia, hemoglobinuria, RBC morphology, hyperbilirubinemia, bilirubinuria, and Coombs' test in blood loss and hemolytic scenarios.

Regenerative Anemias - Hemolysis

• Hemolysis, destruction of RBCs, is a category for classifying anemia, involving extravascular (phagocytosed by macrophages) and intravascular (RBC lysis) hemolysis.

Extra-vs-Intravascular Hemolysis

• A comparison table analyzing the onset, hemoglobinemia, hemoglobinuria, morphology changes, hyperbilirubinemia, bilirubinuria, MCHC, and reticulocytosis of extravascular vs intravascular hemolysis.

Hemolytic Anemias - Overview

• Hemolytic anemias can arise from immune-mediated diseases, oxidative damage, infectious causes, and fragmentation of RBCs.

Cases

• Case studies (like "Lela", "Bruiser", and "Baloo") illustrate specific examples of anemia presentation, analysis, and conclusions.

Non-Regenerative Anemias

• Includes anemia from insufficient/inadequate bone marrow responses due to decreased production.
• Various causes like inflammatory diseases, endocrine diseases, chronic kidney disease, iron deficiency, toxins/infections, and bone marrow diseases also cause non-regenerative anemias.

Anemia of Inflammatory Disease (AID)

• A commonly occurring, but usually mild, type of non-regenerative anemia associated with chronic inflammation, infection, or neoplasia; causes include sequestration of iron, decreased erythropoietin release, shortened RBC lifespan.
• Typically characterized by mild normocytic/normochromic anemia.

Anemia of Endocrine Disease

• Often mild, caused by decreased metabolic rate (like hypoadrenocorticism or hypothyroidism) and characterized by normocytic and normochromic anemia.

Anemia with Chronic Kidney Disease (CKD)

• Variable anemia related to epo production problems and other correlated with CKD severity.
• Characterized by inappropriate concentrated urine and other laboratory findings.

Iron Deficiency Anemia

• Can be caused by physiologic reasons in young animals, chronic blood loss, nutritional issues (rarely in animals).
• The anemia can be initially regenerative but often transitions to non-regenerative. Anemia can appear normocytic/macrocytic, and normochromic/hypochromic,
• Associated with findings such as hypochromic, microcytic RBCs, thrombocytosis, and hypoproteinemia.

Iron Kinetics

• Control of iron stores relies on total body stores and absorption rate.
• Iron is absorbed by enterocytes, stored in ferritin, transferred by transferrin, and stored in macrophages in the liver, spleen, and bone marrow.

Iron Measurement

• Serum Iron: iron bound to transferrin.
• Total Iron-binding Capacity (TIBC): measures the capacity of transferrin to bind iron.
• Transferrin Saturation: measures the percentage of transferrin bound to iron.
• Ferritin: reflects total body iron stores, including values found in the blood (species-specific).
• Bone marrow iron stores: gold standard, but invasive.

Iron Tests Overview

• Diagnostic methods for iron, their significance and limitations
• Includes tables illustrating the role of inflammation in affecting iron tests.

Non-regenerative Anemia: Infectious Causes

• Anemia related to various infectious agents—FIV, Cytauxzoon felis, FeLV (often associated with macrocytosis), neoplasia, aplastic anemia in cats.
• Also related to diseases such as equine infectious anemia (EIA) and Ehrlichia canis in dogs—associated with other clinical findings that help narrow down the diagnostics.

Non-regenerative Anemia: Aplastic Anemia

• Bone marrow failure resulting in a decrease of all types of blood cells (pancytopenia).
• Can be caused infections, drugs, toxins, radiation, and idiopathic causes.

Non-regenerative Anemia: Myelophthisis

• Involves crowding out of bone marrow cells, frequently associated with neoplasia (cancer) and characterized by decreased blood cells.
• Can present as anemia, thrombocytopenia, and/or leukopenia and is often indicated by specific morphology findings on a blood smear.

Non-regenerative, Immune-Mediated Anemia

• Mild to severe non-regenerative anemia.
• Immunological targeting of RBC precursors in bone marrow, sometimes with spherocytes in peripheral blood.
• Can be seen with various immune-related diseases in both cats and canines.

Questions

• Complete the eLC pre-lab assignment.
• Prep for the anemia lab on Monday.

Test your knowledge on the various types of anemia and the characteristics of red blood cells. This quiz covers key concepts such as rubricytosis, microcytic anemia, and the diagnostic role of reticulocytes. Perfect for students in medical or veterinary programs keen on understanding hematology.