Anemia: Classification, Etiology, and Manifestations

• Chapter 29 covers anemia, its classification, etiology, clinical manifestations, and specific types, in addition to polycythemia, iron overload disorders, alterations in leukocyte function, infectious mononucleosis, and lymphoid neoplasms.

Definition of Anemia

• Anemia is defined by a reduction in the total number of erythrocytes in circulating blood or a decrease in hemoglobin quality/quantity.
• Anemia can result from blood loss, impaired erythrocyte production, or increased erythrocyte destruction

Classification and Etiology of Anemia

General Causes

• Acute blood loss, also known as posthemorrhagic anemia, can result from trauma or surgery leading to rapid hemorrhage, cardiovascular collapse, shock, and death.
• Chronic blood loss, due to slow bleeding (ulcers, malignancy), results in iron deficiency anemia (IDA) from persistent loss.
• Diminished erythropoiesis (production) can result in microcytic anemia associated with iron deficiency or macrocytic anemia associated with Vitamin B12/Folate deficiency.

Morphological Classification

• Normocytic-Normochromic anemia can be caused by blood loss, hemolysis, or chronic disease.
• Microcytic-Hypochromic Anemia, characterized by small and pale RBCs, can be caused by iron deficiency or thalassemia.
• Macrocytic Anemia is characterized by large RBCs, Vitamin B12, or folate deficiency.

Clinical Manifestations of Anemia

• General symptoms result from tissue hypoxia and compensatory mechanisms.

Specific Types of Anemia

Acute Blood Loss

• Acute blood loss can lead to cardiovascular collapse, shock, and death, 24-hour plasma replacement results in hemodilution and decreased hematocrit.
• Compensation mechanisms include bone marrow release of neutrophils and platelets, erythropoietin stimulation increasing RBC production.
• Treatment involves saline, albumin, dextran, or plasma to restore volume and blood transfusion.

Chronic Blood Loss

• Slow and continuous bleeding when the bone marrow can’t keep up with RBC loss can be caused commonly by GI bleeding (ulcers, malignancy) leading to Iron Deficiency Anemia (IDA).
• Treatment involves identifying and treating source of blood loss, alongside iron supplementation.

Anemias of Diminished Erythropoiesis

• Defective RBC production occurs due to impaired DNA synthesis.

Macrocytic (Megaloblastic) Anemia

• Is caused by large RBCs due to defective DNA synthesis.
• Etiology can be due to vitamin B12 or folate deficiency.
• Causes can include; nutritional deficiency (low intake of leafy greens, eggs, meats), malabsorption (GI disorders, pregnancy, chronic infections, chemotherapy). or medications (chemotherapy, drugs affecting DNA synthesis).

Treatment of Anemia

• Involves addressing the underlying cause, providing iron, Vitamin B12, or Folate supplementation, removing toxic agents (drugs, infections, chronic disease management) and transfusion therapy for severe cases.

Pernicious Anemia (PA)

• Pernicious anemia is a type of megaloblastic anemia caused by vitamin B12 deficiency due to intestinal malabsorption.
• Absence of intrinsic factor (IF), necessary for B12 absorption in the ileum, is the main underlying disorder.
• Congenital IF deficiency is an autosomal recessive inheritance.
• Acquired IF deficiency is due to autoimmune processes against gastric parietal cells or IF.
• Associated autoimmune diseases (autoimmune thyroiditis, type 1 diabetes mellitus)., and chronic H. pylori infections.
• Deficiency of IF leads to Vitamin B12 malabsorption.
• Vitamin B12 deficiency leads to impaired DNA synthesis in RBCs, resulting in megaloblasts in bone marrow and macrocytes in circulation.
• Individuals with PA have an increased risk of gastric cancer.
• Clinical signs develop slowly over 20-30 years, and includes weakness, fatigue, paresthesia in feet and fingers, difficulty walking.
• Loss of appetite, abdominal pain, weight loss, smooth, beefy red tongue (glossitis), lemon-yellow skin, and hepatomegaly and splenomegaly can occur.
• Neurologic symptom involving sensory neuropathy, spinal cord involvement, and cognitive impairment may occur.
• Lab findings include; anti-parietal and anti-IF antibodies, low vitamin B12 levels, and decreased reticulocyte count, and testing bone marrow with aspiration and gastric biopsy.
• Treatment includes; vitamin B12 injections weekly, then monthly lifelong, high dose oral B12 alternatives, and monitoring for gastric cancer and IDA.

Folate Deficiency Anemia

• Megaloblastic anemia is caused by folic acid deficiency, affecting DNA/RNA synthesis.
• Common in alcoholics and malnourished individuals, due to malabsorption conditions, but does not involve intrinsic factor for absorption.
• Folate deficiency affects thymine synthesis leading to megaloblastic RBC precursors and macrocytic anemia.

Megaloblastic Anemia from Medications

• Is caused by drugs interfering with DNA synthesis; immunomodulators and chemotherapy.
• Treatment involves discontinuing the drug if possible, or supplementing B12/folate.

Microcytic-Hypochromic Anemias

Iron Deficiency Anemia (IDA)

• This is the most common nutritional disorder.
• Causes: dietary deficiency, impaired absorption, increased requirement (pregnancy, growth, menstruation), chronic blood loss, chronic diarrhea, eating disorders, H. pylori infection, parasitic infections, lead poisoning.
• Pathophysiology: Iron stores depleted results in low hemoglobin synthesis.
• Inflammation impairs iron availability.
• Clinical Manifestations: Nonspecific early symptoms: fatigue, weakness, pallor.
• Severe symptoms: Koilonychia, Dysphagia, and cognitive impairment.

Normocytic-Normochromic Anemia

• Normocytic-Normochromic Anemia include Anemia of Inflammation (AI) and Aplastic Anemia (AA).

Anemia of Inflammation (Al)

• Al develops after one to two months of disease activity.
• Causes: decreased erythrocyte lifespan, suppressed erythropoietin production, ineffective bone marrow response to erythropoietin, altered iron metabolism.
• Inflammatory cytokines increase iron sequestration in macrophages, reduce iron absorption, and suppress erythropoiesis.

Aplastic Anemia (AA)

• Bone marrow failure leading to pancytopenia (anemia, neutropenia, thrombocytopenia).
• Hypocellular bone marrow replaced with fat.
• Increased risk with elevated inflammatory cytokines.
• Rapid onset leading to high mortality.

Hemolytic Anemia

• Premature accelerated erythrocyte destruction occurs either extravascularly or intravascularly
• Congenital or acquired through autoimmune processes, drug exposure or transfusion reactions.

Autoimmune Hemolytic Anemia (AIHA)

• Autoantibodies and complement attack eyrthrocytes caused by aging, genetic predisposition, autoimmune diseases, infections, medications, lymphomas, and organ transplants.
• Types: warm autoimmune hemolytic anemia and cold agglutinin AIHA are common types.