Anemia Overview and Causes

Anemia Overview

• Anemia is characterized by an abnormally low level of hemoglobin or circulating red blood cells (RBCs), or both.
• This leads to a decreased oxygen-carrying capacity of the blood.

Causes of Anemia

• Impaired RBC production:
  • Nutritional deficiencies
  • Aplastic anemia
• Increased RBC destruction:
  • Hemolytic anemia
    • Sickle cell
    • Thalassemia
• Massive or chronic blood loss:
  • Trauma
  • Gastrointestinal (GI) bleed

General Manifestations of Anemia

• Low hemoglobin
• Hypoxia (deficient oxygen transport)
• Compensatory mechanisms to increase oxygen delivery

Diagnostic Tests for Anemia

• Complete Blood Count (CBC):
  • Hemoglobin (Hgb)
  • Hematocrit (Hct)
  • RBC count
  • RBC size (MCV) and color (MCHC) to differentiate anemia types
• Blood Smear: Stained smear of blood viewed under a microscope
• Bone Marrow Aspiration: If the blood smear is abnormal, a bone marrow aspiration is performed to view bone marrow samples. Possible sites for this are the posterior iliac crest or sternum.

CBC- MCV and MCHC

• MCV (mean corpuscular volume):
  • ↓ MCV = microcytic (small cell) anemia
  • ↑ MCV = macrocytic (large cell) anemia
  • Normal MCV = normocytic anemia
• MCHC (mean corpuscular hemoglobin concentration):
  • ↓ MCHC/colour = hypochromic
  • ↑ MCHC/colour = hyperchromic
  • Normal MCHC/colour = normochromic

Additional Diagnostic Tests for Specific Anemias

• Iron level (including ferritin and total iron-binding capacity (TIBC))
• Serum B12 level
• Gastric acid levels
• Antibodies to intrinsic factor
• Schilling test (B12 excretion)

Anemias of Deficient RBC Production

• Iron Deficiency Anemia: Often caused by blood loss or dietary deficiency.
• Megaloblastic Anemias: Vitamin B12 deficiency (pernicious anemia)- Impaired DNA synthesis causes enlarged red blood cells.
• Aplastic Anemia: Bone marrow depression
• Chronic Disease Anemias: Chronic inflammation, renal failure, or chronic infections.

Iron-Deficiency Anemia

• Decreased iron for hemoglobin synthesis results in decreased oxygen-carrying capacity.
• RBCs are hypochromic and microcytic, with poikilocytosis (irregular shape) and anisocytosis (irregular size).

Iron-Deficiency Anemia: Etiology and Treatment

• Etiology: Chronic blood loss, deficient diet, increased demand
• Treatment: Improved diet, iron supplements, identify cause of blood loss.

Iron-Deficiency Anemia: Symptoms

• Fatigue, lethargy, weakness, pallor (paleness), cold intolerance, loss of concentration, irritability, and loss of appetite.

Vitamin B12 Deficiency Anemia

• Megaloblastic anemia- RBCs are large and often oval-shaped.
• Poikilocytosis (irregular shapes) and teardrop shapes are common as well.

B12-deficiency anemia: Etiology, Treatment and Prognosis

• Etiology: Vitamin B12 deficiency, pernicious anemia (from atrophic gastritis).
• Treatment: Regular Vitamin B12 injections.
• Prognosis: Good with treatment.

B12-deficiency anemia: Manifestations

• Classic anemia symptoms plus neurologic symptoms like numbness, tingling, burning in hands and feet.

Aplastic Anemia

• RBCs are normal in size and shape, but there are not enough due to failure of the red bone marrow.
• Bone marrow is fatty and cannot produce sufficient RBCs.

Aplastic Anemia: Etiology, Pathophysiology and Manifestations

• Etiology: Congenital, industrial chemicals (e.g., benzene), infections, chemotherapy drugs, idiopathic.
• Pathophysiology: Exposure leads to decreased bone marrow function, thus reducing RBC, WBC, and platelet production
• Manifestations: Insidious onset characterized by fatigue, weakness, pallor, petechiae, ecchymosis, bleeding, and increased risk of infection.

Aplastic Anemia: Diagnosis and Treatment

• Diagnosis: CBC and bone marrow biopsy, which reveals the presence or absence of bone marrow activity.
• Treatment: Correction of the underlying cause, red blood cell transfusions, medications like erythropoietin and corticosteroids, and sometimes bone marrow transplantation.

Hemolytic Anemia

• Excessive hemolysis (destruction) of abnormal or fragile RBCs by the liver, spleen, and bone marrow.
• Pathophysiology- RBC destruction results in excess byproducts (iron, bilirubin), decreased circulating RBCs, decreased oxygen-carrying capacity, and increased clumping resulting in potential embolisms/clots.

Hemolytic Anemia: Manifestations

• Mild- classic anemia symptoms
• Severe- Jaundice, hemoglobinuria, hemoglobinemia, hypotension, dyspnea, splenomegaly, back and joint pain.

Hemolytic Anemia: Diagnosis and Treatment

• Diagnostics- Additional diagnostic tests including LDH and Coomb's test. These check for antibody presence on RBC and tissue damage.
• Treatment- Determined by the cause of the hemolytic anemia.

Sickle Cell Disease

• Recessive inheritance pattern.
• Mutation in beta chains (HbS) of hemoglobin causes sickling when oxygen is low, resulting in long protein rods in deoxygenated red blood cells.

Sickle Cell Disease: Pathophysiology

• When hemoglobin is deoxygenated, beta chains link, forming long protein rods that deform the red blood cells into a sickle shape.

Sickle Cell Disease: Consequences

• Vessel occlusion- ischemia, acute pain crisis, infarctions (Chronic damage in the liver, spleen, heart, kidneys, bones)
• Pulmonary infarction, acute chest syndrome, cerebral infarction that leads to stroke.

Sickle Cell Disease: Diagnosis

• Screening programs (heel-stick samples for electrophoresis to separate HbS from HbA and HbF)
• Neonatal diagnosis: clinical findings and hemoglobin electrophoresis
• Prenatal diagnosis: amniocentesis

Sickle Cell Anemia: Treatment

• No cure, treatment aims to reduce symptoms, avoid triggers, and manage pain.
• Pain control, hydration, transfusions, antibiotics, and immunizations are treatments.
• Hydroxyurea is used to prevent complications and pain crises.

Thalassemias

• Inherited disorders of hemoglobin synthesis (absent or defective a or β chains of adult hemoglobin)
• Results in abnormal hemoglobin and premature RBC destruction.
• Develops hypochromic, microcytic anemia.
• Decrease in Hgb and therefore RBC production. RBCs are abnormal in shape and short-lived, leading to excessive hemolysis.

Thalassemias: Subtypes and Populations Affected

• Two main subtypes based on defective chain—α and β thalassemia. Populations affected are geographically defined. Asians are often affected by α-thalassemia while Mediterranean and other similar regions are affected by β-thalassemia.

Thalassemias: Pathogenesis (β-thalassemia)

• Beta chains are defective and fewer in number. Excess alpha chains lead to abnormal cell membranes, premature RBC lysis, ineffective hematopoiesis, and increased erythropoietin causing marrow expansion.

Thalassemias: Pathogenesis (α-thalassemia)

• Gene deletions result in defective alpha-chain synthesis
• Deletions cause unstable hemoglobin chains.

Thalassemias: Manifestations (β-thalassemia)

• Usual signs of anemia, bone deformities, splenomegaly, hepatomegaly, high iron levels, low Hgb causing blood and tissue oxygen issues, and increased risk of thrombotic events such as strokes.

Thalassemias: Diagnosis and Treatment (β and α -thalassemia)

• Diagnosis: Microscopic exam of RBCs showing microcytes and hypochromic cells, high iron levels, and increased erythropoietin levels.
• Treatment: Bone marrow and stem cell transplantation, splenectomy, iron chelation therapy (for high iron levels), and possible future transfusion dependence in severe cases.