Macrocytic-Normochromic Anemias

Macrocytic-Normochromic Anemias

• Focuses on Pernicious, Megaloblastic, and Folate Deficiency anemias.
• Defective DNA synthesis in hematopoietic precursor cells is the cause
• Leads to ineffective erythropoiesis and intramedullary hemolysis.
• Characterized by macrocytic anemia, where MCV is greater than 100 fL, potentially with pancytopenia
• Morphologic hallmark is megaloblasts with nuclear-cytoplasmic dyssynchrony

Pernicious Anemia (Vitamin B12 deficiency, autoimmune)

• Autoimmune destruction of parietal cells results in decreased intrinsic factor and impaired B12 absorption in the ileum
• Vitamin B12 is essential for DNA synthesis and neurological function
• Lack of B12 results in ineffective erythropoiesis and neurologic damage (demyelination).
• Anemia symptoms include fatigue, pallor, and dyspnea
• Neurological symptoms include paresthesias, ataxia, and cognitive impairment
• GI symptoms come in the form of glossitis, and weight loss
• Diagnosis involves low serum B12, high methylmalonic acid and homocysteine, presence of anti-intrinsic factor antibodies, and elevated serum gastrin
• Treatment involves parenteral B12 injections followed by high-dose oral therapy and lifelong therapy for autoimmune forms

Folate Deficiency Anemia

• Occurs due to low dietary intake, alcoholism, pregnancy, or malabsorption, mainly in the jejunum
• Folate is necessary for thymidine synthesis in DNA replication
• Deficiency leads to megaloblastic changes without neurological symptoms
• Anemia has the same hematologic signs as B12 deficiency, but without neurologic symptoms
• Diagnosis involves low serum and RBC folate, high homocysteine, and normal methylmalonic acid
• Oral folic acid supplementation is the key to treatment

Microcytic-Hypochromic Anemias

• Focuses on Iron-deficiency and Sideroblastic anemia
• Iron-Deficiency Anemia is most common

Iron-Deficiency Anemia

• Caused by chronic blood loss, such as GI bleeding or menstruation, and/or poor intake or absorption due to low stomach acid or GI surgery
• Decreased iron leads to decreased heme synthesis, resulting in small, pale RBCs
• Clinical manifestations include fatigue, pallor, dizziness, koilonychia (spoon nails), and pica (craving non-food items)
• Diagnosis involves low Hb, Hct, ferritin, and serum iron, along with high total iron-binding capacity (TIBC)
• Treatment includes oral iron supplements, with vitamin C for absorption, and treating the underlying cause

Sideroblastic Anemia (SIDER = IRON)

• Can be congenital or acquired due to alcohol, lead poisoning, or drugs like isoniazid
• Defective mitochondrial heme synthesis leads to iron trapped in mitochondria, forming ring sideroblasts
• Clinical manifestations include anemia symptoms along with signs of iron overload like hepatomegaly and heart failure.
• Diagnosis involves a bone marrow biopsy showing ringed sideroblasts, increased serum iron and ferritin, and normal or decreased TIBC
• Treatment involves removing the cause, administering vitamin B6, and iron chelation if overloaded

Normocytic-Normochromic Anemias

• Focuses on Aplastic, Post-hemorrhagic, Hemolytic anemia, and Anemia of chronic inflammation

Aplastic Anemia

• Autoimmune destruction of bone marrow, radiation, toxins, or viral infections causes it, with CD8 cytotoxic cells involved
• Bone marrow failure results in pancytopenia
• Clinical manifestations include fatigue, bleeding (thrombocytopenia), and infections (leukopenia)
• Diagnosis involves a bone marrow biopsy showing hypocellular marrow with fatty infiltration
• Treatment includes immunosuppressive therapy or bone marrow transplant

Post-Hemorrhagic Anemia

• Acute or chronic blood loss from trauma, surgery, or GI bleeding causes it
• Loss of blood volume and RBCs leads to hypovolemia and anemia
• Symptoms of hypovolemia such as hypotension, tachycardia, or shock (if severe) manifest
• Later reticulocytosis occurs
• Diagnosis involves low Hb/Hct and increased reticulocytes
• Treatment includes fluid resuscitation, blood transfusion, and addressing the source of bleeding

Hemolytic Anemia

• This can be intrinsic, such as hereditary spherocytosis, sickle cell, G6PD deficiency, or extrinsic due to autoimmune factors, infections, or mechanical destruction
• Premature RBC destruction results in elevated bilirubin and erythropoiesis compensation
• Clinical manifestations include jaundice, dark urine, splenomegaly, and fatigue
• Diagnosis involves increased reticulocytes, LDH, and indirect bilirubin, along with decreased haptoglobin and a positive Coombs test (if autoimmune)
• Treatment depends on the cause and may include immunosuppression, transfusions, or splenectomy

Anemia of Chronic Inflammation (Chronic Disease)

• The second-most common type, caused by chronic infections, autoimmune diseases, or cancers
• Inflammatory cytokines (IL-6) increases hepcidin, which decreases iron availability and suppresses erythropoietin production and bone marrow response
• Clinical manifestations include mild to moderate anemia and fatigue
• Diagnosis involves normal/high ferritin, low serum iron, and low TIBC
• Treatment involves addressing the underlying disease and considering erythropoietin therapy if severe