Anemia & RBC disorders Flashcards
Microcytic Hypochromic anemia (morphologic classification)
- iron deficiency (bleeding being a major cause of this type)
- thalassemia
Macrocytic Anemia (morphologic classification)
- B12, folate deficiency
- reticulocytosis
Polychromasia
bigger, purple cells on blood smear
- purple bc have RNA in them thus have recently exreted their nucleus bc RNA doesn’t last long w/o a nucleus thus we know these cells are newly minted from the marrow
Laboratory finding in Hemolytic Anemia
- increased indirect (unconjugated) bilirubin
- increased Lactate Dehydrogenase (LDH) from lysed RBCs
- decreased haptoglobin (free hemoglobin is bound to haptoglobin and cleared by liver)
- increased reticulocytes (and polychromasia on blood smear)
Intravascular hemolysis: positive plasma/urine hemoglobin
Extravascular hemolysis: negative plasma/urine hemoglobin (bc not in circulation)
Hereditary Spherocytosis
- autosominal dominant disorder common in Northern Europeans
- mutation in spectrin, ankyrin (most common (50%)), or band 3 (cytoskeleton membrane proteins)
- decreased membrane stability leads to fragmentation and formation of spherocytes (smaller, rounder, denser RBC), which are removed by the spleen
G6PD deficiency
enzyme deficiency that results in the decreased ability to regenerate glutathione, an antioxidant, due to lack of NADPH, which in turn increases the susceptibility of RBCs to oxidative stress, resulting in periodic hemolytic anemia with exposure to oxidative conditions.
- X-linked recessive
- common variants: G6PD A (african populations) and G6PD Mediterranean
- RBCs containing Heinz bodies (oxidized hemoglobin) are removed by the spleen giving bite cells and blister cells
- can be set off by: anti-malarial drugs, sulfa drugs, infections, fava beans
- hemolysis self limited as young RBCs have sufficient enzyme
- DO NOT test within 2-3 weeks of hemolysis bc reticulocytes have functioning G6PD thus acute attacks will give false negatives
Alpha thalassemia
- Gene deletion of one to all four alpha globin chains
- 1-2 deletions = usually asymptomatic
- 3 deletions = moderate anemia
- 4 deletions = hydrops fetalis and intrauterine fetal death
Diagnosis: on newborn screen due to production of Hemoglobin Barts (abnormal type of hemoglobin that consists of four gamma globins instead of the normal two alpha and two gamma globins) - occur most commonly in patients of Asian or African origin (protects against malaria bc high RBC turnover limits infection)
Beta Thalassemia
point mutations in beta globin gene introns, near splice junctions
- hypochromic microcytic RBCs
- abnormal processing of mRNA
- decreased beta chain formation & excess alpha chains
- Beta thalassemia trait: heterozygous; mild anemia with microcytosis; lab tests = increase in Hgb A2 level (>3.5%)
- Beta thalassemia major: needs frequent transfusions; prominent facial bones; “hair on end” appearance of skull X-ray due to increased erythropoiesis
- predominant in patients of Mediterranean descent (protects against malaria bc high RBC turnover limits infection)
Sickle Cell Anemia
point mutation in the β chain of hemoglobin leads to substitution of Valine for glutamic acid thus can’t make Beta chains
- abnormal hemoglobin aggregates when deoxygenated, resulting in sickle shaped erythrocytes which cause vascular occlusion (esp. in spleen sinusoids) and ischemia
- bone pain and splenic atrophy leading to infections and infarcted spleen
- Howell Jolly bodies: retained nuclear material (that is usually cleared by the spleen) seen in peripheral blood in asplenic patients
- sickled cells removed by macrophages
- No Hgb A (bc can’t make beta chains)
Acquired Hemolytic Anemias
- antibodies develop to part of RBC membrane
- IgG (most common) binds to RBC membrane which is then removed by the spleen leading to formation of spherocytes
- spherocytes sequested and removed by spleen
- Positive direct antiglobulin (Coombs) test*
Megaloblastic Anemia
type of macrocytic anemia
- impaired DNA synthesis (e.g., from vitamin B12 or folic acid deficiency)
Morphology:
- oval macrocytes: large, oval nucleated red blood cell precursors that contain uncondensed chromatin
- Hypercellular marrow w/ relatively immature nuclei compared to the cytoplasm (“nuclear/cytoplasm asynchrony”)
- hypersegmented neutrophils (>5 lobes)
Vit. B12 and Folate
Vit. B12 = presents with neurologic defects; homocysteine and methylmalonic acid synthesis
Folate = no neurologic defects; homocysteine synthesis; lab tests order RBC folate levels (bc serum folate can be replenished after a meal)
- hypersegmented neutrophils
Iron deficiency
Causes: diet deficiency, increased need (growing, pregnant), blood loss
- Ferritin: protein that stores iron; low ferritin = iron deficiency (be careful though bc ferritin is elevated in inflammatory sites thus not 100% reliable)
- Transferrin: delivers iron to tissues; high transferrin = iron deficiency
Labs: decreased serum iron and iron saturation
- Gold standard: bone marrow biopsy
Anemia of Chronic inflammation
- normocytic or mildly microcytic anemia
- inflammatory cytokines stimulate hepcidin synthesis which:
1. sequesters iron in macrophages
2. decreases intestinal absorption of iron
3. impairs hemoglobin synthesis bc iron is not delivered to erythrocytes
Aplastic anemia
- marrow failure with pancytopenia (loss of all cells in marrow)
- immune mediated T-cell destruction
- hypocellular marrow = “all fat, no cells”
