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Questions and Answers
What are the signs and symptoms associated with anemia?
What are the signs and symptoms associated with anemia?
Define anemia.
Define anemia.
Anemia is defined as a reduction in circulating red blood cell mass.
Microcytic anemias have a mean corpuscular volume (MCV) less than ___ µm³.
Microcytic anemias have a mean corpuscular volume (MCV) less than ___ µm³.
80
Iron deficiency anemia is the most common type of anemia.
Iron deficiency anemia is the most common type of anemia.
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Match the following stages of iron deficiency with their descriptions:
Match the following stages of iron deficiency with their descriptions:
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What is the most severe form of β-Thalassemia?
What is the most severe form of β-Thalassemia?
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What is the primary protective hemoglobin present in β-Thalassemia major at birth?
What is the primary protective hemoglobin present in β-Thalassemia major at birth?
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Macrocytic anemia is characterized by an MCV greater than ____.
Macrocytic anemia is characterized by an MCV greater than ____.
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Vitamin B12 deficiency is more common than folate deficiency.
Vitamin B12 deficiency is more common than folate deficiency.
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What is the protective effect of high levels of HbF at birth in sickle cell disease?
What is the protective effect of high levels of HbF at birth in sickle cell disease?
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Which of the following are complications of extensive sickling in sickle cell disease?
Which of the following are complications of extensive sickling in sickle cell disease?
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Sickle cell trait results in less than 50% HbS in red blood cells.
Sickle cell trait results in less than 50% HbS in red blood cells.
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Sickle cell disease is characterized by the presence of 90% ____, 8% HbF, and 2% HbA2.
Sickle cell disease is characterized by the presence of 90% ____, 8% HbF, and 2% HbA2.
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Match the following laboratory findings with sickle cell disease:
Match the following laboratory findings with sickle cell disease:
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Which test is the most important for immune hemolytic anemia?
Which test is the most important for immune hemolytic anemia?
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What is the most common cause of microangiopathic hemolytic anemia?
What is the most common cause of microangiopathic hemolytic anemia?
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Malaria results in extravascular hemolysis with splenomegaly.
Malaria results in extravascular hemolysis with splenomegaly.
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Anemia due to underproduction is characterized by low corrected __________ count.
Anemia due to underproduction is characterized by low corrected __________ count.
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Match the following terms with their definitions:
Match the following terms with their definitions:
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Study Notes
Sickle Cell Disease
- HbF protects against sickling, and high levels of HbF at birth are protective for the first few months of life
- Treatment with hydroxyurea increases levels of HbF
Complications of Sickle Cell Disease
- Cells continuously sickle and de-sickle while passing through the microcirculation, resulting in complications related to RBC membrane damage
- Extravascular hemolysis:
- RBCs with damaged membranes are removed by the reticuloendothelial system, leading to anemia, jaundice, and increased risk for bilirubin gallstones
- Massive erythroid hyperplasia ensues, resulting in:
- Expansion of hematopoiesis into the skull and facial bones
- Extramedullary hematopoiesis with hepatomegaly
- Risk of aplastic crisis with parvovirus B19 infection of erythroid precursors
- Intravascular hemolysis:
- RBCs with damaged membranes dehydrate, leading to hemolysis with decreased haptoglobin and target cells on blood smear
- Vaso-occlusion:
- Dactylitis: swollen hands and feet due to vaso-occlusive infarcts in bones
- Autosplenectomy: shrunken, fibrotic spleen
- Acute chest syndrome: vaso-occlusion in pulmonary microcirculation
- Pain crisis
- Renal papillary necrosis: results in gross hematuria and proteinuria
Sickle Cell Trait
- Presence of one mutated and one normal chain, resulting in <50% HbS in RBCs
- Generally asymptomatic with no anemia; RBCs with <50% HbS do not sickle in vivo except in the renal medulla
- Extreme hypoxia and hypertonicity of the medulla cause sickling, leading to microinfarctions and resulting in microscopic hematuria and decreased ability to concentrate urine
Laboratory Findings
- Sickle cells and target cells are seen on blood smear in sickle cell disease, but not in sickle cell trait
- Metabisulfite screen causes cells with any amount of HbS to sickle; positive in both disease and trait
- Hb electrophoresis confirms the presence and amount of HbS
- Disease: 90% HbS, 8% HbF, 2% HbA2 (no HbA)
- Trait: 55% HbA, 43% HbS, 2% HbA2
Hemoglobin C
- Autosomal recessive mutation in the β chain of hemoglobin
- Normal glutamic acid is replaced by lysine
- Less common than sickle cell disease
- Presents with mild anemia due to extravascular hemolysis
- Characteristic HbC crystals are seen in RBCs on blood smear
Paroxysmal Nocturnal Hemoglobinuria (PNH)
- Acquired defect in myeloid stem cells resulting in absent glycosylphosphatidylinositol (GPI)
- Renders cells susceptible to destruction by complement
- Blood cells coexist with complement
- Decay accelerating factor (DAF) on the surface of blood cells protects against complement-mediated damage
- Absence of GPI leads to absence of DAF, rendering cells susceptible to complement-mediated damage
- Intravascular hemolysis occurs episodically, often at night during sleep
- Mild respiratory acidosis develops with shallow breathing during sleep and activates complement
- RBCs, WBCs, and platelets are lysed
- Intravascular hemolysis leads to hemoglobinemia and hemoglobinuria
- Sucrose test is used to screen for disease; confirmatory test is the acidified serum test or flow cytometry to detect lack of CD55 (DAF) on blood cells
- Main cause of death is thrombosis of the hepatic, portal, or cerebral veins
Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency
- X-linked recessive disorder resulting in reduced half-life of G6PD
- Renders cells susceptible to oxidative stress
- RBCs are normally exposed to oxidative stress, particularly H2O2
- Glutathione (an antioxidant) neutralizes H2O2, but becomes oxidized in the process
- NADPH, a by-product of G6PD, is needed to regenerate reduced glutathione
- ↓G6PD ↓ → NADPH ↓ → reduced glutathione → oxidative injury by H2O2 → intravascular hemolysis
- Two major variants: African and Mediterranean
- African variant: mildly reduced half-life of G6PD leading to mild intravascular hemolysis with oxidative stress
- Mediterranean variant: markedly reduced half-life of G6PD leading to marked intravascular hemolysis with oxidative stress
- High carrier frequency in both populations is likely due to protective role against falciparum malaria
- Oxidative stress precipitates Hb as Heinz bodies
- Causes of oxidative stress include infections, drugs, and fava beans
- Heinz bodies are removed from RBCs by splenic macrophages, resulting in bite cells
- Leads to predominantly intravascular hemolysis
- Presents with hemoglobinuria and back pain hours after exposure to oxidative stress
- Heinz preparation is used to screen for disease; enzyme studies confirm deficiency
Immune Hemolytic Anemia (IHA)
- Antibody-mediated (IgG or IgM) destruction of RBCs
- IgG-mediated disease usually involves extravascular hemolysis
- IgG binds RBCs in the relatively warm temperature of the central body
- Membrane of antibody-coated RBC is consumed by splenic macrophages, resulting in spherocytes
- Associated with SLE, CLL, and certain drugs
- IgM-mediated disease can lead to intravascular hemolysis
- IgM binds RBCs and fixes complement in the relatively cold temperature of the extremities
- RBCs inactivate complement, but residual C3b serves as an opsonin for splenic macrophages resulting in spherocytes
- Associated with Mycoplasma pneumoniae and infectious mononucleosis
- Coombs test is used to diagnose IHA; testing can be direct or indirect### Anemia
- Anemia is a condition characterized by a reduction in circulating red blood cell (RBC) mass, leading to signs and symptoms of hypoxia.
- Symptoms include:
- Weakness, fatigue, and dyspnea
- Pale conjunctiva and skin
- Headache and light-headedness
- Angina, especially with pre-existing coronary artery disease
Classification of Anemia
- Anemia can be classified based on mean corpuscular volume (MCV) into:
- Microcytic anemia (MCV < 80 µm³)
- Normocytic anemia (MCV = 80-100 µm³)
- Macrocytic anemia (MCV > 100 µm³)
Microcytic Anemia
- Microcytic anemia is caused by decreased production of hemoglobin.
- RBC progenitor cells in the bone marrow are large and normally divide multiple times to produce smaller mature cells.
- Microcytosis occurs due to an "extra" division, which maintains hemoglobin concentration.
- Types of microcytic anemia include:
- Iron deficiency anemia
- Anemia of chronic disease
- Sideroblastic anemia
- Thalassemia
Iron Deficiency Anemia
- Iron deficiency anemia is caused by decreased levels of iron.
- Iron deficiency is the most common nutritional deficiency in the world, affecting approximately 1/3 of the population.
- Iron is consumed in heme and non-heme forms.
- Absorption of iron occurs in the duodenum, and it is transported in the blood by transferrin.
- Stored intracellular iron is bound to ferritin, which prevents iron from forming free radicals.
- Laboratory measurements of iron status include:
- Serum iron
- Total iron-binding capacity (TIBC)
- % saturation
- Serum ferritin
- Iron deficiency is usually caused by:
- Dietary lack
- Blood loss
- Infants: breast-feeding (human milk is low in iron)
- Children: poor diet
- Adults: peptic ulcer disease, menorrhagia, or pregnancy
- Elderly: colon polyps/carcinoma, or hookworm
- Stages of iron deficiency:
- Storage iron is depleted (↓ ferritin; ↑ TIBC)
- Serum iron is depleted (↓ serum iron; ↓ % saturation)
- Normocytic anemia (bone marrow makes fewer, but normal-sized, RBCs)
- Microcytic, hypochromic anemia (bone marrow makes smaller and fewer RBCs)
- Clinical features of iron deficiency include:
- Anemia
- Koilonychia
- Pica
- Laboratory findings include:
- Microcytic, hypochromic RBCs with ↑ red cell distribution width (RDW)
- ↓ ferritin; ↑ TIBC; ↓ serum iron; ↓ % saturation
- ↑ Free erythrocyte protoporphyrin (FEP)
- Treatment involves supplemental iron (ferrous sulfate).
Anemia of Chronic Disease
- Anemia of chronic disease is associated with chronic inflammation or cancer.
- Chronic disease results in production of acute phase reactants from the liver, including hepcidin.
- Hepcidin sequesters iron in storage sites, limiting iron transfer to erythroid precursors and suppressing erythropoietin (EPO) production.
- Laboratory findings include:
- ↑ ferritin; ↓ TIBC; ↓ serum iron; ↓ % saturation
- ↑ Free erythrocyte protoporphyrin (FEP)
- Treatment involves addressing the underlying cause.
Sideroblastic Anemia
- Sideroblastic anemia is caused by defective protoporphyrin synthesis.
- Protoporphyrin is synthesized via a series of reactions involving aminolevulinic acid synthetase (ALAS), aminolevulinic acid dehydratase (ALAD), and ferrochelatase.
- Iron is transferred to erythroid precursors and enters the mitochondria to form heme.
- If protoporphyrin is deficient, iron remains trapped in mitochondria, forming a ring around the nucleus of erythroid precursors (ringed sideroblasts).
- Laboratory findings include:
- ↑ ferritin; ↓ TIBC; ↑ serum iron; ↑ % saturation
- Sideroblastic anemia can be congenital or acquired, due to:
- Congenital defect in ALAS
- Acquired causes: alcoholism, lead poisoning, vitamin B6 deficiency
Thalassemia
- Thalassemia is caused by decreased synthesis of the globin chains of hemoglobin.
- Inherited mutation; carriers are protected against Plasmodium falciparum malaria.
- Divided into α- and β-thalassemia based on decreased production of alpha or beta globin chains.
- Normal types of hemoglobin are HbF (α2γ2), HbA (α2β2), and HbA2 (α2δ2).
- α-Thalassemia is usually due to gene deletion, with:
- One gene deleted: asymptomatic
- Two genes deleted: mild anemia with ↑ RBC count
- Three genes deleted: severe anemia
- Four genes deleted: lethal in utero (hydrops fetalis)
- β-Thalassemia is usually due to gene mutations, with:
- Two β genes are present on chromosome 11; mutations result in absent (β0) or diminished (β+) production of the β-globin chain.
- β-Thalassemia minor (β/β+): mildest form of disease, usually asymptomatic with an increased RBC count.### β-Thalassemia Major
- Most severe form of the disease, presenting with severe anemia a few months after birth
- High HbF (α2γ2) at birth provides temporary protection
- Unpaired α chains precipitate and damage RBC membrane, leading to:
- Ineffective erythropoiesis
- Extravascular hemolysis (removal of circulating RBCs by the spleen)
- Consequences:
- Massive erythroid hyperplasia
- Expansion of hematopoiesis into the skull and facial bones
- Extramedullary hematopoiesis with hepatosplenomegaly
- Risk of aplastic crisis with parvovirus B19 infection
- Chronic transfusions are often necessary, leading to risk of secondary hemochromatosis
- Blood smear shows:
- Microcytic, hypochromic RBCs
- Target cells
- Nucleated red blood cells
- Electrophoresis shows:
- HbA2 and HbF with little or no HbA
Macrocytic Anemia
- Definition: Anemia with MCV > 100 μm3
- Causes:
- Folate deficiency
- Vitamin B12 deficiency
- Other causes (e.g., alcoholism, liver disease, and certain medications)
- Folate deficiency:
- Dietary folate is obtained from green vegetables and some fruits
- Absorbed in the jejunum
- Deficiency develops within months due to minimal body stores
- Causes:
- Poor diet
- Increased demand (e.g., pregnancy, cancer, and hemolytic anemia)
- Folate antagonists (e.g., methotrexate)
- Vitamin B12 deficiency:
- Dietary vitamin B12 is complexed to animal-derived proteins
- Liberated by salivary gland enzymes and absorbed in the ileum
- Deficiency takes years to develop due to large hepatic stores
- Causes:
- Pernicious anemia (autoimmune destruction of parietal cells)
- Pancreatic insufficiency
- Damage to the terminal ileum (e.g., Crohn disease or Diphyllobothrium latum)
- Clinical and laboratory findings:
- Macrocytic RBCs with hypersegmented neutrophils
- Glossitis
- Subacute combined degeneration of the spinal cord
- Decreased serum vitamin B12
- Increased serum homocysteine
- Increased methylmalonic acid
Normocytic Anemia
- Definition: Anemia with normal-sized RBCs (MCV = 80-100 μm3)
- Causes:
- Increased peripheral destruction
- Underproduction
- Reticulocyte count:
- Normal reticulocyte count is 1-2%
- Identified on blood smear as larger cells with bluish cytoplasm
- Corrected count > 3% indicates good marrow response and suggests peripheral destruction
- Peripheral RBC destruction (hemolysis):
- Divided into extravascular and intravascular hemolysis
- Extravascular hemolysis:
- Involves RBC destruction by the reticuloendothelial system
- Clinical and laboratory findings:
- Anemia with splenomegaly
- Jaundice due to unconjugated bilirubin
- Increased risk for bilirubin gallstones
- Intravascular hemolysis:
- Involves destruction of RBCs within vessels
- Clinical and laboratory findings:
- Hemoglobinemia
- Hemoglobinuria
- Hemosiderinuria
- Decreased serum haptoglobin
Normocytic Anemias with Predominant Extravascular Hemolysis
- Hereditary spherocytosis:
- Inherited defect of RBC cytoskeleton-membrane tethering proteins
- Membrane blebs are formed and lost over time, rendering cells round (spherocytes)
- Spherocytes are less able to maneuver through splenic sinusoids and are consumed by splenic macrophages
- Clinical and laboratory findings:
- Spherocytes with loss of central pallor
- Increased RDW and MCHC
- Splenomegaly, jaundice with unconjugated bilirubin, and increased risk for bilirubin gallstones
- Increased risk for aplastic crisis with parvovirus B19 infection
- Diagnosed by osmotic fragility test
- Treatment is splenectomy
- Sickle cell anemia:
- Autosomal recessive mutation in β chain of hemoglobin
- Gene is carried by 10% of individuals of African descent
- Sickle cell disease arises when two abnormal β genes are present, resulting in >90% HbS in RBCs
- HbS polymerizes when deoxygenated, causing sickling
- Increased risk of sickling occurs with hypoxemia, dehydration, and acidosis
Microangiopathic Hemolytic Anemia
- Intravascular hemolysis that results from vascular pathology
- RBCs are destroyed as they pass through the circulation
- Occurs with microthrombi (e.g., TTP-HUS, DIC, HELLP), prosthetic heart valves, and aortic stenosis
- Schistocytes are present on blood smear
Anemia due to Underproduction
- Decreased production of RBCs by bone marrow
- Characterized by low corrected reticulocyte count
- Etiologies:
- Causes of microcytic and macrocytic anemia
- Renal failure
- Damage to bone marrow precursor cells
- Parvovirus B19:
- Infects progenitor red cells and temporarily halts erythropoiesis
- Leads to significant anemia in the setting of preexisting marrow stress
- Treatment is supportive
- Aplastic anemia:
- Damage to hematopoietic stem cells, resulting in pancytopenia
- Etiologies:
- Drugs or chemicals
- Viral infections
- Autoimmune damage
- Biopsy reveals an empty, fatty marrow
- Treatment:
- Cessation of any causative drugs
- Supportive care with transfusions and marrow-stimulating factors
- Immunosuppression
- Bone marrow transplantation as a last resort
- Myelophthisic process:
- Pathologic process (e.g., metastatic cancer) that replaces bone marrow
- Hematopoiesis is impaired, resulting in pancytopenia
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Description
This quiz covers the basics of anemia, including the reduction in circulating red blood cell mass, signs and symptoms of hypoxia, and related health issues.
