Anemia 2011


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Anemia 2011

  1. 1. Anemia April 4, 2011 Clinical Medicine IPatrick Carter MPAS, PA-C
  2. 2. Objectives• Define anemia.• For aplastic anemia, discuss its: – Etiology – Clinical manifestations – Laboratory findings – Diagnostic evaluation – Treatment• For the following disorders, describe the pathophysiology, clinical presentation, significant historical and physical findings, diagnostic work- up, management and patient education issues for: – Iron deficiency anemia – Hemolytic anemia – Vitamin B12 deficiency – Hereditary spherocytosis – Folic acid deficiency – G6PD deficiency
  3. 3. Objectives• Describe the pathophysiology, clinical presentation, significant historical and physical exam findings, diagnostic work-up, management, prognosis and patient education issues associated with: – Sickle cell anemia and related syndromes – Beta thalassemia major – Alpha thalassemia trait – Beta thalassemia minor• For anemia of chronic disease, discuss its relationship to and significance as it pertains to: – Renal failure – Hypothyroidism• For acute blood loss anemia, explain its clinical manifestations, laboratory findings and therapy.• Discuss the clinical presentation, significant historical and physical exam findings, diagnostic work-up and treatment for polycythemia vera.
  4. 4. Objectives• For the following disorders, describe the pathophysiology, clinical presentation, significant historical and physical findings, diagnostic work-up, management and patient education issues for: • Hemolytic anemia • Vitamin B12 deficiency • Hereditary spherocytosis • Folic acid deficiency • G6PD deficiency• Describe the pathophysiology, clinical presentation, significant historical and physical exam findings, diagnostic work-up, management, prognosis and patient education issues associated with sickle cell anemia and related syndromes
  5. 5. Objectives• For aplastic anemia, discuss its: • Etiology • Clinical manifestations • Laboratory findings • Diagnostic evaluation • Treatment
  6. 6. Anemia• For adults, anemia is present if the Hgb/Hct is: – < 13.5/41 in men – < 12/37 in women• Pathophysiologic classification – Cell Size – Diminished production – Accelerated Loss
  7. 7. Anemia• MCV – mean corpuscular volume – Measure of avg size of a single RBC – NL range is 80-95 fL – Microcytic (<80) – heme and globin synthesis – Macrocytic (>100) – DNA synthesis – Normocytic – Hypoproliferative disorder
  8. 8. Anemia
  9. 9. Anemia
  10. 10. Anemia• MCHC – mean corpuscular hemoglobin concentration – Measure of the avg concentration of Hgb within a single RBC – Hypochromic – cell has a deficiency of Hgb – Normochromic – values are normal
  11. 11. Iron Deficiency Anemia• Essentials of diagnosis – Microcytic, hypochromic anemia – Serum ferritin < 12 mcg/L – Caused by bleeding in adults unless proven otherwise – Responds to iron therapy• General considerations – Most common cause of anemia worldwide – Iron is needed in the synthesis of hemoglobin – AA/ Hispanic women > Caucasian women > men
  12. 12. Iron Deficiency Anemia• General considerations – Most of the rest is stored as ferritin – Average American diet contains 10-15 mg of iron per day • Only 10% of this is absorbed • Absorption occurs in the stomach, duodenum, and upper jejunum • Bioavailability best with heme iron (red meat) – Menstrual losses can be significant in women • With heavy menses, women must absorb 3-4 mg of iron from their diet each day • Require iron supplementation
  13. 13. Iron Deficiency Anemia• General considerations – Iron requirements also increased in pregnancy, periods of rapid growth – Decreased iron absorption after gastric surgery – Most important cause is blood loss in adults • GI bleeding • Chronic aspirin use • Must search for source of GI blood loss in adults
  14. 14. Iron Deficiency Anemia• Signs and symptoms – Pica – Fatigue – Tachycardia/Palpitations – Tachypnea on exertion – pallor• Severe deficiency – Smooth tongue – Koilonychia • "spoon nails." It refers to abnormally thin nails (usually of the hand) which have lost their convexity, becoming flat or even concave in shape – Cheilosis • inflammatory lesion at the labial commissure, or corner of the mouth, and often occurs bilaterally. The condition manifests as deep cracks or splits. In severe cases, the splits can bleed when the mouth is opened and shallow ulcers or a crust may form
  15. 15. Iron Lab Studies• Ferritin – storage protein of iron• Transferrin – plasma protein that transports iron to the bone marrow – What is measured with serum iron• TIBC – total iron binding capacity – What degree of transferrin is open for binding of iron
  16. 16. Iron Deficiency Anemia• Laboratory findings – Decreased serum ferritin – Decreased serum iron – Decreased MCV – Increased total iron-binding capacity (TIBC) – Peripheral blood smear • Hypochromic, microcytic cells • Anisocytosis (unequal size) • Poikilocytosis (abnormally shaped) – Target cells – Pencil-shaped cells
  17. 17. Iron def anemia Normal
  18. 18. Iron Deficiency Anemia• Differential diagnosis – Anemia of chronic disease – Thalassemia – Sideroblastic anemia (usually normocytic)• Treatment – Ferrous sulfate 325 mg TID • May cause constipation • Take on empty stomach or with acidic juice (OJ) to increase absorption • Hct should return to normal within 2 months • Continue 3-6 months after Hct has returned to normal
  19. 19. Iron Deficiency Anemia• Treatment – Parenteral iron • Indications – Intolerance to oral iron – Refractory disease – GI disease or previous surgery • Risk of anaphylaxis • Preferred drug is sodium ferric gluconate (Ferrlecit) – IV dose 1.5 – 2 g given over 4-6 hours
  20. 20. Anemia of Chronic Disease• Essentials of Diagnosis – Anemia (normocytic or microcytic) – Normal or Increased Ferritin – Underlying Chronic Disease • Chronic infection • Chronic inflammation • Cancer • Liver disease • Renal failure – decrease in EPO
  21. 21. Anemia of Chronic Disease• Signs and symptoms – Clinical features of the causative condition• Laboratory findings – Hct mildly or moderately reduced – MCV usually normal – Serum ferritin normal or increased• Treatment – Not usually needed – EPO for renal failure or cancer or Inflammatory Bowel • Very expensive • Reserved for patients dependent on transfusions
  22. 22. The Thalassemias• Essentials of diagnosis – Microcytosis out of proportion to the degree of anemia – Positive family history or lifelong history of microcytic anemia – Abnormal RBCs (microcytes, acanthocytes, and target cells) – With β-thalassemia, elevated levels of hemoglobin A2 or F
  23. 23. The Thalassemias• General considerations – Hereditary disorders – Reduction in the synthesis of globin chains – Normal adult hemoglobin • 98% hemoglobin A (α2β2) • 1-2% hemoglobin A2 (α2δ2 ) • 1-2% hemoglobin F (α2γ2) – α-thalassemia has reduced α-globin chains – β-thalassemia has reduced β-globin chains
  24. 24. The Thalassemias– Clinical severity varies widely depending on the degree to which the synthesis of the affected globin is impaired– Described as “trait” when there are lab features without significant clinical impact– Described as “major” when the disorder is life- threatening
  25. 25. The Thalassemias• Signs and symptoms – Alpha-thalassemias • Most commonly in persons from southeast Asia or China, and less so in African Americans • Normally adults have 4 copies of the alpha globin chaing (gene) • 3 alpha-globin chains = silent carrier (hematologically NL) • 2 alpha-globin chains = alpha-thalassemia trait – Clinically normal with normal life expectancy – Mild microcytic anemia
  26. 26. The Thalassemias• Signs and symptoms – Alpha-thalassemias 1 alpha-globin chain = Hgb H disease  Chronic hemolytic anemia  Pallor and splenomegaly  Transfusions may be required in times of stress • No alpha-globin chains = hydrops fetalis – Stillbirth
  27. 27. The Thalassemias• Laboratory findings – Alpha-thalassemia trait • Mild anemia • Hct between 28 – 40% • MCV strikingly low (60-75) • RBC normal or increased • PBS shows microcytes, hypochromia, some target cells and acanthocytes • Hemoglobin electrophoresis – No increase in hemoglobin A2 or F – No hemoglobin H (β4 tetramer)
  28. 28. The ThalassemiasAcanthocytes
  29. 29. The Thalassemias• Laboratory findings – Hemoglobin H disease ( one alpha globin gene) • More marked hemolytic anemia • Hct between 22 – 32% • MCV low (60-70) • PBS abnormal with microcytes, hypochromia, target cells and poikilocytosis • Elevated reticulocyte count • Hemoglobin electrophoresis – Hemoglobin H 10 – 40%
  30. 30. The Thalassemias
  31. 31. The Thalassemias– Beta-thalassemias • Most often persons of Mediterranean descent, less so southeast Asians, Chinese and African Americans • Beta-thalassemia major – Homozygous for beta-thalassemia – Normal at birth until 6 months of age – Severe anemia requiring transfusions – Growth failure – Bony deformities – Hepatosplenomegaly – Jaundice
  32. 32. The Thalassemias• Signs and symptoms – Beta-thalassemias • Beta-thalassemia intermedia – Homozygous but a milder form – Chronic hemolytic anemia – Transfusions in times of great stress • Beta-thalassemia minor – Heterozygous – Clinically insignificant microcytic anemia
  33. 33. The Thalassemias• Laboratory findings – Beta-thalassemia minor • Modest anemia • Hct between 28 – 40% • MCV low (55-75) • RBC normal or increased • PBS mildly abnormal with microcytes, hypochromia, and target cells • Hemoglobin electrophoresis – Elevation of hemoglobin A2 (4-8%) – Occasional elevation of hemoglobin F (1-5%)
  34. 34. The Thalassemias• Laboratory findings – Beta-thalassemia major • Severe anemia • Hct less than 10% without transfusion • PBS bizarre with severe poikilocytosis, microcytes, hypochromia, target cells, basophilic stippling, nucleated RBCs • Hemoglobin electrophoresis – Little or no hemoglobin A – Hemoglobin F is the major type present
  35. 35. The ThalassemiasTarget cells basophilic stippling
  36. 36. The Thalassemias
  37. 37. The Thalassemias• Differential diagnosis – Iron deficiency – Other hemoglobinopathies• Treatment – Mild thalassemia requires no treatment – Hemoglobin H disease • Folate supplements • Avoid iron supplements and oxidative drugs like sulfonamides
  38. 38. The Thalassemias• Treatment – Severe thalassemia • Regular transfusion schedule • Folate supplements • Splenectomy, if needed for hypersplenism • Deferoxamine (chelates iron) • Beta thalassemia major – Allogeneic bone marrow transplantation
  39. 39. Sideroblastic Anemia• Essentials of Diagnosis – Elevated Serum Iron & Transferrin Levels – Bone marrow shows ringed sideroblasts• Acquired Bone Marrow Disorder – Myelodysplasia that terminates in Acute Leukemia – Chronic ETOH Abuse – Lead Poisoning• Failure to incorporate heme into protoporphyrin to form hemoglobin• Iron accumulates in the mitochondria
  40. 40. Sideroblastic Anemia• Signs & Symptoms – Generalized anemia symptoms• Laboratory – Moderate anemia with Hct 20-30% – Serum Iron & Transferrin elevatd – MCV usually normal or slightly elevated – Diagnosis made with Bone Marrow biopsy • Ringed sideroblasts
  41. 41. Sideroblastic Anemia• Treatment – Occasionally require transfusion is required – Does not respond to Erythropoietin Therapy
  42. 42. Macrocytic Anemias• Vitamin B12 deficiency• Folic acid deficiency• When either is lacking there is a defect in DNA synthesis that affects the rapidly dividing cells in the bone marrow
  43. 43. Macrocytic Anemias*note that the RBCs are larger than the WBC)
  44. 44. Vitamin B12 Deficiency• Essentials of Diagnosis – Macrocytic Anemia – Macro-ovalocytes and hypersegmented neutrophils on PBS – Serum Vitamin B12 level less than 100 pg/ml
  45. 45. Vitamin B12 Deficiency General Considerations  All vitamin B12 is absorbed from the diet (foods of animal origin)  After ingestion, vitamin B12 binds to intrinsic factor, a protein secreted by gastric parietal cells  Avg Western diet contains 5-30μg daily  Body stores are typically between 2-3mg, sufficient for 3-4 years if supplies are completely cut off
  46. 46. Causes of vitamin B12 deficiency• Decreased IF production • Alteration in release of – pernicious anemia (most B12 from dietary protein common cause) – Helicobacter pylori – chronic atrophic gastritis infection – Gastrectomy – PPI, H2 antagonist, antacids• Decreased B12 absorption – surgical resection of the • Dietary deficiency (only ileum in vegans) – severe Crohns disease
  47. 47. Vitamin B12 Deficiency• Signs and Symptoms – May be asymptomatic – As anemia becomes more severe • Pallor • Glossitis • Gastrointestinal disturbances (eg, anorexia, diarrhea) • Neurologic manifestations – Paresthesias – Difficulty with position/vibration sensation and balance – In advanced cases - cerebral function altered, dementia – Megaloblastic anemia (MCV >100), which may be severe – If Neurological symptoms present and normal MCV • Check B12 level
  48. 48. Vitamin B12 Deficiency• Differential Diagnosis – Folic acid deficiency – Myelodysplastic syndrome – Other cause of peripheral neuropathy, ataxia, or dementia
  49. 49. Vitamin B12 Deficiency• Laboratory Tests – CBC • Hematocrit may be as low as 10–15% • MCV – Strikingly elevated: 110–140 fL – May be normal if coexistent thalassemia or iron deficiency is present – Low serum vitamin B12 level, often < 100 ng/L (normal 160-200 ng/L), establishes diagnosis
  50. 50. Vitamin B12 Deficiency• Laboratory Tests – Peripheral blood smear • Macro-ovalocytes are characteristic • Hypersegmented neutrophils with mean lobe count > 4, or 1 six-lobed neutrophil • Anisocytosis and poikilocytosis – Reticulocyte count reduced – Pancytopenia present in severe cases
  51. 51. Vitamin B12 Deficiency
  52. 52. Vitamin B12 Deficiency Treatment  Vitamin B12, 100 μg IM QD for 1 week, then every week for 1 month, then every month for life  Oral cobalamin, 1000 μ g PO QD, may be tried instead of parenteral therapy but must be continued indefinitely
  53. 53. Vitamin B12 Deficiency Follow-Up  Brisk reticulocytosis occurs 5–7 days after therapy, and the hematologic picture normalizes in 2 months  Follow serum vitamin B12 levels  CNS symptoms and signs are reversible if the onset is <6 months, otherwise may be permanent
  54. 54. Folic Acid Deficiency• Essentials of Diagnosis – Macrocytic anemia – Macro-ovalocytes and hypersegmented neutrophils on PBS – Normal Serum Vitamin B12 Levels – Reduced Folate Level
  55. 55. Folic Acid Deficiency General considerations  Folic acid is present in most fruits and vegetables (especially citrus fruits and green leafy vegetables)  Daily requirements of 50–100 μg/day usually met in the diet  Total body stores of folate is 10mg, enough to supply requirements for 2–3 months  Folate is absorbed rapidly from the upper small intestine  Transported in the plasma either unbound or bound to albumin
  56. 56. Folic Acid Deficiency–Causes • Most common is inadequate dietary intake  Alcoholics, anorectic patients, persons who do not eat fresh fruits and vegetables, those who overcook food • Decreased absorption (gluten-induced enteropathy) • Antifolate drugs - phenytoin, methotrexate, trimethoprim-sulfamethoxazole) • Increased requirement - chronic hemolytic anemia, pregnancy, • Increased loss – dialysis • Alcohol
  57. 57. Folic Acid Deficiency Signs & Symptoms  Similar to Vitamin B12  No neurologic abnormalities, unlike vitamin B12 deficiency Laboratory  Megaloblastic anemia identical to that in vitamin B12 deficiency (eg, macro-ovalocytes, hypersegmented neutrophils  Red Blood Cell Level < 150 ng/mL  Serum vitamin B12 level normal  Distinguish from anemia of liver disease  macrocytic anemia with target cells but no megaloblastic changes
  58. 58. Folic Acid Deficiency Treatment  Folic acid, 1 mg PO Daily Rapid improvement in sense of well-being, reticulocytosis in 5–7 days, and total correction of hematologic abnormalities within 2 months MAKE SURE that your patient does not also have B12 deficiency – folate can improve their symptoms but not prevent the neurological damage
  59. 59. Hemolytic Anemias• General considerations – Coombs positive hemolytic anemia may be autoimmune or related to drugs, infection, lymphoproliferative disease, Rh or ABO incompatibility – Coombs negative hemolytic anemia may be intrinsic RBC disease • Abnormal hemoglobin: sickle cell disease, thalassemia, methemoglobinemia • Membrane defect: hereditary spherocytosis, hereditary elliptocytosis, paroxysmal nocturnal hemoglobinuria • Enzyme defect: G6PD deficiency, pyruvate kinase deficiency
  60. 60. Hemolytic Anemias• General considerations – Coombs negative hemolytic anemia may be extrinsic • Microangiopathic hemolytic anemia • Thrombotic thrombocytopenic purpura (TTP) • Hemolytic-uremic syndrome (HUS) • Prosthetic valve hemolysis • Vasculitis • Malignant hypertension • Splenic sequestration • Plasmodium, Clostridium, Borrelia infection • Burns
  61. 61. Hereditary Spherocytosis• Essentials of Diagnosis – Positive Family History – Splenomegaly – Sperhocytes and Increased Reticulocytes on PBS – Microcytic / Hyperchromic Anemia (if present)• General considerations – Disorder of RBC membrane, leading to chronic hemolytic anemia – Autosomal dominant disease of variable severity – Hemolysis occurs because of trapping of RBCs within the spleen
  62. 62. Hereditary Spherocytosis Clinical Findings  Often diagnosed in childhood, but milder cases discovered incidentally late in life  Anemia may or may not be present because bone marrow may be able to compensate for shortened RBC survivalSigns & Symptoms  Severe anemia (aplastic crisis) may occur with folic acid deficiency or infection  Jaundice and pigment (calcium bilirubinate) gallstones and cholecystitis in chronic hemolysis  Palpable spleen
  63. 63. Hereditary Spherocytosis Diagnosis  Anemia my or may not be present  If present, anemia is Microcytic and variable severity; hematocrit may be normal  Hyperchromic - increased mean corpuscular hemoglobin concentration, often > 36 g/dL  Reticulocytosis ALWAYS present  Peripheral blood smear shows small percentage of spherocytes, small cells that have lost their central pallor  Indirect bilirubin often increased  Coombs test negative  Increased osmotic fragility
  64. 64. Hereditary Spherocytosis• Treatment – Folic acid, 1 mg PO Daily – Splenectomy, which eliminates site of hemolysis – Splenectomy may not be necessary in very mild cases discovered late in adult life
  65. 65. Glucose 6-phosphate Dehydrogenase Deficiency Essentials of Diagnosis  X-linked recessive disorder affects 10–15% of African American males  Episodic hemolysis  Minimally abnormal PBS  Reduced levels of G6PD between hemolytic episodes General considerations  Hereditary enzyme defect causes episodic hemolytic anemia from RBCs decreased ability to deal with oxidative stresses  Hemoglobin may become oxidized, forming precipitants (Heinz bodies) which cause membrane damage, leading to removal of RBCs by spleen
  66. 66. Glucose 6-phosphate Dehydrogenase Deficiency• Vast majority of patients are asymptomatic throughout lifetime without chronic hemolytic anemia, but are at risk of hemolytic anemia when challenged with oxidative agents• 3 Triggers of hemolysis  Fava beans  Infection  Drugs (antimalarials; sulphonamides; antibiotics – Cipro, Macrobid; analgesics – pryidium, aspirin; Vit C >1g)
  67. 67. Glucose 6-phosphate Dehydrogenase Deficiency• Signs & Symptoms – when hemolytic anemia is present – Pallor – Fatigue/weakness – Tachycardia – Jaundice – Splenomegaly – Dark, tea-colored urine (due to hemoglobinuria)
  68. 68. Glucose 6-phosphate Dehydrogenase Deficiency• Laboratory – Coombs test - negative – CBC with peripheral smear • CBC is normal between hemolytic episodes • During hemolytic episode – Normocytic, normochromic anemia (varying severity) – Reticulocytosis • RBC smear, although not diagnostic, may reveal "bite" cells • Heinz bodies may be seen on peripheral blood smear with crystal violet stain – G6PD enzyme assays negative or <12 IU/g – G6PD enzyme assays may be misleadingly normal if performed shortly after hemolytic episode when enzyme- deficient RBCs have been removed – may need to repeat test 3-4 weeks later
  69. 69. Glucose 6-phosphate Dehydrogenase DeficiencyBite cells Heinz bodies
  70. 70. Glucose 6-phosphate Dehydrogenase Deficiency• Treatment – Avoid known oxidative triggers – Typically, no treatment necessary, unless anemia is severe which may require transfusion – Hemolytic episode self-limited, even with continued use of offending drug, because older RBCs (with low G6PD activity) removed and replaced with young RBCs (with adequate G6PD activity) – Few patients will have chronic hemolytic anemia
  71. 71. Sickle Cell Anemia
  72. 72. Sickle Cell Anemia• Essentials of Diagnosis – Recurrent Painful Episodes – Positive Family History – Irreversibly sickled cells on PBS – Hemoglobin S is the major hemoglobin seen on electrophoresis• General Considerations – Hemoglobin S gene is carried in 8% of African Americans – Sickle cell anemia (Hgb S) occurs in 1 birth in 400 in African Americans – Onset during first year of life, when hemoglobin F levels fall
  73. 73. Sickle Cell Anemia• General Considerations – When deoxygenated, Hgb S can form gelatinous polymers that stiffen the RBC membrane, increase viscosity, and cause dehydration – leading to the sickled shape – The rigid and adherent cells clog small capillaries and venules, causing tissue ischemia, acute pain and gradual end-organ damage – They also possess altered sticky membranes (retic) that are abnormally adherent to the endothelium of small venules – Sickling is increased by increased RBC hemoglobin S concentration, RBC dehydration, acidosis, and hypoxemia – Sickling is retarded by hemoglobin F; high hemoglobin F levels are associated with more benign course
  74. 74. Sickle Cell Anemia• Patients with heterozygous genotype (Hgb AS) have sickle cell trait• Patients with homozygous genotype (Hgb S) have sickle cell disease
  75. 75. Sickle Cell Trait (Hgb AS)• Signs & Symptoms  Clinically normal  Acute vasoocclusion occurs only under extreme conditions (vigorous exertion at high altitude)  Painless hematuria sometimes present in adolescent males• Diagnostic testing – CBC and PBS normal – Hemoglobin electrophoresis shows that Hgb S comprises ~40% of hemoglobin and Hgb A 60%• Treatment – No treatment necessary – Genetic counseling appropriate
  76. 76. Sickle Cell Anemia (Hgb SS)• Signs and Symptoms – Vary significantly – some pt are virtually asymptomatic while others suffer repeated crises requiring hospitalization – Chronic hemolytic anemia produces • Jaundice • Pigment (calcium bilirubinate) gallstones • Splenomegaly (early childhood only) • Splenic Infarct and atrophy in adulthood or Splenectomy • Poorly healing ulcers over the lower tibia
  77. 77. Sickle Cell Anemia (Hgb SS)• Signs and Symptoms – Pulmonary hypertension is associated with decreased survival – Increased susceptibility to infection occurs as a result of hyposplenism and complement defects – Anemia may be life-threatening during hemolytic or aplastic crises – Aplastic crises occur when bone marrow compensation is reduced by infection or folate deficiency
  78. 78. Sickle Cell Anemia (Hgb SS)• Signs and Symptoms – Pain crisis - acute painful episodes (from vasooclusion) • Manifested by acute pain and tenderness, fever, tachycardia and anxiety • Bones, priapism, stroke – but can occur anywhere in the body • last hours to 2 weeks • Frequency and severity vary greatly • Repeated crises requiring hospitalization (>3/yr) correlate with reduced survival in adult life • Provocative factors – infection, fever, excessive exercise, anxiety, abrupt changes in temperature and hypoxia
  79. 79. Sickle Cell Anemia (Hgb SS)• Signs and Symptoms – Acute chest syndrome • Chest pain, tachypnea, fever, cough, and arterial O2 desaturation • Can mimic pneumonia, PE, bone marrow infarction, myocardial ischemia or lung infarction • Thought to reflect in situ sickling within the lung producing pain and temporary pulmonary dysfunction • Repeated episodes correlate with reduced survival – Renal necrosis – leads to failure in adults, a common late cause of death
  80. 80. Sickle Cell Anemia (Hgb SS)• Signs and Symptoms – Repeated vasoocclusion affects • Eyes (retinopathy) • Heart (cardiomegaly, hyperdynamic precordium, systolic murmurs) • Lungs (Pulm HTN) • Spleen (infarction, asplenia) • Kidney (infarction of renal medullary papillae, renal tubular concentrating defects, and gross hematuria) • Bone (ischemic necrosis, staphylococcal or salmonella osteomyelitis)
  81. 81. Sickle Cell Anemia (Hgb SS)• Laboratory Tests – Elevated serum indirect bilirubin and lactase dehydrogenase (LDH); serum haptoglobin low – CBC and PBS • Hematocrit usually 15–30% • Reticulocyte count elevated • PBS: irreversibly sickled cells comprise 5–50% of RBCs; reticulocytosis (10–25%); nucleated RBCs; Howell-Jolly bodies and target cells • White blood cell count characteristically elevated to 12,000–15,000/L; thrombocytosis may occur
  82. 82. Sickle Cell Anemia (Hgb SS)• Laboratory Tests – Hemoglobin electrophoresis confirms diagnosis • Sickle cell anemia (homozygous S) – HgbS 95-97% – Hgb F 2-5% – No hemoglobin A• Imaging Studies – Chest radiograph in acute chest syndrome – Bone radiographs show characteristic abnormalities
  83. 83. Sickle Cell Anemia (Hgb SS)• Treatment – Folic acid, 1 mg PO QD – Hydroxyurea • Consider in pts experiencing repeated episodes of acute chest syndrome or with >3 pain crises a year requiring hospitalization • Increases Hgb F levels • Reduces frequency of painful crises in patients whose quality of life is disrupted by frequent pain crises • Long-term safety uncertain
  84. 84. Sickle Cell Anemia (Hgb SS)• Treatment – Acute painful episodes • Identify precipitating factors • Treat infections if present • Aggressive analgesia administration • Vigorous hydration • Administer oxygen ONLY if hypoxic • Transfusion for extreme cases (doesn’t shorten the crisis)
  85. 85. Sickle Cell Anemia (Hgb SS)• Treatment – Acute chest syndrome • Medical emergency, treat in ICU • O2 if sat <90% • Maintain HCT >30• Exchange transfusion primarily indicated for treatment of intractable pain crises, priapism, and stroke• Allogeneic bone marrow transplantation under investigation as possible curative option for severely affected children
  86. 86. Sickle Cell Anemia (Hgb SS)• Treatment – Prenatal diagnosis and genetic counseling should be made available to those with personal or family history – No specific treatment is available for sickle cell anemia – Pneumococcal and H. flu vaccination reduces incidence of infections• Prognosis – With improved supportive care, average life expectancy is between ages 40 and 50
  87. 87. Autoimmune Hemolytic Anemia• Essentials of Diagnosis – Acquired anemia caused by IgG autoantibody – Spherocytes on PBS – Elevated Reticulocyte Levels – Postive Coombs Test• General Considerations – Acquired Disorder – 50% idiopathic – Associated with SLE, Chronic Lymphocytic Leukemia, and Lymphoma
  88. 88. Autoimmune Hemolytic Anemia• Signs & Symptoms – “Rapid Onset” Anemia – May be “Life Threatening” – Fatigue – Angina – CHF – Jaundice – Splenomegaly
  89. 89. Autoimmune Hemolytic Anemia• Laboratory – Anemia is variable but can have Hct < 10% – Elevated Reticulocyte level – PBS demonstrates Spherocytes – Elevated Indirect Bilirubin – Positive Direct Coombs Test• Differential – Important to exclude drug induced hemolytic anemia
  90. 90. Autoimmune Hemolytic Anemia• Treatment – Prednisone – Rituximab – Immunosuppressive Agents – High Dose Immune Globulin – Splenectomy if prednisone ineffective or recurs• Prognosis – Good if no underlying SLE, Leukemia, or Lymphoma
  91. 91. Cold Agglutinin Disease• Essentials of Diagnosis – Elevated Reticulocyte Level – Spherocytes on PBS – Coombs test positive for complement only – Positive Cold Agglutinin Test• General Considerations – Acquired hemolytic anemia – most idiopathic • Can see in post infectious mycoplasma or mononucleosis – IgM autoantibody directed at I antigen on RBC – Occurs at temps less than 37 degrees Celsius in fingers, toes, ears, nose
  92. 92. Cold Agglutinin Disease• Signs & Symptoms – Mottled or numb fingers or toes when exposed to cold – Episodic hemoglobinuria when exposed to cold• Laboratory – Mild anemia – Elevated Reticulocyte Level – PBS shows spherocytes – Direct Coombs test positive to complement only – Positive Cold Agglutinin Test
  93. 93. Cold Agglutinin Disease• Treatment – Avoid the cold – Hemolysis takes place in liver so Prednisone & Splenectomy ineffective – Rituximab is treatment of choice – High Dose Immune Globulin – Immunosuppressive agents
  94. 94. Aplastic Anemia• Essentials of Diagnosis – Pancytopenia – No abnormal cells seen on PBS – Hypocellular Bone Marrow• General Considerations – Condition of Bone Marrow Failure – Results from Injury to or Abnormal expression of stem cells – Age distribution is biphasic • Peak in the teens-twenties and a second peak in the elderly
  95. 95. Aplastic Anemia
  96. 96. Aplastic Anemia• Signs & Symptoms – Weakness, Fatigue – Vulnerability to Infections easily – Mucosal and skin bleeding – Pallor – Purpura – Petechiae – NOT PRESENT • Hepatosplenomegaly • Lymphadenopathy • Bone Tenderness
  97. 97. Aplastic Anemia• Laboratory Tests – Pancytopenia, although in early disease only one or two cell lines may be reduced – Anemia may be severe – Reticulocytes ALWAYS decreased – Large RBCs (macrocytosis) – Neutrophils and platelets reduced in number, no immature or abnormal forms seen
  98. 98. Aplastic Anemia• Laboratory Tests – Severe aplastic anemia defined by neutrophils < 500/μL, platelets < 20,000/μL, reticulocytes < 1%, and bone marrow cellularity < 20%• Diagnostic Procedures – Bone marrow aspirate and bone marrow biopsy appear hypocellular, with scant amounts of normal hematopoietic progenitors; no abnormal cells are seen – In severe cases the biopsy if virtually 100% fat
  99. 99. Aplastic Anemia• Treatment – Supportive measures only for mild cases – Antibiotics to treat infections – Red blood cell and platelet transfusions as necessary – Bone marrow transplant is treatment of choice for children and young adults – Immunosuppressant for older adults• Prognosis – Median survival without treatment is 3 months – Bone Marrow transplant is highly successful in children and young adults