Anemia
What are microcytic, hypochromic anemias?
"FAST Lead" 1. Fe deficiency 2. Anemia of chronic disease 3. Sideroblastic Anemia 4. α-Thalassemia 5. β-thalassemia 6. Lead poisoning
If an anemia is macrocytic, what labs should you order?
RBC folate Serum B12
Review: What is autoimmune hemolytic anemia?
(+) Direct Coombs Test: A test that checks for antibodies attached to red blood cells - which will, of course, be (+) in autoimmune hemolytic anemia. Pearls: Direct Coombs test along with ↑ Retic, ↑ LDH, ↓ Haptoglobin, and ↑ Bilirubin (indirect) in a patient with SLE, CLL, prior blood transfusions, organ transplant or bone marrow transplant.
Review: What is hereditary spherocytosis?
(+) osmotic fragility test: which mixes RBCs with varying concentrations of saline, abnormally shaped RBCs will be fragile and fall apart. Pearls: ↑ Retic, ↑ LDH, ↓ Haptoglobin, and ↑ Bilirubin (indirect) and the presence of spherocytes. The patient will have acute hemolytic events - jaundice, splenomegaly, bilirubin cholelithiasis, definitive diagnosis is (+) osmotic fragility test, treat with folic acid, supportive transfusion and splenectomy for moderate to severe cases. Diagnosis: RBC fragility assay, RBC autohemolysis assay, and direct antiglobulin (Coombs) test Treatment: treat with folic acid, supportive transfusion and splenectomy for moderate to severe cases.
How is aplastic anemia diagnosed?
A bone marrow biopsy is crucial to determine the cellularity or the extent of depletion of the hematopoietic elements.
What is splenic dysfunction of sickle cell disease?
A child with sickle cell disease is vulnerable to life-threatening infection by 4 months of age due to splenic dysfunction. Splenic dysfunction is caused by sickling of the RBCs within the spleen, resulting in an inability to filter microorganisms from the bloodstream in most patients. Splenic dysfunction is followed, eventually, by splenic infarction, usually by 2-4 years of age. The loss of normal splenic function makes the patient susceptible to overwhelming infection by encapsulated organisms, especially Streptococcus pneumoniae and other pathogens. The hallmark of infection is fever. A febrile patient with a sickle cell disease (temperature >38.5°C) must be evaluated immediately. Current precautions to prevent infections include prophylactic daily oral penicillin begun at diagnosis and vaccinations against pneumococcus, Haemophilus influenzae type b, meningococcus, hepatitis B virus, and influenza virus.
Which of the following is a cause of microcytic anemia? A. Anemia of chronic disease B. Folate deficiency C. Vitamin B12 deficiency D. Hereditary spherocytosis
A. Anemia of chronic disease Anemia of chronic disease is one of the causes of microcytic anemia.
A patient's blood film shows spherocytes and his direct Coombs test is positive. What is his most likely diagnosis? A. Autoimmune hemolytic anemia B. Hereditary spherocytosis C. Hereditary elliptocytosis D. Microangiopathic hemolytic anemia
A. Autoimmune hemolytic anemia Positive direct Coombs test is diagnostic of autoimmune hemolytic anemia. Spherocytes are seen in this condition.
A 4-year-old Greek boy is brought in by his mother to the hospital because of 2 days of fever, "coke"-colored urine, and jaundice. The pregnancy was uneventful except the infant was found to have hyperbilirubinemia that was treated with phototherapy. The mother explains that the child has been well with no prior events like this. He has not taken any medications. The mother states that he recently spent two days at his grandmother's house where he was exposed to different food than is normally in his diet. Which of the following would be expected in this child on peripheral blood smear? A. Bite cells B. Ringed sideroblasts C. Schistocytes D. Spherocytes E. Target cells
A. Bite cells The patient in this vignette most likely has glucose-6-phosphate dehydrogenase (G6PD) deficiency as evidenced by hemolytic anemia induced by fava beans. The finding on peripheral smear is most consistent with bite cells.
Which of the following is not evidence of hemolysis? A. Decreased reticulocytes B. Hemosidenuria C. Increased unconjugated bilirubin D. Decreased haptoglobin
A. Decreased reticulocytes In hemolysis, bone marrow compensation results in reticulocytosis.
What are aplastic crises?
Aplastic crises may complicate any chronic hemolytic anemia. Human parvovirus B19 (the cause of fifth disease) infects erythroid precursors and shuts down erythropoiesis. In children with chronic hemolytic anemia, these periods of severe reticulocytopenia can lead to an acute exacerbation of the anemia that may precipitate cardiovascular decompensation. Transient erythroid aplasia is without consequence in individuals with normal RBC survival. Recovery from parvovirus infection in hemolytic disease is spontaneous, but patients may need transfusion if the anemia is severe.
A female patient presents with weakness and fatigue for the past three months. A CBC was ordered and revealed the following values: RBC 3.8 X 10(6)mcL (4.7-6.1 x 10(6)mcL) HCT 27% (35-45%) Hgb 9.2 gms/dL (12-15.5 gms/dL) MCV 120 fL (80-100 fL) MCH 35 pg (26-34 pg) On physical examination which of the following would be a consistent finding for this type of anemia? A. Paresthesia of the hands and feet B. Hepatosplenomegaly C. Tachycardia D. Jaundice
A. Paresthesia of the hands and feet Neurological manifestation is the earliest type most commonly seen with megaloblastic anemia most commonly from vitamin B12 deficiency.
Absorption of vitamin B12 requires intrinsic factor that is secreted by which of the following? A. Parietal cells B. Chief cells C. Mucous cells D. Enteroendocrine cells
A. Parietal cells Parietal cells are responsible for acid secretion and intrinsic factor.
Which of the following is not seen in aplastic anemia? A. Reticulocytosis B. Thrombocytopenia C. Hypocellular bone marrow D. Neutropenia
A. Reticulocytosis Aplastic anemia is always associated with reticulocytopenia. All other options are correct.
How does hemolytic anemia present clinically?
Acute onset of pallor from anemia depends on severity and bone marrow response. Splenomegaly. Jaundice with high indirect bilirubin - too much for the liver to keep up with. ↑ LDH. -All hemolytic anemias are going to have ↑ LDH (LDH is part of the red blood cell membrane and will therefore be increased in the blood as RBCs are broken down), ↓ Haptoglobin*, and ↑ Bilirubin (indirect) Reduced serum haptoglobin. Increased reticulocytes. Positive coombs test if autoimmune etiology.
How is hemolytic anemia diagnosed?
An elevated corrected reticulocyte count (over 2.0) in the presence of falling hemoglobin, elevated indirect bilirubin, and elevated LDH is the hallmarks of hemolytic anemia. A direct Coombs or direct antiglobulin test (DAT) may identify antibodies on the RBCs. An indirect Coombs test may identify antibodies in the patient's serum. Other helpful tests include hemoglobin electrophoresis for hemoglobinopathies, Heinz body stain for G6PD deficiency, osmotic fragility for spherocytosis and elliptocytosis, D-dimer, PT, aPTT, and a pregnancy test if thrombocytopenia is present.
Review: What is aplastic anemia?
Aplastic anemia is a normocytic-normochromic anemia that results from a loss of blood cell precursors, causing hypoplasia of bone marrow, RBCs, WBCs, and platelets and anemia without reticulocytosis. Present with severe pallor and weakness, petechiae, ecchymosis and mucosal bleeding, and severe infection along with ↓ WBC, ↓ RBC, ↓ Platelets, and no reticulocytosis. Aplastic anemia is the only anemia where all three cell lines are decreased. Many cases are idiopathic, but often chemicals, drugs, or radiation may be involved. Look for drug causes: ACE inhibitors, Sulfonamides, Phenytoin (Dilantin), Chloramphenicol, Chemotherapy, and Radiation.
What are laboratory findings in aplastic anemia?
Aplastic anemia is suspected in patients, particularly young patients, with pancytopenia (eg, WBC < 1500/μL, platelets < 50,000/μL). In aplastic anemia, RBCs are normochromic-normocytic (normal MCV). ↓ Platelets: often far below 50,000/μL ↓ Reticulocytes: helps identify aplastic anemia in sickle cell patients, who usually have a high baseline reticulocyte count Serum iron is elevated.
Review: How is G6PD deficiency treated?
Avoidance of triggers and supportive care. During acute hemolysis, treatment is supportive; transfusions are rarely needed. Patients are advised to avoid drugs or substances that initiate hemolysis.
The result of a patient's iron studies showed: reduced serum iron, reduced serum total iron binding capacity (TIBC), raised serum ferritin, normal serum soluble transferrin receptors, Iron present in bone marrow, reduced iron in erythroblasts. What is the patient's most likely diagnosis? A. Iron deficiency anemia B. Anemia of chronic disease C. Sideroblastic anemia D. Thalassemia trait
B. Anemia of chronic disease Iron studies of a patient with anemia of chronic disease: reduced serum iron, reduced serum Total Iron Binding Capacity (TIBC), normal or raised serum ferritin, normal serum soluble transferrin receptors, Iron present in bone marrow, absent or reduced iron in erythroblasts.
A 20-year-old healthy male was treated 4 days ago for an MRSA skin infection with sulfamethoxazole-trimethoprim (Bactrim). The infection is improving but he is increasingly weak and his sclera have turned yellow. Today his hemoglobin is 11 g/ dL (13.5 to 18 g/ dL) and his MCV is 85 (80 to 100 fL); the corrected reticulocyte count is elevated. What is the best test for the most likely diagnosis? A. Homocysteine level B. Heinz body stain C. Hemoglobin electrophoresis D. Erythropoietin level E. Iron studies
B. Heinz body stain G6PD deficiency causes a hemolytic anemia when the patient is exposed to oxidant medications, like sulfa or antimalarials, or eating Fava beans. Heinz body stains for G6PD deficiency. Folate and B12 deficiency causes elevated homocysteine levels. Hemoglobin electrophoresis quantifies proteins. Erythropoietin levels are low in chronic renal disease. Iron studies are warranted in microcytic anemia.
Which of the following is an extrinsic cause of hemolytic anemia? A. Hereditary elliptocytosis B. Hemolytic-uremic syndrome C. Thalassemia D. Severe hypophosphatemia
B. Hemolytic-uremic syndrome Hemolytic-uremic syndrome is an example of Microangiopathic hemolytic anaemia (MAHA), where fragmentation of red cells occurs in an abnormal microcirculation.
Which of the following has been implicated in the etiopathogenesis of anemia of chronic diseases (ACD)? A. Hephaestin B. Hepcidin C. Ferroportin D. Transferrin
B. Hepcidin The key regulatory protein that accounts for the findings characteristic of ACD is hepcidin, which is produced by the liver. Hepcidin binds to ferroportin on the membrane of iron exporting cells, such as small intestinal enterocytes and macrophages, internalizing the ferroportin and thereby inhibiting the export of iron from these cells into the blood (and hence to the main target cells and proteins of iron).
The result of a patient's iron studies showed: reduced serum iron, reduced serum ferritin, absent iron in bone marrow. What is the patient's most likely diagnosis? A. Anemia of chronic disease B. Iron deficiency anemia C. Sideroblastic anemia D. Thalassemia trait
B. Iron deficiency anemia Iron studies of a patient Iron deficiency anemia: reduced serum iron, reduced serum ferritin, absent Iron in bone marrow.
Which of the following is not an etiology of aplastic anemia? A. Dyskeratosis congenita B. Pneumonia C. Fanconi anemia D. Parvovirus B19 infection
B. Pneumonia Pneumonia is not a cause of aplastic anemia.
The most useful test to initially monitor the response of a patient with iron deficiency anemia to iron therapy is: A. Ferritin level B. Reticulocyte count C. Haptoglobin level D. Transferrin level
B. Reticulocyte count Reticulocyte response to iron therapy is usually evident within a week. The other options, while reasonable, will have a slower response to therapy.
Which of the following statements about iron deficiency anemia is incorrect? A. Can present as pica, koilonychia, cheilosis, and dysphagia. B. The reticulocyte count may be high. C. Is treated with ferrous sulfate. D. Can be caused by zinc deficiency.
B. The reticulocyte count may be high. Reticulocyte count in iron deficiency anemia is usually low or inappropriately normal.
Schumm's test is used to determine the blood level of: A. Haptoglobin B. Bilirubin C. Methemalbumin D. Methemoglobin
C. Methemalbumin Schumm's test is a blood test that uses spectrophotometer to determine the blood level of methemalbumin. All other options are incorrect.
What is the etiology of beta-chain hemoglobinopathies?
Beta-chain hemoglobinopathies in the United States are more prevalent than alpha-chain disorders, possibly because these abnormalities are not symptomatic in utero. The major beta hemoglobinopathies include those that alter hemoglobin function, including hemoglobins S, C, E, and D, and those that alter beta-chain production, the β-thalassemias. Because each RBC has two copies of chromosome 11 and they express both β-globin genes, most disorders of beta chains are not clinically severe, unless both beta chains are abnormal. By convention, when describing β-thalassemia genes, β0 indicates a thalassemic gene resulting in absent beta-chain synthesis, whereas β+ indicates a thalassemic gene that permits reduced but not absent synthesis of normal β chains. Disorders of the beta chain usually manifest themselves clinically between 4 and 12 months of age when fetal hemoglobin nadirs, unless they have been detected prenatally or by cord blood screening.
What are laboratory findings in beta thalassemia minor?
Blood smears of patients with beta-thalassemia minor also reveal microcytic RBCs. In addition, target cells and basophilic stippled RBCs, caused by precipitation of alpha-chain tetramers, may also be present. The diagnosis of beta thalassemia minor is based on an elevated of hemoglobin A2 and F levels.
What is marrow infiltration by malignant cells?
Bone marrow infiltration by malignant cells commonly leads to a normochromic, normocytic anemia. The mechanism by which neoplastic cells interfere with RBC and other marrow cell synthesis is multifactorial. The reticulocyte count is often low. Immature myeloid elements may be released into the peripheral blood because of the presence of the infiltrating tumor cells. An examination of the peripheral blood may reveal lymphoblasts; when solid tumors metastasize to the marrow, these cells are seldom seen in the peripheral blood. Teardrop cells may be seen in the peripheral blood. A bone marrow examination is frequently necessary in the face of normochromic, normocytic anemia.
How can iron deficiency anemia be prevented?
Bottle-fed infants should receive an iron-containing formula until 12 months of age. Exclusively breast-fed infants older than 6 months of age should receive an iron supplement. The introduction of iron-enriched solid foods at 6 months of age, followed by a transition to a limited amount of cow's milk and increased solid foods at 1 year, can help prevent iron deficiency anemia. Adolescent females who are menstruating should have a diet enriched with iron-containing foods. A vitamin with iron may also be used.
Which of the following Rh genotypes in a mother and father would represent a risk for hemolytic disease of the newborn? A. Mother Rh-positive, father Rh-negative B. Mother Rh-positive, father Rh-positive C. Mother Rh-negative, father Rh-positive D. Mother Rh-negative, father Rh-negative
C. Mother Rh-negative, father Rh-positive If an Rh-negative woman carries an Rh-positive fetus, she may develop antibodies against Rh when fetal blood cells enter her circulation.
An 82-year-old woman is brought to the ER after her neighbor saw her fall in the hallway. She lives alone and remarks that she's been feeling weak lately. She notes that she's been experiencing decreased appetite, palpitations, and fatigue. On exam, she is frail, with pale conjunctiva and tachycardia. The exam is otherwise normal. Her lab tests are notable for: Hgb 9.4, MCV 109, homocysteine 15.1 micromol/L (normal range 5.8-11.9 micromol/L), and methylmalonic acid 0.2 micromol/L (normal range 0 - 0.4 micromol/L). Based on her presentation as well as this data, her physician suspects she is deficient in a nutrient. Body stores of this nutrient usually last how long? A. 4-5 days B. 2-3 weeks C. 4-5 months D. 1-2 years E. > 10 years
C. 4-5 months This woman is most likely deficient in folic acid. The body stores enough folic acid to last 4-5 months. Folic acid deficiency is common in the elderly, who sometimes subsist on a "tea and toast" diet. Other vulnerable groups include patients with the following risk factors: alcoholism, gastrointestinal disease (celiac disease, inflammatory bowel disease, short bowel syndrome), pregnancy, increased cell turnover, and medications that inhibit folate metabolism (i.e. - methotrexate, phenytoin, sulfasalazine). The deficiency presents with a megaloblastic anemia. Although this deficiency can present with similar findings to B12 deficiency, it does not cause neurological deficits while B12 deficiency does.
Causes of iron deficiency anemia do not include: A. Chronic gastrointestinal blood loss B. Celiac disease C. Excessive vomiting D. Zinc deficiency
C. Excessive vomiting Excessive vomiting cannot lead to iron deficiency but rather dehydration and electrolyte derangement.
Which of the following drugs is not associated with aplastic anemia? A. Chloramphenicol B. Busulfan C. Levodopa D. Azathioprine
C. Levodopa Levodopa is not associated with aplastic anemia.
Which of the following physical findings suggest pernicious anemia? A. Splenomegaly and hepatomegaly B. Petechiae and ecchymosis C. Loss of position and vibratory sensation D. Cheilosis and koilonychia
C. Loss of position and vibratory sensation Loss of position and vibratory sensation are common neurologic findings in pernicious anemia.
If an anemia is normocytic, what labs should you order?
Coombs test Iron studies Bilirubin
What are laboratory findings in folate deficiency?
CBC and serum vitamin B12 and folate levels. CBC may indicate megaloblastic anemia indistinguishable from that of vitamin B12 deficiency. If serum folate is < 3 deficiency is likely. A normal methylmalonic acid (MMA) level may differentiate folate deficiency from vitamin B12 deficiency because MMA levels rise in vitamin B12 deficiency but not in folate deficiency.
What is hemolytic anemia?
Caused by premature breakdown of RBCs 1) Intracorpuscular defects: RBC membrane defects -Hereditary Spherocytosis 2) Extracorpuscular defect: -Autoimmune Hemolytic Anemia -G6PD Deficiency -Drug effect - Chemotherapy
A positive direct Coombs' test may be seen in which of the following conditions? A. G6PD deficiency B. Sickle cell anemia C. Hereditary spherocytosis D. Autoimmune hemolytic anemia
D. Autoimmune hemolytic anemia
Which of the following is not a cause of anemia of chronic disease? A. Malignancy B. Inflammatory bowel disease C. Rheumatoid arthritis D. Hereditary spherocytosis
D. Hereditary spherocytosis Hereditary spherocytosis is a hemolytic cause of anemia. Anemia of chronic disease occurs in the setting of chronic infection, chronic inflammation or neoplasia. It is not related to bleeding, hemolysis or marrow infiltration.
Which of the following conditions is caused by a disorder in the red blood cell membrane? A. G6PD deficiency B. Folate deficiency C. Sickle cell anemia D. Hereditary spherocytosis
D. Hereditary spherocytosis The cell membrane defect of spherocytosis leads to hemolysis due to trapping of the cells by the spleen.
Which of the following is incorrect regarding aplastic anemia? A. Aplastic anaemia is defined as pancytopenia with hypocellularity (aplasia) of the bone marrow B. Can result in recurrent bacterial or fungal infections. C. Can be caused by chloramphenicol D. Immunosuppressive treatment of choice is antithymocyte globulin (ATG) plus cyclophosphamide.
D. Immunosuppressive treatment of choice is antithymocyte globulin (ATG) plus cyclophosphamide. Immunosuppressive treatment of choice is antithymocyte globulin (ATG) plus cyclosporine.
Review: How is G6PD deficiency diagnosed?
Diagnosis is made by G6PD assay HEINZ BODIES and BITE CELLS on smear Hemolysis labs: ↑ indirect bilirubin, ↓ haptoglobin, and ↑ lactate dehydrogenase
Review: How does iron deficiency anemia present clinically?
Fatigue with exercise, palpitations, shortness of breath, weakness, headaches, and tinnitus. Tachycardia, tachypnea on exertion, pallor, glossitis, angular cheilitis, pica, koilonychia, jaundice, and splenomegaly.
Review: How is iron deficiency anemia treated?
Ferrous sulfate 3 mg/kg once or twice daily (20% elemental iron) - Give between meals with juice (not milk). Ferrous fumarate (33% elemental iron) 100-200 mg/day in 2-3 doses. Ferrous gluconate (12% elemental iron) 3-6 mg/kg/day in 3 doses.
What is the pathophysiology of G6PD deficiency?
G6PD deficiency reduces energy available to maintain the integrity of the red cell membrane, which shortens RBC survival. Hemolysis selectively affects older RBCs among affected blacks and among most affected whites. Hemolysis occurs commonly after fever, acute viral or bacterial infections, and diabetic acidosis. Less commonly, hemolysis occurs after exposure to drugs or to other substances that produce peroxide and cause oxidation of Hb and RBC membranes. These drugs and substances include primaquine, salicylates, sulfonamides, nitrofurans, phenacetin, naphthalene, some vitamin K derivatives, dapsone, phenazopyridine, nalidixic acid, methylene blue, and, in some whites, fava beans. Whether continued use of the offending drug leads to a compensated hemolytic state or lethal hemolysis depends on the degree of G6PD deficiency and the oxidant potential of the drug. Chronic congenital hemolysis (without drug use) occurs in some whites. Because older cells are selectively destroyed in blacks, hemolysis is usually self-limited, affecting < 25% of RBC mass. In whites, the deficiency is more severe, and profound hemolysis may lead to hemoglobinuria and acute kidney injury.
Review: What is G6PD deficiency?
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked enzymatic defect common in blacks that can result in hemolysis after acute illnesses or intake of certain drugs. Drugs that commonly cause hemolysis in patients with G6DP deficiency: -Antimalarials: primaquine, pamaquine -Analgesics: phenacetin, acetylsalicylic acid -Others: sulfonamides, dapsone
What is haptoglobin and why is it low with hemolytic anemia?
Haptoglobin attaches to this released hemoglobin, which is also called "free" hemoglobin. Free hemoglobin is not contained within red blood cells. The level of free hemoglobin is usually very low. But it rises when red blood cells are dying. When the haptoglobin and hemoglobin attach, the new molecule goes to the liver. There, parts of it (such as iron and amino acids) are recycled. The haptoglobin is destroyed. When red blood cells are actively being destroyed, haptoglobin disappears faster than it is created. Thus, the levels of haptoglobin in the blood drop.
An 8-year-old presents with splenomegaly. CBC results reveal the following: WBC- 6,300/microliter, Hgb- 10.5 g/dl, Hct- 31%, MCV- 87 fL, MCHC- 39 g/dl, MCH- 28 pg, and platelets- 317,000/mL. Examination of the RBC morphology reveals 80% spherocytes. Which of the following would be most helpful in confirming the diagnosis? A. Direct Coombs test B. Osmotic fragility C. G-6-PD level D. Serum ferritin
Hereditary spherocytosis presents with a normocytic, normochromic anemia and many spherocytes. Diagnosis is confirmed with a positive osmotic fragility test.
What is cold antibody hemolytic anemia?
In the cold antibody type, the autoantibodies become most active and attack red blood cells only at temperatures well below normal body temperature.
What is warm antibody hemolytic anemia?
In the warm antibody type, the autoantibodies attach to and destroy red blood cells at temperatures equal to or in excess of normal body temperature.
Review: What is the etiology of iron deficiency anemia?
Iron deficiency is the most common cause of anemia and usually results from blood loss. In men, the most frequent cause is chronic occult bleeding, usually from the GI tract. In premenopausal women, menstrual blood loss is a common cause. Another possible cause of blood loss in men and women is chronic intravascular hemolysis.
What are side effects of treatment for iron deficiency anemia?
Liquid preparations—gray staining of teeth or gums Brush teeth or rinse with water after administration GI upset (ferrous gluconate better tolerated)
What is the earliest finding in iron deficiency anemia?
Low serum ferritin (stores are low)
Review: How is aplastic anemia diagnosed?
Most accurate test: bone marrow biopsy. -Normal cell morphology -Hypocellular bone marrow with fatty infiltration
Review: What is lead poisoning?
Other causes of ↓ MCV include lead poisoning (look for this in a patient with neurological symptoms), sideroblastic anemia, basophilic stippling, and thalassemia. Treatment is with EDTA.
Review: What is the epidemiology of G6PD deficiency?
Oxidative Stress (infection or drug-induced) + African American Male + Heinz bodies X-linked (look for males), damaged hemoglobin (G6PD protects RBC membrane) causes HEINZ BODIES and BITE CELLS on smear. Look for a trigger event: Antimalarials, sulfa drugs, ASA, febrile illness - causes breakdown of RBCs. 10% of male blacks in the U.S are affected.
Pure RBC aplasia (normal WBC/platelets) may be caused by what infectious agent?
Parvovirus B19, typically in patients with underlying hemolytic anemia.
How will a patient with G6PD deficiency present clinically?
Patient will present as → a 20-year-old healthy male was treated 4 days ago for an MRSA skin infection with sulfamethoxazole-trimethoprim (Bactrim). The infection is improving but he is increasingly weak and his sclera have turned yellow. Today his hemoglobin is 11 g/ dL (13.5 to 18 g/ dL) and his MCV is 85 (80 to 100 fL); the corrected reticulocyte count is elevated, he has an increased indirect bilirubin and decreased haptoglobin. The peripheral smear demonstrates bite cells and Heinz bodies.
How will patients with B12 deficiency present clinically?
Patient will present as → a 38-year-old man with a history of a gastric bypass for morbid obesity comes to your office with a hemoglobin level of 10 g/ dL. His MCV is 88 mm3. His ferritin level is 35 mcg/ L, and his red cell distribution width is high. His reticulocyte count is high. Further questioning reveals mild anorexia, diarrhea, glossitis, and distal paresthesia. On exam you notice she has a swollen red tongue.
How is B12 deficiency anemia diagnosed?
Pernicious anemia + schilling test + ↓ intrinsic factor and parietal cell antibodies. Check antibody to intrinsic factor; positive test is confirmatory for Pernicious Anemia, but sensitivity is only 50-70%
How long does it take to correct iron deficiency anemia?
Six weeks to correct anemia Six months to replete iron stores Recheck blood counts every 3 months x 1 year Hgb rises little for 2 weeks but then rises 0.7 to 1 g/wk until near normal, at which time rate of increase tapers Increasing reticulocyte count is an indication that iron is working
How is hereditary spherocytosis treated?
Splenectomy, after appropriate vaccination, is the only specific treatment but is rarely needed. It is indicated in patients < 45 yr with Hb persistently < 10 g/dL, jaundice or biliary colic, or persistent aplastic crisis. If the gallbladder has stones or other evidence of cholestasis, it should be removed during splenectomy. Although spherocytosis persists after splenectomy, the cells survive longer in the circulation. Usually, symptoms resolve, and anemia and reticulocytosis decrease. However, RBC fragility remains high.
How is folate deficiency treated?
Supplemental oral folate. Folate 400 to 1000 μg po once/day replenishes tissues and is usually successful even if deficiency has resulted from malabsorption. The normal requirement is 400 μg/day. (Caution: In patients with megaloblastic anemia, vitamin B12 deficiency must be ruled out before treating with folate. If vitamin B12 deficiency is present, folate supplementation can alleviate the anemia but does not reverse, and may even worsen, neurologic deficits).
What are the two types of autoimmune hemolytic anemia?
There are two main types of autoimmune hemolytic anemia: -Warm antibody hemolytic anemia -Cold antibody hemolytic anemia
Review: How is aplastic anemia treated?
Treat by stopping causative agent if applicable. RBC transfusion, leukoreduced, platelet transfusion. Curative: bone marrow transplant for healthy patients under 50. Immunosuppressive agents for over 50 or those with comorbidities: anti-thymocyte globulin plus cyclosporine, and prednisone. Hematopoietic growth factor G-CSF (filgastrim) reduces the incidence of infections, but it does NOT alter the course of the disease, response to IST, or survival rate.
How is autoimmune hemolytic anemia treated?
Treated first line with steroids, in more severe and persistent cases, may need splenectomy and even blood transfusions.
How is B12 deficiency treated?
Treatment for B12 deficiency is replacement: usually IM (if pernicious anemia) or sublingual.
How is anemia of chronic disease treated?
Treatment of underlying disorder/ Recombinant EPO and iron supplements. Treat with exogenous erythropoietin analogs (epoetin alfa (Procrit, Epogen) should only be initiated if the hemoglobin is < 10 gm/dl and these agents must be stopped once hemoglobin is > 11 gm/dl due to increased chance of MI and stroke.
What is the etiology of B12 anemia?
Vitamin B12 deficiency can be malabsorptive (ETOH, gastric bypass) but may also be secondary to ↓ intrinsic factor (pernicious anemia).
What are laboratory findings of B12 deficiency anemia?
↑ MCV (macrocytic) + Hypersegmented neutrophils, neuropathy (loss of proprioception and ↓ vibratory sense), ↑ Methylmalonic acid in early B12 loss Homocysteine ↑, normal folate
What is folate deficiency?
↓ Folate, ↑ MCV (macrocytic anemia). There are two macrocytic anemias (folate deficiency and vitamin B12 deficiency). Unlike ↓ vitamin B12, folate deficiency has no neurological symptoms. Folate deficiency is common. It may result from inadequate intake, malabsorption, or use of various drugs. Deficiency causes megaloblastic anemia (indistinguishable from that due to vitamin B12 deficiency). Maternal deficiency increases the risk of neural tube birth defects.
Review: What are laboratory findings in iron deficiency anemia?
↓ MCV (microcytic), ↑ TIBC, ↓ Ferritin (low iron stores) ↓ MCH (hypochromic)
What does normocytic mean?
80-100 MCV (normal)
Review: What are the non-megaloblastic anemias?
Alcohol use disorder Liver disease
What is the etiology of alpha chain hemoglobinopathies?
Because alpha chains are needed for fetal erythropoiesis and production of hemoglobin F (α2γ2), alpha-chain hemoglobinopathies are present in utero. Four alpha genes are present on the two number 16 chromosomes. Single gene deletions produce no disorder (silent carrier state) but can be detected by measuring the rates of α and β synthesis or by using molecular biological techniques. Deletion of two genes produces α-thalassemia minor with mild or no anemia and microcytosis. Deletion of all four α genes leads to hydrops fetalis, severe intrauterine anemia, and death, unless intrauterine transfusions are administered.
What is Fanconi anemia?
Fanconi anemia is a constitutional form of aplastic anemia that usually presents in the latter half of the first decade of life and may evolve over years. A group of genetic defects in proteins involved in DNA repair have been identified in Fanconi anemia, which is inherited in an autosomal recessive manner. The diagnosis is based on demonstration of increased chromosomal breakage after exposure to agents that damage DNA. The repair mechanism for DNA damage is abnormal in all cells in Fanconi anemia, which may contribute to the increased risk of malignancies. Acute leukemia develops in 10% of cases. Other malignancies that can occur include solid tumors of the head and neck, gastrointestinal tumors, and gynecological tumors.
How does hereditary pyropoikilocytosis present clinically?
Far more significant hemolysis occurs in hereditary pyropoikilocytosis. The peripheral blood smear in hereditary pyropoikilocytosis often includes elliptocytes, spherocytes, fragmented RBCs, and striking microcytosis. Such patients may have bizarre blood smears in the newborn period with small, fragmented RBCs.
If an anemia is microcytic, what labs should you order?
Ferritin Iron TIBC
How is Fanconi anemia treated?
HSCT can cure the pancytopenia caused by bone marrow aplasia. Many patients with Fanconi anemia and approximately 20% of children with aplastic anemia seem to respond for a time to androgenic therapy, which induces masculinization and may cause liver injury and liver tumors. Androgenic therapy increases RBC synthesis and may diminish transfusion requirements. The effect on granulocytes, and especially the platelet count, is less impressive.
What laboratory findings would you expect in thalassemia?
HbF increased, Low MCV, Hemolysis
What is the etiology of iron deficiency anemia?
Infants fed cow's milk when younger than 1 year of age, toddlers fed large volumes of cow's milk, and menstruating adolescent females who are not receiving supplemental iron are at high risk for iron deficiency. Dietary iron deficiency anemia is most common in bottle-fed toddlers who are receiving large volumes of cow's milk and eat minimal amounts of food high in iron content.
What is priapism?
Priapism occurs in males, usually between 6 and 20 years old. The child experiences a sudden, painful onset of a tumescent penis that will not relax. Therapeutic steps for priapism include the administration of oxygen, fluids, analgesia, and transfusion when appropriate to achieve a hemoglobin S less than 30%. Urgent partial exchange transfusion is often required to lower the hemoglobin S.
How is G6PD deficiency treated?
The treatment of G6PD deficiency is supportive. Transfusions are indicated when significant cardiovascular compromise is present. Maintaining hydration and urine alkalization protects the kidneys against damage from precipitated free hemoglobin. Hemolysis is prevented by avoidance of known oxidants, particularly long-acting sulfonamides, nitrofurantoin, primaquine, dimercaprol, and moth balls (naphthalene). Fava beans (favism) have triggered hemolysis, particularly in patients with the Mediterranean variant. Serious infection also is a potential precipitant of hemolysis in G6PD-deficient young children.
What is the epidemiology of thalassemia minor?
They are prevalent in certain ethnic groups (Mediterranean, Southeast Asian, African Americans). Individuals of Asian descent are at risk of having three or four alpha genes deleted, resulting in hemoglobin disease (beta-4 tetramers) or hydrops fetalis, which is largely Bart (gamma-4 tetramers) hemoglobin.
How are hemolytic anemias caused by disorders extrinsic to the red blood cell treated?
Transfusion for the treatment of autoimmune hemolysis is challenging because crossmatching is difficult because the autoantibodies react with virtually all RBCs. In addition to transfusion, which may be lifesaving, management of autoimmune hemolytic anemia depends on antibody type. Management may involve administration of corticosteroids and, at times, intravenous immunoglobulin. Corticosteroids reduce the clearance of sensitized RBCs in the spleen.
What is the etiology of beta thalassemia major (Cooley anemia)?
β-Thalassemia major is caused by mutations that impair beta-chain synthesis. Because of unbalanced synthesis of alpha and beta chains, alpha chains precipitate within the cells, resulting in RBC destruction either in the bone marrow or in the spleen.
What is the epidemiology of beta thalassemia major (Cooley anemia)?
β-Thalassemia major is seen most commonly in individuals of Mediterranean or Asian descent.
What does microcytic mean?
<80 MCV
What does macrocytic mean?
>100 MCV
What laboratory evaluation should be performed for anemia?
A hemoglobin or hematocrit test indicates the severity of the anemia. After anemia has been substantiated, the work-up should include a complete blood count with differential, platelet count, indices, and reticulocyte count. Examination of the peripheral blood smear assesses the morphology of RBCs, white blood cells (WBCs), and platelets. All cell lines should be scrutinized to determine whether anemia is the result of a process limited to the erythroid line or a process that affects other marrow elements. Using data obtained from the indices and reticulocyte count, the work-up can be organized on the basis of whether RBC production is adequate or inadequate and whether the cells are microcytic, normocytic, or macrocytic.
What is thrombotic microangiopathy?
A second form of acquired hemolytic disease is caused by mechanical damage to the RBC membrane during circulation. In thrombotic microangiopathy the RBCs are trapped by fibrin stands in the circulation and physically broken by shear stress as they pass through these strands. Hemolytic uremic syndrome, disseminated intravascular coagulation (DIC), thrombotic thrombocytopenic purpura, malignant hypertension, toxemia, and hyperacute renal graft rejection can produce thrombotic microangiopathy. The platelets are usually large, indicating that they are young, but have a decreased survival even if the numbers are normal. Consumption of clotting factors is more prominent in DIC than in the other forms of thrombotic microangiopathy. The smear shows RBC fragments (schistocytes), microspherocytes, teardrop forms, and polychromasia.
How does acute anemia present clinically?
Acute onset of anemia can result in a poorly compensated state, manifested as an elevated heart rate, a systolic flow murmur, poor exercise tolerance, headache, excessive sleeping (especially in infants) or fatigue, irritability, poor feeding, and syncope. In contrast, chronic anemia often is exceptionally well tolerated in children because of their cardiovascular reserve. Usually, children
What are acute painful events?
Acute painful events are the most common type of vasoocclusive events. Pain usually localizes to the long bones of the arms or legs but may occur in smaller bones of the hands or feet in infancy (dactylitis) or in the abdomen. Painful events usually last 2-7 days. Repeated painful events within the femur may lead to avascular necrosis of the femoral head and chronic hip disease. Treatment of painful events includes administration of fluids, analgesia (usually opioids and nonsteroidal antiinflammatory drugs), and oxygen if the patient is hypoxic. Appropriate use of analgesics is imperative to control pain. Patients with sickle cell disease often require high doses of opioids due to tolerance to provide adequate pain control. The frequency of acute painful events increases with age. In addition, chronic daily pain irrespective of an acute vasoocclusive event is associated with increasing age, occurring in 30% of adults and 23-40% of children. Chronic nervous system sensitization is likely a key driver of the chronic pain seen in patients with sickle cell disease.
How do patients with Fanconi anemia present clinically?
All cell lines; microcephaly, absent thumbs, cafe-au-lait spots, cutaneous hyperpigmentation, short stature; chromosomal breaks, high MCV and hemoglobin F; horseshoe or absent kidney; leukemic transformation; autosomal recessive trait.
What is thalassemia minor?
Alpha thalassemia and beta-thalassemia minor are common causes of microcytosis, either with or without a mild hypochromic, microcytic anemia.
What are the hemolytic anemias?
Alpha-chain hemoglobinopathies Beta-chain hemolgobinopathies Beta-thalassemia major (Cooley anemia) Sickle cell disease
What are alterations in plasma lipids?
Alterations in plasma lipids, especially cholesterol, may lead to damage to the RBC membrane and shorten RBC survival. Lipids in the plasma are in equilibrium with lipids in the RBC membrane. High cholesterol levels increase the membrane cholesterol and the total membrane surface without affecting the volume of the cell. This condition produces spur cells that may be seen in abetalipoproteinenmia and liver diseases. Hemolysis occurs in the spleen, where poor RBC deformability results in erythrocyte destruction. Circulating toxins (e.g. snake venoms and heavy metals) that bind sulfhydryl groups may damage the RBC membrane and induce hemolysis. Vitamin E deficiency can also cause an acquired hemolytic anemia as a result of abnormal sensitivity of membrane lipids to oxidant stress.
What bone marrow findings are indicative of anemia?
An appropriate bone marrow response to anemia includes an elevated absolute reticulocyte number, suggesting increased RBC production. This implies either hemolysis or blood loss. Anemia with a normal reticulocyte number suggests decreased or ineffective production for the degree of anemia. Reticulocytopenia signifies either an acute onset of anemia such that the marrow has not had adequate time to respond; that reticulocytes are being destroyed in the marrow (antibody mediated); or that intrinsic bone marrow disease is present.
What is normocytic anemia?
Anemia is a common component of chronic inflammatory disease. Hepcidin, a protein made in the liver, plays a key role in iron homeostasis. Inflammation causes an increase in the production of hepcidin, interrupting the process of iron release by macrophages and the absorption of iron from the intestines leading to anemia.
How are anemias classified?
Anemias are classified based on the size and hemoglobin content of the cells. Hypochromic, microcytic anemia is caused by an inadequate production of hemoglobin. The most common causes of this type of anemia are iron deficiency and thalassemia. Most normocytic anemias are associated with a systemic illness that impairs adequate marrow synthesis of red blood cells (RBCs). Vitamin B12 and folic acid deficiencies lead to macrocytic anemia. Hemolytic diseases are mediated either by disorders intrinsic or extrinsic to the RBC that increase cell destruction. The most common RBC membrane disorders are hereditary spherocytosis and hereditary elliptocytosis. In both of these disorders, abnormalities of proteins within the cytoskeleton lead to abnormal RBC shape and function. Numerous RBC enzyme deficiencies may lead to hemolysis, but only two are common: glucose-6-phosphate dehydrogenase (G6PD) deficiency and pyruvate kinase deficiency.
What is autoimmune hemolytic anemia?
Autoimmune hemolytic anemia is usually an acute, self-limited Coombs-positive process that develops after an infection (Mycoplasma, Epstein-Barr, or other viral infections) due to the production of autoantibodies that cause red cell destruction. Autoimmune hemolytic anemia may also be the presenting symptom of a chronic autoimmune disease (systemic lupus erythematosus, lymphoproliferative disorders, or immunodeficiency). Drugs may induce a Coombs-positive hemolytic anemia by forming a hapten on the RBC membrane (penicillin) or by forming immune complexes (quinidine) that attach to the RBC membrane. Antibodies then activate complement-induced intravascular hemolysis. The third type of drug-induced immune hemolysis occurs during treatment with alpha-methyldopa and a few other drugs. In this type, prolonged drug exposure alters the RBC membrane, inducing neoantigen formation. Antibodies are produced that bind to the neoantigen; this produces a positive antiglobulin test result far more commonly than it actually induces hemolysis. In each of these conditions, the erythrocyte is an innocent bystander.
What are the normocytic anemias?
Chronic inflammatory disease Infiltration by malignant cells Congenital hypoplastic anemia Transient erythroblastopenia of childhood Aplastic crises
What is congenital hypoplastic anemia?
Congenital hypoplastic anemia (Diamond-Blackfan syndrome), a lifelong disorder, usually presents in the first few months of life or at birth with severe anemia and mild macrocytosis or normocytic anemia. This RBC disorder is due to a deficiency of bone marrow RBC precursors. More than a third of patients have short stature. Many patients (50-66%) respond to corticosteroid treatment but must receive therapy indefinitely. Patients who do not respond to corticosteroid treatment are transfusion dependent and are at risk of the multiple complications of long-term transfusion therapy, especially iron overload. These patients have a higher rate of developing leukemia or other hematological malignancies than the general population.
How is sickle cell disease treated?
Direct therapy of sickle cell disease is evolving. The mainstay of care is supportive measures. The use of chronic RBC transfusions to treat patients who have had a stroke has been very successful. Chronic RBC transfusions have also been used successfully for short time periods to prevent recurrent vasoocclusive events, including pain, acute chest syndrome, and priapism. Hydroxyurea, which increases hemoglobin F, decreases the number and severity of painful events, frequency of acute chest syndrome and need for transfusions in children as early as 1 year of age. Current published clinical care guidelines from the National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI) for patients with sickle cell disease recommend hydroxyurea should be initiated in asymptomatic children with severe sickle cell disease (HbSS or HbSβ0-thalassemia). HSCT using a matched sibling donor has cured many children with sickle cell disease. HSCT using alternative donors for children, without a suitable sibling match, is being studied.
What differential diagnoses should be considered when evaluating a patient for marrow failure/pancytopenia?
Features that suggest bone marrow failure and mandate an examination of bone marrow include a low reticulocyte count, teardrop forms of RBCs (implying marrow replacement, not just failure), presence of abnormal forms of leukocytes or myeloid elements less mature than band forms, small platelets, and an elevated MCV in the face of a low reticulocyte count. Pancytopenia resulting from bone marrow failure is usually a gradual process, starting with one or two cell lines but later involving all three cell lines. Features suggesting increased destruction including reticulocytosis, jaundice, immature erythroid or myeloid elements on the blood smear, large platelets and increased serum bilirubin and lactic dehydrogenase.
Review: What are the megaloblastic (immature cells) anemias?
Folate deficiency B12 deficiency Copper deficiency Drug-induced
What are the enzymopathies?
G6PD deficiency Pyruvate kinase deficiency
How does G6PD deficiency present clinically?
G6PD deficiency has two common presentations. Individuals with the A- variant have normal hemoglobin values when well but develop an acute episode of hemolysis triggered by serious (bacterial) infection or ingestion of an oxidant drug. The RBC morphology during episodes of acute hemolysis is striking, appearing to have "bites" taken out of them (cookie cells). These are areas of absent hemoglobin that are produced by phagocytosis of Heinz bodies by splenic macrophages; as a result, the RBCs appear blistered. Clinically evident jaundice, dark urine resulting from bilirubin pigments, hemoglobinuria when hemolysis is intravascular, and decreased haptoglobin levels are common during hemolytic episodes. Early on, the hemolysis usually exceeds the ability of the bone marrow to compensate, so the reticulocyte count may be low for 3-4 days.
What is the etiology of G6PD deficiency?
G6PD deficiency is an abnormality in the hexose monophosphate shunt pathway of glycolysis that results in the depletion of reduced nicotinamide adenine dinucleotide phosphate (NADPH) and the inability to regenerate reduced glutathione. When a patient with G6PD is exposed to significant oxidant stress, hemoglobin is oxidized, forming precipitates of sulfhemoglobin (Heinz bodies), which are visible on specially stained preparations. The gene for G6PD deficiency is on the X chromosome. The severity of hemolysis depends on the enzyme variant. In many of the G6PD variants the enzymes become unstable with aging of the RBC and cannot be replaced because the cell is anucleated. Older cells are most susceptible to oxidant-induced hemolysis. In other variants the enzyme is kinetically abnormal.
What is beta thalassemia minor?
Genotypic abnormality: Heterozygous beta-0 and beta-+ thalassemia Clinical phenotype: Microcytosis, mild anemia
What is beta thalassemia major (Cooley anemia)?
Genotypic abnormality: Homozygous beta-0 thalassemia. Clinical phenotype: Severe hemolysis, ineffective erythropoiesis, transfusion dependency, hepatosplenomegaly, iron overload.
What is alpha thalassemia?
Genotypic abnormality: aa/-- or a-/a- Clinical phenotype: Mild microcytic anemia
What is the etiology of hereditary elliptocytosis?
Hereditary elliptocytosis is a disorder of spectrin dimer interactions that occurs primarily in individuals of African descent. The transmission of the two variants is usually autosomal. dominant.
What is hereditary pyropoikilocytosis?
Hereditary pyropoikilocytosis (unusual instability of the erythrocytes when they are exposed to heat at 45°C) is the result of a structural abnormality of spectrin.
What are the membrane disorders?
Hereditary spherocytosis Hereditary elliptocytosis
How does hereditary spherocytosis present clinically?
Hereditary spherocytosis varies greatly in clinical severity, ranging from an asymptomatic, well-compensated, mild hemolytic anemia that may be discovered incidentally to a severe hemolytic anemia with growth failure, splenomegaly, and chronic transfusion requirements in infancy necessitating early splenectomy.
What is the etiology of aplastic anemia?
In a child with aplastic anemia, pancytopenia evolves as the hematopoietic elements of the bone marrow disappear and the marrow is replaced by fat. In developed countries, aplastic anemia is most often idiopathic. The disoder may be induced by drugs such as chloramphenicol and felmabate or by toxins such as benzene. Aplastic anemia also may follow infections, particularly hepatitis and infectious mononucleosis. Immunosuppression of hematopoiesis is postulated to be an important mechanism in patients with postinfectious and idiopathic aplastic anemia.
How does iron deficiency anemia present clinically?
In addition to cardiovascular manifestations of anemia, central nervous system (CNS) abnormalities (apathy, irritability, poor concentration) have been linked to iron deficiency, presumably resulting from alternations of iron-containing enzymes (monoamine oxidase) and cytochromes. Poor muscle endurance, gastrointestinal dysfunction, and impaired WBC and T-cell function have been associated with iron deficiency. Iron deficiency in infancy may be associated with later cognitive deficits and poor school performance.
How is iron deficiency anemia treated?
In an otherwise health child, a therapeutic trial of oral iron is the best diagnostic study for iron deficiency as long as the child is re-examined and a response is documented. The response to oral iron includes rapid subjective improvement, especially in neurological function (within 24-48 hours) and reticulocytosis (48-72 hours); increase in hemoglobin levels (4-30 days); and repletion of iron stores (in 1-3 months). The usual therapeutic dose of 4-6 mg/day of elemental iron induces an increase in hemoglobin of 0.25-0.4 g/dL per day (a 1%/day increase in hematocrit). If the hemoglobin level fails to increase within 2 weeks after institution of iron treatment, careful re-evaluation for ongoing blood loss, development of infection, poor compliance, malabsorption, or other causes of microcytic anemia is required.
What is aplastic crisis?
In aplastic crisis, parvovirus B19 infects RBC precursors in the bone marrow and induces transient RBC aplasia with reticulocytopenia and a rapid worsening of anemia because of the very short life span of sickle RBCs. Simple transfusion therapy is indicated for sequestration and aplastic crises when the anemia is symptomatic.
What is transient erythroblastopenia of childhood?
In contrast to the congenital hypoplastic anemias, transient erythroblastopenia of childhood, a normocytic anemia caused by suppression of RBC synthesis, usually appears between 6 months and 5 years of age in an otherwise normal child. Viral infections are thought to be the trigger, although the mechanism leading to RBC aplasia is poorly understood. The onset is gradual, but anemia may become severe. Recovery is usually spontaneous. Transfusion of packed RBCs may be necessary if the anemia becomes symptomatic before recovery.
How does chronic anemia present clinically?
In contrast, chronic anemia often is exceptionally well tolerated in children because of their cardiovascular reserve. Usually, children with chronic anemia will have minimal tachycardia and a systolic flow murmur on examination.
What is the prognosis of hemolytic anemias caused by disorders extrinsic to the red blood cell?
In drug-induced hemolysis, withdrawal of the drug usually leads to resolution of the hemolytic process. More than 80% of children with autoimmune hemolytic anemia recover spontaneously.
What are laboratory findings in iron deficiency anemia?
In iron deficiency anemia, the cells are hypochromic and microcytic. Serum iron: Low Serum iron-binding capacity: High Serum ferritin: Low Marrow iron stores: Low or absent Marrow sideroblasts: Decreased or absent Free erythrocyte protoporphyrin: High Hemoglobin A2 or F: Normal Red blood cell distribution width: High
What laboratory findings would you expect in B12 and folate deficiency?
Increased MCV, Increased LDH, Decreased haptoglobin.
Review: What are the hemolytic anemias?
Intrinsic -Hereditary spherocytosis -G6DP deficiency -Pyruvate kinase deficiency -Sickle cell anemia -HbC disease Extrinsic -Autoimmune hemolytic anemia
Review: What are the non-hemolytic anemias?
Iron deficiency Anemia of chronic disease Chronic kidney disease Aplastic anemia
What are hemolytic anemias caused by disorders extrinsic to the red blood cell?
Isoimmune hemolysis Autoimmune hemolytic anemia Thrombotic microangiopathy Alterations in plasma lipids
What is isoimmune hemolysis?
Isoimmune hemolysis is caused by active maternal immunization against fetal antigens that the mother's erythrocytes do not express. Examples are antibodies to the A, B and Rh D antigens; other Rh antigens; and the Kell, Duffy, and other blood groups. Anti-A and anti-B hemolysis is caused by the placental transfer of naturally occurring maternal antibodies from mothers who lack A or B antigen (usually blood type O). Positive results of the direct antiglobulin (Coombs) test on the infant's RBCs, the indirect antiglobulin test on the mother's serum, and the presence of spherocytes and immature erythroid precursors (erythroblastosis) on the infant's blood smear confirm this diagnosis. Isoimmune hemolytic disease varies in clinical severity. There may be no clinical manifestations or the infant may exhibit jaundice, severe anemia, and hydrops fetalis.
What is lead poisoning?
Lead poisoning may be associated with a hypochromic, microcytic anemia because most patients have concomitant iron deficiency. The history of living in an older home (built before 1980) with chipped paint or lead dust should raise suspicion of lead poisoning, especially in a child with pica. The lead content of water should also be assessed due to the potential for lead containing pipes. Basophilic stippling in the blood smear is common. Lead intoxication rarely causes hemolytic anemia. Detection by routine screening, removal from exposure, chelation therapy, and correction of iron deficiency are crucial to the potential development of affected children.
What laboratory findings would you expect in lead poisoning?
Low MCV, Basophilic stippling, Increased free erythrocyte porphyrins
What laboratory findings would you expect in iron deficiency anemia?
Low ferritin, Low serum Fe, High TIBC
What are the macrocytic anemias?
Marrow failure/pancytopenia Fanconi anemia
What are laboratory findings in anemia of chronic disease?
Normal or ↓ MCV, ↓ TIBC, Normal or ↑ Ferritin (because it is not being transported and utilized) ↓ serum erythropoietin levels in anemia of renal failure. Symptoms and signs of an underlying disorder. CBC and serum iron, ferritin, transferrin, and transferrin receptor.
What is anemia of chronic disease?
Normal or ↓ MCV, ↓ TIBC, ↑ Ferritin (high iron stores) ↓ serum erythropoietin. Diagnostic studies: Normochromic/normocytic anemia initially. Treatment: Erythropoietin and treat the underlying disease.
What is stroke?
Overt stroke occurs in approximately 8-10% of patients with SS disease. These events may present as the sudden onset of an altered state of consciousness, seizures, or focal paralysis. Silent stroke, which is defined as evidence of cerebral infarction on imaging studies but a normal neurological examination, is more common and occurs in approximately 20% of patients with SS disease. A significant change in school performance or behavior has been associated with silent stroke. Children with Hg SS disease older than 3 years should be screened for increased risk of stroke using transcranial Doppler (TCD). Chronic monthly transfusions are indicated in those with overt stroke and abnormal TCDs and should be considered for those with silent strokes.
What is the etiology of marrow failure/pancytopenia?
Pancytopenia is a simultaneous quantitative decrease in formed elements of the blood--erythrocytes, leukocytes, and platelets. Patients more often exhibit symptoms of infection or bleeding than anemia because of the relatively short life span of WBCs and platelets compared with the life span of RBCs. Causes of pancytopenia include failure of production (implying intrinsic bone marrow disease), sequestration (hypersplenism), and increased peripheral destruction.
What is pyruvate kinase deficiency?
Pyruvate kinase deficiency is much less common than G6PD deficiency and represents a clinical spectrum of disorders caused by the functional deficiency of pyruvate kinase. Some individuals have a true deficiency state, and others have abnormal enzyme kinetics. The metabolic consequence of pyruvate kinase deficiency is adenosine triphosphate (ATP) depletion, impairing RBC survival. Pyruvate kinase deficiency is usually an autosomal disorder, and most children who are affected (and are not products of consanguinity) are double heterozygotes for two abnormal enzymes. Hemolysis is not aggravated by oxidant stress due to the profound reticulocytosis in this condition. Aplastic crises are potentially life threatening. The spleen is the site for RBC removal in pyruvate kinase deficiency. Most patients have amelioration of the anemia and a reduction of transfusion requirements after splenectomy.
What is splenic sequestration crisis?
Sickle cell disease is complicated by sudden, occasionally severe and life-threatening events caused by the acute intravascular sickling of the RBCs, with resultant pain or organ dysfunction (i.e., crisis). In two different clinical situations, an acute, potentially life-threatening decline in the hemoglobin level may be superimposed on the chronic compensated anemia. Splenic sequestration crisis is a life-threatening, hyperacute drop in the hemoglobin level (blood volume) secondary to splenic pooling of the patient's RBCs and sickling within the spleen. The spleen is moderately to markedly enlarged, and the reticulocyte count is elevated. Simple transfusion therapy is indicated for sequestration and aplastic crises when the anemia is symptomatic.
How does beta thalassemia major (Cooley anemia) present clinically?
Signs and symptoms of β-thalassemia major result from the combination of chronic hemolytic disease, decreased or absent production of normal hemoglobin A, and ineffective erythropoiesis. The anemia is severe and leads to growth failure and high-output heart failure. Ineffective erythropoiesis causes increased expenditure of energy and expansion of the bone marrow cavities of all bones, leading to osteopenia, pathological fractures, extramedullary erythropoiesis with resultant hepatosplenomegaly, and an increase in the rate of iron absorption.
How are membrane disorders treated?
Splenectomy corrects the anemia and normalizes the RBC survival in patients with hereditary spherocytosis, but the morphological abnormalities persist. Splenectomy should be reserved for any child with severe hereditary spherocytosis and symptoms referable to chronic anemia or growth failure. Splenectomy should be deferred until age 5 years, if possible, to minimize the risk of overwhelming postsplenectomy sepsis and to maximize the antibody response to the polyvalent pneumococcal and meningococcal vaccine. In several reports, partial splenectomy seems to improve the hemolytic anemia and maintain splenic function in host defense.
How is aplastic anemia treated?
Survival rate is approximately 20% in severe aplastic anemia with supportive care alone, although the duration of survival may be years when vigorous blood product and antibiotic support is provided. For children with severe aplastic anemia--defined by an absolute reticulocyte count less than 50,000, absolute neutrophil count less than 500/mm3, platelet count less than 20,000/mm3, and bone marrow cellularity on biopsy specimen less than 25% of normal--the treatment of choice is hematopoietic stem cell transplantation (HSCT) from a sibling with identical human leukocyte antigen (HLA) and compatible mixed lymphocytes. When HSCT occurs before the recipient is sensitized to blood products, survival rate is greater than 80%. The treatment of aplastic anemia is evolving, with two major options: potent immunosuppressive therapy or unrelated or partially matched HSCT.
What is the anemia of sickle cell disease?
The anemia of hemoglobin SS disease is usually a chronic, moderately severe, hemolytic anemia that is not routinely transfusion dependent. The severity depends in part on the patient's phenotype. Manifestations of chronic anemia include jaundice, pallor, variable splenomegaly in infancy, a cardiac flow murmur, and delayed growth and sexual maturation. Decisions about transfusion should be made on the basis of the patient's clinical condition, the hemoglobin level, and the reticulocyte count.
What is the anemia of chronic inflammation?
The anemia of inflammation may be normocytic or, less often, microcytic. This may pose a clinical challenge, when children with inflammatory disorders associated with blood loss (i.e. inflammatory bowel disease) exhibit a microcytic anemia. A trial of iron therapy is not indicated without a specific diagnosis in children who appear to be systemically ill.
What are the best indicators of the severity of hemolysis?
The best indicators of the severity of hemolysis are the hemoglobin level and the elevation of the reticulocyte count. Biochemical evidence of hemolysis includes an increase in levels of bilirubin and lactate dehydrogenase and a decrease in haptoglobin.
What is the etiology of hereditary spherocytosis?
The biochemical basis of hereditary spherocytosis and hereditary elliptocytosis are similar. Both conditions appear to have a defect in the protein lattice (spectrin, ankyrin, protein 4.2, band 3) that underlies the RBC lipid bilayer and provides stability of the membrane shape. In hereditary spherocytosis, pieces of membrane bud off as microvesicles because of abnormal vertical interaction of the cytoskeletal proteins and uncoupling of the lipid bilayer from the cytoskeleton. When the RBC loses membrane, cell shape changes from a biconcave disk to a spherocyte. The RBC is less deformable when passing through narrow passages in the spleen. The transmission of the two variants is usually autosomal dominant, but spontaneous mutations caused heredtiary spherocytosis are common.
What are laboratory findings in alpha thalassemia?
The blood smear reveals only microcytosis with alpha-thalassemia minor. Outside of the neonatal period, when Bart hemoglobin is no longer detectable, the hemoglobin electrophoresis is usually normal in alpha-thalassemia minor.
What are important historical components suggestive of anemia?
The causes of anemia often can be suspected from a careful history adjusted for the patient's age. Anemia at any age demands a search for blood loss. A history of jaundice, pallor, previously affected siblings, drug ingestion by the mother, or excessive blood loss at the time of birth provides important clues to the diagnosis in newborns. A careful dietary history is crucial. A history of jaundice, pallor, and/or splenomegaly are often present with hemolytic anemia. Because of increased bilirubin production, gallstones (bilirubinate) are a common complication of chronic hemolysis. In later childhood and adolescence, the presence of constitutional symptoms, unusual diets, drug ingestion, or blood loss, especially from menstrual bleeding, often points to a diagnosis.
How are membrane disorders diagnosed?
The clinical diagnosis of hereditary spherocytosis should be suspected in patients with even a few spherocytes found on the blood smear because the spleen preferentially removes spherocytes. An incubated osmotic fragility test confirms the presence of spherocytes and increases the likelihood of the diagnosis. The osmotic fragility test result is abnormal in any hemolytic disease in which spherocytes are present (e.g., in antibody-mediated hemolysis). Genetic studies (band 3 gene mutation) can also be done to confirm the diagnosis of hereditary spherocytosis.
What is the etiology of sickle cell disease?
The common sickle cell syndromes are hemoglobin SS disease, hemoglobin S-C disease, hemoglobin S-β0-thalassemia, hemoglobin S-β+-thalassemia, and rare variants. The specific hemoglobin phenotype must be identified because the clinical complications differ in frequency, type, and severity. As a result of a single amino acid substitution (valine for glutamic acid at the β6 position), sickle hemoglobin crystallizes and forms a gel in the deoxygenated state. When reoxygenated, the sickle hemoglobin is normally soluble. The so-called reversible sickle cell is capable of entering the microcirculation. As the oxygen is extracted and saturation declines, sickling may occur, occluding the microvasculature. The surrounding tissue undergoes infarction, inducing pain and dysfunction. This sickling phenomenon is exacerbated by hypoxia, acidosis, fever, hypothermia, and dehydration.
How is G6PD deficiency diagnosed?
The diagnosis of G6PD deficiency is based on decreased NADPH formation. However, G6PD levels during an acute, severe hemolytic episode may be normal because the most deficient cells have been destroyed and reticulocytes are enriched with G6PD. Repeating the test at a later time when the patient is in a steady-state condition, testing the mothers of boys with suspected G6PD deficiency, or performing electrophoresis to identify the precise variant present aids in diagnosis.
What is anemia?
The diagnosis of anemia is determined by comparison of the patient's hemoglobin level with age-specific and sex-specific normal values. The easiest quantitative definition of anemia is any hemoglobin or hematocrit value that is 2 standard deviations below the mean for age and gender. However, in certain pathological states, anemia may be present with a normal hemoglobin level (e.g. cyanotic cardiac or pulmonary disease or abnormally high hemoglobin affinity for oxygen). This is a physiological definition of anemia. Anemia is often a manifestation of another other primary process and may accentuate other organ dysfunction.
How is sickle cell disease diagnosed?
The diagnosis of hemoglobinopathies is made by identifying the precise amount and type of hemoglobin using hemoglobin electrophoresis, isoelectric focusing, or high-performance liquid chromatography. Every member of an at-risk population should have a precise hemoglobin phenotype performed at birth (preferably) or during early infancy. All U.S. states perform newborn screening for sickle cell disease.
What diseases are most commonly associated with anemia of chronic disease?
The most common causes are (a) chronic renal failure and (b) anemia resulting from connective tissue disorders. Seen in many different types of diseases: RA, SLE, HIV, CA, Cirrhosis, Chronic Infections etc. Anemia of Renal Failure: -Erythropoiesis is impaired because of decreases in both erythropoietin (EPO) production and marrow responsiveness to EPO. Presence of renal insufficiency or failure + ↓ serum erythropoietin levels.
How does hereditary elliptocytosis present clinically?
The most common variant of hereditary elliptocytosis is a clinically insignificant morphological abnormality without shortened RBC survival. The less common variant is associated with spherocytes, ovalocytes, and elliptocytes with a moderate, usually compensated, hemolysis.
What is the epidemiology of G6PD deficiency?
The most common variants of G6PD deficiency have been found in areas where malaria is endemic. G6PD deficiency protects against parasitism of the erythrocyte. The most common variant with normal activity is termed type B and is defined by its electrophoretic mobility. The approximate gene frequencies in African Americans are 70% type B, 20% type A, and 10% type A-. Only the A- variant, termed the African variant, is unstable. Ten percent of black males are affected. A group of variants found in Sardinians, Sicilians, Greeks, Sephardic and Oriental Jews, and Arabs is termed the Mediterranean variant and is associated with chronic hemolysis and potentially life-threatening hemolytic disease. Because the gene for G6PD deficiency is carried on the X chromosome, clinical hemolysis is most common in males. Heterozygous females who have randomly inactivated a higher percentage of the normal gene may become symptomatic, as may homozygous females with the A- variant (0.5-1% of females of African descent).
How are hemolytic anemias caused by disorders extrinsic to the red blood cell diagnosed?
The peripheral blood smear in autoimmune hemolytic anemia usually reveals spherocytes and occasionally nucleated RBCs. The reticulocyte count varies because some patients have relatively low reticulocyte counts as a result of autoantibodies that cross react with RBC precursors.
What physical exam findings are consistent with anemia?
The physical examination may point to the potential causes. The physiological stability of the patient may be abnormal with acute blood loss and acute hemolysis, manifesting as tachycardia, blood pressure changes, and, most ominously, an altered state of consciousness. The presence of jaundice suggests hemolysis. Petechiae and purpura indicate a coagulopathy. Hepatosplenomegaly and adenopathy suggest infiltrative disorders. Growth failure or poor weight gain suggests anemia of inflammation (previously termed anemia of chronic disease). An essential element of the physical examination is the investigation of the stool for the presence of occult blood.
What is the epidemiology of iron deficiency anemia?
The prevalence of iron deficiency, the most common cause of anemia in the world, is approximately 9% in toddlers, 9-11% in adolescent females, and less than 1% in adolescent males. Iron deficiency anemia occurs in approximately one third of children who are iron deficient. Children from low socioeconomic status in the US may be at increased risk for iron deficiency because of poor dietary intake. Breast-fed infants are less likely to have iron deficiency than bottle-fed infants because, although there is less iron in breast milk, this iron is more efficiently absorbed. However, infants who continue to be exclusively breast fed in the second half of the first year of life are at risk for iron deficiency.
What are laboratory findings in thalassemia minor?
The thalassemia minor syndromes (i.e., alpha-thalassemia trait, beta-thalassemia trait) are characterized by a mild hypochromic, microcytic anemia with a low absolute reticulocyte count. The RBC count is usually elevated.
How is beta thalassemia major (Cooley anemia) treated?
Treatment of β-thalassemia major is based on a hypertransfusion program that corrects the anemia and suppresses the patient's own ineffective erythropoiesis, limiting the stimulus for increased iron absorption. This suppression permits the bones to heal, decreases metabolic expenditures, increases growth, and limits dietary iron absorption. Splenectomy may reduce the transfusion volume, but it adds to the risk of serious infection. Chelation therapy with deferoxamine or deferasirox should start when laboratory evidence of iron overload (hemochromatosis) is present and before there are clinical signs of iron overload (nonimmune diabetes mellitus, cirrhosis, heart failure, bronzing of the skin, and multiple endocrine abnormalities). HSCT in childhood, before organ dysfunction induced by iron overload, has had a high success rate in β-thalassemia major and is the treatment of choice.
What are vaso-occlusive painful events?
Vasoocclusive painful events may occur in any organ of the body and manifest as pain and/or significant dysfunction. The acute chest syndrome is a vasoocclusive crisis within the lungs with evidence of a new infiltrate on chest radiograph. It is often associated with infection and infarction. The patient may first complain of chest pain but within a few hours develops cough, increasing respiratory and heart rates, hypoxia, and progressive respiratory distress. Physical examination reveals areas of decreased breath sounds and dullness on chest percussion. Treatment involves early recognition and prevention of arterial hypoxemia. Oxygen, fluids, judicious use of analgesic medications, antibiotics, bronchodilators, and RBC transfusion (rarely exchange transfusion) are indicated as therapy for acute chest syndrome. Incentive spirometry may help reduce the incidence of acute chest crisis in patients presenting with pain in the chest or abdomen.
