Flash Player 9 (or above) is needed to view presentations.
We have detected that you do not have it on your computer. To install it, go here.

Like this presentation? Why not share!

Slide 1 - US Army Medical Department Center






Total Views
Views on SlideShare
Embed Views



0 Embeds 0

No embeds



Upload Details

Uploaded via as Microsoft PowerPoint

Usage Rights

© All Rights Reserved

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.


12 of 2

  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
  • really help for haematology material
    Are you sure you want to
    Your message goes here
  • nice, adequate information
    Are you sure you want to
    Your message goes here
Post Comment
Edit your comment
  • The following presentation is entitled Anemias. Your presenter for this lesson is Michael McGrath, an independent Physician Assistant consultant.
  • The learning objectives for this lesson are :Define anemias; and Describe the etiology, pathology, clinical features, diagnostic studies, and management of iron deficiency anemia, A- and B- Thalassemias, sickle cell anemia, aplastic anemia, and megaloblastic anemia.
  • Additional learning objectives for this lesson are: Identify the causes, diagnosis, and treatment of Vitamin B12 deficiency and total body folate deficiency; and, Describe the causes, clinical features, diagnosis and treatment of Glucose 6 Phosphate Dehydrogenase (G6PD) deficiency.
  • Human beings require extensive numbers of differentiated blood cells each day. The mature blood cells are derived from the undifferentiated stem and progenitor cells in a complex series of maturational and divisional steps not yet completely understood. The intricacies of this system are enormous requiring 1.5 times 10 to the 9 th power erythrocytes and 1.5 times 10 to the 9 th power white blood cells to be produced each hour of the day during the life of the individual.
  • The process in which the pluripotent hematopoietic stem cell differentiates into the many highly specialized circulating blood cells is called hematopoiesis or hemopoiesis. Hemopoiesis is defined as the orderly continuous process by which primitive hemopoietic progenitor cells give rise to the mature circulating blood cells involved in oxygen transport, host defense, and hemostasis.
  • Hemopoiesis is hierarchical. Pluripotent hemopoietic stem cells give rise to multi-potent progenitors that eventually become committed to a specific lineage that is, lymphoid, erythroid, myeloid or megakaryocytic. With malignant transformation the affected progenitor cells arise from a single affected cell. An explanation of the basis for the acute leukemias and the chronic myeloproliferative disorders will be found through research on the pluripotent hematopoietic stem cell.
  • Anemia represents a reduction in the body’s red cell mass and the reduction in hemoglobin concentration under normal circumstances. The quantity of red blood cells is maintained within appropriate parameters through the regulatory feedback stimulus of the humoral factor erythropoietin. This feedback loop ensures that the hemoglobin mass for oxygen delivery matches the body’s needs and that production equals destruction of red blood cells under stable conditions. The red cell survival time in the peripheral circulation is 90-120 days. Each day approximately 1% of the body’s red blood cells need to be replaced. When the homeostasis of red blood cell production and destruction is upset, anemia may occur. This pathologic process can have multiple etiologies.
  • Anemia can be caused by a primary derangement in the marrow or accelerated loss of red blood cells in the periphery. Systemic pathology may disturb erythropoiesis or cause accelerated loss or destruction in the peripheral blood. Anemia is a sign of underlying pathology and the etiology must be determined.
  • Anemia is defined as hematocrit or hemoglobin below the lower limit of normal. For men the lower limit is a hematocrit of less than 41% or hemoglobin less than 13.5g/dL. For women the limit is a hematocrit less than 36% or hemoglobin less than12g/dL.
  • In the general evaluation of the patient with suspected anemia, pay attention to clinical manifestations, what is found on the physical exam, what family history reveals, and lab studies. We’ll look at these in detail.
  • Clinical manifestations may include fatigue, dyspnea, lightheadedness, decreased exercise tolerance, headache, or angina.
  • The physical exam may reveal pallor, glossitis, jaundice, splenomegaly, neurological abnormalities, bone tenderness, or hemoccult positive feces.
  • To complete the evaluation, obtain a detailed family history of anemia. Then complete lab studies. Determine the reticulocyte production index (RPI). The reticulocyte count should increase in anemia in order to maintain the hemoglobin level. The reticulocyte is an early blood cell, 1-2 days old, that is set loose from the bone marrow. The absence of an increase in the reticulocyte count shows the marrow is unable to compensate for the anemia.
  • The lab reports the reticulocytes as a percentage of the circulating RBCs. The reticulocyte production index (RPI) can be calculated from hematologic data. The calculation converts the reticulocyte count, expressed as a percentage, to an index reflecting the production rate, expressed as a multiple of normal. The correction factor is a predetermined laboratory reference used to calculate RPI. Betty: CPT Archer asked for more info on the correction factor on slides 14 and 15. Suzanne responded and I reorganized the screen calculations but it still does not look great. All the info. Suzanne provided was added to narration on this slide. I think this will suffice and we do not need to add to slide 15 narration.
  • This slide shows the patient hematocrit along with the correction factor.
  • A Reticulocyte Production Index (RPI) of less than 2.0 indicates inadequate bone marrow response or hypo-proliferation. An RPI of greater than 3.0 represents appropriate bone marrow response.
  • Reviewing other parameters of the complete blood count (CBC) may also be valuable in the anemia workup. Abnormalities in the white blood cell (WBC) and/or platelet counts may lead you to suspect a chronic disease process such as a malignancy or a primary bone marrow dysfunction. . The Mean Corpuscular Volume (MCV) needs to be evaluated. The MCV is a measure of the average red blood cell size or volume. After the MCV has been determined, and if there are any abnormalities, then you maybe able to determine if a microcytosis or macrocytosis is present. From this you may then explore various etiologies of anemia. Red Cell Distribution Width (RDW) is checked since red blood cells are usually about equal in size with little variation. Any wide variability in the RDW is known as anisocytosis. The increased RDW may indicate an impending abnormality in hemoglobin or MCV. Anemia may be classified on the basis of RBC size and distribution width.
  • In any suspicion of anemia, the peripheral blood smear should be inspected. The abnormalities need to be described and defined. Hemoccult tests should be done 3 times and, if positive, a colonoscopy and endoscopy should be arranged
  • Total body iron equals approximately 3800mg in adult males and 2500mg in adult females. Iron is present in hemoglobin, a small amount in myoglobin and iron-containing enzymes, and the remainder in a storage form. In normal circumstances, stored iron amounts to 1000mg for men and 300mg for women. 16mg of iron is present in the hemoglobin of developing erythrocytes daily.
  • The following explains the pathway of iron in the body: 1. Iron is placed in developing red blood cells in the bone marrow. The young blood cells are released into the blood stream and circulate for 120 days; 2. Old erythrocytes are removed from circulation by macrophages of the spleen and bone marrow. Iron is liberated from the hemoglobin (Hb) and stored as ferritin and hemosiderin or released to transferrin, the plasma iron transporting protein; and, 3. Iron bound to transferrin is carried in the plasma to the bone marrow for uptake by the erythroid precusors.
  • Iron is absorbed maximally in the duodenum and jejunum. Under normal circumstances, small losses of less than 1.0mg/day occur in males mainly through desquamation of epithelial cells. Losses are higher in females of childbearing years secondary to menstrual blood loss, averaging approximately 1.5mg/day. Normally the amount of iron absorbed from the diet equals the obligatory loss, and an increase in the amount of dietary loss is associated with a decrease in the proportion eventually absorbed. Sources of iron are heme iron, contained in meat, fish and liver, which is more readily absorbed and non-heme iron which is contained in vegetables and legumes.
  • Iron is absorbed maximally in the duodenum and jejunum. Under normal circumstances, small losses of less than 1.0mg/day occur in males mainly through desquamation of epithelial cells. Losses are higher in females of childbearing years secondary to menstrual blood loss, averaging approximately 1.5mg/day. Normally the amount of iron absorbed from the diet equals the obligatory loss, and an increase in the amount of dietary loss is associated with a decrease in the proportion eventually absorbed. Sources of iron are heme iron, contained in meat, fish and liver, which is more readily absorbed and non-heme iron which is contained in vegetables and legumes. Vitamin C and amino acids promote the absorption of non-hem e iron. Tea and vegetable fiber increase uptake of non-heme iron. Presence of gastric acid helps to keep non-hem e iron in the soluble, ferrous form that is taken up better.
  • Iron deficiency is the most common nutritional deficiency world wide. In the United States, the prevalence is high in women of childbearing age, in infants, and adolescents whose rapid growth require increased iron supply to support an increase in red cell mass. Iron deficiency in men or in non-menstruating women is the result of blood loss, often from the G.I. tract.
  • Lack of body iron is divided into two categories: Iron deficiency without anemia; the storage iron is absent but the deficit in iron is not large enough to decrease the hemoglobin level to below normal; and, Iron deficiency anemia; the deficit is so severe that stores are absent and the hemoglobin is frankly below the normal range.
  • Causes of iron deficiency include Inadequate dietary iron for high physiologic requirement or blood loss. Blood loss almost always signifies pathological blood loss of some sort. Some examples are G.I. bleeding due to ulcerations, tumors, diverticulas, polyps and vascular malformations, hookworm infestations, and frequent blood donations. Approximately 50% of renal dialysis patients develop iron deficiency.
  • The slide indicates the clinical features of iron deficiency anemia.
  • In summary, laboratory findings will determine if the degree of anemia is mild to severe, mean corpuscular volume is decreased, red cell distribution width is decreased.
  • Laboratory findings will also determine if white blood cells are normal, platelets are normal to increased, and if serum ferritin is low. The serum ferritin is a very helpful measure of total body iron stores and a low level of 12microg/L is diagnostic of iron deficiency. Usually the transferrin saturation is less than 15% (normal 20%-50%) in iron deficiency anemia. The iron studies would usually indicate low serum iron, increased total iron binding capacity, low transferrin saturation and low serum ferritin. Early in the course of iron deficiency anemia, the red cells may be normochromic and normocytic, but as the condition progresses, you will see a microcytic, hypochromic anemia.
  • To manage iron deficiency, identify the cause and correct if possible. With oral iron therapy, the adult dose is 200mg of elemental iron per day. The pediatric dose is 5mg/kg of elemental iron per day in tablet or elixir form.
  • Oral iron therapy usually corrects anemia within 4-6 weeks, but should continue for an additional 3-6 months to replenish iron stores as indicated by a return of the serum ferritin concentration to a normal range of 50-100mg/L.
  • In management of iron deficiency in patients who fail oral therapy, parenteral iron may be considered. Two forms of parenteral iron are presently available: Iron dextran (INFeD) and iron sucrose preparations such as sodium ferric gluconate complex or FERRLECIT and ferric hydroxide complex or VENOFER. Severe reactions are less with the iron sucrose than with the iron dextran preparations.
  • Now let’s consider inherited disorders that result in anemias. Thalassemias are inherited disorders which result from a decreased rate of synthesis of alpha or beta globin chains of the hemoglobin molecule. The cause of the thalassemia and its diagnosis is based on the fact that each chromosome 16 normally has two identical copies of the alpha-globin gene while only a single copy of the beta-globin gene exists on chromosome 11. Most alpha thalassemias are due to deletions of one or both of the alpha-loci while Beta-thalassemias are generally due to point mutations. Thalassemias occur predominately in persons of Mediterranean descent and the hallmark of the disease is insufficient alpha or beta chain production. It should be noted that Alpha-globin is determined by four genes and beta-globin by only two genes. Clinically, the thalassemias are divided into hydrops fetalis, B-Thalassemia major which is transfusion dependent, thalessemia intermedia characteristically by moderate anemia with splenomegaly and iron overload, and thalassemia minor occurring in a symptom-less carrier.
  • In Alpha-Thalassemia the production of a-globin is decreased due to a gene deletion or inactivation. If the presence of a normal a-locus is designated by “a” and the absence of that locus is designated by ” –”, then five combinations exist. The combinations and their clinical consequences are shown on this slide and the two following screens.
  • With the A-Thalassemia trait, the genotype a-/a- is present in 7% of Africans. The genotype a-/a– is also common in S.E. Asia. The MCV is lower than 78dL and there is slight anemia. The hemoblobin (Hb) Barts shows in 2-10% of newborns.
  • Diagnosis of exclusion includes iron deficiency, B-Thalassemia, or hereditary sideroblastic. Do not confuse with iron deficiency and do not treat with iron.
  • With Hemoglobin H disease, Hemoglobin H (B4) stains with cresyl blue and is visualized by Hb electrophoresis. The genotype is a-/-- and it occurs in S.E. Asia. 20-40% Hb Barts is found in newborns and 5-40% Hb H is found in adults.
  • Variable hemolytic anemia (microcytic) and splenomegaly are found. There is ineffective erythropoiesis and iron-loading.
  • Now let’s look at B-Thalassemia which results from a basic molecular defect or absent or reduced production of b-globin chains. It represents a broad spectrum of abnormalities ranging from mild to moderate anemia to Thalassemia major, a devastating disease in which no functional b-chains are formed. B-Thalassemia major is known as Mediterranean or Cooley’s Anemia. Before the advances in therapy of regular transfusions and iron chelation, B-Thalassemia was usually fatal.
  • The pathophysiology of B-Thalassemia major shows increased, but ineffective erythropoiesis. There is erythroid marrow expansion with bony deformities, progressive splenomegaly, extra-medullary hematopoiesis, and increased iron absorption and progressive iron deposition in tissues.
  • Clinical features include skeletal changes such as osteopenia, expanded marrow cavity, thin cortex, thalassemic facies in which the skull shows prominent frontal and parietal bones with enlarged maxilla; extra-medullary hematopoiesis; growth retardation; delayed sexual maturation; myocardial iron overload which can result in heart failure or arrhythmias.
  • Additional clinical features include hepatic iron loading which can result in fibrosis or cirrhosis; pigmented gall stones, and severe microcytic anemia and splenomegaly.
  • Prognosis shows that with no drugs, death occurs by age 5 from infections or cachexia which is general ill health and malnutrition. Episodic blood transfusions have produced survival until the second decade. Aggressive blood transfusions show death at approximately age 20 from iron overload which causes cardiac involvement. Aggressive blood transfusions plus iron chelation shows prolonged survival.
  • Management includes hypertransfusion at the beginning of the child’s second or third year to maintain Hb at approximately 10g/dL, splenectomy for increasing blood transfusion dependency, iron chelation with Desferrioxamine starting after age 3. Also consider bone marrow transplantation and increase the synthesis of fetal hemoglobin.
  • With B-Thalassemia minor there are no clinical symptoms. Labs show mild to absent microcytic anemia. The peripheral blood smear shows microcytosis, hypochromia, targeting, and/or basophylic stippling. Hemoglobin electrophoresis and quantitation shows HbA greater than 90%, HbA2 at 3.5-8.0%, and HbF is normal to slightly increased.
  • Let’s consider another heritable disorder. Hemoglobin S, the sickle hemoglobin, is the most common heritable hematologic disease affecting humans world wide. The highest prevalence of HbS is in tropical Africa and among the blacks in countries that participated in the slave trade. Studies of DNA polymorphisms suggest that the Beta sickling gene arose from three independent mutations in tropical Africa – Benin, Nigeria, and central West Africa and these account for one common chromosome. A second haplotype is found in Senegal and African west coast and a third is seen in the Central African Republic. A fourth type is associated with a different DNA structure found in Saudi Arabia and in central India and not associated with the African haplotypes. In the United States, Latin America and the Caribbean, approximately 8% of the blacks carry the sickling gene. There are multiple genotypes and phenotypes of the sickling hemoglobin in sickle cell disease. Note that sickle cell trait (HbAs) is not a disease.
  • Usually persons affected with sickle cell disease are without symptoms until the second half of the first year of life. This is due to the expression of HbSS being limited during fetal and early postnatal life by a sufficient quantity of HbF to limit any sickling. There is no single pattern of symptoms, but the symptoms may include pain and swelling in hands and feet, fatigue, paleness, shortness of breath, eye problems, yellowing of skin or eyes, and delayed growth.
  • But let’s look first at lab values for a person with sickle cell trait. Remember that sickle cell trait is not a disease. Individuals with sickle cell trait show minimal lab abnormalities. There may be normal mean corpuscular volume (MCV) and mean corpuscular hemaglobin (MCH), normal blood smear, and normal reticulocyte count. HbA is at 60% and HbS at 40%. There are normal levels of HbA2 and HbF.
  • Sickle cell anemia laboratory features usually show a moderate to severe normocytic normochromic anemia showing by 3 months of age and persisting through life. The average hemoglobin ranges from 6.0 – 10.0g/dl. In adults with HbSS, the mean MCV is 90. Blood smears show a variable number of sickled forms, target cells, cigar-shaped cells, and ovalocytes. Features of accelerated erythropoiesis may include polychromatophilia, basophilic stippling, and normoblastosis. Howell-Jolly bodies reflect functional asplenia. The white blood cell count is consistently elevated due to an increase in the number of mature granulocytes. Platelets are generally increased reflecting reduced or absent splenic sequestration.
  • The diagnosis of sickle cell anemia rests on the electrophoretic chromatographic studies of the separation of the hemoglobin from prepared peripheral blood. In sickle cell anemia, the predominant hemoglobin is S, HbF is present, and HbA2 concentration is normal.
  • Management of sickle cell anemia includes folic acid at 1mg by mouth once each day because of chronic hemolysis. Hydroyurea at 15-35mg/kg by mouth has been shown to increase levels of HbF and decrease incidence of varo-occlusive pain episodes. RBC transfusions may be necessary in severe anemia, prevention of new or recurrent cerebrovascular accident (CVA) or acute chest syndrome, preoperatively. Stem cell transplant has been used in children under age 16 and is now being extended to some adults to attempt to normalize hemoglobin synthesis.
  • Now let’s look at some another anemia. Aplastic anemia usually presents with bleeding, especially in skin and mucous membranes. Fatigue, fever or infection is often noted. Mortality is mainly secondary to infection, especially a fungus infection such as aspergillosis. There is a pancytopenia due to severely hypoplastic or aplastic bone marrow.
  • Etiologies of aplastic anemia include idiopathic in 50% of the cases; chemicals, for example those in the benzene family and insecticides; chemotherapy with alkylating agents, antimetabolites, or anthrocyclines; ionizing radiation; and, viral infections in approximately 10% of the cases as seen with seronegative hepatitis, EBV, CMV, HIV, or Parvovirus. Leukemia is the underlying disease in 1-5% of presenting patients. 15% of aplastic anemia patients develop myelodysplasia and leukemia. Other etiologies include medications such as Chloramphenicol and sulfa drugs and auto-immune disorders such as systemic lupus erythematosis.
  • For aplastic anemia, the definitive diagnosis is based on the bone marrow biopsy findings. Epidemiology shows that approximately 2 persons per million are affected. Aplastic anemia is more prevalent in the Orient. In Bangkok four persons per million are found and also a higher rate in rural Thailand. China shows similar figures. It is a disease of the young, with peak incidence in the late adolescence and early adulthood.
  • Hematopoesis is markedly reduced in all cases. Stem cells are not entirely absent based on the fact that there may be recovery of hematopoiesis in a high number of patients with non-replacement therapy. Autoimmunity is showing as a major pathogenic mechanism. It appears to involve cytotoxic lymphocytes; interferon and tumor necrosis factor affect cells inducing marked destruction and apoptosis or premature cell death resulting in subsequent deficiency if primitive blood cells. Therapy is supportive therapy with blood product transfusions and antibiotics. The definitive treatment is either bone marrow transplantation or immunosuppression. Comparative studies indicate no difference in long-term survival between transplantation and immunosuppression. In severe disease, the immunosuppressive regimen of antithymocyte globulin (ATG) plus cyclosporine show an initial response rate of about 65%.
  • Megaloblastic anemia is an important cause of macrocytic anemia. The cause is impaired DNA (deoxyribonucleic acid) synthesis. Cell division is impaired which causes the cells to become enlarged. Megaloblastic and macrocytic are not interchangeable terms, since not all megaloblastic anemias are macrocytic. The most common causes of megaloblastic anemia are Vitamin B12 and folic acid deficiency. In the anemias of cobalamin (B12), and folate deficiency, the bone marrow reveals cells of the myeloid series to be exceptionally large. The polymorphonuclear leukocytes (PMNs) in peripheral blood are larger than normal and usually have an increased number of nuclear lobes. The morphologic changes in the bone marrow and peripheral blood resulting from lack of cobalamin (B12) and/or folate are identical, but only cobalamin deficiency gives rise to neurologic problems. Folate and Vitamin B12 are both critical for a specific enzymatic step in the synthesis of DNA. Retarded replication of DNA is responsible for the megaloblastic anemia that occurs with deficiency of either of these vitamins.
  • Now let’s look at Vitamin B12 deficiency. Total body Vitamin B12 is 1-10mg, over one-half of which is stored in the liver. Daily dietary requirement is about 2 micrograms and normal stores represent a three to four year supply for the body requirement. This is why temporary dietary loss does not result in deficiency. Vitamin B12 is absorbed in the terminal ileum. Intrinsic factor which is produced by the parietal cells of the stomach is necessary for Vitamin B12 absorption.
  • Causes of B12 deficiency include pernicious anemia and lack of intrinsic factor; gastrectomy; pancreatic insufficiency; G.I. bacterial overgrowth (small bowel formations); Vitamin B12 malabsorption due to ileal resection, disease affecting the terminal ileum such as inflammatory bowel disease, tropical sprue, amoebiasis, or tuberculosis or fish tape worm (Diphyllobothrium layum); or, exposure to nitrous oxide which can chemically interact with the vitamin. Neurological findings may gradually develop and may appear early or late in the disease. Findings include loss of position and vibratory sense, ataxia, motor defects and dementia.
  • To diagnose, measure serum cobalamin (Vitamin B12) levels. If the measurement is borderline, then an elevated serum or urine methylmalonic acid provides evidence of deficiency. The LDH-1 isoenzyme which is of erythrocyte origin frequently is greater than LDH-2. Elevated indirect bilirubin, serum iron, and reduced haptoglobin reflect the ineffective erythropoiesis in the bone marrow and is characteristic of this form of anemia.
  • The cause of the deficiency can be determined from a clinical history and a Schilling test. In the Schilling Test a test dose of B12 is administered. Intestinal absorption is measured with and without exogenous intrinsic factor. In pernicious anemia and severe ileal disease, the test dose of B12 is not absorbed. Adding intrinsic factor corrects malabsorption in pernicious anemia but not ileal disease.
  • For treatment, megaloblastic anemia in pernicious anemia responds well to intramuscular injections of Vitamin B12. A reticulocytosis begins after 72 hours, serum uric acid rises, and hypokalemia may develop as the new blood cells incorporate potassium. Severe hypokalemia and cardiac arrhythmias can occur. Monitor the serum potassium carefully and replace as necessary.
  • For treatment, megaloblastic anemia in pernicious anemia responds well to intramuscular injections of Vitamin B12. A reticulocytosis begins after 72 hours, serum uric acid rises, and hypokalemia may develop as the new blood cells incorporate potassium. Severe hypokalemia and cardiac arrhythmias can occur. Monitor the serum potassium carefully and replace as necessary. The suggested B12 I.M. injection schedule is 1000mg each day intramuscularly or subcutaneously for 1-2 weeks to replace stores. Then 1000mg I.M. every month for life. For maintenance you may also consider large oral or sublingual doses at 1000mg/day.
  • Total body folate deficiency can cause megaloblastic anemia. The total body folate in the adult is 5-10mg with approximately half stored in the liver. Usually folate deficiency accompanies Vitamin B12 deficiency. Treatment with Folic acid therapy should involve a daily oral dose of 0.5-1.0mg. Doses of greater than 1.0mg/day can correct the megaloblastic anemia of Vitamin B12 deficiency without preventing, or improving the neurological manifestations. Therefore, B12 would also need to be administered.
  • G6PD deficiency comes under the broad category of hemoltyic anemia. Hemolysis, the hallmark of hemolytic anemia, is defined as the premature destruction of RBCs. There are 2 causes: abnormal factors in the intravascular environment: acquired and intrinsic RBC defects which are genetically determined.
  • G6PD deficiency is a hereditary hemolytic disorder which involves an RBC enzyme defect. The inheritance is sex linked, affecting males, and carried by females who show approximately half normal red cell G6PD values. Hemoglobin and RBC membranes are usually protected from oxidative stress but with G6PD deficiency this protection is decreased.
  • A clinical feature is rapidly developing intravascular hemolysis. Agents which may cause hemolytic anemia in G6PD deficiency include: infections and other acute illnesses, for example, diabetic ketoacidosis; drugs such as antimalarials for example, Primaquine, Pamaquine, Chloroquine, Fasidar, or Maloprim; Sulfonomides and sulphones; other antibacterial agents for example, Nitrofurantoins or Chloramphenicol; analgesics for example, aspirin but moderate doses are safe; anti-helminths; miscellaneous for example, vitamins, K analoques, naphthalene in mothballs, and Probenecid; and, Fava beans.
  • With G6PD deficiency, diagnosis shows that between crises, the blood count is normal. During crisis, the peripheral smear may show contracted and fragmented cells, “bite” cells and “blister” cells which have bad Heinz bodies removed by the spleen. The Heinz bodies may be seen in the reticulocytes. Do an RBC assay using fluorescence and check G6PD level. CBC may show normocytic, normochromic, or mildly increaased MCV. There may also be an elevated reticulocyte count. Chemistry may show increased LDH and indirect bilirubin during crisis.
  • To treat, the offending drug must be stopped, maintain high urine output, and give blood transfusion for severe anemia. Corticosteroids may be useful during the crisis early on.
  • The lesson covered the definition of anemias and the etiology, pathology, clinical features, diagnostic studies, and management of iron deficiency anemia, A- and B-Thalassemias, sickle cell anemia, aplastic anemia, and megaloblastic anemia.
  • This lesson also covered the causes, diagnosis, and treatment of Vitamin B12 deficiency and total body folate deficiency and the causes, clinical features, diagnosis and treatment of Glucose 6 Phosphate Dehydrogenase (G6PD) deficiency.

Slide 1 - US Army Medical Department Center Slide 1 - US Army Medical Department Center Presentation Transcript

  • Anemias
  • Learning Objectives
    • Define anemias.
    • Describe the etiology, pathology, clinical features, diagnostic studies, and management of iron deficiency anemia, A- and B-Thalassemias, sickle cell anemia, aplastic anemia, and megaloblastic anemia.
  • Learning Objectives
    • Identify the causes, diagnosis, and treatment of Vitamin B12 deficiency and total body folate deficiency.
    • Describe the causes, clinical features, diagnosis and treatment of Glucose 6 Phosphate Dehydrogenase (G6PD) deficiency.
  • Anemias
    • Requirements each hour each day
      • 1.5 X 10 9 RBCs
      • 1.5 X 10 9 WBCs
  • Anemias
    • Process
      • Pluripotent hematopoietic stem cell differentiates into specialized blood cells (hematopoiesis or hemopoiesis)
  • Anemias Pluripotent Hematopoietic Stem cell Lymphocytic Progenitor Cells
    • T. Lymphocytes
    • B. Lymphocytes
    Hematopoietic Stem Cells Granuloctic Progenitor Cells Erythroid Progenitor Cells Megakaryocytic Progenitor Cells
  • Anemias
    • Anemia
      • Reduction in red cell mass
      • Reduction in the hemoglobin concentration
      • Homeostasis upset
  • Anemias
    • Possible etiologies
      • Primary derangement of the marrow
      • Accelerated loss of red blood cells peripherally
      • Systemic pathology
    • Sign of underlying pathology
  • Anemias
    • Definition: Hematocrit or Hemoglobin < lower limit of normal
      • Men: Hematocrit <41% or Hemoglobin <13.5g/dL
      • Women: Hematocrit <36% or Hemoglobin <12g/dL
  • Anemias - Evaluation
      • Clinical manifestations
      • Physical exam
      • Family history
      • Lab studies
  • Anemias - Evaluation
      • Clinical manifestations
        • Fatigue
        • Dyspnea
        • Lightheadedness
        • Decreased exercise tolerance
        • Headache
        • Angina
  • Anemias - Evaluation
        • Physical exam
        • Pallor
        • Glossitis
        • Jaundice
        • Splenomegaly
        • Neurological abnormalities
        • Bone tenderness
        • Hemoccult positive feces
  • Anemias - Evaluation
      • Family history: Get details
      • Lab studies
        • Reticulocyte Production Index (RPI)
          • Reticulocyte is early blood cell, 1-2 days old, released from bone marrow
  • Anemias: Lab Studies
    • Reticulocyte = Retic% X ( Pt Hematocrit) % corrected reported 45
    • then
    • Reticulocyte = Retic% corrected Production Correction Factor
    • Index (RPI)
  • Anemias: Lab Studies
    • Patient Hct % Correction factor
    • 40-45% 1.0
    • 35-39% 1.5
    • 25-34% 2.0
    • 15-25% 2.5
    • <15% 3.0
  • Anemias: Lab Studies
    • RPI = < 2.0 Inadequate bone marrow response (hypo-proliferation)
    • RPI = > 3.0 Appropriate bone marrow response
  • Anemias: Lab Studies
    • Other CBC parameters
      • WBC, platelets counts
      • Mean Corpuscular Volume (MCV): measure of av. RBC size or volume
      • Red Cell Distribution Width (RDW): RBC size generally not variable
  • Anemias: Lab Studies
    • Peripheral Blood Smear
      • Inspect, describe, define any abnormalities
    • Hemoccult
      • Do 3 times
      • If +, order colonoscopy / endoscopy
  • Iron Deficiency Anemia
    • Total body iron
      • Adult males – 3800mg
      • Adult females – 2500mg
  • Iron Deficiency Anemia
    • Iron pathway in the body
      • Iron in developing red blood cells
      • Old erythrocytes removed from circulation, iron freed from Hb, stored as ferritin/hemosiderin or released to transferrin
      • Iron bound to transferrin (plasma iron transporting protein) carried to bone marrow for uptake
  • Iron Deficiency Anemia
    • Iron absorption
      • Duodenum, jejunum
    • Sources of iron
      • Heme iron: Meat, fish, liver
      • Non-heme iron: Vegetables, legumes
  • Iron Deficiency Anemia
        • Vit C, amino acids promote absorption
        • Tea, veg. fiber increase uptake
        • Gastric acid helps in solubility
  • Iron Deficiency Anemia
    • Prevalence
      • Common nutritional deficiency worldwide
      • In U.S. found in women of childbearing age, infants, adolescents
      • In men, non-menstruating women
        • Blood loss
  • Iron Deficiency Anemia
    • Categories
      • Iron deficiency without anemia
      • Iron deficiency anemia
  • Iron Deficiency Anemia - Causes
      • Inadequate dietary iron
      • Blood loss
        • Generally signifies pathological loss such as G.I. bleeding, vascular malformations, hookworm infestations, frequent blood donations
      • ~ 50% on renal dialysis show deficiency
  • Iron Deficiency Anemia
    • Clinical features
      • Fatigue
      • Irritability
      • Headaches
      • Paresthesias
      • Pallor
      • Glossitis (a smooth red tongue)
      • Angular cheilitis
      • Koilonychia (spooning of the nails)
      • Pica (eating ice, clay, dirt)
  • Iron Deficiency Anemia
    • Laboratory findings determine if:
      • Degree of anemia is mild to severe
      • Mean corpuscular volume is decreased
      • Red cell distribution width is decreased
  • Iron Deficiency Anemia
    • Laboratory findings determine if:
      • White blood cells are normal
      • Platelets are normal to increased
      • Serum ferritin is low (12microg/L)
  • Iron Deficiency Anemia
    • Management
      • Identify cause, correct if possible
      • Oral iron therapy
        • Adult dose 200 mg/day elemental iron
        • Pediatric dose 5mg/kg/day elemental
  • Iron Deficiency Anemia
    • Management
      • Duration: Anemia usually corrected in 4-6 wks, continue for 3-6 mo, check serum ferritin concentration
  • Iron Deficiency Anemia
    • Management (cont’)
        • Iron dextran (INFeD ® )
        • Iron sucrose (FERRLECIT ® , VENOFER ®
          • Has less severe reaction than with iron dextran
  • Thalassemia
    • Inherited disorders
      • <synthesis of a- or b- globin chains of Hb molecule
      • Occurs often in those of Mediterranean descent
      • Hallmark is insufficient a- or b- chain production
  • A-Thalassemia mild hypochromic in newborns Hb Barts (10%) A-Thalassemia trait aa/-- or a-/a- normal silent carrier aa/a- normal normal aa/aa Heme Findings Phenotype Genotype
  • A-Thalassemia in adults, Hb4 (5-40%) in newborns Hb Barts 20-40% hemolytic disease + ineffective erythropoiesis Hb H disease a-/-- Heme Findings Phenotype Genotype
  • A-Thalassemia stillborn, anemic macerated fetus. Cord blood nearly 100% Hb Barts Hydrops fetalis --/-- Heme Findings Phenotype Genotype
  • A-Thalassemia
    • Prevalence of trait / symptoms
      • a-/a- 7% Africans
      • a-/a- common in S.E. Asia
      • MCV <78dL; slight anemia
      • Hb Barts 2-10% in newborns
  • A-Thalassemia
    • Prevalence of trait / symptoms (cont’)
      • Diagnosis of exclusion (iron deficiency, B-Thalassemia, hereditary sideroblastic)
      • Do not confuse with iron deficiency
      • Do not treat with iron
  • A-Thalassemia
    • Hemoglobin H disease
      • Hb H stains with cresyl blue
      • a-/a-, S.E. Asia
      • 20-40% Hb Barts in newborns; 5-40% Hb H in adults
  • A-Thalassemia
    • Hemoglobin H disease (cont’)
      • Variable hemolytic anemia; splenomegaly
      • Ineffective erythropoiesis, iron-loading
  • B-Thalassemia
    • Molecular defect/absent/reduced production of b-globin chains
    • Broad spectrum of abnormalities
    • Known as Mediterranean or Cooley’s Anemia
    • Fatal prior to transfusion and iron chelation therapy
  • B-Thalassemia-Pathophysiology
      • > erythropoiesis, but ineffective
      • Erythroid marrow expansion with bony deformities
      • Progressive splenomegaly
      • Extra-medullary hematopoiesis
      • >iron absorption, progressive deposition in tissues
  • B-Thalassemia Clinical Features
      • Skeletal changes
      • Extra-medullary hematopoiesis
      • Growth retardation
      • Delayed sexual maturation
      • Myocardial iron overload
  • B-Thalassemia Clinical Features (cont’)
      • Hepatic iron loading
      • Pigmented gall stones
      • Severe microcytic anemia, splenomegaly
  • B-Thalassemia - Prognosis
      • No Rx-death by age 5 from infections, cachexia
      • Episodic blood transfusions-Survival until 20s
      • Aggressive blood transfusions-Death at age 20 from iron overload
      • Aggressive blood transfusions + iron chelation-Prolonged survival
  • B-Thalassemia - Management
      • Hypertransfusion in 2 nd or 3 rd yr to maintain Hb at 10g/dL
      • Splenectomy
      • Iron chelation after age 3
      • Possibly bone marrow transplant
      • Possibly increase synthesis of fetal Hb
  • B-Thalassemia Minor
      • No clinical symptoms
      • Labs
        • Mild to absent microcytic anemia
        • Peripheral blood smear shows microcytosis, hypochromia, targeting, basophylic stippling
        • Hb electrophoresis/quantitation: HbA >90%, HbA2 3.5-8.0%, HbF normal/>
  • Sickle Cell Anemia
    • HbS: Sickle hemoglobin, most common heritable disease worldwide
    • Prevalence
      • > tropical Africa/slave trade blacks
      • Some in Saudi Arabia, India
      • In U.S./Latin Am/Caribbean 8% blacks with gene
      • Note: Sickle cell trait not a disease
  • Sickle Cell Anemia - Symptoms
      • Usually none until 6-12 months old
      • Expression of HbSS limited during fetal and early postnatal life by HbF
      • No single pattern of symptoms, but may include: pain and swelling in hands and feet, fatigue, paleness, shortness of breath, eye problems, yellowing of skin/eyes, delayed growth
  • Sickle Cell Trait - Labs
      • Normal MCV, MCH
      • Normal blood smear
      • Normal reticulocyte count
      • HbA 60%, HbS 40%
      • Normal levels of HbA2, HbF
  • Sickle Cell Anemia – Lab Values
      • Moderate-severe normocytic normochromic anemia by age 3 mo., persistent
      • Av Hb 6.0-10.0g/dL
      • Adults, mean MCV = 90
      • Blood smears: sickled forms
      • Howell-Jolly bodies reflect asplenia
      • >WBC, platelets
  • Sickle Cell Anemia
    • Diagnosis
      • Electrophoretic chromatographic studies
      • HbS predominant, HbF present, HbA2 normal
  • Sickle Cell Anemia
    • Management
      • Folic acid 1mg PO qd
      • Hydroyurea [generic]15-35mg/kg PO
      • RBC transfusions
      • Stem cell transplant in children <16 yr, now for adults
  • Aplastic Anemia - Symptoms
      • Bleeding in skin/mucous membranes
      • Fatigue, fever, infection
      • Mortality secondary to infection
      • Pancytopenia
  • Aplastic Anemia - Etiologies
      • Idiopathic in 50%
      • Chemicals
      • Chemotherapy
      • Ionizing radiation
      • Viral infection
      • Leukemia
      • Medications: Chloramphenicol, sulfa
      • Auto-immune disorders
  • Aplastic Anemia
    • Diagnosis
      • Bone marrow biopsy
    • Epidemiology
      • 2 / million worldwide
      • Prevalent in Orient
      • Peaks in late adolescence/early adulthood
  • Aplastic Anemia
    • Pathogenesis
      • <Hematopoiesis
      • Autoimmunity
    • Therapy
      • Supportive: blood product transfusions, antibiotics
      • Bone marrow transplant, immunosuppression
      • If severe: ATG + cyclosporine
  • Megaloblastic Anemia
    • Cause
      • Impaired DNA synthesis, cell division impaired, cells enlarge
      • Vitamin B12 and folic acid deficiency
  • Vitamin B12 Deficiency
    • What is normal
      • 1-10mg total body Vitamin B12
      • Daily dietary requirement 2 micrograms
  • Vitamin B12 Deficiency
    • Causes of deficiency
      • Pernicious anemia, Gastrectomy
      • Pancreatic insufficiency
      • GI bleeding, Vitamin B12 malabsorption
      • Exposure to nitrous oxide
      • Neurological findings
  • Vitamin B12 Deficiency
    • Diagnosis
      • Check B12 levels. If borderline, then check >serum or urine methylmalonic acid
      • LDH-1 isoenzyme > LDH-2
      • Elevated indirect bilirubin, serum iron, <haptoglobin
  • Vitamin B12 Deficiency
    • Cause
      • Determine from clinical history/Schilling test
      • Schilling test
        • B12 test dose administered
  • Vitamin B12 Deficiency
    • Treatment
      • I.M. Vitamin B12
      • Check for hypokalemia, cardiac arrhythmias, monitor serum potassium
  • Vitamin B12 Deficiency
    • Treatment
      • Suggested I.M. injection schedule
        • 1000mg qd I.M. or sub Q for 1-2 wks, then 1000mg I.M. each mo. for life, maintenance of 1000mg/day oral
  • Total Body Folate Deficiency
    • Can cause megaloblastic anemia
    • Adult has 5-10mg total body folate
    • Usually accompanies Vitamin B12 deficiency
    • Treatment
      • Folic acid therapy: oral 0.5-1.0mg/day
      • Give B12 also
  • Glucose 6 Phosphate Dehydrogenase Deficiency (G6PD)
    • Hemolysis: Hallmark of hemolytic anemia, premature destruction of RBCs
      • Causes: acquired abnormal factors in intravascular environment, intrinsic RBC defects genetically determined
  • Glucose 6 Phosphate Dehydrogenase Deficiency (G6PD)
    • G6PD deficiency: Hereditary hemolytic disorder of RBC enzyme defect, sex linked, affects males, carried by females
    • Hb, RBC membranes at risk
  • G6PD Dediciency
    • Clinical feature
      • Rapidly developing intravascular hemolysis
    • Causative Agents
      • Infections, other illnesses
      • Drugs: antimalarials, sulfonomides, sulphones, other antibacterial agents, analgesics, anti-helminths, miscellaneous, fava bean
  • G6PD Deficiency
    • Diagnosis
      • Between crises, blood count normal
      • During crisis, smear shows contracted and fragmented cells, “bite”/”blister” cells, Heinz bodies in reticulocytes
      • Do RBC assay, check G6PD level
  • G6PD Deficiency
    • Treatment
      • Stop offending drug, maintain >urine output, blood transfusion, corticosteroids
  • Summary
    • Definition of anemias
    • Etiology, pathology, clinical features, diagnostic studies, and management of iron deficiency anemia, A- and B-Thalassemias, sickle cell anemia, aplastic anemia, and megaloblastic anemia
  • Summary
    • Causes, diagnosis, and treatment of Vitamin B12 deficiency and total body folate deficiency
    • Causes, clinical features, diagnosis and treatment of Glucose 6 Phosphate Dehydrogenase (G6PD) deficiency