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ANAEMIA
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Objectives Identify types of Anemia Identify the causes of Anemia.
Classify Anaemia Aetiologically Classify Anaemia Morphologically Laboratory diagnosis
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Definition Anemia: A deficiency in the size or number of red blood cells or in the amount of hemoglobin a red blood cell contains Decrease in blood hemoglobin below a person’s physiological need Hemoglobin concentration below 95th percentile of healthy reference population
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Causes of Anemia Lack of required nutrients Loss of blood
Chronic Disease Genetic Abnormalities Inadequate production of red blood cells
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Symptoms Weakness and fatigue Pale skin and gums Irregular heart beat
Faintness or dizziness Loss of appetite Glossitis
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Hematological Assessment
To detect presence of anemia and type To detect associated nutritional deficiencies Indicate appropriate nutritional support Diagnostic Criteria Men RBC < 4.5 million Hb < 14 g/ dl Packed cell < 42% Women RBC < 4 million Hb < 12 g/dl Packed cell < 37%
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Laboratory Tests CBC (complete blood count) # of red blood cells
Hemoglobin content Hematocrit- proportion TV that is blood cells Blood smear- classify size (mcv) Leukocyte and platelet count Reticulocyte count
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Red Blood Cells Deliver oxygen to tissues in the body
Only live about 120 days Also called Erythrocyte Normal RBC level (M): 5.4 +/- .8 million/ uL (F): 4.8 +/- .6 million/ uL
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Hemoglobin Normal Hemoglobin
Male: g/dL Female: g/dL Hb content indicated by mean corpuscular hemoglobin (MCH) MCH = Hb (g/dl x 10) / RBC (millions/mm3) MCH is decreased in microcytic cells MCH is increased in macrocytic cells
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Hematocrit Pricking the finger and drawing a drop of blood up into a thin glass tube. Another way is to draw a tube of blood from the arm. Centrifuge under prescribed conditions. The proportion of the tube that consists of RBCs is then measured. Let's say that it is 45%. The hematocrit is 45.
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MCV= Hct(PCV) x 10 / RBC (millions/ mm3)
Blood Smear Under a microscope can classify cells Small (microcytic) Normal (normocytic) Large (macrocytic) Size related to Mean Corpuscular Volume MCV= Hct(PCV) x 10 / RBC (millions/ mm3) MCV is decreased in Microcytic RBCs ……….Microcytic Anemia MCV is increased in Macrocytic RBCs………..Macrocytic Anemia
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Leukocyte and platelet count
Low count: indicates marrow failure High count: indicates anemia caused by leukemia or infection Reticulocyte - large, nucleated, immature red blood cells High count: indicates a response to bleeding
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Other Laboratory Tests
The patient is placed in a category based upon the diagnosis from the CBC further testing is needed to confirm diagnosis. Microcytic Anemia Serum iron, total iron binding capacity, serum ferratin are measured Macrocytic Anemia Tests for foliate and vit. B12 are taken Homocysteine levels are measured
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General Treatment for Anemia
Diet Nutritional Supplements: E.g.) Iron, B12, folic acid Treatment of infection or inflammation Erythropoietin- drug to treat low blood cell count (mainly used with renal patients) Blood transfusion Bone Marrow Transplant
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DEFN OF TERMS Cytopenia is a reduction in the number of blood cells. It takes a number of forms: Low red blood cell count: resulting in anemia. Low white blood cell count: leukopenia or neutropenia (because neutrophils make up at least half of all white cells, they are almost always low in leukopenia). Low platelet count: thrombocytopenia. Low granulocyte count: granulocytopenia Low red blood cell, white blood cell, and platelet counts: pancytopenia.
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ANAEMIA CLASSIFICATION
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CRITERIA Morphological Classification
An alternative classification of anaemia is based on the morphology of the red cells, usually their size and staining characteristics. Red cells may be normal in size (normocytic), large (macrocytic), or small (microcytic).
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CRITERIA They stain pink with the stains used in haematology, but there is a central area of pallor which does not exceed 1/3 the diameter of the cell. Cells stained in this way are normochromic. If the central area of pallor is greater than 1/3 the diameter of the cell it is described as hypochromic.
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CRITERIA hypochromic/microcytic, normochromic/normocytic, or
On this basis the anaemia may be classified as hypochromic/microcytic, normochromic/normocytic, or macrocytic.
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The size and staining characteristics of the cells may be objectively measured by the mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), and mean corpuscular haemoglobin concentration (MCHC).
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MORPHOLOGICAL Classifications of Anemia
1. Microcytic - RBC volume < 80 fl oz. (small RBC’s) 2. Normocytic - RBC volume fl oz. (normal RBC’s) 3. Macrocytic - Blood volume < 100 fl oz. (Large RBC’s)
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A. Iron Deficiency Anemia
1. MICROCYTIC ANEMIAS A. Iron Deficiency Anemia Sports Anemia Maternal Anemia B. Copper Deficiency Anemia C. Thalassemia
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A. Iron Deficiency Most common type of deficiency
Cause: Lack of iron in bone marrow At Risk: Some are more at risk than others Vegetarians Infants Pregnant women Menstruating women People with excessive blood loss People with chronic disorders Endurance athletes
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Iron Absorption Increase absorption: Limit Absorption:
Stomach- facilitates absorption by secreting gastric acid Duodenum - where iron absorbed Iron Absorption Increase absorption: Vitamin C Vitamin B6 Iron Stores are low Limit Absorption: Phosphates- fiber rich food High amounts of Cu
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Intake of Iron Age Intake Age Intake Sources of Iron:
Recommended Intake: Age Intake Age Intake Female mg Male mg mg mg mg mg mg 19-up 8 mg 51- up mg Sources of Iron: Beef, chicken, fortified breakfast cereal, beans, whole wheat grains, spinach, ect.
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Sports Anemia At risk: females, vegetarians, endurance athletes, still growing Treatment: eat iron rich foods that contain protein, avoid foods that inhibit absorption
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Maternal Anemia Maternal Anemia- hematocrit less than 32% and hemoglobin less than 11 g/dl Increased blood volume leads to increased demand for iron Usually comes about at the end of pregnancy During pregnancy must have 27 mg/ day Rarely have sufficient iron stores so often a supplement of ferrous salt is recommended (200mg in 3-4 doses/ day).
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Maternal Anemia Studies
there is an association between low maternal hemoglobin concentration and poor pregnancy outcomes. The risk of preterm delivery was doubled. Severe maternal anemia (<8g/dl) is associated wit birth weight values that are g than women who have normal hemoglobin values
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B. Copper Deficiency Copper: essential for life, required for normal infant development, red and white blood cell maturation, and iron transport. Absorbed by stomach and small intestine Absorption decreased by excess dietary iron and zinc RDA: mg/day Cu Deficiency: symptoms similar to iron deficiency Increases vulnerability to infections Kinky hair disease
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Copper Deficiency Research
Anemia’s role in myocardial hypertrophy: Anemia with copper deficiency contributes to heart pathology. Researchers found that RBC administered to copper deficient rats fed fructose prevented anemia and heart hypertrophy. The control group, also copper deficient was fed fructose but wasn’t given RBC. The control group became anemic and had indications of heart hypertrophy. (Fields et al ,1991) Copper deficient rats and membrane fluidity: Rock et al (1995) examined the relationship between copper deficiency and shorter survival of red blood cells. Fluorescence polarization studies show an increase in fluidity in RBC membrane of Copper deficient rats. This suggests that these RBC are more vulnerable to hydrolysis and therefore have shorter survival time.
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C. Thalassemia Severe inherited anemia affecting primarily people in Mediterranean region Microcytic and short lived RBC result from defective hemoglobin synthesis Characterized by excessive amounts of iron absorption that accumulates in the body and leads to dysfunction of heart, liver and endocrine glands Need transfusion to stay alive
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2. MACROCYTIC ANEMIA A. Pernicious B. Folic Acid Deficiency
C. Refractory Anemia
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A. Pernicious Anemia RDA : Vit B12 3 micrograms/ day
Cause: Inability to absorb vitamin B12 B12 attaches itself to intrinsic factor in order to be absorbed. Parietal cells shrink so parietal cells can’t produce intrinsic factor At Risk: people over 60, African Americans, Northern Europeans, strict vegetarians Diagnosis: Schilling test- given radioactive B12 alone and then attached to intrinsic factor Treatment: Foods with B12 – meat, dairy, etc. Lifelong injection B12 directly into bloodstream so don’t need intrinsic factor.
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B. Folic Acid Deficiency Anemia
RDA:400 mg/ day Requirements double during pregnancy Cause: Inadequate absorption, increased excretion, increased requirement, destruction of folic acid. Folic acid and B-12 have interrelated role in synthesis of DNA At risk: Pregnant women, alcoholics, low economic status, women over 30, infants born to folic acid deficient mothers
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Folic Acid Deficiency Sources: leafy green vegetables, oatmeal, peanut butter folate easily destroyed by sunlight, overcooking, storing for extended periods Treatment: increase foods high in folic acid, folic acid supplement, avoid alcohol and tobacco
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C. Refractory Anemia Cause: Damage to DNA of blood cells in the bone marrow. The marrow fills up with blood cell precursors but cant get out into blood stream At risk: Elderly Diagnosis: Low counts of reticulocytes, white blood cells, platelets, but have normal serum B12 and folic acid levels. Treatment: Blood transfusion- after while antibodies form Bone marrow transplant- Advanced age of most people makes it feasible less than 10% of time Survival time : 2.5 years Cause of death usually infection
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3. NORMOCYTIC ANEMIA A. Aplastic B. Anemia of Chronic Disease
C. Inherited Anemia D. Hemolytic Anemia
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A. Aplastic Anemia Cause: The basic structure of the marrow becomes abnormal and causes the hematopoietic cells that make blood cells to die off, these cells are often replaced by fat. Associated with exposure to drugs (anti-cancer), radiation, chemicals, pregnancy At risk: Asian decent, young adults (15-30), and elderly Diagnosis: Blood count low for all formed blood cells, hematopoietic cells replaced with fat Treatment: blood transfusion- temporary help Bone marrow transplant- bone marrow must be compatible with immune system (60-80% success)
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B. Anemia of Chronic Disease
2nd most common type of anemia Cause: Associated with general systemic illnesses that are characterized by inflammation Lupus, rheumatoid arthritis, cancer, etc. Diagnosis: No diagnostic tests- diagnosis made after all other forms of anemia have been ruled out
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C. Inherited Anemia Sickle Cell Anemia
Considered a “black” disease but has been detected in white populations Cause: Results in defective hemoglobin synthesis, produces sickle shaped red blood cells Get caught in capillaries and don’t carry oxygen well, similar to having mini heart attacks Leads to blindness, leg ulcers, stroke, etc. New Hope: A NHLBI study involving 299 patients having painful crisis's associated with sickle cell anemia found that those patients receiving Hydrea (a drug thought to increase levels of hemoglobin in RBC) had half as many painful bouts as those given the placebo. (Mayfield, 1996)
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D. Hemolytic Anemia Cause: abnormally shortened red cell life span due to disease in the small blood vessel Marrow is normal but RBC die faster than marrow can replace it. Treatment: Depends on the underlined cause
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AETIOLOGICAL CLASSIFICATION
CAUSES Broadly, causes of anemia may be classified as impaired red blood cell (RBC) production, increased RBC destruction (hemolytic anemias), blood loss and fluid overload (hypervolemia). Several of these may interplay to cause anemia eventually. Indeed, the most common cause of anemia is blood loss, but this usually does not cause any lasting symptoms unless a relatively impaired RBC production develops, in turn most commonly by iron deficiency
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1. IMPAIRED PRODUCTION A. Disturbance of proliferation and differentiation of stem cells Pure red cell aplasia Aplastic anemia affects all kinds of blood cells. Fanconi anemia is a hereditary disorder or defect featuring aplastic anemia and various other abnormalities. Anemia of renal failure by insufficient erythropoietin production Anemia of endocrine disorders
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B. Disturbance of proliferation and maturation of erythroblasts
Pernicious anemia is a form of megaloblastic anemia due to vitamin B12 deficiency dependent on impaired absorption of vitamin B12. Lack of dietary B12 causes non-pernicious megaloblastic anemia Anemia of folic acid deficiency as with vitamin B12, causes megaloblastic anemia Anemia of prematurity, by diminished erythropoietin response to declining hematocrit levels, combined with blood loss from laboratory testing, generally occurs in premature infants at two to six weeks of age. Iron deficiency anemia, resulting in deficient heme synthesis Thalassemias, causing deficient globin synthesis Congenital dyserythropoietic anemias, causing ineffective erythropoiesis Anemia of renal failure (also causing stem cell dysfunction)
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C. Other mechanisms of impaired RBC production
Myelophthisic anemia or myelophthisis is a severe type of anemia resulting from the replacement of bone marrow by other materials, such as malignant tumors or granulomas. Myelodysplastic syndrome anemia of chronic inflammation
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2. INCREASED DESTRUCTION
Consider Hemolytic anemia Anemias of increased red blood cell destruction are generally classified as hemolytic anemias. These are generally featuring jaundice and elevated lactate dehydrogenase levels.
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A. Intrinsic (intracorpuscular) abnormalities cause premature destruction. All of these, except paroxysmal nocturnal hemoglobinuria, are hereditary genetic disorders. Hereditary spherocytosis is a hereditary defect that results in defects in the RBC cell membrane, causing the erythrocytes to be sequestered and destroyed by the spleen. Hereditary elliptocytosis[ is another defect in membrane skeleton proteins. Abetalipoproteinemia, causing defects in membrane lipids Enzyme deficiencies Pyruvate kinase and hexokinase deficiencies, causing defect glycolysis Glucose-6-phosphate dehydrogenase deficiency and glutathione synthetase deficiency, causing increased oxidative stress
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A. Intrinsic (intracorpuscular)…..
Hemoglobinopathies Sickle cell anemia Hemoglobinopathies causing unstable hemoglobins Paroxysmal nocturnal hemoglobinuria
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B. Extrinsic (extracorpuscular) abnormalities I. Antibody-mediated
Warm autoimmune hemolytic anemia is caused by autoimmune attack against red blood cells, primarily by IgG. It is the most common of the autoimmune hemolytic diseases. It can be idiopathic, that is, without any known cause, drug-associated or secondary to another disease such as systemic lupus erythematosus, or a malignancy, such as chronic lymphocytic leukemia
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Antibody-mediated…… Cold agglutinin hemolytic anemia is primarily mediated by IgM. It can be idiopathic or result from an underlying condition. Rh disease, one of the causes of hemolytic disease of the newborn Transfusion reaction to blood transfusions
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Infections, including malaria Heart surgery Haemodialysis
II. Mechanical trauma to red cells Microangiopathic hemolytic anemias, including thrombotic thrombocytopenic purpura and disseminated intravascular coagulation[ Infections, including malaria Heart surgery Haemodialysis
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3. BLOOD LOSS Anemia of prematurity from frequent blood sampling for laboratory testing, combined with insufficient RBC production Trauma or surgery, causing acute blood loss Gastrointestinal tract lesions, causing either acute bleeds (e.g. variceal lesions, peptic ulcers or chronic blood loss (e.g. angiodysplasia) Gynecologic disturbances, also generally causing chronic blood loss From menstruation, mostly among young women or older women who have fibroids
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4. FLUID OVERLOAD Fluid overload (hypervolemia) causes decreased hemoglobin concentration and apparent anemia: General causes of hypervolemia include excessive sodium or fluid intake, sodium or water retention and fluid shift into the intravascular space. Anemia of pregnancy is induced by blood volume expansion experienced in pregnancy
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ANAEMIA CLASSIFICATION
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Mechanism Examples Blood loss Acute GI bleeding Injuries Childbirth Surgery Chronic Bladder tumors Cancer or polyps in GI tract Heavy menstrual bleeding Kidney tumors Ulcers in the stomach or small intestine
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Deficient erythropoiesis. Classified according to RBC indices.
Microcytic Iron deficiency Iron-transport deficiency Iron utilization defect Iron reutilization defect Thalassemias (also classified under excessive hemolysis due to intrinsic RBC defects) Normochromic- normocytic Aplastic anemia Hypoproliferation In kidney disease In endocrine failure (thyroid, pituitary) In protein depletion Myelodysplasia Myelophthisis Macrocytic Copper deficiency Folate deficiency Vitamin B12 deficiency Vitamin C deficiency
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Excessive hemolysis due to intrinsic RBC defects
Membrane alterations, acquired Hypophosphatemia Paroxysmal nocturnal hemoglobinuria Stomatocytosis Membrane alterations, congenital Hereditary elliptocytosis Hereditary spherocytosis Metabolic disorders (inherited enzyme deficiencies) Embden-Meyerhof pathway defects G6PD deficiency Hemoglobinopathies Hb C disease Hb E disease Hb S-C disease Hb S–β-thalassemia disease Sickle cell disease (Hb S) Thalassemias (β, β-δ, and α)
