Microcytic Hypochromic Anemias PDF

Microcytic Hypochromic anemias Dr. Jehad Alhmoud  They are the anemias in which the MCV and MCH are below their normal values. The anemias associated with iron and heme typically are categorized as impaired production resulting from the lack of raw materials for hemoglobin assembly....

Microcytic Hypochromic anemias Dr. Jehad Alhmoud  They are the anemias in which the MCV and MCH are below their normal values. The anemias associated with iron and heme typically are categorized as impaired production resulting from the lack of raw materials for hemoglobin assembly. They include: 1) Iron Deficiency anemia (IDA) (Iron deficiency; lack of available iron). Iron 2) Anemia of chronic disease (Iron transport disorder). restricted 3) Sideroblastic anemia (Heme synthesis disorder; Inadequate production of protoporphyrin). 4) Thalassemia (Decreased globin synthesis). 1- Iron Deficiency Anemia (IDA)  Iron It is both necessary for life and potentially life-threatening. Essential element in all living cells. Transports oxygen (Hb). Stores oxygen (Mb). Integral part of many enzymes (Cytochrome, Catalase, Peroxidase). Usually bound to other molecules (not found as free). Absorbed in the duodenum and upper part of jejunum.  10% of daily iron is absorbed (1–2mg/day). Iron balance (Quantity) is physiologically regulated by the control of iron absorption at the enterocyte. Iron requirements vary with the age and sex. Only 20% of plasma-bound iron is derived from the gut. Most plasma iron is derived from the breakdown of senescent (old, aging) red cells (iron recycling). Iron metabolism  Iron Deficiency Anemia (IDA) IDA is a common and easily treated condition that occurs when there is not enough iron in the body (The anemia associated with inadequate iron stores). It is the most common type of anemia affecting 1 billion. In IDA, the body does not have enough iron to form hemoglobin, which means there is not enough hemoglobin to carry oxygen to the whole body. It is anemia of severely decreased or absent body iron stores characterized by hypochromic (not enough amount of Hb) and microcytic (more cell divisions while waiting for the cell to be filled with Hb) RBCs.  Causes of Iron deficiency 1) Inadequate intake (dietary deficiency): I. Meat, poultry, fish, eggs, dairy products, or iron-fortified foods (foods that have iron added) are the best sources of iron found in food. II. The most common cause of IDA in the world 2) Increased requirements or need (intake is less than needed): during rapid growth stages (infancy, childhood, adolescence), and pregnancy and lactation (750-900mg). 3) Decreased or impaired absorption: malabsorption, gastrectomy, and others. 4) Chronic blood loss (chronic bleeding): GI bleeding (ulcers, hemorrhoids, tumors, ulcerative colitis), heavy menstrual bleeding (prolonged menorrhagia), and any condition that is associated with chronic bleeding. Stages of Iron Status  Major signs and symptoms of Anemia The major symptom of all types of anemia, including iron-deficiency anemia, is fatigue (feeling tired). Fatigue is caused by having too few red blood cells to carry oxygen to the body. This lack of oxygen in the body can cause people to feel weak or dizzy, have a headache, or even pass out when changing position (for example, standing up). Since the heart must work harder to move the reduced amount of oxygen, signs and symptoms may include shortness of breath and chest pain. This can lead to a fast or irregular heartbeat or a heart murmur. In anemia, the red blood cells don't have enough hemoglobin. Common signs of lack of hemoglobin include pale skin.  Characteristics symptoms Glossitis (inflammation of the tongue). Angular cheilosis or stomatitis (inflammation of the corners of the mouth). Pica (appetite for non food substances such as an ice (pagophagia), clay, starch). Spoon shaped nails (Koilonychia). Hair loss. Some of the signs and symptoms of iron-deficiency anemia are related to its causes, such as blood loss.  Glossitis Red, Smooth , Waxy-appearing tongue with atrophy of papillae Concave or spoon shaped nails, koilonychia  Angular Cheilosis or Stomatitis Ulcerations or Fissures at the Corners of the Mouth  How is iron-deficiency anemia diagnosed? Iron deficiency anemia is diagnosed using a person’s medical history, physical examination, and laboratory diagnostic tests. A doctor can use these methods to determine the verity of the anemia, its cause, and appropriate treatment. Mild to moderate anemia may have no signs or symptoms. Most patients are not diagnosed until relatively late in the progression of iron depletion.  Laboratory Tests Hematological Tests : ✓CBC (screening test) ✓Blood Film ✓Bone Marrow Aspirate Biochemical Tests (iron studies) : ✓Serum Iron ✓Serum Ferritin ✓Total iron-binding capacity (TIBC) ✓Saturation of Transferrin  Hematological Tests CBC: CBC does not become abnormal until late in stage 2 or early in stage 3. ❖Erythrocytes(RBCs) ❖ Leukocytes (WBCs) ✓ Hemoglobin level ↓ ✓ Normal ✓ Hct (PCV) ↓ ✓ RBC count ↓ ❖ Platelets (Thrombocytes) ✓ May be normal or thrombocytosis, especially if ✓ MCV and MCH ↓ the cause is bleeding ✓ MCHC ↓ ✓ RDW ↑ CBC Parameters of IDA ❖Blood Film: ✓ Hypochromic Microcytic RBCs. ✓ Anisocytosis (variation in the size) ✓ Poikilocytosis(variation in the shape) ✓ Pencil (Cigarette) cell Iron deficiency should be suspected when the CBC findings show hypochromic, microcytic anemia with an elevated RDW but no consistent shape changes to the RBCs. Hypochromic microcytic red cells ❖Bone Marrow Aspirate: ✓ The most sensitive indicator of iron deficiency. ✓ High cellularity (Mild to moderate erythroid hyperplasia (25-35%; N 16–18%). ✓ Absence of stainable iron. Normal Iron deficiency Prussian Blue Stain of Bone Marrow: stains hemosiderin Iron present No Iron present ❖Biochemical Tests: ✓ Iron studies remain the backbone for the diagnosis of iron deficiency. ✓ They include serum iron assays, total iron-binding capacity (TIBC), transferrin saturation, and serum ferritin. ❖Iron studies ✓ Serum Iron Concentration (50-160g/dL) ↓ ✓ Total Iron-binding Capacity (TIBC) (250-400g/dL) ↑ ✓ Saturation Of Transferrin, % saturation ((Serum Iron/ TIBC) X 100)(20–55%) ↓ ✓ Serum Ferritin Levels (40-400 ng/mL) ↓ ✓ Free erythrocyte protoporphyrin (FEP) ↑ ✓ Serum Transferrin Receptors (sTfR) ↑ ✓ Serum iron is a measure of the amount of iron bound to transferrin (transport protein) in the serum. ✓ TIBC represents the total number of binding sites for iron in the plasma. ✓ The percent of transferrin saturated with iron can be calculated from the total iron and the TIBC: ✓ Ferritin is a measure of iron stores. Things you need to know about laboratory testing for iron status Iron studies include serum iron concentration, TIBC, % saturation, and ferritin. Ferritin is the specific test to diagnose IDA. Low serum ferritin is highly suggested for iron deficiency anemia. Normal serum ferritin does not always rule out iron deficiency. RDW is the first hematological parameter affected by iron deficiency. Hb, MCV, and MCH are the latest hematological parameters affected by iron deficiency.  IDA Treatment Goals of Treatment ✓ The goals of treating iron-deficiency anemia are to restore normal levels of red blood cells, hemoglobin, and iron as well as to treat the condition causing the anemia. Specific Types of Treatment ✓ Treatment for iron-deficiency anemia is based on the cause and the verity of the condition. ✓ It will include treatment to stop any bleeding, as well as changes in diet and iron supplements as needed. ✓ Severe anemia may require more emergency measures.  The best source of iron is red meat, especially beef and liver. ✓ Iron in meats is more easily absorbed by the body than iron in vegetables and other foods. ✓ Chicken, turkey, fish, and shellfish also are good sources of iron. ✓ Other foods high in iron are eggs, peas, lentils, green leaves, and fruits. Treatment for Severe and Life-Threatening Anemia ✓ Severe anemia may need to be treated with hospitalization, blood transfusions, and iron injections.  Oral Iron Therapy The optimal daily dose-200 mg of elemental iron ✓ Ferrous Gluconate 5 tablets/ day Fumarate 3 tablets/ day Sulfate 3 tablets/ day Iron is absorbed more completely when the stomach is empty to maximize its absorption. It is necessary to continue treatment for 3-6 months after the anemia is relieved to restore the iron store.  Summary Microcytic hypochromic anemias, those anemias that have decreased MCV and MCH below the normal range, include iron deficiency anemia (IDA), Sideroblastic anemia, anemia of chronic disease, and thalassemia. Most of the functional iron is found in Hb and it is stored in ferritin. IDA is the most common type of anemia and it is caused by severe decreased or absent body iron stores which may be due to chronic blood loss, decreased iron intake, increased iron requirement, and decreased or impaired absorption.  There are some people at increased risk of developing IDA: Women of childbearing age, pregnant women, people with poor diets, people who donate blood frequently, infants and children, especially those born prematurely, and vegetarians who don’t replace meat with another iron-rich food. IDA occurs through three stages: the depletion storage stage, the iron deficiency without anemia stage, and the IDA stage. RDW is the first CBC parameter that is changed in IDA. Hb, MCV and MCH are the last CBC parameters that are changed in IDA.  Ferritin is the specific test for IDA diagnosis. BM aspirate is the sensitive test for IDA. In IDA, the lab results are: ↓ Hb, MCV, MCH, MCHC, RBC count, Hct, serum iron, % saturation, and ferritin. ↑ RDW, TIBC Blood film of IDA shows hypochromic microcytic RBCs, aniso-poikilocytosis, and pencil cells. Characteristic signs and symptoms of IDA include pica, gastritis, angular stomatitis, and Koilonychia. Disorders of iron kinetics and heme metabolism 2- Anemia of chronic inflammation  Anemia is commonly associated with systemic diseases, including chronic inflammatory conditions such as rheumatoid arthritis, chronic infections such as tuberculosis or human immunodeficiency virus infection, and malignancies. This anemia ranks only behind iron deficiency anemia in incidence worldwide and is common among hospitalized patients. Etiology: Although the anemia associated with chronic systemic disorders was originally called anemia of chronic disease, chronic blood loss is not among the conditions leading to the anemia of chronic disease. Chronic blood loss results in quantitative iron deficiency.  Anemia of chronic disease is more correctly termed anemia of chronic inflammation because inflammation is the unifying factor among the three aforementioned general types of conditions in which this anemia is seen. The central feature of anemia of chronic inflammation is sideropenia in the face of abundant iron stores. The cause is now understood to be largely impaired ferrokinetics and thus iron-restricted erythropoiesis. However, impaired erythropoiesis and shortened RBC life span are also contributors. - Although there is plenty of iron in the body, it is unavailable to develop RBCs because it is sequestered in the macrophages and hepatocytes. iron is present in abundance in storage but unavailable to developing erythroblasts. - Lactoferrin binds to macrophages and liver cells that take up and salvage the iron. - This is iron-restricted erythropoiesis.  Lactoferrin is an iron-binding protein in the granules of neutrophils. Its avidity for iron is greater than that of transferrin. Lactoferrin is important to prevent phagocytized bacteria from using intracellular iron for their metabolic processes. Lactoferrin may also protect the phagocyte from oxidized iron that forms when reactive oxygen species (ROS) are produced during phagocytosis. During infection and inflammation, neutrophil lactoferrin is released into the blood and extracellular spaces with the death of neutrophils. There it scavenges iron that would otherwise induce oxidative damage. In this way, lactoferrin is anti-inflammatory. When it is carrying iron, lactoferrin binds to macrophages and liver cells that take up and salvage the iron. Erythroblasts cannot acquire iron salvaged by lactoferrin directly because they do not have lactoferrin receptors. The result of these effects during chronic inflammation is a functional iron deficiency; iron is present in abundance in storage but unavailable to developing erythroblasts.  Laboratory diagnosis The peripheral blood picture in anemia of chronic inflammation is mild anemia, with hemoglobin concentration usually 8 to 10 g/ dL and without reticulocytosis. The cells are usually normocytic and normochromic. Although microcytosis and hypochromia can be seen, they typically represent coexistent iron deficiency. The inflammatory condition leading to the anemia also may cause leukocytosis, thrombocytosis, or both. Iron studies show low serum iron and TIBC values as the production of transferrin by hepatocytes is regulated by intracellular iron levels. The serum ferritin level, as an acute phase reactant, is usually increased.  The hemoglobin content of reticulocytes will be decreased, demonstrating iron-restricted erythropoiesis, but the Soluble transferrin receptor (sTfR) will be normal, reflecting normal intracellular iron. The bone marrow shows hypoproliferation of the RBCs, consistent with the lack of reticulocytes in the peripheral blood. Prussian blue stain of the bone marrow confirms abundant stores of iron in macrophages, although not in RBC precursors. Bone marrow examination is not usually required in the diagnostic evaluation. Treatment: At present, the best course of treatment is effective control or alleviation of the underlying condition. However, various anti-hepcidin therapies are being investigated. It is expected that the sTfR/ log ferritin will rise most dramatically in iron deficiency as the numerator rises and the denominator falls; in anemia of chronic inflammation, both remain essentially normal and thus a normal ratio results. 3- Sideroblastic anemia Sideroblastic: Inadequate production of protoporphyrin also leads to diminished production of heme and thus hemoglobin, but with a relative excess of iron. Blockages of protoporphyrin production at various stages in the heme synthetic pathway lead to accumulations of various porphyrins. Iron metabolism can be perturbed, resulting in excess accumulations of iron, usually without anemia. This condition is called hemochromatosis. Prescence of many pathological ring sideroblasts in the bone marrow. Erythroblast containing numerous iron granules arranged in a ring around the nucleus. 15% or more of marrow erythroblasts are ring sideroblasts. There is also usually erythroid hyperplasia with ineffective erythropoiesis. They can be found in lower numbers in various hematological conditions.  The myelodysplastic syndromes are all disorders of the hematopoietic stem cells in the bone marrow (only related to myeloid lineage).  Lead poisoning Lead inhibits both haem and globin synthesis at several points. In addition, it interferes with the breakdown of RNA by inhibiting the enzyme pyrimidine 5′ nucleotidase, causing accumulation of denatured RNA in red cells. The RNA gives an appearance called basophilic stippling on the ordinary (Romanowsky) stain. The anemia may be hypochromic or predominantly hemolytic, and the bone marrow may show ring sideroblasts. Free erythrocyte protoporphyrin is raised. Differential diagnosis of hypochromic anaemia  Regulation of iron absorption Dietary Iron: Iron is present in food as ferric hydroxide, ferric protein, and heam-protein complexes. Iron content and absorption differ from food to food. Meat is better than vegetable, egg, or dairy food. Impaired ferrokinetics: Hepcidin is a hormone produced by hepatocytes to regulate body iron levels, particularly absorption of iron in the intestine and release of iron from macrophages and hepatocytes. Hepcidin interacts with and causes degradation of transmembrane protein ferroportin, which exports iron from enterocytes into the blood, thus reducing the amount of iron absorbed into the blood from the intestine. Macrophages and hepatocytes also use ferroportin to export and recycle iron into the blood and are affected by hepcidin. When systemic body iron levels decrease, hepcidin production by hepatocytes decreases, and enterocytes export more iron into the blood. Macrophage and hepatocyte release of iron also increases. When systemic iron levels are high, hepcidin increases, enterocytes export less iron into the blood, and macrophages and hepatocytes retain iron.  Hepcidin is an acute-phase reactant which indicated as an inflammation markers that exhibit significant changes in serum concentration during inflammation. During inflammation, the liver increases the synthesis of hepcidin in response to interleukin-6 produced by activated macrophages. This increase occurs regardless of systemic iron levels in the body. As a result, during inflammation, there is a decrease in iron absorption from the intestine and iron release from macrophages and hepatocytes. Although there is plenty of iron in the body, it is unavailable to develop RBCs because it is sequestered in the macrophages and hepatocytes. A second iron-related acute phase reactant seems to contribute to anemia of chronic inflammation, although probably to a much smaller extent than hepcidin. Because of high hepcidin, however, the macrophages and hepatocytes cannot export iron and it remains sequestered away from erythroblasts.