ANEMIA AND ITS TREATMENT

Anemia is a condition in which the body does not have enough healthy red blood cells. Red blood cells provide oxygen to body tissues.

Causes, incidence, and risk factors 

While many parts of the body help make red blood cells, most of the work is done in the bone marrow. Bone marrow is the soft tissue in the center of bones that helps form blood cells.

Healthy red blood cells last between 90 and 120 days. Parts of your body then remove old blood cells. A hormone called erythropoietin made in your kidneys signals your bone marrow to make more red blood cells.

Hemoglobin is the oxygen-carrying protein inside red blood cells. It gives red blood cells their red color. People with anemia do not have enough hemoglobin.

Possible causes of anemia:

Certain medications

Chronic diseases such as cancer, ulcerative colitis, or rheumatoid arthritis

Genetics: Some forms of anemia, such as thalassemia, can be inherited

Kidney failure

Blood loss (for example, from heavy menstrual periods or stomach ulcers)

Poor diet

Pregnancy

Problems with bone marrow such as lymphoma, leukemia, or multiple myeloma

Problems with the immune system that cause the destruction of blood cells (hemolytic anemia)

Surgery to the stomach or intestines that reduces the absorption of iron, vitamin B12, or folic acid

Too little thyroid hormone (underactive thyroid, or hypothyroidism)

Testosterone deficiency

Symptoms

Possible symptoms include:

Chest pain

Dizziness or light-headedness (especially when standing up or with activity)

Fatigue or lack of energy

Headaches

Problems concentrating

Shortness of breath (especially during exercise)

Some types of anemia may have other symptoms, such as:

Constipation

Problems thinking

Tingling

Signs and tests

Pale skin

Rapid heart rate

Heart murmur

Blood tests used to diagnose:

Blood levels of vitamin B12, folic acid, and other vitamins and minerals

Red blood count and hemoglobin level

Reticulocyte count

Ferritin level

Iron level

Iron deficiency Anemia

Iron deficiency anemia occurs when the dietary intake or absorption of iron is insufficient, and hemoglobin, which contains iron, cannot be formed.The principal cause of iron deficiency anemia in premenopausal women is blood lost during menses. Iron deficiency anemia can be caused by parasitic infections, such as hookworms. Intestinal bleeding caused by hookworms can lead to fecal blood loss and heme/iron deficiency. Chronic inflammation caused by parasitic infections contributes to anemia during pregnancy in most developing countries.Iron deficiency anemia is an advanced stage of iron deficiency.Iron deficiency ranges from iron depletion, which yields little physiological damage, to iron deficiency anemia, which can affect the function of numerous organ systems.

Hemolytic Anemia

Hemolytic anemia occurs when the bone marrow is unable to increase production to make up for the premature destruction of red blood cells and the abnormal breakdown of red blood cells  either in the blood vessels (intravascular hemolysis) or elsewhere in the body (extravascular). It has numerous possible causes, ranging from relatively harmless to life-threatening. The general classification of hemolytic anemia is either inherited or acquired. Treatment depends on the cause and nature of the breakdown.Symptoms of hemolytic anemia are similar to other forms of anemia (fatigue and shortness of breath), but in addition the breakdown of red cells leads to jaundice and increases the risk of particular long-term complications such as gallstones and pulmonary hypertension.

Megaloblastic anemia

Megaloblastic anemia is a disorder of the bone marrow. There is a presence of erythroblasts in the bone marrow with delayed nuclear maturation because of defective DNA synthesis.

In megaoblastic anaemia Erythrocytes are larger and have higher nuclear-to-cytoplasmic ratios compared to normoblastic cells. Neutrophils can be hypersegmented, and megakaryocytes are abnormal. Risk Factors for Megaloblastic anaemia are Vitamin B12 deficiency ,Folic acid deficiency and Conditions with neither B12 nor folate deficiency, e.g. orotic aciduria, where there is a defect in pyrimidine synthesis, therapy with drugs interfering with DNA synthesis and myelodysplasia. 

Anemia of chronic disease

Anemia of chronic disease is a form of anemia seen in chronic illness e.g. from chronic infection, chronic immune activation, or malignancy.In Anemia of chronic disease,In response to the inflammatory cytokines (IL-6) the liver produces increased amounts of hepcidin. Hepcidin in turn stops ferroportin from releasing iron stores. Inflammatory cytokines also appear to affect other important elements of iron metabolism, including decreasing ferroportin expression, and probably directly blunting erythropoiesis by decreasing the ability of the bone marrow to respond to erythropoietin.Anemia of chronic disease may also due to the neoplastic disorder and non infectious inflammmatory diseases. Neoplastic disorder include Hodgkin’s disease lung and breast carcinoma and non infectious inflammmatory diseases include Rheumatoid arthritis and systemic lupus erythematosus.

Anemia of chronic disease is often a mild normocytic anemia, but can sometimes be more severe, and can sometimes be a microcytic anemia.

ANEMIA PHARMACOLOGY 

ANDROGENS (eg, oxymetholone): Anabolic steroids are synthetic derivatives of testosterone. These drugs enhance the production and urinary excretion of erythropoietin in patients with anemias due to bone marrow failure and often stimulate erythropoiesis in anemias due to deficient red cell production. The actions of anabolic steroids are similar to those of male sex hormones, therefore the possibility of causing serious disturbances of growth and sexual development in young children does exist.

COMPLEMENT INHIBITOR (eg, eculizumab): Eculizumab is a monoclonal antibody which binds with high specificity and affinity to the complement protein C5. When bound to C5, eculizumab prevents the protein from cleaving into C5a and C5b and inhibits the formation of the terminal complement complex C5b-9. This action inhibits the terminal complement-mediated intravascular hemolysis of abnormal red blood cells (RBCs) found in paroxysmal nocturnal hemoglobinuria (PNH). PNH patients are deficient in terminal complement inhibitors which make PNH RBCs susceptible to continuous terminal complement-mediated destruction.

ERYTHROPOIESIS-STIMULATING AGENTS (ESAs): Erythropoietin is a glycoprotein that stimulates red blood cell production. Endogenous production of erythropoietin is normally regulated by the level of tissue oxygenation. Hypoxia and anemia generally increase the production of erythropoietin, which in turn stimulates erythropoiesis. 

Recombinant erythropoietin (eg, epoetin alfa) and erythropoiesis-stimulating proteins (darbepoetin alfa) stimulate red blood cell production by the same mechanism of action as endogenous erythropoietin. Darbepoetin alfa differs in that it has a longer circulatory survival (half-life: 21hours) than recombinant erythropoietin (half-life: 4–13hours).

Sufficient time should be allowed to determine a patient's responsiveness to ESAs before adjusting the dose. Because of the time required for erythropoiesis and the RBC half-life, an interval of 2-6 weeks may occur between the time of a dose adjustment and a significant change in hemoglobin.

GONADOTROPIN-RELEASING HORMONE (GnRH) ANALOGUES: Leuprolide acetate is a long-acting GnRH analogue that is used in combination with iron therapy to treat anemia caused by acute or chronic blood loss associated with uterine leiomyomata. Repeated dosing of leuprolide acetate causes reduced secretion of pituitary gonadotropins leading to inactivity of dependent tissues and functions. This effect has been shown to reduce uterine and fibroid volume and excessive vaginal bleeding, thereby alleviating anemia caused by uterine leiomyomata.

HEMATINICS: 

Iron supplements: Iron is essential for the maintenance of normal hemoglobin synthesis and erythropoiesis. Treatment of iron deficiency anemias can generally be managed with oral iron supplementation. Oral iron supplements are available as carbonyl iron [elemental iron (eg, Ferralet 90)] or as various salt formulations which are similar in absorption and bioavailability, but differ in their percentage of elemental iron. 

Ferrous fumarate - 33% elemental iron

Ferrous gluconate - 12% elemental iron 

Ferrous sulfate - 20% elemental iron

Ferrous sulfate; exissicated - 32% elemental iron

Proper dosing of these supplements is based on the elemental iron content. Liquid formulations of iron may stain teeth.

Parenteral therapy is used when oral iron therapy is not feasible, cannot be tolerated, or iron losses are large. Preparations for parenteral therapy include iron dextran, iron sucrose, and sodium ferric gluconate. Use caution when administering parenteral iron therapy as acute hypersensitivity and anaphylactic reactions may occur; iron sucrose and sodium ferric gluconate have a lower incidence of these reactions. Of these agents, sodium ferric gluconate has the fastest onset of action but may require more frequent dosing. 

Vitamins: Vitamin B12 (eg, cyanocobalamin) is a vitamin essential for erythropoiesis. Rapidly dividing cells (eg, bone marrow and myeloid cells) have the highest requirement for Vitamin B12. Cyanocobalamin is available as an injection and as topical nasal preparations for the treatment of pernicious anemia and other megaloblastic anemias due to Vitamin B12 deficiency.

Folic acid and folic acid derivatives: Folic acid, which is necessary for the maintenance of normal erythropoiesis, is reduced by dihyrofolate reductase to tetrahydrofolic acid. Tetrahydrofolic acid is involved in the formation of thymidylates of nucleic acids and subsequently DNA synthesis. Folic acid deficiency impairs this process, resulting in megaloblastic and macrocytic anemias. Leucovorin is a folic acid derivative composed of a mixture of active tetrahydrofolic acid derivatives that do not require enzymatic reduction. Caution should be used if megaloblastic and pernicious anemias due to Vitamin B12 deficiency are suspected as folic acid and its derivatives may mask the signs of this condition.

SUBSTITUTED UREA (eg, hydroxyurea): Although the exact mechanism of action of hydroxyurea in treating sickle cell anemia is unknown, it is believed that the agent causes an immediate inhibition of DNA synthesis by acting as a ribonucleotide reductase inhibitor, without interfering with the synthesis of ribonucleic acid. Known pharmacologic effects of hydroxyurea that may contribute to its beneficial effects include increasing hemoglobin F levels in RBCs, decreasing neutrophils, increasing the water content of RBCs, increasing deformability of sickled cells, and altering the adhesion of RBCs to endothelium.

by

Akshaya Srikanth, Dr.Chandra Babu*

Pharm.D Intern, *Asst.Prof of Medicine

RIMS Medical College, Kadapa, A.P

INDIA