ANEMIA

-Manithottiyle Angelo Simon2301310005

Pharm D 4th yearSRM College of Pharmacy

SRM University

Anemias are a group of diseases characterized by a decrease in haemoglobin or

RBCs, resulting in decreased oxygen carrying capacity of blood.

The decrease may result from blood loss, increased destruction of RBCs

(hemolysis), or decreased production of RBCs.

Anemia, like a fever, is a sign that requires investigation to determine the

underlying etiology.

The most serious complications of severe anemia arise from tissue hypoxia. Shock,

hypotension, or coronary and pulmonary insufficiency can occur. This is more

common in older individuals with underlying pulmonary and cardiovascular

disease.

WHAT IS IT?

BASED ON MORPHOLOGY

BASED ON ETIOLOGY

BASED ON PATHOPHYSIOLOGY

CLASSIFICATION:

A)BASED ON MORPHOLOGY1) Macrocytic anemias Where cells are larger than normal. Mean corpuscular volume(MCV) >100 fL

Megaloblastic anemia Cells are larger than normal in size because of impaired DNA synthesis. Vitamin B12 deficiency Folate deficiency Can be caused by inadequate dietary intake, decreased absorption and inadequate

utilization. Deficiency of intrinsic factor can cause a decrease in absorption of vitamin B12 in the

GIT which is caused by alcohol dependence, pernicious anemia etc. Folate deficiency can be caused due to hyper utilization during pregnancy, hemolytic

anemia, myelofibrosis, malignancy, chronic inflammatory disorders, long-term dialysis or growth spurt .

Drugs can cause anemia by reducing absorption of folate (eg. phenytoin) or by interfering with corresponding metabolic pathways(eg. methotrexate).

2) Microcytic anemia RBCs are lesser in size than normal. MCV <80fL MCHC <32 g/dLIron deficiency anemia Iron deficiency anemia develops when body stores of iron drop too low to support

normal red blood cell (RBC) production. Inadequate dietary iron, impaired iron absorption, bleeding, or loss of body iron in

the urine may be the cause.Sickle-cell anemia RBCs become sickle shaped. Presence of abnormal hemoglobin called hemoglobin S in RBC. Genetic causes; abnormal genes which are inherited from parents. Present from birth. Most infants do not present any symptoms until they are 5-6 months age. Causes painful swelling of the hands and feet called dactylitis, fatigue and jaundice

in children. Some complications are: Acute pain(sickle-cell or vaso-occlusive crisis), acute

chest syndrome, stroke, pulmonary hypertension, liver complications etc.

Sickle cell anemia

Thalassemia Inherited blood disorders that can result in abnormal formation of hemoglobin. 2 types: Alpha-thalassemia and Beta-thalassemia. Hemoglobin consists of 4 globin chains bound to the heme molecule. There are 4 major types of globins: alpha (α), beta (β), gamma (γ), and delta (δ).

The dominant hemoglobin in adults (hemoglobin A) is composed of 2 alpha and 2 beta chains.

Two minor forms of hemoglobin constitute a small percentage of normal blood: hemoglobin F , composed of 2 alpha chains and 2 gamma chains, and hemoglobin A2, composed of 2 alpha chains and 2 delta chains.

A very tightly controlled globin chain production process keeps the ratio of alpha chains to non-alpha chains at 1.00 (± 0.05).

In thalassemia , this ratio is disrupted. Alpha thalassemias involve HBA1 and HBA2 genes. Beta thalassemias are due to mutations in HBB gene. Patients are always at risk of severe anemia and require lifelong transfusions. Iron overload: Patients have excessive iron levels in the body either from the

disease or continuous transfusions. Iron gets accumulated in tissues and causes damage to heart, liver and endocrine system.

Iron chelation therapy is required to manage iron overload.

3)Normocytic anemia Common form of anemia that occurs with older age. Manifests with a decrease in haemoglobin and hematocrit but not MCV or MCH or

MCHC. Causes include: Recent blood loss Hemolysis Bone marrow failure Anemias of chronic disease Renal failure Endocrine disorders Myelodysplastic anemias(Blood cancer) Anemias of chronic disease is a hypoproliferative anemia associated with chronic

infectious or inflammatory processes, tissue injury, or conditions that release proinflammatory cytokines.

The pathogenesis is based on shortened RBC survival, impaired bone marrow response, and disturbance of iron metabolism.

1)Deficiency Iron Vitamin B12 Folic acid Pyridoxine2)Central-caused by impaired bone marrow function Anemia of chronic disease Anemia of the elderly(normocytic anemia) Malignant bone marrow disorders Myelodysplastic syndrome, leukaemia, aplastic anemia, multiple myeloma, PNH(Paroxysmal nocturnal hemoglobinuria).3)Peripheral Bleeding (hemorrhage) Hemolysis(Hemolytic anemia)

B)BASED ON ETIOLOGY

Hemolytic anemia A condition in which there is premature destruction of RBCs before their life span

of 120 days is completed and the bone marrow is not able to compensate for the RBC loss.

Mild anemia is asymptomatic but severe anemia can be life threatening and can cause angina and cardiopulmonary decompensation.

Hereditary disorders may cause hemolysis as a result of erythrocyte membrane abnormalities, enzymatic defects, and hemoglobin abnormalities. Hereditary disorders include the following:

Glucose-6-phospate dehydrogenase deficiency Sickle cell disease Hereditary spherocytosis Acquired causes of hemolysis include the following: Immune disorders Toxic chemicals and drugs Antiviral agents (eg, ribavirin ) Physical damage Infections [18]

1)Excessive blood loss Recent hemorrhage Trauma Peptic ulcer Gastritis Haemorrhoids2)Chronic hemorrhage Vaginal bleeding Peptic ulcer Intestinal parasites Aspirin and other NSAIDs3)Excessive RBC destruction RBC antibodies Drugs Physical trauma to RBCs

3)BASED ON PATHOPHYSIOLOGY:

Excessive sequestration in the spleen Heredity Disorders of hemoglobin synthesis4)Inadequate production of mature RBCs Deficiency of nutrients(B12, folic acid, iron, protein) Deficiency of erythroblasts Aplastic anemia Isolated(often transient) erythroblastopenia Folic acid antagonists Antibodies5)Conditions with infiltration of bone marrow Lymphoma Leukaemia Myelofibrosis Carcinoma

7)Endocrine abnormalities Hypothyroidism Adrenal insufficiency Pituitary insufficiency8)Chronic renal disease9)Chronic inflammatory disease Granulomatous diseases Collagen vascular diseases10)Hepatic diseases

Paleness of skin due to iron deficient anemia

Aplastic anemia is a syndrome of bone marrow failure characterized by peripheral pancytopenia and marrow hypoplasia.

Although often normocytic, mild macrocytosis can also be observed in association with stress erythropoiesis and elevated fetal hemoglobin levels.

Occurs primarily due to bone marrow failure. On morphologic evaluation, the hematopoietic elements in the bone marrow are

less than 25%, and they are largely replaced with fat cells. Symptoms: Fatigue Dyspnea Paleness Tachycardia Frequent infections Mostly genetic cause

APLASTIC ANEMIA:

Signs and symptoms depend upon the onset and cause of the anemia, and on the individual.

Acute-onset anemia:

Tachycardia

Light headedness

Breathlessness

Chronic anemia:

Weakness

Fatigue

Vertigo

Faintness

Cold sensitivity

Pallor

Loss of skin tone

CLINICAL PRESENTATION:

Iron-deficiency anemia:

Glossal pain

Smooth tongue

Reduced salivary flow

Pica(compulsive eating of non-food items)

Pagophagia (compulsive eating of ice)

Vitamin B12 and folate deficiency anemia:

Pallor

Icterus

Gastric mucosal atrophy

Pica

Glossitis

Rapid diagnosis is essential because it anemia is often a sign of underlying

pathology.

Signs and symptoms

Complete Blood count

Reticulocyte index

Peripheral blood smear report

Stool examination

Serum iron for Iron-deficiency anemia

TIBC(Total Iron Binding Capacity)

Macrocytic anemias-Raised MCV(80-110 FL)

Hypersegmented polymorphonuclear leukocytes for macrocytic anemia

DIAGNOSIS:

Iron deficiency anemia: Oral iron therapy containing soluble ferrous iron salts which are not enteric coated and not

slow or sustained release is recommended at a daily dosage of 200 mg in two or 3 divided doses.

In case of dietary absorption iron is best absorbed from meat, fish and poultry and poorly from vegetables, grain products, diary products and eggs.

Parenteral iron is required in cases where there is malabsorption of iron from diet , intolerance of oral iron or non compliance. Parenteral administration however does not hasten the hematologic process.

TREATMENT

SALT ELEMENTAL IRON(%) ELEMENTAL IRON PROVIDED

Ferrous sulphate 20 60-65mg/324-325 mg tab

18 mg iron/5 ml syrup

44mg iron/5 ml elixir

15 mg iron/0.6 ml drop

Ferrous sulphate(exsiccated) 30 65 mg/200 mg tablet

60 mg/187 mg tab

50 mg/160 mg tab

SALT ELEMANTAL IRON(%) ELEMENTAL IRON PROVIDED

Ferrous gluconate 12 36 mg/325 mg tablet

27 mg/240 mg tab

Ferrous fumarate 33 33 mg/ 100 mg tab

63-66mg/200 mg tab

106 mg/324-325 mg tab

33 mg/5 ml suspension

Polysaccharide iron complex

100 150 mg cap

50 mg tab

100 mg /5 ml elixir

Carbonyl iron 100 50 mg caplet

TREATMENT:

Vitamin B12 Deficiency anemia: Oral vitamin B12 supplementation is as effective as parenteral therapy. Oral cobalamin is initiated at 1-2 mg daily for 1-2 weeks followed by 1 mg daily. Parenteral therapy is more rapid acting than oral therapy and should be given if

neurologic symptoms are present. An intranasal gel formulation can be advantageous for patients who are homebound, have

cognitive impairment, or experience dysphagia. A widely used regimen is cyanocobalamin 1000 µg daily for a week, then weekly for a

month, and then monthly. When symptoms resolve, daily oral administration can be initiated.

Folate-deficiency anemia: Oral folate 1 mg daily for 4 months is usually sufficient, unless the underlying etiology

cannot be corrected.. If malabsorption is present, the daily dose should be increased to 5 mg.Anemia of chronic disease: Treatment must focus on correcting reversible causes. Iron therapy is not effective when inflammation is present. Epoetin alfa  is a human erythropoietin produced in cell culture using recombinant DNA

technology which stimulates erythropoiesis and facilitates formation of new RBCs.

It is used in cases of anemia associated with chronic renal failure and chemotherapy. In case of renal failure associated anemia it is to be used only if hemoglobin levels go

<10 g/dl. Initial dosage is 50-100 units/kg thrice weekly. If no increase in hemoglobin after 6-8 weeks of administration then increase to 150

units/kg thrice weekly or in patients with AIDS to 300 units/kg weekly.Hemolytic Anemia: Management consists of administration of folic acid supplements. Corticosteroids such as prednisone prevents phagocytosis of antibody covered RBCs and

thus is useful in autoimmune hemolytic anemia. Iron supplements are contraindicated in hemolytic anemia.Thalassemia: Management includes administration of folic acid supplements and iron chelation

therapy. Iron chelating agents- Deferoxamine mesylate & Deferasirox. Approximately 8mg of iron is bound by 100 mg of deferoxamine from ferritin and

hemosiderin but not from transferrin and it gets excreted in urine and bile. Given via IM inj, SC bolus, slow infusion or continuous infusion. Deferasirox is available as tablet for oral suspension and it binds to iron with affinity

ratio of 2:1