Anaemia in general practice

1. Anaemia in general practice Draljoharaalmeneessier 2013

2. Iron deficiency is the most prevalent nutritional problem in many parts of the world and the most common cause of anemia in Saudi Arabia

3. By the end of this session, the learner should be able to: • Highlight the prevalence of anemiain Saudi Arabia • Highlight the etiology of anemia • Understand the pathophysiology of anemia • Discuss the clinical features of anemia • Recognize the effect of anemiaon individuals, family, community and environment. • Discuss the evidence based approach and management of patients with anemia in family medicine setting

4. Epidemiology • Iron deficiency anemia (IDA) is the most common nutritional disorder in the world, as it is in the Eastern Mediterranean Region • The prevalence of anemia in the Gulf Region ranged from 15 to 48% in women of childbearing age. • In Saudi Arabia the overall country prevalence was 30 to 56%. • A study conducted in Riyadh City among schoolgirls showed that Iron Deficiency Anemia (IDA) prevalence was 40.5% among female adolescents (16-18) years old. Al-Quaiz J, Iron deficiency anemia A study of risk factors Saudi Med J 2001; Vol. 22 (6): 490-496

5. The overall prevalence of anemia in Saudi children was 24.8 per cent. • The prevalence was highest in the children from the Eastern province (41.3 per cent) and lowest in the central province (16.5 per cent). • The majority of the anemia in the eastern and south-western provinces was hypochromic-microcytic, while in the north-western and central provinces normochromic-normocyticanemia occurred most Elhazmi MA The pattern for common anaemia among Saudi children J Trop Pediatr (1999) 45 (4): 221-225.

6. HbS gene frequency in different areas and cities of Saudi Arabia

7. Definition Generally defined, anemia is present when the hemoglobin concentration is below a normal value based on the reference population. The mean normal value of hemoglobin is dependent on age, gender, race, and altitude. According to WHO criteria, the lower limit of normal in adults is 13 g/dL in men and 12 g/dL in women.

8. Pathophysiology • Anemia can be caused by: • Decreased red cell production, which may be due to lack of nutrient (B12, folic acid, iron) or bone marrow failure. • Increased red cell destruction secondary to hemolysis. • Increased red cell loss caused by acute or chronic bleeding.

9. Symptoms / signs suggestive of Anaemia Pallor Pale conjunctivae Flow murmur Lethargy Poor growth Signs of cardiac failure Weakness Listlessness Shortness of breath

10. Investigations • Full blood examination, • Blood film and reticulocyte count. • Any further investigations will be determined by the blood film appearance.

11. Morphologic classification of anemia by: red blood cell size (microcytic, normocytic, macrocytic) and hemoglobin content (hypochromic, normochromic,hyperchromic) Macrocytic (Megaloblastic) anemia: Vitamin B12 deficiency (pernicious) and folic acid deficiency anemia (most common). Microcytic, hypochromic anemia: Iron deficiency (most common) Normochromic, normocytic: Recent blood loss and Hemolysis (most common)

13. The classification is based on the MCV:

14. Algorithm for evaluation and treatment of iron deficiency anemia

16. Anemias

17. Sickle Cell Anemia • Normal Hb is HbA. • HbShas valine substituted for glutamic acid as the sixth amino acid in the beta chain of Hb. • Sickled RBCs are more rigid and may become “lodged” when passing through microvasculature, resulting in vascular occlusions. • The sickled RBCs surface contains aminophospholipids, which augments the ability of the RBC to initiate coagulation and adhere to vascular endothelium leading to vaso-occlusive episodes and multiorgan damage. • Symptoms and treatment • The kidney is commonly affected by microinfarction. Although, vaso-occlusive events are uncommon. If they do occur, they usually are caused by hypoxic conditions resulting from excessive exercise or high altitudes. • Treatment of sickle cell anemia is largely directed toward prophylaxis against infections and supportive management of vaso-occlusive crises.

18. The following are symptoms and complications of sickle cell disease Hemolytic Anemia Hemolytic anemia in patients with sickle cell disease is caused by splenic sequestration of abnormal RBC. Sequestration reduces the RBC life span from 120 days to 15 to 25 days. Management of the underlying anemia may include splenectomy following the first splenic sequestration event. Alternatively, patients can be treated with transfusions and careful observation.

19. symptoms and complications of sickle cell disease Infections Patients with sickle cell disease have a high incidence of infections, especially pneumococcal infections, due to altered B-cell immunity and granulocyte function. Pneumonia caused by S. pneumoniae can worsen hypoxia, causing progression to vaso-occlusion. Because of such complications, the prophylactic administration of penicillin has significantly reduced morbidity and mortality from pneumonia in children <3 years of age, but prophylaxis is recommended to be continued through age 5.

20. The following are symptoms and complications of sickle cell disease • Vascular Occlusion Episodes • Vascular occlusion episodes, or “sickle cell crises,” cause severe pain and organ damage. • The pain typically lasts 2 to 6 days and should be managed with narcotic analgesics. • Treatment for Frequent Vaso-occlusive Crises • Hemoglobin F (HbF) has a protective effect against hemoglobin polymerization. • Hydroxyureahas been found to increase HbF synthesis, which, in turn, may decrease sickling of RBC and the occurrence of disease-related complications. • Hydroxyureais used prophylactically in patients with recurrent vaso-occlusive crises, but not in treatment of the crises.

21. Iron deficiency anemia • can be caused by: • Chronic blood loss due to peptic ulcer disease, hemorrhoids, menstruation and ingestion of GI irritants such as NSAIDs. • Decreased absorption due to gastrectomy, or ingestion of medications that complex with iron, decreasing its absorption. • Increased requirement during infancy, pregnancy and lactation. • Inadequate dietary intake of iron (less than 1 to 2 mg/day), as in prolonged non supplemented breast-feeding • lack of available iron will result in a decreased hemoglobin synthesis and subsequent impairment of red blood cell oxygen-carrying capacity.

22. Treatment (Iron Therapy) • Oral Administration • The goals of iron therapy are to normalize the Hb concentrations and to replete iron stores. • The preferred route of iron administration is oral route. • The ferrous form of iron is absorbed three times more readily than the ferric form. • The usual adult dose of ferrous sulfate is 325 mg (one tablet) administered three times daily, between meals. • Hematologic response is usually seen in 2 to 3 weeks with a 1 g/dL increase in hemoglobin, anemia can be resolved in 1 to 2 months; • however, iron therapy should be continued for 3 to 6 months after the hemoglobin is normalized to replete iron stores.

23. Side effects • Oral iron therapy produces dark stools. Gastric side effects, which occur in 5% to 20% of patients, including nausea, epigastric pain, constipation, abdominal cramps, and diarrhea. • Drug-drug interactions • Foods, especially dairy products, decrease the absorption of iron by 40% to 50%. Drugs that increase the pH of the stomach (antacids, proton pump inhibitors, and H2 blockers) will decrease the solubility of ferrous salts and thus reduce iron absorption. • Absorptions of both iron and tetracycline are decreased when administered concomitantly;therefore, the iron should be taken 2 hours before or 3 hours after the tetracycline.

24. Parenteral Iron Therapy Parenteral iron therapy is indicated when there is failure to respond to oral therapy (due to nonadherence, or malabsorption). Iron can be given parenterally in the form of ferric gluconate, iron dextran, and iron sucrose. Side effects of parentral iron Anaphylactoid reactions can occur in about 1% of patients treated with parenteral iron therapy. Other side effects seen with parenteral iron agents include hypotension, nausea and vomiting, cramps, and diarrhea.

25. Thallasemia • Pathophysiology • Patients with α-thalassemia have a decrease in α-globin chain production relative to β-globin chain, with the formation of β4 (HbH) inclusion bodies. Red blood cells bearing these inclusion bodies are removed rapidly from the circulation by the reticuloendothelial system, shortening their survival. The resulting mild anemia is compensated partially by an increase in red blood cell production. • In contrast, patients with β-thalassemia have a decrease in β-globin chain production relative to α-globin chain production, which leads to an excess of α-globin chains. Unbound α-globin chains are extremely insoluble and precipitate in red blood cell precursors leading to defective erythroid maturation (ineffective erythropoiesis). The few cells that do emerge into the peripheral circulation are removed rapidly in the spleen and liver.

26. Thallasemia Clinical manifestation The resulting profound anemia increases circulating levels of erythropoietin and causes a massive expansion of bone marrow. In sever cases this lead to bone abnormalities and growth retardation. The spleen is actively involved in removing the abnormal mature cells from the circulation and become enlarged (spleenomegaly). Treatment There is currently no effective treatment for thalassemia major. Many patients with sever forms are blood transfusion dependant from early age. Although intensive blood transfusion programs have led to markedly improved survival, patients die from iron overload unless chelation therapy is instituted and maintained. Desferrioxamine and deferiprone are used for chelation of iron.

27. Vitamin B12 Deficiency Anemia The typical diet contains 5 to 15 mcg/day of vitamin B12, an amount sufficient to replace the 2 mcg lost daily. The total body stores of vitamin B12 range from 2,000 to 5,000 mcg. In the stomach, the vitamin B12is bound to intrinsic factor, which protects it from degradation by GI microorganisms. Intrinsic factor is essential for the absorption of vitamin B12. Specific mucosal receptors in the distal ileum allow for attachment of the intrinsic factor-B12 complex. In the liver, vitamin B12 is converted to coenzyme B12, which is essential for hematopoiesis, maintenance of myelin throughout the entire nervous system, and production of epithelial cells. Aetiology Vitamin B12 deficiency can result from decreased intake or malabsorption. Malabsorption occur if the distal ilium is removed. In addition, the gastric mucosa may be unable to produce intrinsic factor under conditions such as total and partial gastrectomy or autoimmune destruction (Pernicious anemia).

28. Vitamin B12 Deficiency Anemia Pathogenesis and symptoms Lack of vitamin B12 traps the folate as methyltetrahydrofolate and prevents DNA synthesis. So vitamin B12 is a coenzyme essential for hematopoiesis, maintenance of myelin throughout the entire nervous system, and production of epithelial cells. Therefore, vitamin B12 deficiency is associated with sore tongue, and numbness or tingling in the extremities (peripheral neuropathy) Treatment Parenteral vitamin B12 in a dose sufficient to provide the daily requirement of approximately 2 mcg, and to replenish tissue stores (about 2,000 to 5,000 mcg;) is given for treatment of vitamin B12 deficiency anemia. To replete vitamin B12 stores, cyanocobalamin (1,000 mcg) IM once a week for 4 to 6 weeks followed by 1,000 mcg/month for lifetime maintenance therapy in case of pernicious anemia .

29. Folic Acid Deficiency Anemia Etiology Folate deficiency can result from decreased intake or increased requirement (during pregnancy). Folate deficiency also can occur due to ingestion of drugs that alter folate metabolism (e.g., trimethoprim, pyrimethamine, methotrexate, sulfasalazine anticonvulsants) Pathogenesis and symptoms .Within the cells the methyl group is removed (in a reaction requiring vitamin B12) to form the active tetrahydtofolate which acts as a coenzyme involved in a number of reactions including DNA and RNA symthesis. Defect in DNA synthesis mainly affect cells with rapid turnover such as red blood cells and gastrointestinal cells, hence sore tongue and anemia seen in folate deficiency.

30. Folic Acid Deficiency Anemia Treatment Folate deficiency is usually managed by replacement therapy. The normal daily requirement of folic acid is about 100 mcg/ day. Despite this, the usual treatment doses given are 1-5 mg /day of oral folic acid. Even in malabsorption states sufficient folate is absorbed because of these large doses. The RBC morphology should begin to revert back to normal within 24 to 48 hours after therapy is initiated, and the anemia should be corrected in 1 to 2 months. Large doses of folate can partially reverse hematologic abnormalities caused by vitamin B12 deficiency; however, folate cannot correct neurologic damage caused by vitamin B12 deficiency. Therefore, folate deficiency absolutely must be differentiated from vitamin B12 deficiency .

31. Summary • Anemia is a common disorder among Saudis • Iron deficiency anemia is the most common among women and children in Saudi Arabia. The cause of deficiency should be explored. • Effective management of Sickle cell and Thallasaemia major my prevent premature death • Different therapy modalities should be tried according to the types of anemia

32. Thank you