anemia.ACU.pdf

Anemia DR Dina Attia Professor of Tropical Medicine Faculty of Medicine, Beni-Suef University Faculty of Medicine, Al Ahram Canadian University 2024  Anemia Definition: Decreased of the...

Anemia DR Dina Attia Professor of Tropical Medicine Faculty of Medicine, Beni-Suef University Faculty of Medicine, Al Ahram Canadian University 2024  Anemia Definition: Decreased of the hemoglobin concentration and often the hematocrit and the erythrocytic number below normal values Male: Hemoglobin (Hb): < 13.0 g/dl Hematocrit (Hkt): < 42 % Female: Hemoglobin (Hb): < 12.0 g/dl Hematocrit (Hkt): < 38 % Classifications I. Decreased red cell production: 1. Decreased proliferation: Aplastic anemia Myelophthisic anemia Anemia with organ failure: renal, hepatic, endocrine 2. Decreased red cell maturation Hypochromic anemias Megaloblastic anemias Myelodysplastic anemias II. Increased red cell destruction: hemolytic anemias III. Increased red cell loss: acute post hemorrhagic anemia IV. Dilutional anemias: Hypersplenism Features of anemia Symptoms: General: easy fatigue, lassitude and stunted growth in children CVS: exertional dyspnea, palpitation, precipitation of angina, intermittent claudication's, high CO heart failure. Neurological: headache, dizziness, tinnitus, syncope, lack of concentration, numbness, tingling of feet and hands. Renal: polyuria, slight proteinuria. Genital: menstrual irregularities, impotence Signs: Pallor. Hyperdynamic circulation. Edema of lower limbs.  Iron deficiency anemia Most common type of anemia I. Etiology 1. Decreased iron intake Infants, children and vegetarian and elderly. 2. Decreased iron absorption Achlorhydria: stomach resection, atrophic gastritis, cancer stomach. Malabsorption syndrome. Celiac disease and inflammatory bowel disease (IBD). 3. Increased iron requirements Females in the childbearing periods (menstruation, pregnancy and lactation). Growth periods (infancy and adolescents). Athlete Treatment of vitamin B12 deficiency. 4. Increased iron loss ▪ Menorrhagia GIT bleeding: − Esophageal varices, erosive gastritis and peptic ulceration and hiatus hernia. − Tumors − IBD, colonic diverticulosis, hemorrhoids. − Ancylostoma worn infestation. ▪ Repeated blood donation and hemodialysis. ▪ Repeated pregnancies. ▪ Recurrent epistaxis, hematuria and bleeding from wounds (operative and post traumatic). ▪ Hemorrhagic blood diseases. ▪ Hemoglobinuria. II. Clinical picture: 1. Features of iron deficiency anemia Skin and mucous membrane: − Nails are brittle, striated, flattened with loss of luster. In server cases spooning (koilonychia). − Diffuse hair loss, dry skin − Chronic aphthous ulcers of the mouth, angular stomatitis and glossitis. Perverted appetite (pica). Splenomegaly in 10% of cases. 2. General features of anemia  Special types: 1. Plummer-Vinson syndrome: Middle aged females + features of iron deficiency anemia. Stomatitis, spooning and splenomegaly + Dysphagia due to esophageal web (post cricoid) precancerous. 2. Ancylostoma anemia: Features of iron deficiency anemia. Pica+ abdominal pain, alternating diarrhea and constipation, parotid enlargement and blood eosinophilia, ova in stools III. Investigations For diagnosis of iron deficiency anemia: Complete blood count − RBCs: number, Hb, Hct are below normal − WBCs and platelets: usually normal Eosinophilia in ancylostoma infestation. − BM examination: Erythroid hyperplasia, decreased iron in macrophages Blood chemistry: − Serum iron: decreased (N: 70-170 ɥg%) − TIBC increased (N: 250-450 ɥg%) − Transferrin saturation decreased (N: 30%) − Serum ferritin decreased (10-300 ɥg%) BM: iron staining decreased  For diagnosis of the cause: Stool examination Occult blood, ancylostoma ova Investigations for GI hemorrhage − Endoscopies (esophagogastroduodenoscopy, colonoscopy, capsule endoscopy) Investigations for hemostatic disorders Gastric function tests to detect achlorhydria and malabsorption syndrome. Urogenital assessment I. Treatment of the cause II. Replacement therapy Goal: correct anemia and replenish iron stores 1. Oral iron 2. Parenteral iron III. Transfusion therapy Hb < 7-8 g/dl  Megaloblastic anemia I. Etiology: 1. Vitamin B12 deficiency Decreased intake: vegetarian. Decreased absorption: − Intrinsic factor deficiency in pernicious anemia, gastrectomy, atrophic gastritis − Malabsorption syndrome − Bacterial overgrowth, blind loop syndrome. − Diphyllobothrium latum worm − Maldigestion by H pylori gastritis, pancreas insufficiency. − Drugs: longterm PPI, metformin Decreased utilization − Congenital enzyme deficiency − Lack of transcobalamin II Increased requirements − Pregnancy − Malignancy 2. Folic acid deficiency Decreased intake − Lack of vegetables, alcoholics Decreased absorption − Malabsorption syndrome − Alcoholism − Drugs Phenytoin, methotrexate, pyrimethamine, trimethoprim, azathioprine, triamterene. Decreased utilization: − Congenital enzyme deficiency − Increased requirements − Pregnancy − Malignancy − Hyperactive hematopoiesis in hemolytic anemia Increased loss − Pregnancy − Hemodialysis II. Clinical presentation: Hematologic manifestation −Features of anemia −Features of leukopenia: fever and recurrent infections −Features of thrombocytopenia: purpura −Hepatosplenomegaly Gastrointestinal symptoms −Atrophic glossitis with red glazed tongue and burning sensation, stomatitis −Atrophic gastritis with dyspepsia, anorexia, nausea and vomiting with increased risk of gastric carcinoma. −Intestinal atrophy with abdominal pain, diarrhea and malabsorption  Neurological features with B12 deficiency − Peripheral neuropathy: pain and paresthesia of the limbs followed by stock and gloves hypothesia − Ankle reflex is lost − Subacute combined degeneration of the spinal cord − Posterior column: deep sensory loss with sensory ataxia − Pyramidal tract: weakness of the lower limbs with positive Babinski’s sign − Tone and deep reflexes are decreased (posterior column and peripheral neuropathy). Associated autoimmune diseases in pernicious anemia − Vitiligo − Grave’s disease or Hashimoto’s disease.  Investigations Red cells − Features of macrocytic anemia − Decreased Hb, RBCs count, Hct − Anisocytosis and poikilocytosis − Reticulocytes are deceased, increase with treatment − Howell-jolly bodies WBCs − Leucopenia − Large hypersegmented neutrophils Platelet count − Thrombocytopenia (< 50.000 /mml) − Giant platelets Bone marrow examination: − Hypercellular megaloblastic consisting of giant cells with abnormal morphology  Blood chemistry − Increased serum indirect bilirubin, LDH, haptoglobin − Increased serum iron − Serum B12 and Folic acid by radioimmunoassay Diagnosis of pernicious anemia − Pathological shilling test: decreased absorption of Vit B12 without intrinsic factor, normal with intrinsic factor intake − Autoantibodies: antiparietal and anti-intrinsic factor antibodies − Upper endoscopy with biopsy chronic atrophic gastritis type-A − Follow up every 2 years to exclude malignancy − Antithyroid antibodies and iron studies  Treatment Replacement therapy −Vitamin B12 deficiency −Folic acid deficiency Transfusion therapy −Hb < 7-8 g/dl Symptomatic treatment −Anemic heart failure  Hemolytic anemias Definition: anemia due to shortening lifespan of RBCs (normal 120 days) < 100 days. Hemolysis may be intravascular or extravascular Etiology: I. Corpuscular Hereditary − Membrane defect: − Hereditary spherocytosis Hemoglobin defect − Thalassemias − Sickle cell anemia − Unstable hemoglobin Enzyme defect − Glucose-6-phosphate dehydrogenase deficiency − Pyruvate kinase deficiency Non-hereditary enzyme defect: Paroxysmal nocturnal hemoglobinuria II. Extra-corpuscular 1. Immune induced hemolytic anemia Alloimmune − Incompatible blood transfusion − Hemolytic disease of the newborn (RH incompatibility) Autoimmune − Warm reacting antibodies − Drug induced antibodies − Penicillin, hapten IgG type − Quinidine or neoantigen IgM type − Alpha-methyl dopa autoimmune type − Cold reacting antibodies − Proximal cold hemoglobinuria 2. Infections: Malaria 3. Hypersplenism 4. Traumatic − Microangiopathic hemolytic anemia, DIC, HUS, TTP − Marsh hemolobinuria − Artificial and calcified cardiac valves 5. Chemicals − Snake venom − Copper in Wilson syndrome − Amphotericin B 6. Malignancies  Clinical picture of hemolytic anemias: Manifestations of anemia. Manifestations of hemolytic jaundice: lemon yellow color, dark colored stools and normal colored urine. Hepatosplenomegaly Pigmented stones in gallbladder may result in obstructive jaundice Different types of crises: Hemolytic crises Aplastic crises Megaloblastic crises Vaso-occlusive crises.  Investigations: Diagnosis of hemolytic anemias CBC Normocytic normochromic with reticulocytosis Macrocytic with folate deficiency Microcytic with intravascular hemolysis Blood film for diagnosis WBCs and platelet count are normal Bone marrow: erythroid hyperplasia Shortened life span of RBCs Increased serum indirect bilirubin, fecal stercobilinogen and urinary urobilinogen. Increased serum LDH.  For diagnosis of intravascular hemolysis Hemoglobinuria Hemosiderinuria Hemoglobinemia Marked diminished plasma haptoglobin and hemopexin Presence of methaemalbumin in plasma Diagnosis of the cause  Hereditary spherocytosis Most common hereditary anemia Autosomal dominant deficiency of red cell membrane lipoprotein (spectrin) leading to 1. RBCs are spherocyes and microspherocytes 2. Decreased deformability of RBCs with consequent destruction in the spleen 3. Increased osmotic fragility Clinical presentation − Onset during childhood − Positive family history − Features of anemia Investigations: − Diagnosis of hemolytic anemia − Blood film: spherocytes and microspherocytes − Osmotic fragility test is increased, hemolysis at 0.7-0.4 % − MCHC: increased Treatment − Splenectomy − Transfusion therapy − Folic acid 5mg/d − Treatment of complications  Sickle cell anemia Hereditary autosomal recessive abnormality in the beta chain structure leading to the formation of HbS Homozygous leading to sickle cell anemia and heterozygous leading sickle cell trait Upon exposure to hypoxia, HbS forms insoluble aggregates leading to − RBCs becomes sickle shaped − Decreased deformability of RBCs leading to destruction − Vascular occlusions Clinical presentation: − Common in blacks in central Africa − Heterozygotes are usually asymptomatic, in severe hypoxia and infections, manifestations may develop − Homozygotes: condition starts as early as 2nd month after birth − Features of hemolytic anemia − Painful vaso-occlusive crises and organ infarctions with severe abdominal, back and extremities pain, may be lower grade fever.  Complications due to: 1. vascular occlusion may lead to: − Splenic infarctions: autosplenectomy and hyposplenism − Renal infarctions: hematuria and chronic renal failure − Bone infarctions: hand and foot syndrome and avascular necrosis of the femur head − Pulmonary vascular occlusions and corpulmonale − Cerebral vascular occlusion with various neurological manifestations − Retinal detachment − Priapism and later impotence − Leg ulcers 2. Increased susceptibility to infections − Pneumococcal infections − Osteomyelitis by salmonella and staff aureus organisms 3. Iron overload due to repeated blood transfusions. Investigations Diagnosis of hemolytic anemias Blood film: sickle cells after addition of Na- metabisulphite Hemoglobin electrophoresis or high-pressure liquid chromatography: HbS (90%)  Treatment: 1. Analogous stem cell transplantation 2. Hydroxyurea 3. Symptomatic treatment: Analgesics Oxygen IV fluids ACE inhibitor in case of proteinuria Prophylaxis: − Avoidance of exposure to hypoxia in high altitudes, surgery. − Prophylaxis against infections: starting from the 3rd month after birth until 5 years old with penicillin. − Immunization against infections: influenza, pneumococcal Hemophilus influenzae − Vitamin D and folic acid − Yearly echocardiography and abdominal ultrasonography  Beta-thalassemia Thalassemia minor: Hb A slightly reduced, HbF (5-10%), HbA2 (5-10%) presents with mild anemia and splenomegaly. Thalassemia intermedia Thalassemia major: reduced HbA, HbF (80-90%) − Onset during childhood − Features of severe hemolytic anemia requiring blood transfusion with secondary hemochromatosis due to iron overload − Stunted growth, mongoloid facies, bone deformities − Organ damage due to iron overload, cardiomyopathy, skin pigmentations, diabetes mellitus, liver cirrhosis and arthritis. Investigations Diagnosis of hemolytic anemia Blood film: target cells, hypochromic, microcytosis, Hb electrophoresis or high-pressure liquid chromatography: Hb F increased (80-90%) X-ray Skull: hair-on end appearance Long bone: thin cortex and wide medulla Serum iron and ferritin increased Treatment: Analogous stem cell transplantation Repeated blood transfusions with iron chelation using deferoxamine Folic acid 5mg/d Splenectomy may be indicated in case of cytopenias (hypersplenism). Prevention: Genetic counseling Prenatal diagnosis.  Glucose-6 Phosphate Dehydrogenase Deficiency G6PD deficiency X-linked chromosomal recessive affecting males and homozygotes females. Heterozygote females show variable presentation. Clinical presentation Upon exposure to oxidative stress, acute intravascular hemolysis develops. Oxidative stresses are: Drugs: antimalarials, antipyretics, sulphonamides, suphones, water soluble analogues of vitamin K. Mothballs. Infections: pyogenic infections and viral hepatitis. Diabetic ketoacidosis and uremia. Many variants GdA- variant: common in black and enzyme defect is mild GdMed variant: common in Mediterranean, enzyme defect is severe Favism: common in Mediterranean, hemolysis upon ingestion of fava beans Investigations Diagnosis of hemolytic anemia Diagnosis of intravascular hemolysis Blood film: Heinz-bodies Assay of G6PD Treatment No specific treatment Avoidance of exposure to oxidative stresses Blood transfusion in severe cases with folic acid supplementation.