HEMATOLOGY

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HEMATOLOGY
ANEMIAS
Prof / Mervat Abdallah Hesham
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Hematopoiesis Development
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Sites of hematopoiesis

• First Trimester - Yolk Sac
• Second Trimester -Liver and Spleen
• Third Trimester - Central, Peripheral Skeleton
• Adulthood - Axial Skeleton , Vertebral Bodies
  , Sternum Ribs Pelvis
• Hematopoiesis may re-xpand into fetal sites in
  times of severe demand, 
•      e.g. thalassemia

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• Anemia
• Decrease in Hgb.
• Decrease in rbc
• decrease in hct

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ANEMIACauses

• Blood loss
• Decreased production of red blood cells (Marrow
  failure)
• Increased destruction of red blood cells
• Hemolysis
• Distinguished by reticulocyte count
• Decreased in states of decreased production
• Increased in destruction of red blood cells

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Clinical picture of anemia

• Symptoms of anemia
• pallor, fatigue, lethargy, dizziness, and
  anorexia.
• Jaundice and, occasionally, dark urine may be
  present with significant hemolysis.
• Failure to thrive indicates a long-
• standing condition

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• Physical signs
• tachycardia, tachypnea
• pallor, jaundice, edema, and signs of bleeding
• systolic ejection murmur
• signs of CHF (eg, tachycardia, gallop rhythm,
  tachypnea, cardiomegaly, hepatomegaly).
• Splenomegaly
• dysmorphic features and other congenital
  anomalies

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Different ways to classify anemias

• Size and hemoglobin content of rbc
• Mechanism of its production

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Classification according to mechanism

• 1- Blood loss acute and chronic
• 2- Excessive destruction of rbcs
• 3- Decreased production of rbcs

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decreased red cell production

• 1- Marrow failure
• Diamond-Blackfan anemia
• Aplastic crisis
• Aplastic anemia
• 2- Impaired erythropoietin production
• Anemia of chronic disease in renal
  failure
• Chronic inflammatory diseases
• Hypothyroidism
• Severe protein malnutrition
• 3- Defect in red cell maturation
• Nutritional anemia secondary to iron,
  folate, or vitamin B-12 deficiency
• Sideroblastic anemias

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increased red cell destruction (hemolysis)

• Intracellular causes
• 1-Red cell membrane defects (eg, hereditary
  spherocytosis, elliptocytosis)
• 2-Enzyme defects (eg, G-6-PD deficiency, pyruvate
  kinase deficiency)
• 3-Hemoglobinopathies (sickle cell , Thalassemias
  )
• Extracellular causes
• 1-Antibodies (autoimmune hemolytic anemia)
• 2-Infections, drugs, toxins
• 3-Thermal injury to red blood cells (with severe
  burns)
• 4-Mechanical injury (hemolytic-uremic syndrome,
  cardiac valvular defects)

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Laboratory diagnosis of anemia

• CBC, reticulocyte count, and review of the
  peripheral smear
• Bilirubin level, lactate dehydrogenase (LDH)
  (hemolytic anemia)
• Direct antiglobulin or Coombs test (autoimmune
  hemolytic anemia)
• Hemoglobin electrophoresis (hemoglobinopathies)
• Red cell enzyme studies (eg, G-6-PD, pyruvate
  kinase)
• Osmotic fragility (spherocytosis)
• Iron, TIBC, ferritin (iron deficiency anemia)

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• Folate, vitamin B-12 (macrocytic/megaloblastic
  anemia)
• Bone marrow aspiration and biopsy
• Viral titers (eg, Epstein-Barr virus,
  cytomegalovirus)
• BUN/creatinine levels to assess renal function
• Thyroxine (T4)/thyroid-stimulating hormone (TSH)
  to rule out hypothyroidism

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Treatment of anemia

• 1- Transfusion with packed RBCs (PRBC) is the
  universal treatment
• 2-Medications for specific forms of anemia (eg,
  corticosteroids for autoimmune hemolytic anemia,
  iron therapy for iron deficiency anemia).
• 3-Recombinant erythropoietin (renal failure),
  chemotherapy , prematurity )

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Hemolytic anemias

• Hemolytic anemia is a disorder in which the red
  blood cells are destroyed faster than the bone
  marrow can produce them.

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Clinical Features

• Pallor
• Jaundice
• Splenomegaly
• No bile in urine
• Pigment gall stones in chronic forms
  
• Crisis aplastic, hemolytic, vascular
• Ankle ulcers

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• Clinical Features of Sickle Cell Disease

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Clinical picture of thalassemia
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Laboratory Evaluation

• Features of RBC breakdown
• Hyperbilirubinemia
• Increased Urine UBG Faecal
  stercobilinogen.
• Low or absent Haptoglobins
• Haemoglobinaemia, Haemoglobinuria,
  Haemosiderinuria
• Methhaemalbuminaemia
• Features of increased RBC Production
• Reticulocytosis
• Marrow erythroid hyperplasia bone
  changes
• Specific tests
• Morphology, Osmotic Fragility,coombs test
• Decreased RBC survival 51Cr labelling.
• Hemoglobin electrophoresis, enzyme
  abnormality

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Treatment for hemolytic anemia

• blood transfusions
• corticosteroid medications
• surgical removal of the spleen
• immunosuppressive therapy
• Iron chelation therapy

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• Structure Synthesis of Haemoglobin
• Hb in adult Hb A Hb F Hb A2
• Structure a2 ß 2 a2 ?2 a2d2
• Normal 96-98 0.5-0.8 .5-3.2

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Nutritional anemia
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Nutritional anemia

• Iron deficiency
• Vit. B12 and folate deficiencies
• Vitamin-deficiency (vit.A, vit. B group, vit.
  C/scurvy, vit.E)
• Mineral deficiencies other than iron (copper and
  zinc)
• Starvation (anorexia, war prisoners,
  conscientious objector)
• Kwashiorkor (protein deficiency)
• Alcoholism in adolescent

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Mechanism of Nutritional Anaemias

• Impaired dietary intake
• I intake or delivery to small intestine
• Maldigestion
• inability to digest macronutrients
• Malabsorption
• impaired nutrient transport across
  intestinal mucosa
• Impaired metabolism
• altered metabolism of energy and nutrients
• Nutrient excretion
• excessive loss of nutrients
• Increased requirements

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Iron Deficiency Anemia
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• Causes of Iron deficiency Anemia
• 1-Iron store depletion
• Inadequate intake-Rapid Growth- Blood donation
• 2-Abnormal Iron looses
• menses in childbearing age women, iron transfer
  to the fetus during pregnancy, hookworm
  infestation or intake of aspirin or other
  anti-inflammatory drug

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• Infants at High Risk for Iron Deficiency
• Low birth weight
•  Perinatal bleeding
•  Low hemoglobin at birth
•  High growth rate
•  Low socioeconomic status
•  Chronic hypoxia- high altitude
•  Frequent infections
•  Early cow milk /- solid food intake
•  Frequent tea intake
•  Low meat, Vit C intake

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Clinical Presentation

• Asymptomatic
• Pallor
• Irritability, exercise intolerance, fatigue, and
  tachycardia
• Koilonychia
• In severe Fe-deficient patients, fingernails
  become brittle and ridged, and eventually
  "spoon-shaped" or concave.
• Tongue may atropy("glossitis")

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• Impaired neuromuscular response (total exercise
  time and maximum workload are all affected
  adversely).
• Behavioral studies report irritable, disruptive,
  have short-attention spans, and lack interest in
  their surroundings.

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Laboratory investigations

• Low hematocrit and hemoglobin
• Small red blood cells
• Low serum ferritin
• Low serum iron level
• High iron binding capacity (TIBC) in the blood
• Blood in stool (visible or microscopic)

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• Prevention of Iron Deficiency
• Improve Dietary intake of iron
• Breast feed to 1 yr (at least)
• Iron-fortified formula to 1 yr (if not BF)
• No solid foods before 6 mo
• No cow's milk or tea before 1 yr

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• 5- two months usually need to achieve normal Hb
  and then 2 more months of therapy for
  replenishing stores
• 6-maintenance afterwards if indicated at 2mg/kg/d
• 7-IM and IV iron ( iron dextran) available but
  rarely indicated
• 8-Transfusion rarely needed and if so give
  slowly and small amount with diuretic to avoid
  added strain to heart

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Treatment of iron deficiency Anemia

• -encourage iron rich foods and vit C
• -start iron therapy at 4-6 mg/kg/d 3-using the
  ferrous sulfate ( fer in sol) preferably ( up to
  200mg/d max) or ferrous gluconate
• -check retic count at 1 week and Hb at 2-3 weeks
  ( should be reaching midway level)

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Megaloblastic Anemia
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Causes of Megaloblastic Anemia

• Vitamin B12 Deficiency
• inadequate B12 intake
• malabsorption from the gut
• intestinal disease (fish tapeworms or
  inflammation)
• lack of intrinsic factor or its receptor
• transcobalamin II (TCII) deficiency

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• Folate Deficiency
• inadequate folate intake
• increased folate loss of need
• malabsorption from the gut
• defective intracellular metabolism (inherited
  defects)
• antimetabolites used in chemotherapy

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Clinical Data

• Some patients can have GI symptoms such as loss
  of appetite, weight loss, nausea, and
  constipation.
• Patients may have a sore tongue and canker
  sores.
• Patients may have symptoms of anemia.

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• Early neurological symptoms include paresthesias
  in the feet and fingers, poor gait, and memory
  loss.
• At later stages, patients can have severe
  disturbances in gait, loss of position sense,
  blindness due to optic atrophy, and psychiatric
  disturbances. In some patients, neurological
  impairment can occur without anemia.

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Laboratory diagnosis

• Complete blood count (shows anemia with large red
  blood cells)
• Bone marrow examination
• Serum B-12
• Schilling test (may identify poor absorption as
  cause of vitamin B-12 deficiency)
• Serum folate

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Treatment of Megaloblastic Anemias

• Due to folic acid deficiency
• --oral folate (5 mg per day for 4 months)
• Due to vitamin B12 deficiency
• --parenteral (by shot NOT in ingestion) vitamin
  B12 (6 doses of 100 µg of vitamin B12 over a
  period of 2-3 weeks
• --pernicious anemia treatment is life-long
  administration of vitamin B12

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Aplastic anemia
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• Defenition
• aplastic anemia is a failure of the bone marrow
  to cells. Cells.properly form all types of
  blood
• Causes
• 70 of aplastic anemia cases are idiopathic, but
  other known causes are
• Hereditary
• Fanconi anemia
• Dyskeratosis congenital
• Schwachman-Diamond syndrome
• Amegakaryocytic thrombocytopenia

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• Acquired
• 1-Direct stem cell destruction
• 2-Drugs (Chemotherapy-Chloramphenicol -
  Sulfonamides - Phenytoin )
• 3-Toxic chemicals (Benzene Toluene
  Insecticides)
• 4-Infection (viral hepatitis)
• 5-Immune disorders
• 6-Collagen vascular diseases (Systemic Lupus
  Erythematosus )
• 7-Radiation therapy

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Clinical features

• Anemia fatigue and pallor
• Thrombocytopenia unexplained or excessive
  bleeding, easy bruising
• Neutropenia fever, mucosal ulcerations,
  bacterial infection

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Clinical features of Fanconi anemia

• - Short stature
• - Anomalies of the thumb and arm
• - skeletal abnormalities (hip abnormalities,
  spinal malformations, scoliosis )
• - Abnormalities of the gastrointestinal tract
  ,kidney and heart.
• - Skin discoloration
• - Small head or eyes
• - Mental retardation

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Laboratory diagnosis

• 1- Complete blood count shows anemia, decreased
  white blood cell count, decreased platelets , low
  reticulocytic counts.
• 2-Bone marrow biopsy shows few blood
• 3-Chromosome breakage and other tests for
  fanconi anemia

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Treatment

• 1- Transfusions(red blood and platelet
  transfusions).
• 2- immunosuppressive drugs
• antilymphocyte globulin (ALG)
• cyclosporine
• G-CSF GM-CSF (stimulate white
  blood cell production)
• Androgens
• 3- Bone Marrow Transplantation

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MORPHOLOGICAL CLASSIFICATION OF ANEMIA IN CHILDREN
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Microcytic hypochromic anemia

• 1-Iron deficiency
• 2- Thalassemia syndrome
• 3-Anemia of chronic infection and
  inflammations
• 4-Sideroblastic anemias
• 5-Lead poisoning

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Normocytic, Normochromic anemia

• i) Post-hemorrhage - early stage
• ii) Hemolytic anemia,
• iii) IDA - early stage,
• iv) Systemic diseases like endocrinal, renal and
  hepatic diseases
• v) Bone marrow disorders like hypoplastic
  anemia, myeloinfiltration, dyserythropoiesis,
  myelodysplasia and masked megaloblastosis.

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Macrocytic anemia

• Non-megaloblastic anemia like
• Hemolytic anemia, Liver disorder,
  obstructive jaundice , Post splenectomy, Bone
  marrow disorders like hypoplastic anemia ,
  dyserythropoietic anemia
• Megaloblastic anemias like
• Folate deficiency, B12 deficiency, Congenital
  disorders of DNA synthesis like Orotic aciduria
  

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