Hematological Diseases

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Hematological Diseases

• A. Apirakaramwong, Ph.D.
• Department of Biopharmacy,
• Faculty of Pharmacy,
• Silpakorn University

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Learning Objectives

• State concepts of hematopoiesis and describe how
  hematopoiesis will change in abnormal states
• Describe types, causes, and pathophysilology of
  some importance disorders of red cells, white
  cells as well as pletelets
• Explain how to identify such importance disorders
  by gathering data from laboratory tests as a role
  of pharmacists
• State main symptoms and sign, also suggest
  suitable therapy for those disorders

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Hematopoiesis

• Pluripotent stem cell Myeloid stem cell
  Lymphoid stem cell
• Myeloid stem cell erythrocyte, granulocyte,
  megakaryocyte
• Lymphoid stem cell B, T lymphocyte
• Cytokines ILs, CSF, EPO, TPO
• ?????? 1

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Hematopoiesis
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Bands
Reticulocyte
Howard,MR, and Hamilton, PJ, p.3, 2002.
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Peripheral thin blood smear (Wright stain)
Eosinophil
Neutrophil
Platelete
Neutrophil
Lymphocyte
Basophil
Monocyte
http//www-medlib.med.utah.edu/WebPath/HEMEHTML/HE
ME100.html
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Normal values- formed elements of blood (1)
Morphology of Blood cell - Blood smear ( thin
film)
?????????? Hutson,PR, p. 443, 2004 ??? Lichtman,
MA, et. al., p. 3-4, 2003
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RI and Anemia
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Normal values- formed elements of blood (2)

• ESR RBC ????????? (agglutination)
  ??????????????????????/?? ESR (???????? 3 ???? 9)
  eg. ESR ? ?????? macrocytosis (volume ??? RBC ?)
• Platelet (/microliter) 1.5-4.5 ???
• platelet ? ??????????????? RBC ???? microcytic
  RBC
• ? ??????? platelet clump
• Serum ferritin
• Fe (store in 1. ferritin ?????????? macrophage
  and 2. Hemosiderin in cells transfer by
  transferrin)
• serum ferritin ????????????? Fe (IDA)

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Normal values- formed elements of blood (3)

• Serum iron, Total iron-binding capacity (TICB)
• serum Fe ??? Fe-transferrin
• serum iron 1/3 TICB
• IDA ??? TICB ?????????????????????? transferrin
  ????? ??? saturation transferrin ???? ????
• serum iron 100 mcg/dL TICB 300 mcg/dL
• sat trans (100/300) x100 33
• ??? sat trans lt 15 ---gt IDA

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Normal values- formed elements of blood (4)

• WBC diffential
• Granulocytes
• Neutrophils
• seg, PMN, polys (???? lobes) ????????--gt
  endothelium until stimulated (????????,
  glucocorticoid)
• bans, stabs
• Eosinophils/basophils eos/parasite
  baso/allergy
• Monocytes/macrophages T,B cell function
• Lymphocytes (T, B, NK cells)

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Terms in blood smear (????? 4 ???? 12)
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Red cell Disorders

• Anemia
• 1. Acute/chronic Blood loss
• 2. Hemolytic anemias
• Hereditary Spherocytosis
• hemoglobinopathies Sickle cell anemia,
  Thalassemias,
• red cell enzyme defects G6PD deficiency
• Trauma
• 3. Impaired production Megaloblastic anemia,
  Iron deficiency anemia (IDA), anemia from chronic
  diseases(ACD)
• 4. Aplastic (hypoplastic) anemia
• Polycythemia

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White blood cell disorders

• Leukopenia
• Neutrophenia
• Lymphocytopenia
• Leukocytosis
• Granulocytosis
• Lymphocytosis
• Neoplastic proliferations of white cells
• Malignant lymphoma
• Leukemias

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Platelet disorders

• Quantitative disorders
• thrombocytopenia (40,000/ mL)
• thrombocytosis (1,000,000/ mL )

• Qualitative disorders
• Inherited
• Acquired

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Coagulation disorders

• Hemophilias
• Coagulation disorders
• Von Willebrand disease
• Vitamin K deficiency
• DIC
• Afrinogenemia
• Liver diseases

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Red cells

• Production (erythropoiesis)
• 120 days
• produce in bone marrow 1 week
• renal interstitial tubular cell EPO (stimulated
  by hypoxia)
• hemoglobin HbA (alpha2 beta2)
• HbA2 (alpha2 delta 2), HbF (alpha2 gamma2)
• Fe (80) Hb (13) Mb rest ferritin and
  hemosiderin absorption in heme iron (Fe 2) or
  noneheme iron with vit C
• produce rapidly when Vit B12, folate and Fe
  adequate

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Red cells (cont.)

• Membrane
• elasticity, deformibility, ATP from glycolysis ,
  NADPH (PPP) glutathione
• spectrin-actin, ankyrin
• Degradation
• spleen phagocytosis
• Hb--heme oxygenase--gtFe, biliverdin--gt bilirubin
  --gt bilt salt

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Red cell membrane

Aster J., p 399, 2003
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Anemia

• ?????, MCV ?
• ??????? ??????
• Microcytic
• Macrocytic
• Poikilocytosis (shape)
• Anisocytosis (size)
• ????????
• Hypochromic
• Hyperchromic

http//www-medlib.med.utah.edu/WebPath/HEMEHTML
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Anemia

• Hb or Hct lt normal range
• hypoxia
• compensation by ? EPO, erythropoiesis, cardiac
  output
• ?????
• ??? ????????? ?????? ??????? ?????? ???????? ???
  ?????????????
• ????????????? ? ????????????????? kailonychia
  (????????) ?? IDA jaundice in hemolytic anemia
  bone demormities in thalassemia
• ???????????? ???????? 5 ???? 16

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Classification of Anemia

• Anemia of blood loss
• Hemolytic anemia
• Hereditary Spherocytosis (HS)
• Hemoglobinopathies sickle cell anemia and
  thalassemia syndrome
• Red cell enzyme defect (G6PD)
• Trauma to red cells
• Impaired of red cell production
• Iron deficiency anemia (IDA)
• Megaloblastic anemia
• Anemia of chronic disease
• Aplastic anemia

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Anemia of blood loss

• Acute or chronic blood loss (3-4 wk to recover)
• Iron deficiency anemia
• Malnutrition or pregnancy

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Hemolytic anemia

• Normocytic, normochromic
• Bilirubin ?
• ? Erythropoiesis lead to ? reticulocyte
• Intrinsic (Intracorpuscular) defect of RBC
  membrane, Hb, metabolism, enzyme
• Extrinsic membrane defect autoimmune, oxidants

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Hemolytic anemia

• ???????????????????? ?????? ????????? bile
  ?????????
• ????????????? Hgb ???? 1 g/dL ??? 1 ???????
• ?? G6PD, Thalassemia, HS ?????????????
• ?????? ???????? ????????????? ? hemolysis crisis
• ???????????? ????? ??????????? ????
  beta-thalassemia
• ????? ??????, hemoglobinuria, ?????????????? ????
  bone deformities

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Treatment

• ??????????????????? RBC ???
• ????? complication ???? hyperkalemia, kidney
  failure
• ????????????? ???????????? (hypertransfusion)
• ???????????? ???? antimalarial agents
• ?????? folic acid supplement 5 mg/d

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Hemolytic anemia

• Hereditary Spherocytosis (HS)
• Hemoglobinopathies
• sickle cell anemia
• thalassemia syndrome
• Red cell enzyme defect (G6PD)
• Trauma to red cells