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Anemia - General aspects

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Title: Anemia - General aspects


1
Anemia - General aspects
  • Department of Hematology
  • Rui Jin Hospital

2
Anemia
  • Most important
  • Related to many diseases
  • Diagnosed properly
  • Treated properly

3
What is anemia?
  • A reduction below normal in the
  • - concentration of hemoglobin
  • - red blood cells in the blood
  • - hematocrit (?????)
  • The blood hemoglobin concentration often
    preferred
  • - accuracy and reproducibility
  • - value most indicative of the patho-physiologic
    consequences of anemia

4
Normal range - adult
RBC (1012/L) HGB(g/L) Hemotocrit
M 4.0-5.5 (400-550?/mm3) 120-160 (12-16g/dl) 0.4-0.5 (40-50)
F 3.5-5.0 (350-500?/mm3) 110-150 (11-15g/dl) 0.37-0.45 (37-45)
5
Conditions associated with a significant
disproportion between the hematocrit and RBC?
  • Spurious anemia (????)
  • - relative increase in plasma volume
  • hydremia of pregnancy
  • overhydration in oliguric renal failure or
    congestive heart failure
  • chronic diseases and hypoalbuminemia
  • congestive splenomegaly
  • recumbency (??)

6
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7
Pronormoblast
Normoblasts
8
Regulation of erythropoiesis
  • How many are produced?
  • 25 billion /24 hours
  • The entering cells are reticulocytes which should
    be 1 of the total population of circulating
    erythrocytes
  • Erythrocytes last 120 days and are destroyed by
    the spleen
  • Red cell production should equal red cell
    destruction

9
Anemia Etiologies
  • Production defects
  • Blood loss
  • Blood destruction

10
RBC loss without RBC Destruction
  • Hemorrhage
  • - Due to trauma
  • - Due to disorders e.g. cancer, ulcers,
    tuberculosis, and irritable bowel syndrome
    (including ulcerative colitis and Crohns
    disease)
  • Menstrual flow
  • Gynecological disorders (e.g. endometriosis)
  • Pregnancy, especially at gestation
  • Parasitism
  • - Hookworms

11
RBC Destruction
  • Intrinsic Abnormalities
  • Thalassemia
  • G6PD
  • Sickle Cell Anemia
  • Hereditary Spherocytosis
  • Extrinsic Abnormalities
  • Infections
  • Malaria (Plasmodiumm species)
  • Mycoplasma (???)
  • Disseminated Intravascular Coagulation
  • Lead poisoning

12
  • Conditions Associated with Anemias Due to Reduced
    Erythrocyte Production
  • Anemias due to decreased erythropoietin
    production
  • Renal disease
  • Endocrine deficiency (pituitary, adrenal,
    thyroid, testis)
  • Starvation
  • Hemoglobinopathy (reduced oxygen affinity)
  • Anemias due to inadequate marrow response to
    erythropoietin
  • Deficiency state (iron, vitamin B12, folate)
  • Anemia of chronic disease (inflammation,
    infection, or malignancy)
  • Sideroblastic anemia
  • Primary marrow disorders-pure red cell aplasia,
    myelodysplasia, myelofibrosis, leukemia
  • metastasis to bone marrow, osteogenic sarcoma

13
??????? (pathophysiology of anemia)
  • ?RBC??????????
  • ???????Hb???1.34ml?
  • ???????????????????,????
  • ?????????????????

14
???????
  • ???????
  • ?????RBC??,?????????????????,????????
  • ????,??????
  • ???????????,???????

15
???????
  • ??????? ???????????,??????????????,?????,????????
    ??????????
  • ?????? ???????????????,???????????,??????????????

16
???????
  • ???????
  • ????????,RBC?2?3??????(2?3-DPG)?????
  • 2?3-DPG?Hb????????
  • ??Hb O2??????,????????????????????

17
Clinical manifestation
  • First symptom
  • - decreased work tolerance
  • - shortness of breath
  • - palpitations
  • - other signs of cardiorespiratory adjustments
    to anemia
  • - at times, they feel fine, but their friends or
    family notes the pallor

18
The manifestations depend on
  • The reduction in the oxygen-carrying capacity of
    the blood
  • The degree of change in total blood volume
  • The rate at which these two factors developed
  • The capacity of the cardiovascular and pulmonary
    systems to compensate for the anemia
  • The associated manifestations of the underlying
    disorder

19
Cardiorespiratory system
  • Noticeable only after exertion or excitement
  • Dyspnea and awareness of vigorous or rapid heart
    action noted at rest
  • Shortness of breath, tachycardia, dizziness or
    faintness, and extreme fatigue
  • Congestive heart failure, angina pectoris,
    intermittent claudication (?????)

20
Cardiorespiratory system
  • Left ventricular hypertrophy
  • Heart murmurs
  • - systolic in pulmonic area
  • Electrocardiographic changes
  • - depression of the ST junction
  • - U-shaped deformation of the S-T segment
  • - inverted T waves

21
The skin
  • Pallor most evident sign
  • - dilation of the peripheral vessels
  • - degree and nature of the pigmentation
  • - nature and fluid content of the subcutaneous
    tissues
  • - jaundice, cyanosis
  • Detected most accurately in the mucous membranes
    of the mouth and pharynx, conjunctivae, lips, and
    the nail beds, palms of the hands

22
Tell anemia from the color of the skin
  • A waxy, dead whiteness
  • - acute blood loss
  • A distinctly sallow (???)color
  • - chronic anemia
  • A lemon-yellow pallor
  • - pernicious anemia(????)
  • Marked pallor associated with petechiae or
    ecchymoses(??)
  • - acute leukemia

23
Neuromuscular system
  • Headache
  • Vertigo
  • Tinnitus (??)
  • Faintness
  • Scotomata (??)
  • Lack of mental concentration
  • Drowsiness
  • Restlessness
  • Muscular weakness

24
Gastrointestinal system
  • Underlying diseases ulcer, cancer
  • Glossitis and atrophy of the papillae of the
    tongue
  • Painful, ulcerative, and necrotic lesions in the
    mouth and pharynx (aplastic anemia, acute
    leukemia)
  • Dysphagia
  • (chronic iron-deficiency anemia)

25
Others
  • Retinopathy 20
  • - flame-shaped hemorrhages
  • Slight proteinuria
  • Fever of mild degree
  • Hemolytic anemia
  • - jaundice
  • - hemoglobinemia, pain in the abdomen or back

26
Evaluation and diagnosis
  • Medical History
  • Physical examination
  • Laboratory tests
  • Morphologic features

27
Medical history
  • The duration of the symptoms and their onset
    (insidious/acute)
  • Family history of jaundice, splenectomy, bleeding
    disorders, and hemoglobin-associated
    abnormalities
  • Occupation, drugs, solvents and other chemicals

28
Others
  • Stool habits neoplasms of the colon and rectum,
    hemorrhoids
  • Women blood lost during menstruation
  • Child or adolescent growth rate
  • Dietary history
  • Fever infection, lymphoma, collagen disease,
    etc.
  • Bruises, ecchymoses, and petechiae

29
Physical examination
  • Icterus ?? (hemolytic)
  • Sternal tenderness (leukemia)
  • Lymph nodes enlargements (infection, lymphoma,
    leukemia, metastatic carcinoma)
  • Cardiac murmurs (bacterial endocarditis)
  • Liver, spleen, and kidneys

30
Morphologic feature
  • Blood smear
  • Bone marrow examination

31
Classification
  • Impaired erythrocyte production
  • - hypoproliferative
  • iron-deficient erythropoiesis
  • erythropoietic deficiency
  • hypoplastic anemia
  • infiltration
  • - ineffective
  • megaloblastic
  • microcytic
  • Increased erythrocyte production
  • - hemolytic anemia

32
Anemia?
Survival Destruction?
Production?
The key test is the ..
33
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34
The reticulocyte count
  • Increased reticulocytes (greater than 2-3 or
    100,000/mm3 total) are seen in blood loss and
    hemolytic processes, although up to 25 of
    hemolytic anemias will present with a normal
    reticulocyte count due to immune destruction of
    red cell precursors.
  • Retic counts are most helpful if extremely low
    (lt0.1) or greater than 3 (100,000/mm3 total).

35
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36
Another step of diagnosis
  • Anemia
  • Erythrocyte indices
  • blood smear
  • MCVgt100 MCV 80-100 MCVlt80
  • Macrocytic Normocytic Microcytic
  • (????) (?????) (????)

37
Macrocytic anemias
  • Vitamin B12 or folate deficiency
  • Accelerated erythropoiesis
  • - hemolytic anemia
  • Erythroleukemia (????)
  • Increased membrane surface
  • - hepatic disease, obstructive jaundice
  • Refractory anemias
  • - myelodysplastic anemias

38
  • Normal, RBC's. They have a zone of central pallor
    about 1/3 the size of the RBC.). A few small
    fuzzy blue platelets are seen. In the center of
    the field are a band neutrophil on the left and a
    segmented neutrophil on the right.

39
Note the hypersegmented neurotrophil and also
that the RBC are almost as large as the
lymphocyte. Finally, note that there are fewer
RBCs.
40
Vitamin B12 deficiency
  • Dietary deficiency (rare)
  • Lack of intrinsic factor
  • - pernicious anemia
  • - gastric surgery
  • Functionally abnormal intrinsic factor
  • Biologic competition
  • - small-bowel bacterial overgrowth
  • Drug-induced vitamin B12 malabsorption
  • Chronic disease of the pancreas
  • Zollinger-Ellision syndrome
  • Hemodialysis

41
Folate deficiency
  • Dietary deficiency
  • Increased requirements
  • - alcoholism and cirrhosis
  • - pregnancy
  • - infancy
  • Congenital folate deficiency
  • Extensive intestinal resection

42
Diagnosis
  • Smear
  • - Macrocytic (High MCV) RBCs, /- hypersegmented
    neutrophils, /- modest neutropenia
  • B12
  • - Low serum B12 level
  • Folate
  • - Serum folate level -- can normalize with a
    single good meal

43
Neurological presentation of B12 deficiency
  • Paresthesias of fingers toes
  • Reduced vibration sense (256-Hz)
  • Ataxia ???? (Combined system disease)
  • Perversion of taste smell
  • Optic atrophy
  • Dementia (??), Memory Loss Depression
  • Megaloblastic Madness Paranoid Schizophrenia
  • Specific MRI abnormalities

44
Treatment
  • B12 deficiency
  • - B12 1 mg/month IM, or 1-2 mg/day po
  • Folate deficiency
  • - Improved diet, 5mg tablets
  • Monitor for a response to therapy
  • Pernicious Anemia monitor for GI cancers

45
Food
  • B12 deficiency
  • Meat
  • Eggs
  • Folate deficiency
  • Green vegebables
  • Nuts
  • Cereal
  • Fruit
  • Yeast

46
Microcytic anemias
  • Disorders of iron metabolism
  • - iron-deficiency anemia
  • - anemia of chronic disorders
  • Disorders of globin synthesis
  • - thalassemias
  • - hemoglobin E and C disease
  • Sideroblastic anemia

47
The RBC's here are smaller than normal and have
an increased zone of central pallor. This is
indicative of a hypochromic (less hemoglobin in
each RBC) microcytic (smaller size of each RBC)
anemia. There is also increased anisocytosis
(variation in size) and poikilocytosis (variation
in shape).
48
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49
Iron Deficiency Anemia vs. anemia of
chronic disorders
  • Smear
  • - hypochromic and microcytic (low MCV) RBCs,
    usually not seen unless Hct ? 30
  • - platelet count is often elevated
  • Ferritin a measure of total body iron stores,
    but also an acute phase reactant
  • - lt15?g/l Fe deficiency
  • - ?150 ?g/l Not Fe deficiency
  • - 15-150 ?g/l Not conclusive
  • Bone marrow
  • - absent Fe stores Gold standard for IDA

50
Thalassemias
  • Genetic defect in hemoglobin synthesis
  • - ? synthesis of one of the 2 globin chains (?
    or ?)
  • - Imbalance of globin chain synthesis leads to
    depression of hemoglobin production and
    precipitation of excess globin (toxic)
  • - Ineffective erythropoiesis
  • - Ranges in severity from asymptomatic to
    incompatible with life (hydrops fetalis)
  • - Found in people of African, Asian, and
    Mediterranean heritage

51
Thalassemias
  • Diagnosis
  • - Smear microcytic/hypochromic
  • - ?-thal will have an abnormal Hgb
    electrophoresis (?HbA2, ?HbF)
  • - The more severe ?-thal syndromes can have HbH
    inclusions in RBCs
  • - Fe stores are usually elevated
  • Treatment
  • - Mild None
  • - Severe RBC transfusions Fe chelation, Stem
    cell transplants

52
Sideroblastic Anemias
  • Heterogenous grouping of anemias defined by
    presence of ringed sideroblasts in the BM
  • Etiologies
  • - Hereditary (rare)
  • - Myelodysplasia
  • - EtOH
  • - Drugs (INH, Chloramphenicol ???)
  • Treatment
  • - Trial of pyridoxine for hereditary or INH
    induced sideroblastic anemia

53
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54
Normocytic anemias
  • Associated with appropriately increased
    erythrocyte production
  • - posthemorrhagic anemia
  • - hemolytic anemia
  • Associated with impaired marrow response
  • - intrinsic bone marrow disease
  • hypoplasia
  • infiltration of the bone marrow
  • - decreased erythropoietin secretion
  • renal

55
Therapy
  • Etiology
  • ??????????????????
  • ??????????????????????????????????????
  • ???????????????????B12,???????????

56
Therapy
  • Drug treatment
  • 1.Iron?????????????
  • ????????????????
  • 2.Folic acid and VitaminB12
  • ????????????????????
  • ???????????

57
Therapy
3. Vitamin B6 100mg 23?/d???????????? 4.Gluc
ocorticoid(?????) ??????????
??????????????????? ???,????????? 5.
Androgen(???) ??(gt36?)???????????
????????????????? 6. Epoetin(EPO)????????
58
Therapy
  • Transfusion support
  • ??????????????????
  • ?????????????????
  • ??????????????????

59
Therapy
  • Splenectomy
  • ? ??????????,?????????
  • ? ????????????????????????????,?????
  • ? ???????????????????????,??????

60
Therapy
  • Marrow transplantation
  • - ?????????
  • - ??????????????
  • - ?????????
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