Anemia - General aspects

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Anemia- General aspects

• Department of Hematology
• Rui Jin Hospital

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Anemia

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

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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

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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)
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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 (??)

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Pronormoblast
Normoblasts
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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

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Anemia Etiologies

• Production defects
• Blood loss
• Blood destruction

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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

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RBC Destruction

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

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• 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

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???????(pathophysiology of anemia)

• ?RBC??????????
• ???????Hb???1.34ml?
• ???????????????????,????
• ?????????????????

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???????

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

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???????

• ??????? ???????????,??????????????,?????,????????
  ??????????
• ?????? ???????????????,???????????,??????????????
  

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???????

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

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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

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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

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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 (?????)

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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

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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

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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

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Neuromuscular system

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

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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)

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Others

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

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Evaluation and diagnosis

• Medical History
• Physical examination
• Laboratory tests
• Morphologic features

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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

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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

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Physical examination

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

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Morphologic feature

• Blood smear
• Bone marrow examination

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Classification

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

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Anemia?
Survival Destruction?
Production?
The key test is the ..
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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).

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Another step of diagnosis

• Anemia
• Erythrocyte indices
• blood smear
• MCVgt100 MCV 80-100 MCVlt80
• Macrocytic Normocytic Microcytic
• (????) (?????) (????)

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Macrocytic anemias

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

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• 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.

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Note the hypersegmented neurotrophil and also
that the RBC are almost as large as the
lymphocyte. Finally, note that there are fewer
RBCs.
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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

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Folate deficiency

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

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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

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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

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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

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Food

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

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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

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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).
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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

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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

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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

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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

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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

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Therapy

• Etiology
• ??????????????????
• ??????????????????????????????????????
• ???????????????????B12,???????????

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Therapy

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

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

• Transfusion support
• ??????????????????
• ?????????????????
• ??????????????????

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Therapy

• Splenectomy
• ? ??????????,?????????
• ? ????????????????????????????,?????
• ? ???????????????????????,??????

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Therapy

• Marrow transplantation
• - ?????????
• - ??????????????
• - ?????????