Approach to Patients with Anemia

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Approach to Patients with Anemia
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Anemia in Adults

• Definition

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Anemia in Adults

• Definition
• Common definition
• Male Hb lt 14(13.5) g/ dL
• Female Hb lt 12(11.5) g/ dL

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Classification

• Clinical findings
• Acute
• Chronic
• Red cell kinetics
• Reticulocyte count or reticulocyte production
  index (RPI 2.5)
• Impaired production
• Hypoproliferative
• Marrow damage (Infiltration/fibrosis/malignany..)
• Iron deficiency
• Marutration disorder
• Folate/Vit. B12 deficiency
• Excessive destruction
• Hemolysis, blood loss, hypersplenism
• Red cell size
• MCV

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Anemia

• History taking

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Anemia

• History taking
• Onset duration of symptoms

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Anemia

• History taking
• Onset duration of symptoms
• Family history jaundice, gall stone, splenectomy
• Drug history
• Dietary history(alcohol?)
• Change in stool habits
• Amount of blood loss during menstruation
• Bleeding tendency
• Color of urine( hematuria, hemoglobinuria)
• Renal disease, liver disease, chronic disease,
  endocrinopathy, or maligancy
• Surgery

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Anemia

• Physical examination

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Anemia

• Physical examination
• Sclera icterus
• Tongue mucosa
• Sternal tenderness
• Live, spleen, lymphadenopathy
• Petechiae, bruises, ecchymosis

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Anemia

• Initial laboratory evaluation

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Anemia

• Initial laboratory evaluation
• CBC WBC differential count
• Reticulocyte count
• Peripheral blood smear

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Anemia

• Initial laboratory evaluation
• CBC WBC differential count
• MCV
• WBC count and differentiation
• Platelet count
• Reticulocyte count
• Reticulocyte index
• Absolute reticulocyte count
• Peripheral blood smear
• RBC morphology

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CBC WBC Differential Count

• Thrombocytopenia or abnormal WBC number or
  presence of abnormal leukocyte
• Bone marrow failure
• Leukemia, aplastic anemia, MDS, myelofibrosis,
  myeloththisis, megaloblastic anemia
• Hypersplenism

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Reticulocyte

• Reticulocyte index
• Rticulocyte count (Ret) reticulocytes in RBC
  population
• Reticulocyte count corrected for anemia Ret
  (patient Hct/ 45)
• Reticulocyte index Ret (patient Hct/ 45) (1/
  maturation index)
• Hct45 MI1
• Hct35 MI1.5
• Hct25 MI2

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Classification of Anemia

• According to symptom
• Acute
• Chronic
• According to reticulocyte count
• Adequate reticulucytosis
• Inadequate reticulocytosis
• According to MCV
• Macrocytic (MCV gt 100 fl)
• Normocytic (MCV 80 100 fl)
• Microcytic (MCV lt 80 fl)

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Evaluation of Anemia
Other hematologic abnormalities
Yes
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Evaluation of Anemia
Other hematologic abnormalities
Yes
Bone marrow examination Leukemia, aplastic
anemia, MDS, myelofibrosis, Myelopththisis, Megalo
blastic anemia
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Evaluation of Anemia
Other hematologic abnormalities
Yes
No
Appropriate reticulocyte response
Yes
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Evaluation of Anemia
Other hematologic abnormalities
Yes
No
Appropriate reticulocyte response
Yes
Evidence of hemolysis Bil, LDH,
haptoglobin Hemosiderin in urine
Yes
No
Evaluate for hemolysis
Evaluate for hemorrhage
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Evaluation of Anemia
Other hematologic abnormalities
Yes
No
Appropriate reticulocyte response
No
Yes
MCV
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Evaluation of Anemia
Other hematologic abnormalities
Yes
No
Appropriate reticulocyte response
No
Yes
MCV
gt 100
80 - 100
lt 80
Macrocytic anemia
Microcytic anemia
Normocytic anemia
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Macrocytic Anemia

• MCVgt100fL
• Megaloblastic anemia
• Nonmegaloblastic macrocytic anemia

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Megaloblastic Anemia

• Vit B12 deficiency
• Folate deficiency
• Combined folate vit B12 deficiency

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Vit. B12 deficiency

• Intragastric events
• Inadequate dissociation of cobalamin from food
  protein
• Total or partial gastrectomy
• Absent intrinsic factor secretion
• Proximal small intestine
• Impaired transfer of cobalamin from R protein to
  intrinsic factor
• Usurpation of luminal cobalamin
• Bacterial overgrowth
• Diphylobothrium latum (fish tapeworm)
• Distal small intestine
• Disease of the terminal ileum

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Pernicious Anemia

• Most common cause of vitamin B12 deficiency
• Occurs in all ages and ethnic backgrounds
• Associated with other autoimmune diseases
• Screen for thyroid disease every 1-2 years
• Pernicious anemia is a systemic disease
• Gastrointestinal tract involvement
• Neurologic involvement

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Nonmegaloblastic Macrocytic Anemia

• Accelerated erythopoiesis (increased reticulocyte
  count)
• Hemolytic anemia
• Post hemorrhagic anemia
• MDS
• Liver disease
• Hypothyroidism
• Drug-induced DNA synthesis block

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Macrocytic Anemia

• Essential laboratory tests
• Blood smear
• Reticulocyte count
• Vit B12 Folate
• BM study for megaloblastic anemia

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Evaluation for Macrocytic Anemia
Peripheral blood smear Hypersegmented(gt6)
neutrophils or oval-macroocytes
Yes
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Evaluation for Macrocytic Anemia
Peripheral blood smear Hypersegmented
neutrophils or macroovalocytes
Yes
Megaloblastic anemia
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Evaluation for Macrocytic Anemia
Peripheral blood smear Hypersegmented
neutrophils or macroovalocytes
Yes
Megaloblastic anemia BM examination Vit B12
folic acid
Vit B12 deficiency
No deficiency
Folate deficiency
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Evaluation for Macrocytic Anemia
Peripheral blood smear Hypersegmented
neutrophils or macroovalocytes
Yes
Megaloblastic anemia BM examination Vit B12
folic acid
Vit B12 deficiency
No deficiency
Folate deficiency
Pernicious anemia Gastric resection Vegetarian
Drug (colchicine,antipsychotics..)
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Evaluation for Macrocytic Anemia
Peripheral blood smear Hypersegmented
neutrophils or macroovalocytes
Yes
Megaloblastic anemia BM examination Vit B12
folic acid
Vit B12 deficiency
No deficiency
Folate deficiency
Poor diet Drug-induced malabsorption(phenytoin) In
creased needs associated with Pregnancy or
chronic hemolysis
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Evaluation for Macrocytic Anemia
Peripheral blood smear Hypersegmented
neutrophils or macroovalocytes
Yes
Megaloblastic anemia suspected BM
examination Vit B12 folic acid
Vit B12 deficiency
No deficiency
Folate deficiency
Inherited disorders of DNA synthesis Drugs
that interfere with DNA
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Evaluation for Macrocytic Anemia
Peripheral blood smear Hypersegmented
neutrophils or macroovalocytes
Yes
No
Megaloblastic anemia
Nonmegaloblastic anemia
Reticulocytosis
Normal or decreased
Increased
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Evaluation for Macrocytic Anemia
Peripheral blood smear Hypersegmented
neutrophils or macroovalocytes
Yes
No
Megaloblastic anemia
Nonmegaloblastic anemia
Reticulocytosis
Normal or decreased
Increased
Hemolytic anemia Hemorrhagic anemia
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Evaluation for Macrocytic Anemia
Peripheral blood smear Hypersegmented
neutrophils or macroovalocytes
Yes
No
Megaloblastic anemia
Nonmegaloblastic anemia
Reticulocytosis
Normal or decreased
Increased
Consider Alcohol toxicity, hypothyroidism, liver
disease
Nil BM examination
MDS, red cell aplasia Acquired sideroblastic
anemia Hereditary dyserythropoietic anemia (types
I III)
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Pathogenic Classification of Microcytic Anemia

• Disorders of iron metabolism
• IDA
• Anemia of chronic disorders
• Disorders of Hemoglobin synthesis
• Thalassemia (a or b)
• Hb E, Hb C, or unstable Hb disease
• Sideroblastic anemia
• Lead intoxication (usually normocytic)

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Microcytic Anemia

• Important laboratory tests
• Blood smear
• Reticulocyte count
• Ferritin, TIBC, serum iron
• Hb electropheresis

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Evaluation for Microcytic Anemia
Reticulocytes
Low/ normal
Serum iron TIBC ferritin
serum iron Normal or TIBC Normal or
ferritin
Serum iron Normal TIBC Ferritin
Normal serum iron Normal TIBC Normal Ferritin
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Evaluation for Microcytic Anemia
Reticulocytes
Low/ normal
Serum iron TIBC ferritin
serum iron Normal or TIBC Normal or
ferritin
Serum iron Normal TIBC Ferritin
Normal serum iron Normal TIBC Normal Ferritin
Iron deficiency
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Evaluation for Microcytic Anemia
Reticulocytes
Low/ normal
Serum iron TIBC ferritin
serum iron Nornal or TIBC Normal or
ferritin
Serum iron NormalTIBC Ferritin
Normal serum iron Normal TIBC Normal Ferritin
Increased ESR Increased CRP
Anemia of chronic disease
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Evaluation for Microcytic Anemia
Reticulocytes
Low/ normal
Serum iron TIBC ferritin
serum iron Nornal or TIBC Normal or
ferritin
Serum iron NormalTIBC Ferritin
Normal serum iron Normal TIBC Normal Ferritin
Hb electropheresis
a-Thalassemia trait b-Thalassemia trait Hb E Hb C
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Evaluation for Microcytic Anemia
Reticulocytes
Low/ normal
Serum iron TIBC ferritin
serum iron Nornal or TIBC Normal or
ferritin
Serum iron NormalTIBC Ferritin
Normal serum iron Normal TIBC Normal Ferritin
BM examination with iron stains
Sideroblastic anemia
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Evaluation for Microcytic Anemia
Reticulocytes
Low/ normal
Increased
Blood smear Bil, LDH, haptoglobin Hb
electropheresis
Homozygous b-thalassemia Hemolytic
elliptocytosis Hereditary pyropoikilocytosis
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Pathogenic Classification of Normocytic Anemia

• Anemia with increased erythropoiesis
• Post hemorrhagic anemia
• Hemolytic anemia
• Decreased erythropoietin secretion
• Impaired source
• Renal insufficiency
• Liver disease
• Reduced stimulus
• Endocrine deficiency
• Protein-calorie malnutrition
• Anemia of chronic disorders
• Impaired marrow response

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Evaluation for Normocytic Anemia
Reticulocytes
Increased
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Evaluation for Normocytic Anemia
Reticulocytes
Increased
Normal or decreased
History of jaundice, splenomegaly Presence of
blood smear abnormalities Elevated bilirubin or
LDH
Yes
No
Hemolysis
Hemorrhagic anemia
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Evaluation for Normocytic Anemia
Reticulocytes
Increased
Normal or decreased
Serum chemistry to screen for renal, hepatic,
and endocrine disease Consider erythropoietin
levels, thyroid studies
Ferritin
Normal or high
Low
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Evaluation for Normocytic Anemia
Reticulocytes
Increased
Normal or decreased
Ferritin
Normal or high
Low
Anemia of chronic disease
IDA
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Evaluation for Normocytic Anemia
Reticulocytes
Increased
Normal or decreased
Serum chemistry to screen for renal, hepatic,
and endocrine disease Consider erythropoietin
levels, thyroid studies
Positive
Anemia or renal disease Anemia of liver
disease Anemia due to endocrine failure
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Evaluation for Normocytic Anemia
Reticulocytes
Increased
Normal or decreased
Serum chemistry to screen for renal, hepatic,
and endocrine disease Consider erythropoietin
levels, thyroid studies
Serum iron
Negative
Normal or high
BM study
Infiltrative disorder Red cell aplasia MDS Dyseryt
hropoiesis (type II)
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Patient 1

• A 65 y/o man visiting our ER due to acute onset
  of RLQ pain.
• CBC WBC 18,000/ uL, Hb 11.4 g/ dL, MCV 93.8 fL,
  Platelet 85,000/ uL

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Patient 1

• Seg 5, lymphocytes 14, monocytes 6, band 2,
  myelocytes 4, promyelocytes 14, blasts 55,
  Auer body ()

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Patient 2

• A 43 y/o woman visiting OPD due to dizziness and
  fatigue for 3 months
• WBC 3,600/uL, Hb 8.6 g/dL, MCV 72.7 fL, RBC
  3,710,000/uL
• Seg 61, lymphocytes 29, monocytes 7,
  eosinophils 2, band 1

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Patient 2

• A 43 y/o woman visiting OPD due to dizziness and
  fatigue for 3 months
• WBC 3,600/uL, Hb 8.6 g/dL, MCV 72.7 fL, RBC
  3,710,000/uL
• Seg 61, lymphocytes 29, monocytes 7,
  eosinophils 2, band 1
• Ferritin 4.4 (19 319) ng/mL
• Stool OB negative

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A woman experienced tachypnea, anemia and hip pain

• 1132451 Mrs.?
• 2003/9/14 admission

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Chief complaint

• Dyspnea and dizziness for a week
• Lt hip pain for 3 days

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• WBC RBC Hb Ht MCV
• 9020 223 3.9 14.4 64.6
• Platelet Lymph Seg Bas Eos
• 164000 38.5 54.9 0.3 0.1
• Mono
• 6.2

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• WBC RBC Hb Ht MCV
• 9020 223 3.9 14.4 64.6
• Platelet Lymph Seg Bas Eos
• 164000 38.5 54.9 0.3 0.1
• Mono Fe TIBC Ferritin
• 6.2 132 255 369.41

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After hematologist consultation

• Check total protein , albumin(9/18)
• IgA , IgG , IgM
• serum / urine protein electrophoresis
• Bence-Jones protein
• Check CEA , CA199
• Do X-ray studies (9/17)
• T-spine , L-spine , pelvis , skull
• Do bone scan study (9/17)
• Bone marrow aspiration biopsy

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• total protein 13.5 mg/dl (6.38.0)
• Albumin 2.5 mg/dl (3.55.1)
• IgA 26.5 mg/dl (70400)
• IgG 9290 !! mg/dl (7001600)
• IgM 18.3 mg/dl (40230)
• ?2-microglobulin 10400 ug/L (7001800)
• Serum / urine protein electrophoresis
• result an IgG / lambda monoclonal spike

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Bone marrow aspiration