Anemia

1
Anemia An Approach

• James Czarnecki, D.O.
• Internal Medicine Resident Lecture Series

2
Background
3
Definition

• Strictly defined as a decrease in red blood cell
  (RBC) mass.
• Usually discovered and quantified by measurement
  of the RBC count, hemoglobin concentration, and
  hematocrit.

4
Frequency

• WHO chose 12.5 g/dL for both adult males and
  females.
• In the US, limits of 13.5 g/dL for men and 12.5
  g/dL for women these values are more realistic.
• Using these values, approximately 4 of men and
  8 of women have lower values.
• A significantly greater prevalence is observed in
  patient populations.

5
Mortality / Morbidity

• Varies greatly depending on etiology.
• Acute hemorrhage has variable mortality depending
  on the site of bleeding (80 with aortic rupture,
  30-50 with bleeding esophageal varices, approx.
  1 with benign peptic ulcers).
• The 2-year fatality rate for severe aplastic
  anemia is 70 without bone marrow transplantation
  or a response to immunosuppressive therapy.

6
Mortality / Morbidity

• Many symptoms associated with anemia are not
  caused by diminished RBC mass.
• Patients with pernicious anemia are often
  asymptomatic when they are detected incidentally
  with an Hb of 6 g/dL.
• Patients with iron deficiency anemia develop
  symptoms at Hb of 10-11 g/dL because of depletion
  of iron-containing protein other than Hb.

7
Mortality / Morbidity

• Tolerance of anemia is proportional to the
  anemias rate of development.
• Symptoms and mortality associated with rapidly
  developing anemia are more profound than in
  slowly developing anemia.

8
Race

• Certain races and ethnic groups have an increased
  prevalence of genetic factors associated with
  certain anemias. For example
• Hemoglobinopathies
• Thalassemia
• G6-PD deficiency

9
Sex

• Anemia is twice as prevalent in females than in
  males. This difference is significantly greater
  during the childbearing years due to pregnancies
  and menses.
• Approximately 65 of body iron is incorporated
  into circulating Hb. Each gram of Hb contains
  3.46 mg of iron.
• Each healthy pregnancy depletes a mother of
  approximately 500 mg of iron.

10
Sex

• A male must absorb about 1 mg of iron to maintain
  equilibrium, a premenopausal female must absorb
  an average of 2 mg daily.
• Females have a markedly lower incidence of anemia
  from X-linked anemias such as G6PD deficiency and
  sex-linked sideroblastic anemia.

11
Age

• Severe genetically acquired anemias (ie, sickle
  cell disease, thalassemia, Fanconi Syndrome) are
  more commonly found in children because they do
  not survive to adulthood.
• During the childbearing years, women are more
  likely to become iron deficient.

12
Age

• Neoplasia increased the prevalence with each
  decade of life and can produce anemia from
• bleeding
• from the replacement of bone marrow with tumor
• from the development of anemia associated with
  chronic disorders

13
Age

• Use of aspirin, NSAIDs, and coumadin increases
  with age and can produce gastrointestinal
  bleeding.

14
Clinical Approach
15
History

• Carefully obtain a history and perform a physical
  examination in every patient with anemia because
  the findings usually provide important clues to
  the etiology of the underlying disorder.
• Areas of inquiry found valuable are the following.

16
History

• The duration can be established by obtaining a
  history of previous blood examination
• Obtain a careful family not only for anemia but
  also for jaundice, cholelithiasis, splenectomy,
  bleeding disorders, and abnormal Hbs.
• Carefully document pregnancies, abortions, and
  menstrual loss.

17
History

• Patients do not appreciate the significance of
  tarry stools. Changes in bowel habits can be
  useful in uncovering neoplasms of the colon.
• Hemorrhoidal blood loss is difficult to quantify,
  and it may be overlooked or overestimated from
  one patient to another.
• Seek a careful history of gastrointestinal
  complaints that may suggest gastritis, peptic
  ulcers, hiatal hernias, or diverticula.

18
History

• Abnormal urine color can occur in renal and
  hepatic disease and in hemolytic anemia.
• A thorough dietary history is important in a
  patient who is anemic. It must include foods that
  the patient both eats and avoids, as well as an
  estimate of their quantity.
• Nutritional deficiencies may be associated with
  unusual symptoms that can be elicited by a
  history.

19
History

• Obtain a history or presence of fever because
  infections, neoplasms, and collagen vascular
  disease can cause anemia.
• Cold intolerance can be an important symptom of
  hypothyroidism or lupus erythematosus.

20
History

• Relation of dark urine to either physical
  activity or time of day can be important in march
  hemoglobinuria, or paroxysmal nocturnal
  hemoglobinuria.
• Explore the presence or the absence of symptoms
  suggesting an underlying disease, such as
  cardiac, hepatic, and renal disease chronic
  infection, or malignancy.

21
Physical
22
Physical

• Too often, the physical is rushed without looking
  at the patient for an unusual habitus or
  appearance of underdevelopment, malnutrition, or
  chronic illness.
• Examine optic fundi carefully, but not at the
  expense of the conjunctivaie and the sclerae,
  which can show pallor, icterus, petechia, or
  telangiectasia.

23
Physical

• Perform systematic examination for palpable
  enlargement of lymph nodes for evidence of
  infection or neoplasia.
• Carefully search for both hepatomgaly and
  splenomegaly. Their presence or absence is
  important, as are the size, the tenderness, the
  firmness, and the presence or absence of nodules.

24
Physical

• A rectal and pelvic examination cannot be
  neglected because tumor or infection of these
  organs can be the cause of anemia.
• The neurologic examination should include tests
  of position sense and vibratory sense,
  examination of the cranial nerves, and testing
  for tendon reflexes.

25
Physical

• The heart should not be ignored because
  enlargement may provide evidence of the duration
  and severity of an underlying anemia, and murmurs
  may be the first evidence of a bacterial
  endocarditis, which could explain an etiology of
  an underlying anemia.

26
Causes
27
Causes

• Genetic
• Hemoglobinopathies
• Thalassemias
• Defects of the RBC cytoskeleton
• Rh null disease
• Hereditary xerocytosis
• Fanconi anemia

28
Causes

• Nutritional
• Iron deficiency
• Vitamin B-12 deficiency
• Folate deficiency
• Starvation and generalized malnutrition
• Hemorrhage
• Immunologic Antibody-mediated abnormalities

29
Causes

• Physical effects
• Trauma
• Burns
• Frostbite
• Prosthetic valves and surfaces
• Drugs and chemicals
• Aplastic anemia
• Megaloblastic anemia

30
Causes

• Chronic diseases and malignancies
• Renal disease
• Hepatic disease
• Chronic infections
• Neoplasia
• Collagen vascular diseases

31
Causes

• Infections
• Virals Hepatitis, infectious mononucleosis,
  cytomegalovirus
• Bacterial Clostridia, gram-negative sepsis
• Protozoal Malaria, leishmaniasis, toxoplasmosis

32
Differentials
33
Differentials

• Aplastic Anemia
• Cooley Anemia
• Hemolytic Anemia
• Iron Deficiency Anemia
• Low LDL Cholesterol
• Megaloblastic Anemia
• Pernicious Anemia

34
Differentials

• Sickle Cell Anemia
• Spur Cell Anemia
• Thalassemia, Alpha
• Thalassemia, Beta

35
Work Up
36
Work Up

• Detection of anemia involves the adoption of
  arbitrary criteria. In the US
• Anemia is suggested in male with Hb levels less
  than 13.5 g/dL and in females with Hb levels less
  than 12.5 g/dL.
• Once the existence of anemia is established,
  investigate the pathogenesis.

37
Work Up

• A rational approach is to begin by examining the
  peripheral smear and laboratory values obtained
  on the blood count. If the anemia is either
  microcytic (MCV lt 84) or macrocytic (MCV gt 96),
  the investigative approach can be then limited.

38
Work Up

• A rapid method of determining whether cellular
  indices are normocytic and normocromic is to
  multiply the RBC and Hb by 3. The RBC multiplied
  by 3 should equal the Hb, and the Hb multiplied
  by 3 should equal the Hct.

39
Work Up

• In microcytic hypochromic anemia, seek a source
  of bleeding.
• The appropriate lab tests are serum iron level
  and TIBC and serum ferritin level.
• If the serum iron level is decreased and TIBC is
  increase, a diagnosis of iron deficiency can be
  made.

40
Work Up

• When a normocytic, normochromic anemia is
  encountered, classify the anemia into 3 possible
  etiologies (ie, blood loss, hemolysis, or
  decreased production).
• In most anemias, one of these causes is the
  dominant factor, however in some, more than a
  single cause may play an important role (ie,
  pernicious anemia).

41
Microcytic Hypochromic Anemia (MCV lt 83 MCHC lt
31)
Serum Iron TIBC Bone Marrow Iron Comment
Iron Deficiency - 0 Responsive to iron therapy
Chronic inflammation - - Unresponsive to iron therapy
Thalassemia major N Reticulocytosis and indirect bilirubinemia
Thalassemia minor N N Target Cells
Lead poisoning N N Basophilic stippling of RBCs
Sideroblastic N Ring sideroblasts in marrow
Hemoglobin N N Hemoglobin electrophoresis
42
Macrocytic Anemia (MCV gt 95)

• Megaloblastic bone marrow
• Deficiency of vitamin B-12
• Deficiency of folic acid
• Drugs affecting DNA synthesis
• Inherited disorders of DNA synthesis

43
Macrocytic Anemia (MCV gt 95)

• Nonmegaloblastic bone marrow
• Liver disease
• Hypothyroidism and hypopituitarism
• Accelerated erythropoiesis (reticulocytes)
• Hypoplastic and aplastic anemia
• Infiltrated bone marrow

44
Various Forms of RBCs

• Macrocyte Larger than normal
• Microcyte Small than normal
• Hypochromic less hemoglobin in cell
• Spherocyte Loss of central pallor, stains more
  densely, often microcytic.
• Target cell hypochromic with central target
  of hemoglobin (liver disease)

45
Various Forms of RBCs

• Leptocyte Hypochromic cell with a normal
  diameter and decreased MCV
• Elliptocyte Oval to cigar shaped (B-12, folate)
• Schistocyte Fragmented helmet-shaped RBC
• Stomatocyte Slitlike area of central pallor in
  erythrocyte (liver disease, acute alcoholism)

46
Various Forms of RBCs

• Tear-shaped RBCs Drop-shaped erythrocyte, often
  microcytic.
• Acanthocyte Five to 10 spicules of various
  lengths and at irregular intervals on the surface
  of RBCs.
• Echninocyte Evenly distributed spicules on
  surface of RBCs, usually 10-30 (uremia, peptic
  ulcer, carcinoma)
• Sickle Cell Elongated cell with pointed ends.
  Hemoglobin S and certain types of hemoglobin C.

47
Imaging Studies
48
Imaging Studies

• Useful in the workup for anemia when a neoplastic
  etiology is suggested.
• Permit discovery of the neoplasm or centrally
  located adenopathy.
• Occasionally, they are useful in detecting or
  confirming the existence of splenomegaly.

49
Procedures
50
Procedures

• Investigate gastrointestinal bleeding by
  endoscopy and radiographic studies to identify
  the bleeding site.
• May leave the source of GI bleeding undetected if
  the lesion is small.
• Bone marrow aspirates and biopsy finding are
  particularly useful in establishing the etiology
  of anemia in patients with decreased production
  of RBCs.

51
Treatment
52
Medical Care

• Transfusion of packed RBCs should be reserved for
  patients who are actively bleeding and for
  patients with a severe and symptomatic anemia
• Nutritional therapy is used to treat iron
  deficiency, vitamin B12, and folic acid.
• Corticosteroids are useful in the treatment of
  autoimmune hemolytic anemia.

53
Medical Care

• Treatment of aplastic disorders includes removal
  of the offending agent whenever it can be
  identified, supportive therapy for the anemia,
  and prompt treatment of infection.

54
Surgical Care
55
Surgical Care

• Surgery is useful to control bleeding in patients
  who are anemic.
• Most commonly, bleeding is from the GI tract, the
  uterus, or the bladder.
• Patients should be hemodynamically stable before
  and during surgery.
• Splenectomy has been advantageous in hereditary
  spherocytosis and hereditary elliptocysosis.

56
Surgical Care

• Bone marrow and stem cell transplantation have
  been used in patients with
• Leukemia
• Lymphoma
• Multiple myeloma
• Myelofibrosis
• Aplastic disease

57
Consultations
58
Consultations

• Surgical consultation is indicated to control
  bleeding, for splenectomy when necessary, and for
  biopsies to establish the presence of neoplasia
• Consultation with gastroenterologists is
  frequently sought to identify a bleeding site in
  the gut.
• Urologic consultation may be needed to
  investigate hematuria.

59
Diet
60
Diet

• Iron deficiency anemia is prevalent in geographic
  locations where little meat is in the diet.
• A strict vegetarian diet requires iron and
  vitamin B-12 supplementation.
• Folic acid deficiency occurs among people who
  consume few leafy vegetables.
• Coexistence of iron and folic acid deficiency is
  common among Third World nations.

61
Activity
62
Activity

• The activity of patients with severe anemia
  should be curtailed until the anemia is partially
  corrected.
• Transfusion can often be avoided by ordering bed
  rest.
• March hemoglobinuria is a rare hemolytic disorder
  usually observed in young males. Individuals
  develop hemoglobinuria after marching or running
  on hard surfaces. Can be treated by curtailing
  the precipitating exercise.

63
Follow Up
64
Follow Up

• Patients with chronic anemia can usually be cared
  for on an outpatient basis.
• Follow-up care is necessary to ensure that
  therapy is being continued and to assess the
  efficacy of treatment.
• The most serious complications of severe anemia
  arise from tissue hypoxia.

65
Follow Up

• Shock, hypotension, or coronary and pulmonary
  insufficiency can occur.
• This is more common in older individuals with
  underlying pulmonary and cardiovascular disease.
• Hemolytic transfusion reactions and transmission
  of infectious disease are risks of blood product
  transfusions.

66
Medical / Legal Pitfalls
67
Medical / Legal Pitfalls

• Negligence in transfusion of either incompatible
  blood or blood containing a potentially
  identifiable infectious agent
• Failure to recognize a hemolytic transfusion
  reaction and to initiate prompt and appropriate
  therapy
• Delayed diagnosis, investigation, and treatment
  of a neoplastic disorder because the etiology of
  an anemia was not pursued in a timely manner

68
Medical / Legal Pitfalls

• Failure to provide appropriate therapy and to
  ensure that the patient has adequate follow-up
  care
• Underestimating the potential severity of an
  anemia.

69
Histopathology
70
Decreased Production of RBCs
71
Microcytic Anemia
72
Peripheral Smear
73
Peripheral Smear
74
Peripheral Smear
75
Bone Marrow Aspirate
76
Bone Marrow Aspirate
77
Competency Exam
78
Question 1

• All of the following are matched correctly,
  except
• Macrocyte Larger than normal
• Microcyte Smaller than normal
• Spherocyte Loss of central pallor
• Schistocyte Hypochromic cell with a normal
  diameter
• Stomatocyte Slitlike area of central pallor in
  an erythrocyte.

79
Question 1

• All of the following are matched correctly,
  except
• Macrocyte Larger than normal
• Microcyte Smaller than normal
• Spherocyte Loss of central pallor
• Schistocyte Hypochromic cell with a normal
  diameter
• Stomatocyte Slitlike area of central pallor in
  an erythrocyte.

80
Question 2

• Which of the following deficiencies would most
  likely lead to megaloblastic anemia?
• A) vitamin E deficiency
• B) vitamin B6 deficiency
• C) iron deficiency
• D) folic acid deficiency
• E) Vitamin B12 deficiency

81
Question 2

• Which of the following deficiencies would most
  likely lead to megaloblastic anemia?
• A) vitamin E deficiency
• B) vitamin B6 deficiency
• C) iron deficiency
• D) folic acid deficiency
• E) Vitamin B12 deficiency

82
Question 3

• The peripheral blood of a patient with iron
  deficiency anemia will most likely show what
  picture?
• a) microcytic, hypochromic red cells
• b) microcytic, normochromic red cells
• c) macrocytic, hypochromic red cells
• d) normocytic, hypochromic red cells
• e) normocytic, normochromic red cells

83
Question 3

• The peripheral blood of a patient with iron
  deficiency anemia will most likely show what
  picture?
• a) microcytic, hypochromic red cells
• b) microcytic, normochromic red cells
• c) macrocytic, hypochromic red cells
• d) normocytic, hypochromic red cells
• e) normocytic, normochromic red cells

84
End of Lecture

• http//im.official.ws