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ANEMIAS

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Title: ANEMIAS


1
  • ANEMIAS
  • Nazzal Bsoul,MD
  • Al Bashir Hospital

2
DEFINITION
  • Anemia Is defined as a reduction in one or more
    of major RBC measurements.
  • Hemoglobin (Hb).
  • Hematocrit (HTC).
  • Red blood cells count (RBCs) .
  • Anemia is not a disease by itself but is one of
    the major signs of disease.
  • May be the first manifestation of a systemic
    disease,along with other nonspecific complaints
    such as fever,weight loss,anorexia.

3
HEMOGLOBIN (Hb)
  • Hb Concentration measures the major
    oxygen-carrying pigment in whole blood.
  • Values are expressed as grams of Hb per dL of
    whole blood (g/dL).
  • Normal range M 13-16,5 g/dL
  • F 12-15,5 g/dL

4
HEMATOCRIT
  • Hematocrit (HTC) Is the percent of a volume
    of whole blood occupied by intact RBCs.
  • Values are expressed as a percentage.
  • Normal range M 41-51.
  • F 37-47.

5
RED BLOOD CELL COUNT (RBCs)
  • RBC Count Is the number of RBCs contained in a
    unit of whole blood.
  • Values are expressed as millions of cells per uL
    of whole blood.
  • Normal range M 4,5-6,5 millions/uL
  • F 3,8-5,8 millions/uL

6
VOLUME STATUS
  • The three measurements are all concentrations.
  • As such they are dependent upon both the RBC mass
    and the plasma volume.
  • 1.In acute bleeding, anemia develops only after
    36-48 hours.
  • 2.Pregnancy RBC mass is increased by 25 and
    plasma is increased by 50.Normal values in
    pregnancy are diffirent.
  • 3. Dehydration.

7
SPECIAL POPULATIONS
  • 1.Living at high altutute.
  • 2.Smoking and air pollution.
  • 3.African-Americanslower values.
  • 4.Populations with a high incidence of
    ch.diseases.
  • 5.Athletes.
  • 6.The elderlyshould not have a lower normal
    range for fear of missing a serious underlying
    disorder.

8
ERYTHROPOESIS -1
  • Erythropoesis takes place in adults within the BM
    under the influence of the stromal framework,a
    number of cytokines,and the eryrhroid specific
    growth factor,erythropoietin(EPO).
  • EPO is a true endocrine hormone produced in the
    kidney.
  • EPO enhances the growth and differentiation of
    the 2 erythroid progenitors.
  • 1.Burst Forming Units-erythroid/BFU-E/.
  • 2.Colony Forming Units-erythroid/CFU-E/.

9
ERYTHROPOESIS-2
  • The rate of RBC production equals the
  • rate of RBC destruction.
  • Approximately 1 of RBCs is removed
  • from the circulation daily.
  • The rate of RBC production can be
  • increased markedly (5-7 folds).


10
CLINICAL CONSEQUENCES OF ANEMIA
  • The signs and symptoms induced by anemia are
    dependent upon the degree of anemia as well as
    the rate at which the anemia has evolved.
  • Symptoms of anemia can result from two factors
  • 1.Decreased O2 delivery to tissues.
  • 2.Hypovolemia (acute bl.loss).

11
COMPENSATORY MECHANISMS
  • Signs and symptoms depend also on the
    compensatory mechanisms.
  • 1.Extraction of O2 by the tissues can increase
    from 25 to 60.
  • 2.Cardiac compensation stroke volume and heart
    rate (cardiac output).
  • Thus normal O2 delivery can be maintained by 1and
    2 at rest at HBG as low as 5g/dL,assuming that
    the intravasc.volume is maintained.
  • Thus symptoms will develop when HBG falls below
    this level at rest or at higher HBG during
    exersion or when cardiac compensation is impaired.

12
SYMPTOMS AND SIGNS
  • Symptomis a sensation or change in health

  • function experienced by the
    patient.
  • It is a subjective report.
  • Fatigue/tiredness
  • Pain.
  • Nausea.
  • Dizziness.

13
SYMPTOMS AND SIGNS-contd
  • Sign is an objective evidence of the
  • presence of a disease or disorder.
  • Signs are discovered and reported by
  • the physician,not by the patient.It is
  • an objective report.
  • Elevated BP.
  • Skin rash.
  • Tachypnea.
  • Tachycardia.

14
SYMPTOMS AND SIGNS OF ANEMIA
  • Dyspnea/S.O.B.on exersion/at rest.
  • Fatigue/tiredness.
  • Signs and symptoms of hyperkinetic state
  • 1.bounding
    pulses.

  • 2.palpitations.
  • 3.roaring in
    ears.
  • In more severe anemiaLethargy,confusion,CHF,angin
    a,MI.
  • Pallor.
  • Headache.
  • Complications of extracellular volume depletion
    (in acute bleeding).

15
CAUSES OF ANEMIA
  • There are 2 interrelated approaches one can use
    to help identify the cause of anemia.
  • 1.Kinetic approach.
  • 2.Morphologic approach.

16
KINETIC APPROACH
  • Anemia can be caused by one or more of 3
    independent mechanisms.
  • 1.Decreased RBC production.
  • 2.Increased RBC destruction.
  • 3.RBC loss.

17
Decreased RBC PRODUCTION
  • If less than 1 of the circulating RBCs is
  • replaced by the BM.
  • 1- Lack of nutrients such as iron,B12,or
  • folate.
  • 2- Primary involvement of the BM such
  • as aplastic anemia,PRCA,MDS,or
  • tumor infiltration.
  • 3- Low levels of trophic hormones,such
  • as EPO in CRF,thyroid
    hormones,and
  • androgens.

18
INCREASED RBC DESTRUCTION
  • A RBC life span below 100 days is the
  • operational definition of hemolysis.
  • Anemia will ensue when the BM is unable
  • to keep up with the need to replace
  • more than 5 of the RBC mass daily.
  • 1-Inherited hemolytic anemias hereditary
  • spherocytosis,SCD,and thalassemia
  • major.
  • 2-Aquired hemolytic anemias AIHA,TTP.

19
RBC LOSS
  • Blood loss is the most common cause of anemia
  • Forms of bleeding
  • 1-Obvious bleeding trauma,melena,
  • hematemesis,or menometrorrhagia.
  • 2-Occult bleedinga slowly bleeding
  • colonic polyp or carcinoma.
  • 3-Iatrogenic bleeding Excessive bl.
  • donations,or repeated venesection.

20
MORPHOLOGIC APPROACH
  • According to RBC size.
  • Mean Corpuscular (Cell) Volume (MCV).
  • RBC size (MCV) is 80-96 femtoliters(fL).
  • Microcyte.
  • Macrocyte.
  • Normocyte.

21
ANEMIAS ACCORDING TO THE RBC SIZE
  • 1.Microcytic anemia.
  • 2.Macrocytic anemia.
  • 3.Normocytic anemia.

22
MICROCYTIC ANEMIAS
  • Are associated with an MCV below 80 fL.
  • 1-Iron Deficiency Anemia (IDA)
  • 2- Anemia of Chronic Disease (ACD)
  • 3-Thalassemias.

23
  • IDA,ACD,and thalassemias are the most
  • 3 common causes of microcytosis in
  • clinical practice.
  • Since all 3 have hypochromic and micro-
  • cytic RBCs on blood film (smear),other
  • factors must be used to establish the
  • diagnosis.

24
IRON DEFICIENCY ANEMIA (IDA)
  • Important discriminating features are
  • 1-Low serum iron concentration.
  • 2-Increased total iron binding capacity
  • (TIBC)
  • 3-Low serum ferritin concentration.
  • 4-High RDW.
  • It is mandatory to determine the cause of
  • iron deficiency.

25
ANEMIA OF CHRONIC DISEASE (ACD)
  • The hallmarks of this condition are
  • 1-Low serum iron.
  • 2-Low TIBC.
  • 3-Normal to increased serum ferritin
  • concentration.
  • The causes are usually related to the
  • presence of chr.infection (TB),
  • inflamation (RA),or malignancy.

26
ALPHA OR BETA THALASSEMIA MINOR
  • Adults with thalassemia are most often
  • heterozygotes for the alpha or beta
  • forms of this syndrome,and may not be
  • anemic.
  • Family history is often negative.
  • P/E may reveal splenomegaly.
  • Blood film microcytosis,hypochromia,
  • target cells,tear-drop forms,and
  • basophilic stippling.

27
MACROCYTIC ANEMIAS
  • Are characterized by an MCV above 100 fL.
  • Reticulocytosis.
  • Vit.B12 def.
  • Folate def.
  • MDS.
  • Hypothyroidism

28
NORMOCYTIC ANEMIAS
  • By definition the MCV is normal.
  • ACD.
  • MDS.

29
MULTIPLE CAUSES OF ANEMIA
  • In pediatric practice anemia is commonly
  • caused by a single disorder.
  • In adults,mainly older adults,multiple
  • causes are frequently present.
  • 1-Ca colon IDA and ACD
  • 2-AIHA on steroids and GI
  • bleeding.
  • 3-RA and NSAIDs ACD and IDA

30
EVALUATION OF THE PATIENT WITH ANEMIA-1
  • Anemia is one of the major signs of disease.
  • It is never normal and its cause should be
    always be sought.
  • History.
  • Physical examination.
  • Simple lab.tests.
  • Other investigations.

31
EVALUATION OF THE ANEMIC PATIENT-2
  • The workup should be directed towards answering
    the following questions
  • 1.Is the patient bleeding (now or in the past) ?
  • 2.Is there evidence of increased RBC destruction?
  • 3.Is the BM suppressed?.
  • 4.Is the patient iron deficient? if so,why?.

32
HISTORY
  • Symptoms related to anemia (melena,CRF,RA)
  • Etnicity and country of origin
    (Hemoglobinopathies).
  • Drug history (NSAIDS).

33
PHYSICAL EXAMINATION
  • Pallor.
  • Jaundice.
  • Tachycardia.
  • Lymphadenopathy.
  • Hepatosplenomegaly.
  • Bone tenderness.

34
LABORATORY EVALUATION-1
  • Complete blood count (CBC) HBG,HCT,
  • RBC count,RBC indices,and
  • WBC count.
  • WBC differential,PLT count,and
  • reticulocyte count.
  • Blood film (Blood smear).
  • Red cell distribution width.

35
LABORATORY EVALUATION-2
  • Red cell indices
  • 1-Mean corpuscular volume.MCV 80-100
  • femtoliter.
  • 2-Mean corpuscular hemoglobin.MCH
  • 27,5-33,2 picograms of hemoglobin
  • per RBC.
  • 3-Mean corpuscular hemoglobin
  • concentration.MCHC.33,4-35,5
  • grams of hemoglobin per dL of RBCs.

36
Red Cell Distribution Width(RDW)
  • RDW is a measure of anisocytosis or variation in
  • red cell size.
  • Increased RDW is commonly found when
  • there is a nutritional
    deficiency(eg,iron
  • ,folate,and Vit.B12).
  • Increased RDW is not specific for any one
  • abnormality.
  • An increased RDW is the mathematical equi-
  • valent of the termanisocytosis,but is
    not
  • diagnostic of any particular morphologic
    finding.

37
LABORATORY EVALUATION-3
  • Reticulocyte count helps to distinguish
  • among the different types of
    anemia.
  • 0,5-1,5 percent.
  • Absolute reticulocyte
    count.25,000-
  • 75,000/uL.
  • Reticulocytes normally survive for 4 days,of
    which 3 days in
  • the BM and one day in the
    peripheral circulation.
  • White blood cell count (WBC count).
  • Neutrophil hypersegmentation.
  • Platelet count (PLT count).

38
OTHER INVESTIGATIONS
  • Bone marrow aspirate and trephine biopsy.
  • Radiological studies.
  • Genetic studies.
  • Immunological studies.

39
BONE MARROW EXAMINATION
  • BM examination generally offers little
  • additional diagnostic information in the
  • more common forms of anemia.
  • Although the absence of stainable iron in
  • BM is considered the gold standard
  • for the diagnosis of ID,this diagnosis
  • is usually established by lab.tests alone.

40
BONE MARROW EXAMINATION-Contd
  • Indications for BM examination in anemic
  • patients include
  • 1-Pancytopenia.
  • 2-The presence of abnormal cells in the
  • circulation (blast forms).

41
EVALUATION FOR ID
  • History menometrorrhagia,symptoms of
  • PUD.
  • Preliminary lab.data Low MCV,low MCH,
  • high RDW,high PLT count.
  • More complete evaluation is needed
  • Serum iron
  • TIBC
  • serum ferritin

42
Clinical Manifestations of Iron Deficiency (ID)-1
  • The presenting symptoms of ID are
  • caused primarily by anemia
  • Weakness,headache,irritability,fatigue,
  • exercise intolerance.
  • Koilonychia (Spoon nails),blue sclerae,
  • glossal pain.
  • Cognitive functions-verbal learning,
  • memory,and concentration.

43
Clinical Manifestations of ID-2
  • Physical performance- ID impairs exercise
  • capacity and causes easy fatiguability
  • PICA and Pagophagia
  • PICAis a perverted apetite for substances
  • not fit as food,such as clay or paper
  • products.
  • Pagophagia is PICA for ice.

44
Causes of ID
  • Blood lossCommon cause.Overt or occult.
  • Decreased iron absorption Relatively
  • uncommon cause.
  • Intravascular hemolysis Hematuria (PNH).
  • Pulmonary hemosiderosis
  • Administration of erythropoietin In anemia
  • of chronic renal failure.

45
Diagnosis of ID-1
  • History and physical examination.
  • Laboratory investigations CBC,RBC
  • indices,and blood film(smear)?pre-
  • sumptive diagnosis of ID.
  • Therapeutic trial of oral iron?positive
  • response (reticulocytosis,followed
  • by an increase in Hb at a rate of
  • about 2-4 g/dL every 3 weeks

46
Diagnosis of ID-2
  • No positive response ?
  • The following lab.investigations are
  • needed at the beginning
  • 1-Serum Iron (SI)
  • 2-Total Iron Binding Capacity (TIBC)
  • 3-Transferrin Saturation (SI TIBC)
  • 4-Serum ferritin level.

47
Search for Source of Bleeding and Iron Loss
  • Diagnosing the cause of ID is much more
  • important than diagnosing ID.
  • History and physical examination.
  • Other investigations Upper and lower
  • endoscopy.

48
Classic Presentation of IDA
  • A multigravid woman in her 40s,presents
  • with tirednes and fatigue and chronic
  • blood loss from menometrorrhagia.The
    following lab.
  • findings were noted
  • 1-The hemoglobin was 8 g/dl,with MCV of 75
    fL.
  • 2-The MCH and MCHC were both low.
  • 3- Blood film showed microcytic,hypochromic
  • red blood cells(RBCs)
  • 4-The serum iron was low and the total iron
    binding
  • capacity(TIBC) was
    elevated,resulting in transferrin
  • saturation lt 15.The plasma
    ferritin
  • concentration was reduced.

49
Classic presentation of IDA-Contd
  • Iron stores were absent after performing
  • the gold strandard test for estimating
  • iron stores via bone marrow aspirate of
  • the patient.
  • Finally,the patient responded briskly to
  • oral iron therapy with a reticulocytosis
  • followed by elevations in the hemo-
  • globin concentration.

50
VITAMIN B12 AND FOLATE DEFICIENCY ANEMIAS
  • Dr.Nazzal Bsoul

51
Vitamin B12
  • Vitamin B12 (Vit.B12),also called cobalmin
  • is a water-soluble vitamin with a key
  • role in normal functioning of the
    brain
  • and nervous system,and for erythro-
  • poiesis.
  • It is normally involved in the metabolism of
  • every cell of the body.
  • It is structurally the most complicated vitamin
  • and it contains the rare element
    cobalt.
  • It is absorbed,mainly in the terminal ileum.

52
Classical Presentation of Vit.B12 and Folate
Deficiency
  • The patient usually presents with severe
  • anemia,and macrocytosis,with or with-
  • out varying neurologic disturbances.
  • However,many patients with B12 deficiency
  • exist who have no or only mild anemia,
  • and macrocytosis may be masked by a
  • concurrent disorder,such as IDA or
  • thalassemia.

53
Diagnosis of B12 and/or Folate Deficiency
  • B12 or folate deficiency should be suspected in
  • patients with one or more of the
  • following findings
  • 1-Oval macrocytic RBCs on blood film,with
  • or without anemia.
  • 2-The presence of hypersegmented neutrophils.
  • 3-Pancytopenia of uncertain cause.
  • 4-Unexplained neurologic signs and symptoms,
  • (dementia,weakness,and parasthesia)

54
Diagnosis of B12 or/and Folate Deficiency-contd
  • Special populations are at increased risk
  • 1-Older adults.
  • 2- Alcoholics.
  • 3- Patients with malnutrition.
  • 4- Vegeterians.
  • Vit.B12 and folate deficiency often coexist
  • and are not easily diffirentiated on a
  • clinical basis.
  • The first step is to test for serum Vit.B12 and
  • folate level.

55
Methylmalonic Acid and Homocysteine
  • Patients with low-normal or even normal
  • serum B12 values may be truly Vit.B12
  • deficient.
  • Measurement of the homocysteine and
  • methylmalonic acid appears to be
  • more sensitive for the diagnosis of
  • these deficiencies than serum Vit.B12
  • and folate levels.

56
Methylmalonic Acid and Homocysteine-contd
  • Vit.B12 deficiency Both serum homo-
  • cysteine and methylmalonic acid (MMA)
  • are elevated.
  • Folate deficiency Only homocysteine level
  • is elevated.

57
EVALUATION OF HEMOLYSIS
  • Hemolysis should be considered if the pt.
  • has a rapid fall in Hb
    ,reticulocytosis,
  • and/or abnormally shaped RBCs
  • (specially spherocytes or fragmented
  • RBCs) on bl.film.
  • Lab.findings in hemolysis
  • High LDH
  • High indirect bilirubin.
  • Low serum haptoglobin.
  • Positive direct coombs test (only in
    case of
  • autoimmune hemolytic anemia).

58
General Causes for Hemolysis
  • 1-Hemolysis due to intrinsic defects (intra-
  • corpuscular).
  • 2-Hemolysis due to causes extrinsic to
  • the RBC (extracorpuscular).

59
Diagnosis of Active Hemolysis
  • Recognizing overt hemolysis is not difficult
  • in a classic patient with
  • New onset of Pallor
  • Jaundice
  • Splenomegaly
  • Anemia
  • Circulating spherocytes.
  • Accurate histrory and physical examination
  • should always be the cornerstone of
    the
  • patients evaluation.

60
Laboratory Findings in Hemolysis
  • Serum lactate dehydrogenase (LDH) and
  • Haptoglobin are the major serum tests
  • in the diagnosis of hemolysis.
  • Reticulocyte count.
  • Other testsIndirect bilirubin.
  • Coombs test.
  • Blood film (smear).
  • Serial evaluation of Hb and Ht

61
Atypical Presentations
  • Hemolysis without anemia if the rate of
  • RBCs destruction falls within the bone
  • marrows compensatory ability.Indirect
  • bilirubil, LDH,and reticulocyte count are
  • high, but without anemia.
  • Hemolysis without reticulocytosis

62
  • THANK YOU
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