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