Title: ANEMIAS
1- ANEMIAS
- Nazzal Bsoul,MD
- Al Bashir Hospital
2DEFINITION
- 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.
3HEMOGLOBIN (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
4HEMATOCRIT
- 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.
5RED 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
6VOLUME 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.
7SPECIAL 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.
8ERYTHROPOESIS -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/.
9ERYTHROPOESIS-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.
12SYMPTOMS AND SIGNS
- Symptomis a sensation or change in health
- function experienced by the
patient. - It is a subjective report.
- Fatigue/tiredness
- Pain.
- Nausea.
- Dizziness.
13SYMPTOMS 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.
14SYMPTOMS 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).
15CAUSES OF ANEMIA
- There are 2 interrelated approaches one can use
to help identify the cause of anemia. - 1.Kinetic approach.
- 2.Morphologic approach.
16KINETIC APPROACH
- Anemia can be caused by one or more of 3
independent mechanisms. - 1.Decreased RBC production.
- 2.Increased RBC destruction.
- 3.RBC loss.
17Decreased 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.
18INCREASED 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.
19RBC 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.
20MORPHOLOGIC APPROACH
- According to RBC size.
- Mean Corpuscular (Cell) Volume (MCV).
- RBC size (MCV) is 80-96 femtoliters(fL).
- Microcyte.
- Macrocyte.
- Normocyte.
21ANEMIAS ACCORDING TO THE RBC SIZE
- 1.Microcytic anemia.
- 2.Macrocytic anemia.
- 3.Normocytic anemia.
22MICROCYTIC 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.
24IRON 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.
25ANEMIA 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.
26ALPHA 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.
27MACROCYTIC ANEMIAS
- Are characterized by an MCV above 100 fL.
- Reticulocytosis.
- Vit.B12 def.
- Folate def.
- MDS.
- Hypothyroidism
28NORMOCYTIC ANEMIAS
- By definition the MCV is normal.
- ACD.
- MDS.
29MULTIPLE 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
30EVALUATION 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.
31EVALUATION 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?.
32HISTORY
- Symptoms related to anemia (melena,CRF,RA)
- Etnicity and country of origin
(Hemoglobinopathies). - Drug history (NSAIDS).
33PHYSICAL EXAMINATION
- Pallor.
- Jaundice.
- Tachycardia.
- Lymphadenopathy.
- Hepatosplenomegaly.
- Bone tenderness.
-
34LABORATORY 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.
35LABORATORY 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.
36Red 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.
37LABORATORY 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).
-
38OTHER INVESTIGATIONS
- Bone marrow aspirate and trephine biopsy.
- Radiological studies.
- Genetic studies.
- Immunological studies.
39BONE 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.
40BONE MARROW EXAMINATION-Contd
- Indications for BM examination in anemic
- patients include
- 1-Pancytopenia.
- 2-The presence of abnormal cells in the
- circulation (blast forms).
41EVALUATION 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
42Clinical 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.
43Clinical 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.
44Causes 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.
45Diagnosis 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
46Diagnosis 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.
47Search 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.
48Classic 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.
49Classic 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.
50VITAMIN B12 AND FOLATE DEFICIENCY ANEMIAS
51Vitamin 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.
52Classical 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.
53Diagnosis 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)
54Diagnosis 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.
55Methylmalonic 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.
56Methylmalonic Acid and Homocysteine-contd
- Vit.B12 deficiency Both serum homo-
- cysteine and methylmalonic acid (MMA)
- are elevated.
- Folate deficiency Only homocysteine level
- is elevated.
57EVALUATION 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).
58General Causes for Hemolysis
- 1-Hemolysis due to intrinsic defects (intra-
- corpuscular).
- 2-Hemolysis due to causes extrinsic to
- the RBC (extracorpuscular).
59Diagnosis 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.
60Laboratory 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
61Atypical 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