2DEFINITIONAnemia: 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/dLF ,5 g/dL
4HEMATOCRITHematocrit (HTC): Is the percent of a volume of whole blood occupied by intact RBCs.Values are expressed as a percentage.Normal range: M %.F %.
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/uLF 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 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-Americans—lower values.4.Populations with a high incidence of ch.diseases.5.Athletes.6.The elderly:should not have a lower normal range for fear of missing a serious underlying disorder.
8ERYTHROPOESIS -1Erythropoesis 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 removedfrom the circulation daily.The rate of RBC production can beincreased markedly (5-7 folds).
10CLINICAL 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).
11COMPENSATORY 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 Symptom:is a sensation or change in health function experienced by the patient.It is a subjective report.Fatigue/tirednessPain.Nausea.Dizziness.
13SYMPTOMS AND SIGNS-cont’d Sign: is an objective evidence of thepresence of a disease or disorder.Signs are discovered and reported bythe physician,not by the patient.It isan 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 anemia:Lethargy,confusion,CHF,angina,MI.Pallor.Headache.Complications of extracellular volume depletion (in acute bleeding).
15CAUSES OF ANEMIAThere are 2 interrelated approaches one can use to help identify the cause of anemia.1.Kinetic approach.2.Morphologic approach.
16KINETIC APPROACHAnemia 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 isreplaced by the BM.1- Lack of nutrients such as iron,B12,orfolate.2- Primary involvement of the BM suchas aplastic anemia,PRCA,MDS,ortumor infiltration.3- Low levels of trophic hormones,suchas EPO in CRF,thyroid hormones,andandrogens.
18INCREASED RBC DESTRUCTION A RBC life span below 100 days is theoperational definition of hemolysis.Anemia will ensue when the BM is unableto keep up with the need to replacemore than 5% of the RBC mass daily.1-Inherited hemolytic anemias: hereditaryspherocytosis,SCD,and thalassemiamajor.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 bleeding:a slowly bleedingcolonic 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 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.
23IDA,ACD,and thalassemias are the most 3 common causes of microcytosis inclinical practice.Since all 3 have hypochromic and micro-cytic RBCs on blood film (smear),otherfactors must be used to establish thediagnosis.
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 ofiron deficiency.
25ANEMIA OF CHRONIC DISEASE (ACD) The hallmarks of this condition are:1-Low serum iron.2-Low TIBC.3-Normal to increased serum ferritinconcentration.The causes are usually related to thepresence of chr.infection (TB),inflamation (RA),or malignancy.
26ALPHA OR BETA THALASSEMIA MINOR Adults with thalassemia are most oftenheterozygotes for the alpha or betaforms of this syndrome,and may not beanemic.Family history is often negative.P/E may reveal splenomegaly.Blood film: microcytosis,hypochromia,target cells,tear-drop forms,andbasophilic stippling.
27MACROCYTIC ANEMIAS Are characterized by an MCV above 100 fL. Reticulocytosis.Vit.B12 def.Folate def.MDS.Hypothyroidism
28By definition the MCV is normal. NORMOCYTIC ANEMIASBy definition the MCV is normal.ACD.MDS.
29MULTIPLE CAUSES OF ANEMIA In pediatric practice anemia is commonlycaused by a single disorder.In adults,mainly older adults,multiplecauses are frequently present.1-Ca colon: IDA and ACD2-AIHA on steroids and GIbleeding.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 it`s 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).
34LABORATORY EVALUATION-1 Complete blood count (CBC): HBG,HCT,RBC count,RBC indices,andWBC count.WBC differential,PLT count,andreticulocyte count.Blood film (Blood smear).Red cell distribution width.
35LABORATORY EVALUATION-2 Red cell indices:1-Mean corpuscular volume.MCVfemtoliter.2-Mean corpuscular hemoglobin.MCH27,5-33,2 picograms of hemoglobinper RBC.3-Mean corpuscular hemoglobinconcentration.MCHC.33,4-35,5grams of hemoglobin per dL of RBCs.
36Red Cell Distribution Width(RDW) RDW is a measure of anisocytosis or variation inred cell size.Increased RDW is commonly found whenthere is a nutritional deficiency(eg,iron,folate,and Vit.B12).Increased RDW is not specific for any oneabnormality.An increased RDW is the mathematical equi-valent of the term”anisocytosis”,but is notdiagnostic of any particular morphologic finding.
37LABORATORY EVALUATION-3 Reticulocyte count: helps to distinguishamong 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 inthe 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 littleadditional diagnostic information in themore common forms of anemia.Although the absence of stainable iron inBM is considered the “gold standard”for the diagnosis of ID,this diagnosisis usually established by lab.tests alone.
40BONE MARROW EXAMINATION-Cont’d Indications for BM examination in anemicpatients include:1-Pancytopenia.2-The presence of abnormal cells in thecirculation (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 ironTIBCserum ferritin
42Clinical Manifestations of Iron Deficiency (ID)-1 The presenting symptoms of ID arecaused 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 exercisecapacity and causes easy fatiguabilityPICA and Pagophagia:PICA:is a perverted apetite for substancesnot fit as food,such as clay or paperproducts.Pagophagia: is PICA for ice.
44Causes of ID Blood loss:Common cause.Overt or occult. Decreased iron absorption: Relativelyuncommon cause.Intravascular hemolysis: Hematuria (PNH).Pulmonary hemosiderosis:Administration of erythropoietin: In anemiaof chronic renal failure.
45Diagnosis of ID-1 History and physical examination. Laboratory investigations: CBC,RBCindices,and blood film(smear)→pre-sumptive diagnosis of ID.Therapeutic trial of oral iron→positiveresponse (reticulocytosis,followedby an increase in Hb at a rate ofabout 2-4 g/dL every 3 weeks
46Diagnosis of ID-2 No positive response ? The following lab.investigations areneeded 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 moreimportant than diagnosing ID.History and physical examination.Other investigations: Upper and lowerendoscopy.
48Classic Presentation of IDA A multigravid woman in her 40’s,presentswith tirednes and fatigue and chronicblood 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,hypochromicred blood cells(RBCs)4-The serum iron was low and the total iron bindingcapacity(TIBC) was elevated,resulting in transferrinsaturation < 15%.The plasma ferritinconcentration was reduced.
49Classic presentation of IDA-Cont’d Iron stores were absent after performingthe “gold strandard” test for estimatingiron stores via bone marrow aspirate ofthe patient.Finally,the patient responded briskly tooral iron therapy with a reticulocytosisfollowed by elevations in the hemo-globin concentration.
50VITAMIN B12 AND FOLATE DEFICIENCY ANEMIAS Dr.Nazzal Bsoul
51Vitamin B12 Vitamin B12 (Vit.B12),also called cobalmin is a water-soluble vitamin with a keyrole in normal functioning of the brainand nervous system,and for erythro-poiesis.It is normally involved in the metabolism ofevery cell of the body.It is structurally the most complicated vitaminand 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 severeanemia,and macrocytosis,with or with-out varying neurologic disturbances.However,many patients with B12 deficiencyexist who have no or only mild anemia,and macrocytosis may be masked by aconcurrent disorder,such as IDA orthalassemia.
53Diagnosis of B12 and/or Folate Deficiency B12 or folate deficiency should be suspected inpatients with one or more of thefollowing findings:1-Oval macrocytic RBCs on blood film,withor 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-cont’d Special populations are at increased risk:1-Older adults.2- Alcoholics.3- Patients with malnutrition.4- Vegeterians.Vit.B12 and folate deficiency often coexistand are not easily diffirentiated on aclinical basis.The first step is to test for serum Vit.B12 andfolate level.
55Methylmalonic Acid and Homocysteine Patients with low-normal or even normalserum B12 values may be truly Vit.B12deficient.Measurement of the homocysteine andmethylmalonic acid appears to bemore sensitive for the diagnosis ofthese deficiencies than serum Vit.B12and folate levels.
56Methylmalonic Acid and Homocysteine-cont’d Vit.B12 deficiency: Both serum homo-cysteine and methylmalonic acid (MMA)are elevated.Folate deficiency: Only homocysteine levelis 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 fragmentedRBCs) on bl.film.Lab.findings in hemolysis:High LDHHigh indirect bilirubin.Low serum haptoglobin.Positive direct coombs’ test (only in case ofautoimmune hemolytic anemia).
58General Causes for Hemolysis 1-Hemolysis due to intrinsic defects (intra-corpuscular).2-Hemolysis due to causes extrinsic tothe RBC (extracorpuscular).
59Diagnosis of Active Hemolysis Recognizing overt hemolysis is not difficultin a classic patient with:New onset of PallorJaundiceSplenomegalyAnemiaCirculating spherocytes.Accurate histrory and physical examinationshould always be the cornerstone of thepatient’s evaluation.
60Laboratory Findings in Hemolysis Serum lactate dehydrogenase (LDH) andHaptoglobin are the major serum testsin the diagnosis of hemolysis.Reticulocyte count.Other tests:Indirect bilirubin.Coombs’ test.Blood film (smear).Serial evaluation of Hb and Ht
61Atypical Presentations Hemolysis without anemia: if the rate ofRBCs destruction falls within the bonemarrow’s compensatory ability.Indirectbilirubil, LDH,and reticulocyte count arehigh, but without anemia.Hemolysis without reticulocytosis: