Presentation on theme: "ANEMIAS Dr. Aamer Aleem Consultant Hematologist"— Presentation transcript:
1ANEMIAS Dr. Aamer Aleem Consultant Hematologist Associate Prof. of MedicineKKUH & College of MedicineRiyadh
2AnemiaAnemia is present when a patient has a reduced amount of hemoglobin per unit volume of blood when compared with the correct reference population for that patient.Males Hb-13-18Females Hb 12-17
3ANEMIA Single cell line(RBC) problem Multiple cell line problem (RBC,WBC,Platelet)-Bone marrow suppression-immunologic disorders-peripheral destruction/sequestration
4Anemia Anemia is generally defined as a hematocrit <40% (hemoglobin <13.0 g/dL) in men or<37% (hemoglobin <12.0 g/dL) in women.(WHO definition)Red blood cell (RBC) indices, which include the mean corpuscular volume (MCV), the mean corpuscular hemoglobin (MCH), the mean corpuscular hemoglobin content (MCHC), and the red-cell distribution width (RDW) index, are further used to define types of anemia.
5AnemiaDespite having a set of peculiar symptoms and signs, anemia is not a disease per se, but a syndrome, as it may arise from an extensive list of causes.It is the chronic syndrome of highest prevalence in clinical medicine.
6Anemia EtiologyBased on Hb, red cell indices, retic count and red cell morphology(1) Inadequate responseA. Hypochromic microcycticB. Normochromic NormocyticC. Macrocytic(2)Adequate responseR/O blood loss---Includes Hemolyticdisorders
7Anemia-symptoms What are the symptoms of Anemia ? General malaise, weakness, fatigue, breathlessness on exertion, palpitations, angina.Desire to eat sand and clay.Menorrhagia common in women.
8Symptoms of AnemiaThe central nervous system, the heart and the muscle mass are the most affected organs, since they are the ones that most need oxygen for their functions.The symptoms increase with physical activity, as this consumes oxygen.With hemoglobin between 9 and 11 g/dL there's irritability, headache and psychic asthenia; in the elder fatigability is observed, and angina may occur.With hemoglobin between 6 and 9 g/dL there's tachycardia, dyspnea and fatigue upon the slightest effort.With hemoglobin below 6 g/dL symptoms are present even in sedentary activities, and when below 3.5 g/dL heart failure is impending and any activity is unfeasible.
10Red Cell IndicesMCV defines the size of the red blood cells and is expressed as femtoliters (10−15; fl) or as cubic microns (μm3). The normal values for MCV are 87 ± 7 fl.MCH quantifies the amount of hemoglobin per red blood cell. The normal values for MCH are 29 ± 2 picograms (pg) per cell.MCHC indicates the amount of hemoglobin per unit volume. In contrast to MCH, MCHC correlates the hemoglobin content with the volume of the cell. It is expressed as g/dl of red blood cells or as a percentage value. The normal values for MCHC are 34 ± 2 g/dl.
11Red Cell IndicesHow to calculate red cell indices
12Glossary of Useful Blood Count Descriptors Anisocytosis: red cells of unequal size. Reflected in increased RDW (Red cell Distribution Width.) Dimorphic Blood Film: two populations of red cells - one microcytic and the other normocytic. Seen in treated or transfused iron deficiency, and sideroblastic anemia Howell-Jolly bodies: round nuclear remnants within the red cells. Indicate splenectomy or hyposplenismMacrocytosis: large red cells Erythroblast: any nucleated red cell precursor Hypersegmented neutrophils: a neutrophil with six or more lobes. Usually (but not inevitably) means vitamin B12 or folate deficiency
13Glossary of Useful Blood Count Descriptors Hypochromia: pale red cells. Always accompanied by microcytosis Leukoerythroblastic: the presence of erythroblasts and myelocytes (which are precursors of mature cells) in the blood. Often indicates marrow infiltration eg by secondary cancer or fibrosisMicroangiopathy: indicates mechanical damage to red cells with red cell fragments on the blood filmMicrocytosis: small red cells Poikilocytosis: a traditional term for red cells of unequal shapePolychromasia: grey coloured red cells on film, indicating presence of increased reticulocytesReticulocyte: an erythrocyte newly released from the bone marrow
14Glossary of Useful Blood Count Descriptors Rouleaux: red cells in stacks, as coins. Indicates high ESR, eg infection, myeloma, cancer, collagen disease, TB etc.Schistocyte: a red cell which has undergone mechanical damage - synonymous with red cell fragmentSpherocyte: a spherical red cell due to disproportionate membrane loss. Either inherited, or acquired from (usually) immune causesSickle cell: a crescent-shaped red cell characteristic of Sickle Cell AnemiaTarget cell: red cell with central area of Hb giving the appearance of a target. Seen in many conditions, including IDA, hemoglobinopathy and liver disease
15RouleauxRouleaux (singular is rouleau) are stacks of red blood cells. They occur when the plasma protein concentration is high, and because of them the ESR (erythrocyte sedimentation rate) is also increased. Conditions which do this include infections, inflammatory and connective tissue disorders, and cancers. In this case, the diagnosis is probably multiple myeloma, as a plasma cell can be seen on the film.
16Erythroblasts & other BM cells Erythroblasts are the precursor cells of erythrocytes. They contain nuclei, and in adults are only found in the bone marrow under normal circumstances. Their presence in the blood may indicate either marrow 'stress', as in hypoxia, severe sepsis, or hemolysis, for example, or some fundamental bone marrow pathology such as replacement by secondary cancer.
17AnisocytosisAnisocytosis means that the red cells are of unequal size. It is a feature of many anemias, and other blood conditions, and does not have much diagnostic value. The 'red cell distribution width' (RDW) is a quantitative measure of the degree of anisocytosis. The RDW is useful in the differential diagnosis of microcytic anemia. Most cases of iron deficiency have a raised RDW, and most cases of thalassemia trait have a normal RDW.
18Dimorphic Red Blood Cells There are two populations of red cells present. One is normocytic, and the other is microcytic. This occurs either because an iron-deficient patient has been transfused or treated with iron, or in the Sideroblastic Anemias.
19Anemia-diagnosis How can we diagnose Anemia ? Blood tests to detect the various components of blood is carried out for proper diagnosis.Red blood cell count may be normal or decreased.Peripheral blood smear shows pale small cells.White blood cell count normal or decreased
20Classification of anemia Anemia can be either acute or chronic.In acute anemia (sudden loss of blood), the lack of blood volume in the circulatory system is more important than the deficiency of hemoglobin. A loss up to 10% of blood volume, as that taking place upon blood donation, is well tolerated. Losses between 10 and 20% cause postural hypotension, dizziness and faint. In losses above 20%, there's tachycardia, cold extremities, extreme paleness and hypotension, followed by shock; should the loss surmount 30%, without immediate replacement of intravenous fluids, the shock rapidly becomes irreversible and fatal.In chronic anemia, there's no decrease in blood volume, which is compensated by an increase in plasma volume.
21Classification of anemia Based on MCVMicrocytic anemiaNormocytic anemiaMacrocytic anemai
22Classification of anemia Based on underlying processBlood loss or def. of nutrientsHemolysisFailure of production
23A diagnostic scheme for anemias Determine the MCVThe most useful initial approach to anemia is based on red cell size. The Mean Corpuscular Volume (MCV) represents a direct measurement of red cell size. When this is reduced, the anemia is referred to as microcytic. It is macrocytic when the MCV is increased, and normocytic when the MCV is normal.
24Anemia-classification One way to classify anemia is by RBC size (i.e., MCV), as microcytic, macrocytic, or normocytic. For the microcytic anemias, the etiologic possibilities are iron deficiency, thalassemia, sideroblastic anemia, and the anemias of chronic disease. Severe microcytic anemia (MCV <70 fL) is caused mainly by iron deficiency or thalassemia. Macrocytic anemia may be the result of megaloblastic (folate or vitamin B12 deficiency) or nonmegaloblastic causes. Folate deficiency can in turn be due to either reduced intake or diminished absorption. Severe macrocytic anemia (MCV >125 fL) is almost always megaloblastic. In some rare cases, macrocytic anemia is related to the myelodysplastic syndromes prior to or after chemotherapy.The causes of normocytic anemias include aplastic anemia, bone-marrow replacement, pure red-cell aplasia, anemias of chronic disease, hemolytic anemia, and recent blood loss. A number of anemias have a genetic etiology. Examples of such inherited disorders include hereditary spherocytosis and sickle-cell (SC) anemia
29Macrocytic anemia D/DMacrocytic anemia may be the result of megaloblastic (folate or vitamin B12 deficiency) or nonmegaloblastic causes. Folate deficiency can in turn be due to either reduced intake or diminished absorption. Severe macrocytic anemia (MCV >125 fL) is almost always megaloblastic.
30The Normocytic Anemias These may be classified as follows:underproduction of erythrocytes due to(1) the anemia of chronic disease(2) marrow failure(3) renal failure (decreased erythropoietin)loss or destruction of erythrocytes due to(1) hemolysis(2) acute blood lossThe reticulocyte count is useful in drawing this distinction, being elevated in (b) and reduced in (a).
31The Normocytic Anemias The causes of normocytic anemias include aplastic anemia, bone-marrow replacement, pure red-cell aplasia, anemias of chronic disease, hemolytic anemia, and recent blood loss. A number of anemias have a genetic etiology. Examples of such inherited disorders include hereditary spherocytosis, sickle-cell (SC) anemia, and thalassemia
33Diagnostic Approach-History Age : Iron def rare without blood loss before 6 months in term infants.Family Hist &Genetics:(1)X-linked: G6PD deficiency(2)Aut dominant: Spherocytosis(3)Aut recessive:Sickle cell,Fanconi anemia(4)Family member with early age ofcholecystectomy/splenectomy(5)Ethnicity (Thalassemia: Mediterranean;G6PD def: (Greeks, Blacks, Middle eastern) (6)Race:B-thal:Mediterranean,African,Asian;A-thal: Blacks, Asians
35Diagnostic Approach-History Diarrhoea-Malabsorption of VitB12/E/Fe Inflammatory bowel disease and anemia of chronic disease with or without blood loss Milk protein intolerance induced blood loss Intestinal resection: Vit B12 defInfection: Giardia:iron malabsorption Intestinal bacterial overgrowth:Vit B12 def Fish tapeworm:Vit B12 def EBV,CMV,Parvovirus:BMsuppression Mycoplasma,Malaria:hemolysis Hepatitis:aplastic anemia Endocarditis, HIV
36Physical exam reveals presence and potential causes of anemia Fever-acute infection,intravascular disease,collagen vascular diseaseJaundice suggests hemolysisPetechia & Purpura—bleeding tendencyHypertension & edema-renal diseaseHepatosplenomegaly and lymphadenopathy—infiltrative diseaseGrowth failure or poor wt. gain—Anemia of chronic disease or organ failureExamine stool for blood; urine for hemoglobinuria(Admit & tranfuse if signs of CHF)
42Microcytic Anemia TEST Iron def ThalMin An of ch dis S.Iron low normal normalS.Ferritin low N/H N/HMarrow iron low N/H N/HHb A2 or F N H=Bthal NN=AthalRDW high normal N/HMCV ÷ RBC - > < 13Sickle/B-thal – Hb S > Hb AAbsence of microcytosis in both parents excludes B-thal or Sickle/B-thal but not A-thal
43Anemia-treatmentHow can Anemia be treated ? As there are many factors causing anemia, the main treatment is for the cause.Specific treatment of disorder causing anemia.Replacement of missing factors (iron, vitamin B12, folate)In many chronic anemias regular blood transfusions are needed (thalassemia, myelodysplastic syndrome)Blood transfusion is usually needed in acute blood loss or if the patient has severe symptoms or in heart failure(Problems of blood transfusion)
44Iron deficiency anemia (IDA) It is a condition when supply of iron in the body to bone marrow falls short of that required for the production of red blood cells. It is the commonest cause of anemia throughout the world.
45Iron Deficiency Anemia The incidence of anemia in the general population is about 1.5%.Iron deficiency related to inadequate replacement of lost iron is the most frequent cause of asymptomatic anemia and has a variety of causes.Iron deficiency is common among women of childbearing age; 10% to 20% of menstruating women have abnormally low concentrations of hemoglobin (usually <12 g per 100 mL).
46Iron Deficiency Anemia What are the causes of IDA ?Increased physiological demand for more red blood cellseg: increased physical activity.In children, during spurts of growth.In women during menstruation, pregnancy, parturitionand lactation.Inadequate dietary intake due to poor economic reasonsor deficient foods.Decreased absorption due to disorders in the digestivesystem.GI blood loss Peptic ulcer, piles, hiatus hernia, carcinoma ofstomach, carcinoma colon, chronic ingestion of a certain typeof pain relievers, hookworm infestation.
47Iron Deficiency Anemia Between 20% and 60% of pregnant women have hemoglobin levels <11 g per 100 mL. Anemia was found in 6% of white women and 17% of black women during the first trimester and in 25% of white women and 46% of black women during the third trimester.
48Iron Deficiency Anemia The high rates of anemia in pregnant women are not attributable to iron deficiency alone, however. In a large study of low-income, urban, mostly minority pregnant women, only 12.5% were iron deficient. Women progressing through pregnancy develop a lowered hematocrit as a result of physiologic hydremia related to a disproportionate increase in plasma volume.
49Iron Deficiency Anemia The daily oral iron requirement for men and postmenopausal women is 0.5 and 1 mgMenstruating and pregnant women have higher requirements: 2 mg and 2.5 mg, respectively.The replacement of lost iron is complicated by the fact that only 5% to 10% of the 10 to 20 mg of the iron in the average adult diet is absorbed.Anemia is less likely to occur in women taking birth control pills and more likely to occur in women with intrauterine devices.
50Iron Deficiency Anemia Because men and postmenopausal women rarely develop iron deficiency that is not related to gastrointestinal blood loss (often occult), an evaluation of gastrointestinal tract must be performed when an iron deficiency is detected in these individuals
51IDA-Practice Point Iron def. is common in children 9mo-3yr Iron def. anemia in a child over 3yr should prompt consideration of occult blood loss.Infants less than 6months generally do not develop iron def.; the exception to this rule is premature infants,who are at risk of iron def.at 4mo, if iron supplementation is not given.
52Iron Deficiency Anemia-Diagnosis Red blood cell count may be normal or decreased.Peripheral blood smear shows pale small cells.Aniso-poikilocytosisWhite blood cell count usually normalSerum iron is reducedTotal iron binding capacity of blood shows an increase.Low serum ferritin
53Iron Deficiency Anemia-Treatment Correction of iron deficiency - to restore hemoglobin level.To replenish iron stores.Oral iron administration is advised. (Side effects of oral iron)Parenteral iron may be needed occasionallyTreat the underlying cause
54Anemia of Chronic Disease Patients with cancer, infection, or inflammation, commonly have a mild-to-moderate anemia caused by red cell underproduction. This 'anemia of chronic disease' is very common, and is usually normocytic. Some cases develop abnormalities of iron metabolism, in which case there may be a microcytosis.
55HemolysisHemolysis is defined as the premature destruction of red blood cells, from whatever cause.Recognising the presence of hemolysisThe simplest tests areRaised reticulocyte countRaised indirect (unconjugated) bilirubinRaised serum LDHDiminished serum haptoglobin concentration. Further more sophisticated testing may be needed in some cases.
56HemolysisA Direct Coombs' Test tells you whether the red blood cells are antibody-coated, and, in the presence of hemolysis, indicates an immune-mediated process (Autoimmune hemolytic anemia).Note that many patients with a positive Direct Coombs' test do not have hemolysis.
58Hemolysis Acquired causes Immune Warm and Cold Autoimmune Hemolytic AnemiaNon-immuneMechanical Damage from leaky heart valvesMicroangiopathic hemolytic anemia (MAHA) like TTP, HUS & DIC
59Lead Poisoning Hypochromic microcytic anemia Associated iron deficiencyChild has pica and is exposed to lead paint or lead dustBlood smear shows basophilic stipling and blood lead is elevated.Removal from exposure,chelation therapy and correction of iron deficiency are important.
60THALASSEMIA Normal Hb is a tetramer of 2 alpha and 2 beta chains Alpha-thalassemia:decrease or total lack of alpha globin synthesisBeta-thalassemia:decrease or total lack of beta globin synthesis
64THALASSEMIA-therapy Red cell transfusion 3-4 weekly-Hb 9-10 Chelation therapy with desferrioxamineSplenectomy if transfusion >200ml/kg/yrFolic acid 5mg dailyPenicillin prophylaxis to all splenectomisedPneumococcal and Hib vaccine before sply.Cholecystectomy for gall stonesBone marrow transplantation is curativeGenetic counselling
65SICKLE CELL DISEASE SA :Sickle cell trait-asymptomatic SS :Sickle cell anemiaS-Bthal:Sickle cell-beta thalSC :Hb SC diseasePathophysiology:Valine replaced by glutamic acid at Beta 6 position With deoxygenation HbS crystallises&gels
66Clinical features Anemia:chronic,onset at 3-4 mo Aplastic crisis:parvo virus B12Sequestation crisis:usuallyspleenHemolytic crisisDactylitis:Hand foot syndrome(infant)Painful crisis:muscle,bone,bone marrow,lung, intestinesCerebrovascular accidentsAcute chest syndrome:infection,infarction,embChronic lung disease:pulmonary fibrosis,restictive lung disease,cor pulmonale
67Clinical features Priapism Ocular:retinopathy Gall bladder disease:stones,cholecystitisRenal:hematuria,conc.deficit,nephropathyCardiomyopathySkeletal:avascular necrosis of femoral headLeg ulceration:in older ptsInfections:pneumococcal pneumonia,meningitis, arthritis,Hinf sepsis,salmonella&staph osteomyelitis,mycoplasma pneumonia,viral infeGrowth failure,delayed pubertyPsychologic problems:chronic illness,chronic pain
68THERAPY Anemia is usually chronic&compensated Blood transfusion only given based on clinical condition,Hb level&retic countCrisis:Splenic sequestration crisis,aplastic crisis,hyperhemolytic crisis-in all of these PRBC is indicated when anemia is sympto.Pain crisis:IVF,analgesia with narcotics,NSAIDsAcute chest syndrome:O2,judicial use of analgesics&fluids,antibiotics,PRBCStroke:O2,fluids,exchange transfusionHydroxyurea:decrease number&severity of VOCBone marrow transplantation
69G6PD deficiency Episodic hemolysis on exposure to oxidants Severity of hemolysis depends on the enzyme variantGene for G6PD is on X chromosomeJaundice,dark urine(bilirubin,hemoglobin),Red cells appear blisteredG6PD levels may be normal with hemolysisTherapy:PRBC,IVF,urine alkalinisationPrevention:avoid oxidants,fava beans,henna