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Classification of Anemia (Adults) Teoman SOYSAL Prof. MD.

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Presentation on theme: "Classification of Anemia (Adults) Teoman SOYSAL Prof. MD."— Presentation transcript:

1 Classification of Anemia (Adults) Teoman SOYSAL Prof. MD

2 Definition of anemia Anemia: A reduction in Anemia: A reduction in – red cell mass – O 2 -carrying capacity It is expressed in terms of reduction in the concentration of Hb (or RBC or Hct%) compared to values obtained from a reference population. It is expressed in terms of reduction in the concentration of Hb (or RBC or Hct%) compared to values obtained from a reference population. ( 2 SD below normal)

3 Reference values (I) ParameterFemale Male ParameterFemale Male RBC (x10 12 /L)4.8+0.65.4+0.9 RBC (x10 12 /L)4.8+0.65.4+0.9 Hb (g/dL)14+216+2 Hb (g/dL)14+216+2 Htc (%)42+547+5 Htc (%)42+547+5

4 Reference values (II) Ret (% / n)0.5-2.5 / 50-100x10 9 /L Ret (% / n)0.5-2.5 / 50-100x10 9 /L MCV (fl)90+7 MCV (fl)90+7 MCH (pg)29+2 MCH (pg)29+2 MCHc (g/dL)34+2 MCHc (g/dL)34+2 RDW (%)11.5-14.5 RDW (%)11.5-14.5

5 50 100200 fl RBC %

6 Reticulocyte Normal Ranges Male: % 0.8 - 2.5 Male: % 0.8 - 2.5 Female: % 0.8 - 4.1 Female: % 0.8 - 4.1 Corrected Rtc: Patient Hb/Normal Hb x Rtc % Reticulocytosis: > 100.000 /mm 3

7

8 Definition of anemia Hb level of a patient which is below the normal ranges of that age and sex. Hb level of a patient which is below the normal ranges of that age and sex. For adults: For adults: WHO criteria define anemia as hemoglobin level lower than 12 g/dL in women and 13 g/dL in men WHO criteria define anemia as hemoglobin level lower than 12 g/dL in women and 13 g/dL in men But: But: The reference values for red cells,Hb or Hct may difer according to – –sex/age – –Race – –Altitude – –Socioeconomical changes – –Study/reference etc

9 BEUTLER andWAALEN BLOOD, 1 MARCH 2006 VOLUME 107, NUMBER 5

10 ageWBC Neutrophyls Eos.BasoLenfoMonoHb 12 mo6-17.51.5-8.5 0.05-0.70-0.20 4-10.5 0.05-1.111.1-14.1 4 y5.5-151.5-8.5 0.02- 0.65 0-0.20 2-8 0-0.811.2-14.3 6 y5-14.51.5-8 0-0.650-0.20 1.5-7 0-0.811.4-14.5 10 y4.5-131.8-8 0-0.600-0.20 1.5-6.5 0-0.811.8-15 21 y4.5-111.8-7.7 0-0.450-0.20 1-4.8 0-0.8E: 16 K: 14 WBC: x10E3/mm 3 Hb:g/dL Age and blood count changes

11 !!!!! Plasma volume changes have to be considered before determining a diagnosis of anemia. Plasma volume changes have to be considered before determining a diagnosis of anemia. –Volume contraction:Underestimation of anemia –Volume overload: Underestimation of Hb level

12 Volume changes/acute bleeding and anemia normal Hct (a/b%): Normal Dehydration Hct:Increased Acute blood loss(early) Hct:unchanged Chronic anemia Hct: Low 12345 Increased plasma volume Hct: Low b a

13 !!!!! A normal Hb in a patient in whom an elevated Hb level is expected may represent anemia.(eg:COPD + Hb:N) A normal Hb in a patient in whom an elevated Hb level is expected may represent anemia.(eg:COPD + Hb:N)

14 !!!!!! Different red cell measures of the same patient may give discordant values in special conditions. (eg: Thalassemia trait) Different red cell measures of the same patient may give discordant values in special conditions. (eg: Thalassemia trait) Eg: Low Hb, high RBC, low MCV Hb: 10 g/dL (anemia) Hb: 10 g/dL (anemia) RBC: 6.5 million/mm3 (erythrocytosis) RBC: 6.5 million/mm3 (erythrocytosis) MVC : 70 fL MVC : 70 fL

15 !!!! Anemia is rarely a disease by itself, Anemia is rarely a disease by itself, It is mostly a manifestation or consequence of an underlying (genetic or acquired) disease. It is mostly a manifestation or consequence of an underlying (genetic or acquired) disease. The finding of anemia has to start attempts to disclose an underlying disease. The finding of anemia has to start attempts to disclose an underlying disease. –What is the cause of anemia ?

16 Anemia leads to two symptom complexes; Tissue hypoxia Tissue hypoxia –Fatigue,dyspnea on exertion etc Compensatory attempts Compensatory attempts –Tachycardia,hyperventilation etc

17 The amount of O 2 necessary to support life is : 250 ml/min The amount of O 2 necessary to support life is : 250 ml/min O 2 carrying capacity of normal blood:1.34 ml/g-Hb (200 ml/L-blood) O 2 carrying capacity of normal blood:1.34 ml/g-Hb (200 ml/L-blood) Cardiac output: 5000 ml/min Cardiac output: 5000 ml/min O 2 delivery to tissues : 1000 ml/min O 2 delivery to tissues : 1000 ml/min

18 Reduced levels of Hb results with reduced oxygen delivery to tissues, leading to tissue hypoxia. Reduced levels of Hb results with reduced oxygen delivery to tissues, leading to tissue hypoxia. The symptoms and findings of anemia concern many different systems/organs due to the widespread nature of hypoxia. The symptoms and findings of anemia concern many different systems/organs due to the widespread nature of hypoxia.

19 The most pronounced effects and symptoms derive from The most pronounced effects and symptoms derive from –skeletal muscles, heart,and central nervous system (due to their greater oxygen demand and compensatory actions). What is the mechanism underlying compensatory mechanisms ? What is the mechanism underlying compensatory mechanisms ?

20 Hypoxia-Inducible Transcription Factor 1 A DNA binding protein A DNA binding protein Regulated by the O 2 tension Regulated by the O 2 tension Regulates genes that promote cell survival under hypoxic conditions Regulates genes that promote cell survival under hypoxic conditions Up-reg. EPO gene Up-reg. EPO gene Up-reg.Glycolytic enzyme genes Up-reg.Glycolytic enzyme genes Up-reg. Angiogenesis Up-reg. Angiogenesis Respiratory control Respiratory control Energy metabolism Energy metabolism

21 EPO producing cells HIF-1 Muscle heart liver kidney Carotid body Glomus cells All cells Vasc. endothelium Erythropoiesis Angiogenesis and vascular tone Energy metabolism Decreased O 2 consumption Iron metabolism Respiration EPO

22 Compensating mechanisms in anemia: The release of oxygen to the tissues is increased (reduced oxygen affinity of Hb) The release of oxygen to the tissues is increased (reduced oxygen affinity of Hb)

23 Compensating mechanisms in anemia The rate of blood circulation and cardiac output increases. The rate of blood circulation and cardiac output increases. An increase in plasma volume maintains total blood volume in normal or near normal ranges. An increase in plasma volume maintains total blood volume in normal or near normal ranges. Redistribution of blood flow. Redistribution of blood flow.

24 Different patients may have different severity of symptoms even for the same level of Hb. Different patients may have different severity of symptoms even for the same level of Hb. The severity of the symptoms of anemia are related to; The severity of the symptoms of anemia are related to; –The severity of anemia –The age,CVS,pulmonary status etc of the patient –The rate of the development of anemia Gradual or Gradual or Rapid onset Rapid onset

25 Clinical symptoms and findings of anemia (1) The symptoms and findings are related to anemia itself or to the underlying disease that causes anemia. The symptoms and findings are related to anemia itself or to the underlying disease that causes anemia. The symptoms and findings related to anemia itself will be mentioned during this course. The symptoms and findings related to anemia itself will be mentioned during this course.

26 Clinical symptoms and findings of anemia (2) Fatigue, weakness Fatigue, weakness –Tiredness, lassitude, reduced exercise tolerence –Generalized muscular weakness Pallor / skin or mucous membranes Pallor / skin or mucous membranes –Skin color may change due to other reasons; eg :Blood flow of skin, subcutaneous fluid, pigment changes

27 Pallor (paleness): Look at Look at –Mucous membranes of mouth and pharynx –Conjunctivae,lips, nail beds,palms Creases of the palms lose their pink colour when the Hb < 7g/dL Creases of the palms lose their pink colour when the Hb < 7g/dL In pernicious anemia there is a lemon yellow pallor. In pernicious anemia there is a lemon yellow pallor. Pallor + mild scleral icterus suggests hemolytic anemia. Pallor + mild scleral icterus suggests hemolytic anemia. Pallor+ petechiae suggests severe bone marrow failure Pallor+ petechiae suggests severe bone marrow failure

28 Some other skin/mucosal changes Some other skin/mucosal changes –Premature graying of hair:pern.anemia –Hair loss and fragility + spooning of the nails:iron deficiency –Chronic leg ulcers:Sickle cell or other hemolytic anemia –Glossitis/burning sense :Pern. anemia, iron deficiency(rare) –Chelitis(angular stomatitis):iron def. –Siideropenic dysphagia: iron def. –Painful ulcerative mouth lesions: aplastic anemia/leukemia

29 Clinical symptoms and findings of anemia (3) Cardiovascular System(1) Palpitation and dyspnea (during activity) Angina pectoris Claudicatio intermittans Murmurs: Mid systolic (rarely diastolic), mainly pulmonary valvular or apical or over major peripheral arteries or jugulary veins

30 Clinical symptoms and findings of anemia (3) Cardiovascular System(2) High output state: Collapsing pulse, high pulse pressure Cardiomegaly Congestive failure Ischemic ECG changes

31 Clinical symptoms and findings of anemia (4) Central nervous system Headache Faintness Giddiness Tinnitus Decreased concentration ability Drowsiness,decreased muscle strength Clouding of consciousness Symptoms are more prominent in older patients Paresthesias:Vitamin B12 deficiency (or other).

32 Clinical symptoms and findings of anemia (5) Reproductive system Menstrual changes: Menstrual changes: –Amenorrhea, –Menorrhagia(mostly a cause of anemia) Loss of libido Loss of libido

33 Clinical symptoms and findings of anemia (6) Gastrointestinal system (these symptoms may indicate underlying disorder that might indeed be a cause of anemia) Anorexia Anorexia Flatulence Flatulence Nausea Nausea Constipation Constipation Weight loss Weight loss These should remind GIS disease as a cause of anemia (eg:a bleeding lesion-ulcer/malignancy etc)

34 Clinical symptoms and findings of anemia (7) Ocular Fundi: Ocular Fundi: –Pale and sometimes sometimes –Hemorrhages –Papillaedema

35 Clinical symptoms and findings of anemia (8) Renal Changes Renal Changes –Slight proteinuria –Concentrating defects –Further reduction of renal function in patients with previous renal impairment (Renal failure itself is a cause of anemia!!!!) Pyrexia: Due to a hypermetabolic state or other underlying disease (which may be a cause of anemia) Pyrexia: Due to a hypermetabolic state or other underlying disease (which may be a cause of anemia)

36 Some Other examples for history and physical examination The duration of symptoms (acute/insidious) The duration of symptoms (acute/insidious) Bleeding ? Nose/skin/urine/mens/stool etc Bleeding ? Nose/skin/urine/mens/stool etc Family history Family history –Anemia, gall stones and splenectomy –Bleeding disorder Occupation, hobbies,dietary history,alcohol or drug use,travel history etc (toxic/infectious contacts) Occupation, hobbies,dietary history,alcohol or drug use,travel history etc (toxic/infectious contacts) Ask for skin and hair/nail changes Ask for skin and hair/nail changes

37 Some Other examples for history and physical examination Pain / mass / fever/systemic overview for an underlying disease Pain / mass / fever/systemic overview for an underlying disease –Renal/endocrine/liver disease or –Chronic infection/malignancy/imflamatory condition Parasitis Parasitis Pregnancies Pregnancies Paresthesias,walking difficulty Paresthesias,walking difficulty Sternal or other bone tenderness Sternal or other bone tenderness Splenomegaly, hepatomegaly Splenomegaly, hepatomegaly Lymphadenomegaly Lymphadenomegaly

38 Diagnosis and investigation: Is the patient anemic? Is the patient anemic? What is the type of anemia? What is the type of anemia? What is the cause of anemia? What is the cause of anemia?

39 Classification of anemia Morphologic Morphologic –Normocytic: MCV= 80-100fL –Macrocytic: MCV > 100 fL –Microcytic : MCV < 80 fL Pathogenic (underlying mechanism) Pathogenic (underlying mechanism) –Blood loss (bleeding) –Decreased RBC production –Increased RBC destruction/pooling

40 Normocytic Anemias Acute post- hemorrhagic anemia Acute post- hemorrhagic anemia Hemolytic anemia (except thalassemia and some other Hb disorders) Hemolytic anemia (except thalassemia and some other Hb disorders) Aplastic anemia Aplastic anemia Pure red cell aplasia Pure red cell aplasia Bone marrow infiltration Bone marrow infiltration Endocrin diseases Endocrin diseases Renal failure Renal failure Liver disease Liver disease Chronic disease anemia Chronic disease anemia Protein malnutrition Protein malnutrition Hypovitaminosis C Hypovitaminosis C

41 Microcytic anemias Iron deficiency anemia Iron deficiency anemia Thalassemia Thalassemia Sideroblastic anemia Sideroblastic anemia Lead poisoning Lead poisoning Anemia of chronic diseases Anemia of chronic diseases (some cases) (some cases)

42 Macrocytic anemias Megaloblastic Megaloblastic Non-megaloblastic Non-megaloblastic

43 Megaloblastic Macrocytic Anemias Vit B 12 deficiency Vit B 12 deficiency Folic acid deficiency Folic acid deficiency Other. Other.

44 Non-megaloblastic Macrocytic Anemias Anemia of acute bleeding Anemia of acute bleeding Hemolytic anemias Hemolytic anemias Leukemias Leukemias (esp: acute) Myelodysplastic syndromes Myelodysplastic syndromes Liver disease Liver disease Aplastic anemia Aplastic anemia Diseases infiltrative to the bone marrow Diseases infiltrative to the bone marrow Alcoholism Alcoholism Hypothyroidism Hypothyroidism Scurvy Scurvy

45 Pathogenic classification (Causes of anemia) Relative (increased plasma volume) Relative (increased plasma volume) Decreased RBC production Decreased RBC production Blood loss Blood loss –Anemia due to acute bleeding Increased RBC destruction Increased RBC destruction

46 Pathogenic classification (Causes of anemia) Decreased RBC production Decreased RBC production –Decreased Hb production –Defective DNA synthesis –Stem cell defects Pluripotent stem cell Erythroid stem cell(progenitors) –Other less defined reasons Blood loss Blood loss –Anemia due to acute bleeding Increased RBC destruction Increased RBC destruction Relative(increased plasma volume) Relative(increased plasma volume)

47 Decreased Hb production Iron deficiency anemia Iron deficiency anemia Thalassemia Thalassemia Sideroblastic anemia Sideroblastic anemia Lead poisoning Lead poisoning

48 Defective DNA synthesis Vit B 12 deficiency Vit B 12 deficiency Folic acid deficiency Folic acid deficiency Other. Other.

49 Pluripotent stem cell defects Pluripotent stem cell defects Aplastic anemia Aplastic anemia Leukemia or myelodysplastic syndromes Leukemia or myelodysplastic syndromes Defective erythroid stem cell Pure red cell aplasia Pure red cell aplasia Anemia of chronic renal failure Anemia of chronic renal failure Endocrin disease anemia Endocrin disease anemia Congenital dyserythropoetic anemias Congenital dyserythropoetic anemias

50 Decreased RBC production due to multipl or undefined mechanisms Anemia of chronic diseases Anemia of chronic diseases Bone marrow infiltration Bone marrow infiltration Anemia due to nutritional defects Anemia due to nutritional defects

51 Anemias caused by increased RBC destruction (hemolytic anemias) Can be classified as; Can be classified as; Hemolysis due to intracorpuscular defects Hemolysis due to intracorpuscular defects Hemolysis due to extracorpuscular defects Hemolysis due to extracorpuscular defectsOr Hereditary hemolytic diseases Hereditary hemolytic diseases Acquired hem. diseases Acquired hem. diseasesOr Intravascular hemolysis Intravascular hemolysis Extravascular hemolysis etc. Extravascular hemolysis etc.

52 1- Abnormalities of RBC interior a. Enzyme defects b. Hemoglobinopathies & Thalassemia M 2-RBC membrane abnormalities a. Hereditary spherocytosis, elliptocytosis etc b. Paroxysmal nocturnal hemoglobinuria c. Spur cell anemia 3- Extrinsic factors a. Hypersplenism b. Antibody : immune hemolysis c. Traumatic & Microangiopathic hemolysis d. Infections, toxins, etc Intracorpuscular Extracorpuscular HereditaryAcquired A Very Simple Classification of Hemolytic Anemias

53 Is the patient anemic ? RBC count RBC count HB level HB level Hct level Hct level Volume status Volume status

54 What is the type of anemia? History and physical exam. History and physical exam. RBC,HB,Hct, RBC,HB,Hct, MCV, MCH,RDW MCV, MCH,RDW Red cell morphology ( peripheral smear) Red cell morphology ( peripheral smear) Reticulocyte count Reticulocyte count –Incresed ? Other Lab. investigations Other Lab. investigations

55 Lab. investigation of anemia(1) WBC count and differential WBC count and differential Platelet count and morphology Platelet count and morphology ESR ESR Biochemistry, special tests and others Biochemistry, special tests and others Bone marrow exam.(only when indicated) Bone marrow exam.(only when indicated)

56 Lab. investigation of anemia(2) Serum values of Serum values of –Iron –TIBC –Ferritin –Bilirubins –Proteins / electrophoresis –LDH –Vit B12 and /or Folic acid (None of these tests are routine screening tests)

57 Lab. Investigation of Anemia(3) Red cell enzymes Red cell enzymes Hb F,A 2,Hb electrophoresis Hb F,A 2,Hb electrophoresis Coombs tests Coombs tests Liver, renal, endocrin functional tests Liver, renal, endocrin functional tests Urinalysis Urinalysis –Hemosiderin Occult GIS bleeding / parasites etc Occult GIS bleeding / parasites etc ( tests should be chosen individually-do not order routinly )

58 Investigation of a microcytic hypochromic anemia Blood Film Serum Iron Serum iron high Serum iron normal/high Serum iron low Marrow for iron Hemoglobin studies Ferritin level Low Normal / High Sideroblastic anemia Thalassemia İron deficiency Anemia of Abnormal Hb chronic disease

59 Investigation of a normocytic, normochromic anemia Reticulocyte count Retic. normal / low Retic. high Bone marrow morphology hemolysis acute blood loss NormalAbnormal Hypoplastic infiltration dysplastic Secondary anemia eg. Inflammation aplastic anemia leukemia myelodysplasia liver disease myelofibrosis Renal failure metastases endocrine failure response to anemia treatment

60 Macrocytic anemia (MCV: high) Blood film Reticulocyte count Retic. HighRetic. Normal/low Bone marrow Non-megaloblasticMegaloblastic Acute blood loss or Hemolytic anemia normoblasticdysplastic(MDS)folate or B12 levels (Other macrocytic anemias) folate Vit B12 deficiency deficiency Treatment response


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