classification of anemia ok
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8/12/2019 Classification of Anemia Ok
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Definition of anemia
Anemia: A reduction in
– red cell mass
–
O2-carrying capacity It is expressed in terms of reduction
in the concentration of Hb (or RBC or
Hct%) compared to values obtainedfrom a reference population.
(2 SD below normal)
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Reference values (I)
Parameter Female Male
RBC (x1012/L) 4.8+0.6 5.4+0.9
Hb (g/dL) 14+2 16+2
Htc (%) 42+5 47+5
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Reference values (II)
Ret (% / n) 0.5-2.5 / 50-100x109/L
MCV (fl) 90+7
MCH (pg) 29+2
MCHc (g/dL) 34+2 RDW (%) 11.5-14.5
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50 100 200 fl
RBC
%
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Reticulocyte Normal Ranges
Male: % 0.8 - 2.5 Female: % 0.8 - 4.1
Corrected Rtc: Patient Hb/Normal Hb x Rtc %
Reticulocytosis: > 100.000 /mm3
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Definition of anemia
Hb level of a patient which is below the normalranges of that age and sex.For adults:
WHO criteria define anemia as hemoglobin levellower than 12 g/dL in women and 13 g/dL in men
But: The reference values for red cells ,Hb or Hct may diferaccording to
–sex/age
– Race – Altitude – Socioeconomical changes – Study/reference etc
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BEUTLER andWAALEN BLOOD, 1 MARCH 2006 VOLUME 107, NUMBER 5
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age WBC Neutrophyls Eos. Baso Lenfo Mono Hb
12 mo 6-17.5 1.5-8.5 0.05-0.7 0-0.20 4-10.5 0.05-1.1 11.1-14.1
4 y 5.5-15 1.5-8.5 0.02-
0.65
0-0.20 2-8 0-0.8 11.2-14.3
6 y 5-14.5 1.5-8 0-0.65 0-0.20 1.5-7 0-0.8 11.4-14.5
10 y 4.5-13 1.8-8 0-0.60 0-0.20 1.5-6.5 0-0.8 11.8-15
21 y 4.5-11 1.8-7.7 0-0.45 0-0.20 1-4.8 0-0.8 E: 16
K: 14
WBC: x10E3/mm3 Hb:g/dL
Age and blood count changes
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!!!!!
Plasma volume changes have to beconsidered before determining a diagnosis
of anemia . – Volume contraction:Underestimation of anemia
– Volume overload: Underestimation of Hb level
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Volume changes/acute bleeding
and anemia
normal
Hct (a/b%):Normal
DehydrationHct:Increased
Acute bloodloss(early)
Hct:unchanged
Chronicanemia
Hct: Low
1 2 3 4 5
IncreasedplasmavolumeHct: Low
b
a
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!!!!!
A normal Hb in a patient in whom anelevated Hb level is expected may
represent anemia .(eg:COPD + Hb:N)
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!!!!!!
Different red cell measures of the samepatient may give discordant values in special
conditions. (eg:Thalassemia trait)Eg: Low Hb, high RBC, low MCV
Hb: 10 g/dL (anemia)
RBC: 6.5 million/mm3 (erythrocytosis)MVC : 70 fL
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!!!!
Anemia is rarely a disease by itself,
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 underlyingdisease . – What is the cause of anemia ?
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Anemia leads to two
symptom complexes; Tissue hypoxia
– Fatigue,dyspnea on exertion etc
Compensatory attempts
– Tachycardia,hyperventilation etc
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The amount of O2 necessary to support lifeis : 250 ml/min
O2 carrying capacity of normal blood:1.34ml/g-Hb (200 ml/L-blood)
Cardiac output: 5000 ml/min
O2 delivery to tissues : 1000 ml/min
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Reduced levels of Hb results withreduced 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.
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The most pronounced effects andsymptoms derive from
–skeletal muscles, heart,and central nervoussystem
(due to their greater oxygen demand and compensatory actions).
What is the mechanism underlyingcompensatory mechanisms ?
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Hypoxia-Inducible
Transcription Factor 1 A DNA binding protein
Regulated by the O2 tension
Regulates genes that promote cellsurvival under hypoxic conditions
Up-reg. EPO gene
Up-reg.Glycolytic enzyme genes Up-reg. Angiogenesis
Respiratory control
Energy metabolism
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EPOproducingcells
HIF-1
Muscle
heartliverkidney
Carotid body
Glomus cells
Allcells
Vasc.endothelium
Erythropoiesis
Angiogenesis andvascular tone
Energymetabolism
Decreased O2
consumption
Iron metabolism
Respiration
EPO
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Compensating mechanisms inanemia:
The release of oxygen to the tissues isincreased (reduced oxygen affinity of Hb)
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Compensating mechanisms inanemia
The rate of blood circulation and cardiacoutput increases.
An increase in plasma volume maintainstotal blood volume in normal or nearnormal ranges.
Redistribution of blood flow.
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Different patients may have different severity ofsymptoms even for the same level of Hb.
The severity of the symptoms of anemia arerelated to;
– The severity of anemia
– The age,CVS,pulmonary status etc of the patient
–The rate of the development of anemia Gradual or
Rapid onset
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Clinical symptoms and findingsof anemia (1)
The symptoms and findings are relatedto anemia itself or to the underlying
disease that causes anemia . The symptoms and findings related to
anemia itself will be mentioned during
this course.
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Clinical symptoms and findings ofanemia (2)
Fatigue, weakness
– Tiredness, lassitude, reduced exercise
tolerence – Generalized muscular weakness
Pallor /skin or mucous membranes
–Skin color may change due to otherreasons;
eg :Blood flow of skin, subcutaneous fluid ,pigment changes
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Pallor (paleness): 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
In pernicious anemia there is a lemon yellow pallor.
Pallor + mild scleral icterus suggests hemolyticanemia.
Pallor+ petechiae suggests severe bone marrowfailure
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Some other skin/mucosal changes – Premature graying of hair:pern.anemia
– Hair loss and fragility + spooning of the nails:irondeficiency
– Chronic leg ulcers:Sickle cell or other hemolyticanemia
– Glossitis/burning sense :Pern. anemia, iron deficiency(rare)
–Chelitis(angular stomatitis):iron def.
– Siideropenic dysphagia: iron def.
– Painful ulcerative mouth lesions: aplastic anemia/leukemia
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Clinical symptoms and findings ofanemia (3)
Cardiovascular System(1)
Palpitation and dyspnea (during activity)
Angina pectoris
Claudicatio intermittans
Murmurs: Mid systolic (rarely diastolic) ,
mainly pulmonary valvular or apicalor over major peripheral arteries
or jugulary veins
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Clinical symptoms and findings ofanemia (3)
Cardiovascular System(2)
High output state: Collapsingpulse, high pulse pressure
Cardiomegaly
Congestive failure
Ischemic ECG changes
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Clinical symptoms and findings ofanemia (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).
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Clinical symptoms and findings ofanemia (5)
Reproductive system
Menstrual changes:
– Amenorrhea ,
– Menorrhagia(mostly a cause of anemia)
Loss of libido
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Clinical symptoms and findings ofanemia (6)
Gastrointestinal system
(these symptoms may indicate underlying disorderthat might indeed be a cause of anemia)
Anorexia
Flatulence
Nausea
Constipation
Weight loss
These should remind GIS disease as acause of anemia
(eg:a bleeding lesion-ulcer/malignancy etc)
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Clinical symptoms and findings ofanemia (7)
Ocular Fundi:
–Pale and
sometimes
–Hemorrhages
–Papillaedema
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Clinical symptoms and findings ofanemia (8)
Renal Changes – Slight proteinuria
– Concentrating defects
– Further reduction of renal function in patientswith previous renal impairment
(Renal failure itself is a cause of anemia!!!!)
Pyrexia: Due to a hypermetabolic state orother underlying disease (which may be a causeof anemia)
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Some Other examples for historyand physical examination
The duration of symptoms (acute/insidious)
Bleeding ? Nose/skin/urine/mens/stool etc
Family history
– Anemia, gall stones and splenectomy
– Bleeding disorder
Occupation, hobbies,dietary history,alcohol or druguse,travel history etc (toxic/infectious contacts)
Ask for skin and hair/nail changes
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Some Other examples for historyand physical examination
Pain / mass / fever/systemic overview for anunderlying disease – Renal/endocrine/liver disease or
–Chronic infection/malignancy/imflamatory condition
Parasitis
Pregnancies
Paresthesias ,walking difficulty
Sternal or other bone tenderness Splenomegaly, hepatomegaly
Lymphadenomegaly
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Diagnosis and investigation:
Is the patient anemic?
What is the type of anemia?
What is the cause of anemia?
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Classification of anemia
Morphologic – Normocytic: MCV= 80-100fL
–Macrocytic: MCV > 100 fL
– Microcytic : MCV < 80 fL
Pathogenic (underlying mechanism) – Blood loss (bleeding)
– Decreased RBC production
– Increased RBC destruction/pooling
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Normocytic Anemias
Acute post-hemorrhagic anemia
Hemolytic anemia
(except thalassemiaand some other Hbdisorders)
Aplastic anemia
Pure red cell aplasia
Bone marrowinfiltration
Endocrin diseases
Renal failure
Liver disease
Chronic disease anemia
Protein malnutrition
Hypovitaminosis C
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Microcytic anemias
Iron deficiency anemia
Thalassemia
Sideroblastic anemia
Lead poisoning
Anemia of chronic diseases
(some cases)
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Macrocytic anemias
Megaloblastic
Non-megaloblastic
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Megaloblastic Macrocytic Anemias
Vit B12 deficiency
Folic acid deficiency
Other.
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Non-megaloblasticMacrocytic Anemias
Anemia of acutebleeding
Hemolytic anemias Leukemias
(esp: acute)
Myelodysplasticsyndromes
Liver disease
Aplastic anemia
Diseases infiltrative
to the bonemarrow
Alcoholism
Hypothyroidism
Scurvy
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Pathogenic classification(Causes of anemia)
Relative (increased plasma volume)
Decreased RBC production
Blood loss – Anemia due to acute bleeding
Increased RBC destruction
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Pathogenic classification(Causes of anemia)
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
– Anemia due to acute bleeding
Increased RBC destruction Relative(increased plasma volume)
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Decreased Hb production
Iron deficiency anemia
Thalassemia
Sideroblastic anemia
Lead poisoning
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Defective DNA synthesis
Vit B12 deficiency
Folic acid deficiency
Other.
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Pluripotent stem cell defects
Aplastic anemia
Leukemia or myelodysplastic syndromes
Defective erythroid stem cell Pure red cell aplasia
Anemia of chronic renal failure
Endocrin disease anemia Congenital dyserythropoetic anemias
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Decreased RBC production due tomultipl or undefined mechanisms
Anemia of chronic diseases
Bone marrow infiltration
Anemia due to nutritional defects
Anemias caused by
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Anemias caused byincreased RBC destruction
(hemolytic anemias) Can be classified as; Hemolysis due to intracorpuscular defects Hemolysis due to extracorpuscular defectsOr Hereditary hemolytic diseases Acquired hem. diseases
Or Intravascular hemolysis Extravascular hemolysis etc.
A Very Simple Classification of Hemolytic Anemias
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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 hemolysisc. Traumatic & Microangiopathic hemolysis
d. Infections , toxins , etc
Hereditary
Acquired
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Is the patient anemic ?
RBC count
HB level
Hct level
Volume status
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What is the type ofanemia?
History and physical exam.
RBC,HB,Hct ,
MCV, MCH,RDW
Red cell morphology ( peripheral smear)
Reticulocyte count
– Incresed ?
Other Lab. investigations
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Lab. investigation of anemia(1)
WBC count and differential
Platelet count and morphology ESR
Biochemistry, special tests and others
Bone marrow exam.(only when indicated)
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Lab. investigation of anemia(2)
Serum values of – Iron
– TIBC
–Ferritin
– Bilirubins
– Proteins / electrophoresis
–LDH
– Vit B12 and /or Folic acid
(None of these tests are routine screening tests )
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Investigation of a microcytic hypochromic anemia
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g y yp
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 ofAbnormal Hb chronic disease
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Investigation of a normocytic, normochromic anemia
Reticulocyte count
Retic. normal / low Retic. high
Bone marrow morphology hemolysis acute blood loss
Normal Abnormal
Hypoplastic infiltration dysplastic
Secondary anemia
eg. I nf lammation aplastic anemia leukemia myelodysplasia
liver disease myelof ibrosis
Renal failur e metastases
endocrine failur e
response to anemia treatment
Macrocytic anemia (MCV: high)
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Blood film
Reticulocyte count
Retic. High Retic. Normal/low
Bone marrow
Non-megaloblastic Megaloblastic
Acute blood loss or
Hemolytic anemia normoblastic dysplastic(MDS) folate or B12 levels
(Other macrocytic anemias)
folate Vit B12
deficiency deficiency
Treatment response
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