ANEMIA
Hematology Department,Huashan
Hospital,Fudan University,Shanghai
XieYan-Hui
DIAGNOSIS AND CLASSIFICATION
Anemia is an absolute decrease in
hematocrit,hemoglobin concentration,or
the RBC count,
Anemia is not a diagnosis,but a sign of
underlying disease.,
Hemoglobin(Hb),male(adult)<120g/L
female(adult)<110g/L
female(gestation)<100g/L
Red cell count male<4.5x1012 /L
female<4.0x1012 /L
Hemocrit(HCT) male<0.42
female<0.37
female(gestation)<0.30
I,Determination of the cause,
A,History
1,Drug administration,
2,Exposure to toxic chemicals
3,Family occurrence,
4,Recent transfusions
5.menstruation(woman)
6.ingestion(child)
7.chronic disease
8,Age at onset,
B,Physical findings and complaints
a,Pale mucous membranes and skins
b,Weakness,loss of stamina,and exercise
intolerance,Hypersensitivity to cold,fever,
c,Tachycardia and polypnea,Heart murmur,
anemia associated cardiac disease,
? Hb<30g/L more than 2 months
? heart enlargement
? ST depression
d,headache,dizziness
e.anorexia,nauxea,abdominal fullness
diarria or constipation,Icterus,
f.menstruation disorder or amenorrea
hemoglobinuria
g,Shock if >1/ 2blood volume lost in
short period,
C,Laboratory findings
1,The Hct is the easiest,most
accurate method for detecting
anemia,Its result should be
interpreted with knowledge of the
hydration status and any
alteration caused by splenic
contraction,
2,Hb and RBC may be used to
further classify the anemia,
II,Classification
A,Size (MCV) and Hb Concentration
(MCHC)
1,Normocytic,macrocytic,microcytic,
2,Normochromic,hypochromic,
(Hyperchromia does not occur)
Type MCV(fl) MCHC(%) MCH(pg) disorder
Macro >100 >32 32-35 megaloblastic anemia
MDS
Normo 80-100 26-32 32-35 aplastic anemia,blood
lost,hemolytic anemia
Micro <80 <26 <32 iron deficiency anemia
sideroblastic anemia
thalassemia
B,Bone marrow response
1,Regenerative
a,Bone marrow actively responds
by increasing its production of
RBC’s,
b,Findings,
(1) Polychromasia,
(2) Reticulocytosis
,
(3) Macrocytosis (increased MCV)
and hypochromia associated with
reticulocytosis,
(4) Hypercellular bone marrow
with a low M/E ratio,
(5) Increase in MCV and RDW
c,The presence of regeneration
suggests an extramarrow cause,
(1) Blood loss
(2) Erythrocyte destruction
(hemolysis)
d,Bone marrow examination
would reveal erythropoietic
hyperplasia
,
2,Non-Regenerative
a,Inadequate bone marrow response
because of a bone marrow disorder,
b,Polychromasia and reticulocytosis
are absent,
?
C,Pathophysiologic mechanism
1.Blood loss–hemorrhagic anemia,
2,Accelerated erythrocyte
destruction–hemolytic anemia,
3,Reduced or defective
erythropoiesis
ANEMIA FROM ACCELERATED
ERYTHROCYTE DESTRUCTION
(HEMOLYTIC ANEMIA)
A,Clinical findings
1,Clinical signs of hemorrhage are
absent,
2,Jaundice may be seen in acute and
severe cases,
3,Hemoglobinuria and red plasma is
seen if significant intravascular
hemolysis occurs
B,Laboratory findings
1,Reticulocyte counts are higher in
hemolytic anemias than external
hemorrhagic anemias
2,Plasma protein concentration is
normal or increased,
3,Neutrophilic leukocytosis and
monocytosis may occur,
4,Evidence of Hb degradation
(hyperbilirubinemia,hemoglobinuria),
5,Abnormal erythrocyte morphology
(Heinz bodies,erythrocytic
parasites,spherocytes,or poikilocytes),
I,Differentiation of the Causes of
Hemolytic Anemias
A,Extravascular hemolysis
1,Mechanisms
a.Autoimmune Mediated--Antibody
and/or C3 mediated ( AIHA,infection,
drug,immune system disorder)
b,Decreased erythrocyte deformability
(a)Shistocytes of microangiopathic anemia
(b) Spherocytes of immune-mediated anemia
(c) Parasitized erythrocytes
(d) Heinz body-containing cells
c,Reduced glycolysis and ATP
content of the erythrocyte( PK
deficiency)
d,Increased macrophage activity
(hypersplenism)
e,Intravascular causes of hemolysis do
not lyse all erythrocytes; some altered
cells may remain that are removed by
phagocytosis,
2,Clinical and laboratory
characteristics of phagocytic
(extravascular) hemolysis,
a.Usually chronic with insidious onset,
b,A regenerative response,
c,Hemoglobinemia and hemoglobinuria
are absent,
d,Hyperbilirubinemia
e,Neutrophilia,monocytosis,and
thrombocytosis
f,Splenomegaly,
h,Low-grade extravascular hemolysis
occurs in many anemias that are
primarily nonhemolytic (e.g.,anemia
of chronic renal disease,iron-
deficiency anemia),Referred to as
the,hemolytic component” of other
types of anemia
B,Intravascular hemolysis–
Erythrocytes are destroyed within
the circulation,
releasing hemoglobin into the plasma
where it is either removed by the liver
or excreted by the kidneys,
1,Mechanisms,The erythrocyte
membrane must be significantly
disrupted to allow escape of the Hb
molecule into the plasma,Most of the
mechanisms of intravascular
hemolysis are extrinsic or
extracorpuscular defects– the
erythrocyte is initially normal,
a,Complement-mediated lysis,
(neonatal isoerythrolysis and transfusion
reactions,PNH )
b,Physical injury(Traumatic,microangio-
pathic anemia,DIC,Coagulation,Vasculitis)
c,Oxidative injury (Heinz body,methemo-
globin)
d.Osmotic lysis( hypotonic intravenous fluids)
e,Other membrane alterations,
(1) Castor beans–ricin,Causes
direct lysis
(2) Snake venoms
(3) Bacterial toxins
(4) Parasites (Babesia)
2.Clinical and laboratory characteristics
of intravcascular hemolytic anemia,
a,Most cases present as peracute or acute
episodes,
b,History may reveal exposure to causative
drugs or plants,recent transfusion of
blood,or recent ingestion of colostrum,
c,A regenerative response occurs,but it may
not be evident in early stages,
d,Hemoglobinemia is the principal
feature of intravascular hemolysis,
(1)Red discoloration of plasma
(2) Increased MCHC
e,Hemoglobinuria
f,Hemosiderinuria
g,Hyperbilirubinemia
h,Additional laboratory findings may
include schistocytes,keratocytes,Heinz
bodies,erythrocytic parasites,positive
Coombs’ test,
ANEMIA FROM REDUCED OR
DEFECTIVE ERYTHROPOIESIS
reduced or defective erythropoisis
long or onset insidious clinic course
I,General considerations,
A,Mechanisms,
1,Precursor cells
Nutrients (iron and B vitamins)
Stimulation (erythropoietin)
2,Bone marrow failure( intramarrow
disease and extramarrow causes)
3,Bone marrow failure may be selective
for the erythroid series or may also
affect the other cell lines,
B,Bone marrow response
1,When the number of precursor cells or
erythropoietic stimulation is inadequate,
the erythroid marrow is hypocellular,
2,Maturation abnormalities which
characterize the nutritional deficiencies,
are associated with a Hypercellular
marrow and ineffective erythropoiesis.,
3,All degrees of bone marrow failure can
occur,from complete aplasia to a
suboptimal response of the erythroid
marrow following hemorrhage or
hemolysis,
II,Differentiation of anemias caused by
reduced or defective erythropoiesis,
erythrocyte morphology,
? blood neutrophil
? platelet numbers
? bone marrow cellularity,
A,Normocytic,normochromic
anemia; normal or increased
neutrophil and platelet numbers;
increased M/E ratio caused by
hypocellular erythroid marrow,
1,Anemia of erythropoietin lack,
a,Chronic renal disease,
Anemia proportional to severity of the
uremia,
b,Endocrinopathies
(1) Cushings
(2) Hypoandrogenism
(3) Hypopituitarism
2,Anemia of chronic disorders (ACD)
a,Occurs in chronic infectious,
inflammatory,or neoplastic disorders,
b,Cytokines involved with the
inflammatory process initiate the anemia,
c,Erythrocyte life span reduced
d,Laboratory findings include,
(1) Low serum iron
(2) Low total iron binding capacity
(3) Increased bone marrow macrophage
iron
(4) Mild-moderate anemia that is usually
nonprogressive
3,Pure red cell aplasia
a,Characterized by a selective loss of
erythroid precursors in the
bone marrow,
b,Thought to be immune mediated,
4,Unknown mechanisms
a,Liver disease
b,Vitamin E deficiency
B,Normocytic,normochromic
anemia; neutropenia and/or
thrombocytopenia; M/E
ratio is difficult to determine
because of hypocellularity,
1,Aplastic anemia
a,pancytopenia,
b,shorter life spans of the cells,
c,Causes
(1) Drugs,chemicals,plants
(2) Irradiation
(3) Cytotoxic T cells or antibody
(4) Infectious agents
2,Myelophthisic anemia
a,The bone marrow is physically
replaced by an abnormal proliferation
of cells,
(1) Myeloproliferative disorders–
leukemias
(2) Myelofibrosis
(3) Osteosclerosis
(4) Diffuse granulomatous
osteomyelitis
(5) Metastatic cancer
3,Anemia caused by infectious
agents
a,Ehrlichiosis(埃里西提病）
b,FeLV（猫白血病病毒）
C,Microcytic,hypochromic anemia;
variable neutrophil and platelet
number; usually a hypercellular
marrow with a variable M/E ratio,
1,Iron deficiency
a,Chronic hemorrhage
b,Dietary deficiency,especially in
young milk-fed
c,Ineffective erythropoiesis early;
d,Laboratory findings,
(1) Low serum iron
(2) Variable iron-binding capacity
(3) Microcytosis
(4) Hypochromasia
(5) Poikilocytes
(6) Hypercellular bone marrow
2,Pyridoxine deficiency,This
vitamin is a cofactor in heme synthesis
and a deficiency leads to a failure to
utilize iron,
3,Copper deficiency,Copper-
containing ceruloplasmin is important
in iron absorption and transfer between
gut,macrophages,and transferrin,
D,Macrocytic,normochromic anemia;
variable neutrophil and platelet number;
M/E ratio usually low because of
hypercellular erythroid marrow,
1,Vitamin B12 and folic acid deficiency,
2,Erythemic myelosis or erythroleukemia,
3,FeLV infection,
THANKS
Hematology Department,Huashan
Hospital,Fudan University,Shanghai
XieYan-Hui
DIAGNOSIS AND CLASSIFICATION
Anemia is an absolute decrease in
hematocrit,hemoglobin concentration,or
the RBC count,
Anemia is not a diagnosis,but a sign of
underlying disease.,
Hemoglobin(Hb),male(adult)<120g/L
female(adult)<110g/L
female(gestation)<100g/L
Red cell count male<4.5x1012 /L
female<4.0x1012 /L
Hemocrit(HCT) male<0.42
female<0.37
female(gestation)<0.30
I,Determination of the cause,
A,History
1,Drug administration,
2,Exposure to toxic chemicals
3,Family occurrence,
4,Recent transfusions
5.menstruation(woman)
6.ingestion(child)
7.chronic disease
8,Age at onset,
B,Physical findings and complaints
a,Pale mucous membranes and skins
b,Weakness,loss of stamina,and exercise
intolerance,Hypersensitivity to cold,fever,
c,Tachycardia and polypnea,Heart murmur,
anemia associated cardiac disease,
? Hb<30g/L more than 2 months
? heart enlargement
? ST depression
d,headache,dizziness
e.anorexia,nauxea,abdominal fullness
diarria or constipation,Icterus,
f.menstruation disorder or amenorrea
hemoglobinuria
g,Shock if >1/ 2blood volume lost in
short period,
C,Laboratory findings
1,The Hct is the easiest,most
accurate method for detecting
anemia,Its result should be
interpreted with knowledge of the
hydration status and any
alteration caused by splenic
contraction,
2,Hb and RBC may be used to
further classify the anemia,
II,Classification
A,Size (MCV) and Hb Concentration
(MCHC)
1,Normocytic,macrocytic,microcytic,
2,Normochromic,hypochromic,
(Hyperchromia does not occur)
Type MCV(fl) MCHC(%) MCH(pg) disorder
Macro >100 >32 32-35 megaloblastic anemia
MDS
Normo 80-100 26-32 32-35 aplastic anemia,blood
lost,hemolytic anemia
Micro <80 <26 <32 iron deficiency anemia
sideroblastic anemia
thalassemia
B,Bone marrow response
1,Regenerative
a,Bone marrow actively responds
by increasing its production of
RBC’s,
b,Findings,
(1) Polychromasia,
(2) Reticulocytosis
,
(3) Macrocytosis (increased MCV)
and hypochromia associated with
reticulocytosis,
(4) Hypercellular bone marrow
with a low M/E ratio,
(5) Increase in MCV and RDW
c,The presence of regeneration
suggests an extramarrow cause,
(1) Blood loss
(2) Erythrocyte destruction
(hemolysis)
d,Bone marrow examination
would reveal erythropoietic
hyperplasia
,
2,Non-Regenerative
a,Inadequate bone marrow response
because of a bone marrow disorder,
b,Polychromasia and reticulocytosis
are absent,
?
C,Pathophysiologic mechanism
1.Blood loss–hemorrhagic anemia,
2,Accelerated erythrocyte
destruction–hemolytic anemia,
3,Reduced or defective
erythropoiesis
ANEMIA FROM ACCELERATED
ERYTHROCYTE DESTRUCTION
(HEMOLYTIC ANEMIA)
A,Clinical findings
1,Clinical signs of hemorrhage are
absent,
2,Jaundice may be seen in acute and
severe cases,
3,Hemoglobinuria and red plasma is
seen if significant intravascular
hemolysis occurs
B,Laboratory findings
1,Reticulocyte counts are higher in
hemolytic anemias than external
hemorrhagic anemias
2,Plasma protein concentration is
normal or increased,
3,Neutrophilic leukocytosis and
monocytosis may occur,
4,Evidence of Hb degradation
(hyperbilirubinemia,hemoglobinuria),
5,Abnormal erythrocyte morphology
(Heinz bodies,erythrocytic
parasites,spherocytes,or poikilocytes),
I,Differentiation of the Causes of
Hemolytic Anemias
A,Extravascular hemolysis
1,Mechanisms
a.Autoimmune Mediated--Antibody
and/or C3 mediated ( AIHA,infection,
drug,immune system disorder)
b,Decreased erythrocyte deformability
(a)Shistocytes of microangiopathic anemia
(b) Spherocytes of immune-mediated anemia
(c) Parasitized erythrocytes
(d) Heinz body-containing cells
c,Reduced glycolysis and ATP
content of the erythrocyte( PK
deficiency)
d,Increased macrophage activity
(hypersplenism)
e,Intravascular causes of hemolysis do
not lyse all erythrocytes; some altered
cells may remain that are removed by
phagocytosis,
2,Clinical and laboratory
characteristics of phagocytic
(extravascular) hemolysis,
a.Usually chronic with insidious onset,
b,A regenerative response,
c,Hemoglobinemia and hemoglobinuria
are absent,
d,Hyperbilirubinemia
e,Neutrophilia,monocytosis,and
thrombocytosis
f,Splenomegaly,
h,Low-grade extravascular hemolysis
occurs in many anemias that are
primarily nonhemolytic (e.g.,anemia
of chronic renal disease,iron-
deficiency anemia),Referred to as
the,hemolytic component” of other
types of anemia
B,Intravascular hemolysis–
Erythrocytes are destroyed within
the circulation,
releasing hemoglobin into the plasma
where it is either removed by the liver
or excreted by the kidneys,
1,Mechanisms,The erythrocyte
membrane must be significantly
disrupted to allow escape of the Hb
molecule into the plasma,Most of the
mechanisms of intravascular
hemolysis are extrinsic or
extracorpuscular defects– the
erythrocyte is initially normal,
a,Complement-mediated lysis,
(neonatal isoerythrolysis and transfusion
reactions,PNH )
b,Physical injury(Traumatic,microangio-
pathic anemia,DIC,Coagulation,Vasculitis)
c,Oxidative injury (Heinz body,methemo-
globin)
d.Osmotic lysis( hypotonic intravenous fluids)
e,Other membrane alterations,
(1) Castor beans–ricin,Causes
direct lysis
(2) Snake venoms
(3) Bacterial toxins
(4) Parasites (Babesia)
2.Clinical and laboratory characteristics
of intravcascular hemolytic anemia,
a,Most cases present as peracute or acute
episodes,
b,History may reveal exposure to causative
drugs or plants,recent transfusion of
blood,or recent ingestion of colostrum,
c,A regenerative response occurs,but it may
not be evident in early stages,
d,Hemoglobinemia is the principal
feature of intravascular hemolysis,
(1)Red discoloration of plasma
(2) Increased MCHC
e,Hemoglobinuria
f,Hemosiderinuria
g,Hyperbilirubinemia
h,Additional laboratory findings may
include schistocytes,keratocytes,Heinz
bodies,erythrocytic parasites,positive
Coombs’ test,
ANEMIA FROM REDUCED OR
DEFECTIVE ERYTHROPOIESIS
reduced or defective erythropoisis
long or onset insidious clinic course
I,General considerations,
A,Mechanisms,
1,Precursor cells
Nutrients (iron and B vitamins)
Stimulation (erythropoietin)
2,Bone marrow failure( intramarrow
disease and extramarrow causes)
3,Bone marrow failure may be selective
for the erythroid series or may also
affect the other cell lines,
B,Bone marrow response
1,When the number of precursor cells or
erythropoietic stimulation is inadequate,
the erythroid marrow is hypocellular,
2,Maturation abnormalities which
characterize the nutritional deficiencies,
are associated with a Hypercellular
marrow and ineffective erythropoiesis.,
3,All degrees of bone marrow failure can
occur,from complete aplasia to a
suboptimal response of the erythroid
marrow following hemorrhage or
hemolysis,
II,Differentiation of anemias caused by
reduced or defective erythropoiesis,
erythrocyte morphology,
? blood neutrophil
? platelet numbers
? bone marrow cellularity,
A,Normocytic,normochromic
anemia; normal or increased
neutrophil and platelet numbers;
increased M/E ratio caused by
hypocellular erythroid marrow,
1,Anemia of erythropoietin lack,
a,Chronic renal disease,
Anemia proportional to severity of the
uremia,
b,Endocrinopathies
(1) Cushings
(2) Hypoandrogenism
(3) Hypopituitarism
2,Anemia of chronic disorders (ACD)
a,Occurs in chronic infectious,
inflammatory,or neoplastic disorders,
b,Cytokines involved with the
inflammatory process initiate the anemia,
c,Erythrocyte life span reduced
d,Laboratory findings include,
(1) Low serum iron
(2) Low total iron binding capacity
(3) Increased bone marrow macrophage
iron
(4) Mild-moderate anemia that is usually
nonprogressive
3,Pure red cell aplasia
a,Characterized by a selective loss of
erythroid precursors in the
bone marrow,
b,Thought to be immune mediated,
4,Unknown mechanisms
a,Liver disease
b,Vitamin E deficiency
B,Normocytic,normochromic
anemia; neutropenia and/or
thrombocytopenia; M/E
ratio is difficult to determine
because of hypocellularity,
1,Aplastic anemia
a,pancytopenia,
b,shorter life spans of the cells,
c,Causes
(1) Drugs,chemicals,plants
(2) Irradiation
(3) Cytotoxic T cells or antibody
(4) Infectious agents
2,Myelophthisic anemia
a,The bone marrow is physically
replaced by an abnormal proliferation
of cells,
(1) Myeloproliferative disorders–
leukemias
(2) Myelofibrosis
(3) Osteosclerosis
(4) Diffuse granulomatous
osteomyelitis
(5) Metastatic cancer
3,Anemia caused by infectious
agents
a,Ehrlichiosis(埃里西提病）
b,FeLV（猫白血病病毒）
C,Microcytic,hypochromic anemia;
variable neutrophil and platelet
number; usually a hypercellular
marrow with a variable M/E ratio,
1,Iron deficiency
a,Chronic hemorrhage
b,Dietary deficiency,especially in
young milk-fed
c,Ineffective erythropoiesis early;
d,Laboratory findings,
(1) Low serum iron
(2) Variable iron-binding capacity
(3) Microcytosis
(4) Hypochromasia
(5) Poikilocytes
(6) Hypercellular bone marrow
2,Pyridoxine deficiency,This
vitamin is a cofactor in heme synthesis
and a deficiency leads to a failure to
utilize iron,
3,Copper deficiency,Copper-
containing ceruloplasmin is important
in iron absorption and transfer between
gut,macrophages,and transferrin,
D,Macrocytic,normochromic anemia;
variable neutrophil and platelet number;
M/E ratio usually low because of
hypercellular erythroid marrow,
1,Vitamin B12 and folic acid deficiency,
2,Erythemic myelosis or erythroleukemia,
3,FeLV infection,
THANKS
