ANEMIAANEMIA

Hematology Department,HuashanHematology Department,Huashan

Hospital,Fudan University,ShanghaiHospital,Fudan University,Shanghai

XieYan-HuiXieYan-Hui

DIAGNOSIS AND CLASSIFICATIONDIAGNOSIS AND CLASSIFICATION

AnemiaAnemia is an absolute decrease in is an absolute decrease in hemathematocritocrit , , hemoglobinhemoglobin concentration, or the concentration, or the RRBCBC count. count. Anemia Anemia is is notnot a a diagnosisdiagnosis, but a , but a signsign of un of underlying disease..derlying disease..

Hemoglobin(Hb): male(adult)<120g/L

female(adult)<110g/L female(gestation)<100g/LRed cell count male<4.5x1012 /L female<4.0x1012 /LHemocrit(HCT) male<0.42 female<0.37 female(gestation)<0.30

I.I. Determination of the causeDetermination of the cause::A. A. HistoryHistory1. 1. DrugDrug administration. administration.2. Exposure to 2. Exposure to toxic chemicalstoxic chemicals 3. 3. Family Family occurrence.occurrence.4. Recent 4. Recent transfusionstransfusions 5.menstruation(woman)5.menstruation(woman)6.ingestion(child)6.ingestion(child)7.chronic disease7.chronic disease8. 8. AgeAge at onset. at onset.

B. Physical findings and complaints

a. Pale mucous membranes and skinsb. 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,dizzinessd. headache,dizzinesse.anorexia,nauxea,abdominal fullnesse.anorexia,nauxea,abdominal fullness diarria or constipation, diarria or constipation, Icterus. Icterus.f.menstruation disorder or amenorreaf.menstruation disorder or amenorrea hemoglobinuriahemoglobinuria g. g. ShockShock if >1/ 2blood volume lost in if >1/ 2blood volume lost in short period. 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 f2. Hb and RBC may be used to f

urther classify the anemiaurther classify the anemia..

II. II. ClassificationClassification

A. Size (MCV) and Hb Concentration A. Size (MCV) and Hb Concentration (MCHC)(MCHC)1. Normocytic, macrocytic, microcytic.1. Normocytic, macrocytic, microcytic.2. Normochromic, hypochromic. (Hype2. Normochromic, hypochromic. (Hyperchromia does not occur)rchromia does not occur)

Type MCV(fl) MCHC(%) MCH(pg) disorderMacro >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 response1. Regenerativea. Bone marrow actively responds by increasing its production of RBC’s.b. Findings:(1) Polychromasia.(2) Reticulocytosis

..(3)(3) Macrocytosis Macrocytosis (increased MCV) (increased MCV) and and hypochromiahypochromia associated with associated with reticulocytosis.reticulocytosis.(4) (4) HypercellularHypercellular bone marrow wit bone marrow with a h a low M/Elow M/E ratio. ratio.(5) Increase in (5) Increase in MCVMCV and and RDWRDW

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.

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C. Pathophysiologic mechanism1.Blood loss–hemorrhagic anemia.

2. Accelerated erythrocyte destruction–hemolytic anemia.

3. Reduced or defective erythropoiesis

ANEMIA FROM ACCELERATED

ERYTHROCYTE DESTRUCTION

(HEMOLYTIC ANEMIA)

A. Clinical findings1. Clinical signs of hemorrhage are abse

nt.2. Jaundice may be seen in acute and se

vere cases.3. Hemoglobinuria and red plasma is see

n if significant intravascular hemolysis occurs

B. Laboratory findings1. Reticulocyte counts are higher in hemolytic anemias than externalhemorrhagic 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 AnemiasA. Extravascular hemolysis

1. Mechanismsa.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. Hyperbilirubinemiae. Neutrophilia, monocytosis, and thrombocytosisf. 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 response1. When the number of precursor cells or e

rythropoietic 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 e

rythroid 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 replac

ed by an abnormal proliferation of cells. (1) Myeloproliferative disorders–leukem

ias (2) Myelofibrosis (3) Osteosclerosis (4) Diffuse granulomatous osteomyeliti

s (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.

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