Anemias

中国医科大学附属第一医院血液科 李艳

CUF-S (

造血干

C

、红系祖

C) ↓ proerythroblast

（原始

RBC

）

↓ Basophilic normoblast

（ 早幼

RBC

）

↓ Polychromatic mormoblast

（中幼

RBC

）

↓ Orthrochromatic normoblast

（晚幼

RBC

）此阶段脱 核进入血循环

↓ Reticulocyte

（网织

RBC

） 经特殊染色见到丝状或网状结构

,

保留残余线粒体 和核糖，仍有继续合成

Hb

的能力（从早幼

RBC

开始）

↓ erythrocyte

Definition

•

A reduction below normal in the concentration of hemoglobin , the mass of red blood cells and/or the hematocrit in the blood.

In men Hb < 120g/L RBC <4.5

×

10 12 /L HCT <0.42 In women Hb < 110g/L RBC<4.0

×

10 12 /L HCT<0.37

Factors influencing Hb concentration

Sex Age Altitude Alterations in plasma volume

★

Classification

Type

Morphologic classification

MCV(um) MCH(PG) MCHC(%) Diagnosis Macrocytic

＞

100 Normocytic 80-100 26-32 Microcytic

＜

80

＞

32

＜

26 32-35 Megaloblastic anemia 32-35

＜

32 AA, HA, Acute posthemorragic anemia IDA, Sideroblastic anemia Thalassemias

Kinetic classification

(Classified according to etiology and pathogenesis)

一、Decreased erythropoiesis

1 Proliferation and differentiation abnormalities of SC

HSC: AA, Fanconis anemia, MDS Erythrocytic progenitors : Pure red cell aplasia, Anemias caused by kidney failure and endocrine disorders

2 Marrow infiltration

leukemias carcinoma multiple myeloma myelofibrosis Malignant histocytosis

3 Production and maturation blockages of differentiating cells

DNA synthesis blockage : Vit B12, falic acid difficiencies,

嘌呤和嘧啶

metabolic defects→Megaloblastic anemia Hb synthesis blockage : Heme production defect : IDA Heptoglobin production defect : Thalassemias

4

Unknown reason or several mechanisms

Sideroblastic anemia Chronic disease anemias (chronic inflummation, infections,

尿毒症

, Hepatic disorders, neoplasm, connective tissue disease, endocrine disorders)

二、

Accelerated destruction of red cells 1

）

Endogenous (intra-erythrocyte defects)

1.

Membrane defects of erythrocytes :

Hereditary :Hereditary spherocytosis (HS) Hereditasy elliplocytosis (HE) Acquired : PNH

2.

Enzyme defects

Glucose--6--Phosphate Dehydrogenase (G6PD) deficiency Pyruvate kinase deficiency

3 .Abnormal haptogllbin synthesis :

Sickle cell anemia, Hemoglobinopathies Thalassemias

2)Extragenous

1.

Immune HA :

AIHA, neonatal HA,mismatched transfusion, drug-induced HA 2.

Mechanical :

march hemoglobinuria , cardiac valves prostheses, microangiopathic hemolytic disorders.

3.

Due to chemical, physical or microrganisms :

Chemical toxin-and drug-induced hemolysis, large scale burned patient (severe burned patient) Infection-induced , benzene, radiation microrganisms: Malaria, virus, etc.

4.

Increased damage of monocyte-macrocyte system :

Hypersplenism

三

.

Blood loss

◆

Acute posthemorrage anemia

◆

Chronic bleeding →IDA

Classified accordind to the proliferative situations of BM

Hyperplastic anemias ( 增生性贫血 ): Hemolytic anemia Anemia caused by blood loss Megaloblastic anemia, IDA Hypoplastic anemias ( 增生减低性贫血 ): AA

Clinical manifestations

Factors influencing symptoms:

Severity of anemia Hb<80~90g/L→symptoms Rapidity of anemia Abrupt loss of 20% of the circulating blood volume → marked pallor, postural hypotension and tachycardia (

心动过速

) The loss of 50% → severe shock even dealth.

In contrast, the gradual loss (even Hb 30~40g/L) of the circulating red cell mass in a patient with pernicious anemia may occur without any symptoms at all.

Why?

•

Red cell 2, 3 DPG (RBC

内

2, 3-

二磷酸甘油酸）

↑

In anemia the oxyhemoglobin dissociation curve usually shifts (

右移

) in a manner to increase the quantity of oxygen released in tissues without oppeciably altering the quantity of osygen bound in the lungs. Red cell 2,3 diphophoglycerate (2,3 DPG) regularly increases in anemic patients to mediate this effect. Maximum elevation of RBC 2,3 DPG increases oxygen delivery only about 30 per cent , but this is a highly efficient form of compensation requiring no significant expenditure of energy.

The aged patients or patients with vascular or cardiac diseases may not stand to milder anemia.

The level of anemia at which symptoms occur is highly variable among individuals as would be expected from the widely differing degrees of physical activity , physical conditioning , circulatory adequacy , and sensitivity or stoicism of the population.

１．

General manifestations: ( Nonspecific and reflect tissue hypoxia) Tiredness, fatigue→ the most common, the earliest symptom Pallor of skin and mucosa→shared chracteristic

２．

Cardiovascular systems : Palpitations and dyspnea on exertion , breathlessness→common symptoms Valvulae murmurs Hb <30g/L, >3m→Anemic cardic disease

3

．

Neurologic system : Headache, Dizziness, Confusion, decreased mental acuity (

记忆力衰退

) ,

晕厥，注意力 不集中，失眠，耳鸣．

severe anemia→Coma 4

．

Digestive system: Anorexia (

食欲不振

)

，厌食

→early megaloblastic anemia Nausea(

恶心

)

，

flatulence(

胀气

)

，

diarrhoea(

腹泻

) or constipation (

便秘

) lingual abnormalities (

舌的改变

)

：

common

5

．

Genitourinary system: severe anemia→ polyurea (

多尿

), hypobaric urine (

尿比重低

), proteinuria (

蛋白尿

):

肾小球滤过功能和小 管分泌及回收功能障碍

female:disturbed menstruation (

月经紊 乱

),

性功能减退多见

6

．

Other: 7. Manifestations of underlying disease:

Diagnosis

The process of correct diagnosis is the one of differential diagnosis.

Steps: 1. To Establish the type of anemia 2. To find out the cause or underlying diseases of anemia

一．

History

1. Cause or inducer of anemia:

Nutrition, special habits for food change in stool habits: stool Guaiacs in all profession influation of surrounding environment chronic diseases menstruation, marriage

2. Developing processes, severity & complications of anemias

Duration and onset of symptoms

3.Important laboratory results, diagnosis, treatments and their effects.

二．

Physical examination

skin and mucosa: pallor, jaundice, petechiae hair and nails adenopathy (

淋巴结肿大

) hepatomegaly-splenomegaly neurologic abnormalities

肛门及妇科盆腔检查

三、

Laboratory findings

１、

The hemogram

（血像）

Routine blood exam(Hb,RBC) The reticulocyte count (RC) RC↑:hyperplastic RC↓:hypoplastic

Reticulocyte Count

• Normal: 0.002-0.015

• Is required in the evaluation of all patients with anemia as it is a simple measure of production • Young RBC that still contains a small amount of RNA • Normally take 1 day for reticulocyte to mature. Under influence of epo takes 2-3 days • 1/120 th of RBC normally

Absolute Retic count

• Retic counts are reported as a percentage: RBC count x Retic % = Absoulte retic count normal: (77+23) x 10 9 /L • Absolute Retic counts need to be corrected for early release ( If polychromasia is present) • Absolute retic/2 (for hct in mid 20’s) • Absolute retic/3 (hct <20)

MCV(the mean corpuscular volume): the most useful of the RBC indices.

MCH,MCHC: are rarely as helpful as the MCV The leukocyte and platelet count: Anemia with a diminished leukocyteand platelet count pancytopenia suggests either primary marrow disease, megaloblastic anemia, or hypersplenism.

Examination of the peripheral blood smear:

2. Examination of bone marrow 骨髓涂片检查：主要观察

BM

增生程度，各系统细胞分类 计数，异常细胞，正常

BM

组织有核细胞与脂肪组织各占

1/2

，前者增多（尤其是红系）见于增生性贫血，后者增 多代表

BM

增生低下，见于

AA

，骨髓小粒是血液稀释与 否的一个重要标志。

Examination of aspirated smears in general gives superior cytologic information while the core biopsy provides crucial information concerning the overall cellularity, as well as the presence of fibrosis, tumor, or granulomas. Both procedures are complemantary and are best performed together when the diagnosis is in doubt. Bone marrow iron staining

1) 2) 3) 4) 5) 6)

3. Some useful ancillary tests

Stools for occult blood Tests for hemolytic anemia such as Coombs’test Tests for nutritional anemia such as serum folic acid, serum Vitamin B12, SI, SF, etc.

Liver and kidney function tests Immunologic tests

影像学检查：钡餐透视，钡灌肠

Treatment

一、

Treatment of the causes The purpose is the treatment of the underlying disease.

Gastric cancer→Pernicious anemia

（恶性贫血） （

megaloblastic anemia

）

二、

Drugs

• • • • • • • 明确病因之前且忌乱投药

Iron agents; calculation of dose falic acid , Vit B 12 Vit B 6 Corticosteroids : AIHA

，

AA, PNH Androgens: may promate reythropoiesis: 1.)

刺激

EPO

分泌。

2

）增强

BM

对

EPO

的效应。

EPO: Anemia caused by kidney diseases Immunosuppression agents ALG (antilymphocyte globulin

）

CsA: Acute and severe AA

三、

Transfusions

• • • •

Avoid of complications as hepatitis and AIDS Whole blood Frozed red cells Washed red cells Leukocyte poor packed cells

（浓缩

RBC

）

Chronic anemia : Hb<60g/L →Transfusion

四、

(Operation) Splenectomy

Hereditary spherocytosis AIHA Hypersplenism

由于胸腺瘤

(Thymoma)

引起的纯红

AA

， 切除胸腺可使部分患者病情缓解。

Chronic ITP

五、

BMT

（

bone marrow transplantation

） •

SAA

•

MDS

Lab Evaluation of Hypoproliferative Anemias

Fe TIBC Ferritin

Fe Deficiency

low High(>300) low

Anemia of Chronic Dx

low

Aplastic anemia

High low Extremely high Normal to high Normal to high

Laboratory findings in anaemia

Drs Shepherd, Dexter, and Rapson Spring 2001

Scanning Electron microscopy: normal red cell