hemolytic anemia--song.ppt

Hemolytic Anemia
Song Qiaoqiao
Hubei University of Science
and Technology
Internal Medicine Department

第九章溶血性贫血
Hemolytic Anemia
1 Outline
2 Hereditary Spherocytosis
3 Autoimmune Hemolytic Anemia
4 Paroxysmal Nocturnal Hemoglobinuria
study point

RBC destruction,decreased RBC life span,but not
exceeding the compensatory ability of BM, no clinically
anemia
hemolytic state
outline
Difinition
RBC destruction,decreased RBC life span
Hemoliysis

result from an increased rate of RBC destruction,
decreased RBC life span
anemia occurs when impaired the ability of the BM
compensation (6-8fold)
Hemolytic anemia

classification( severity of
disease)
chronic
HA
acute
HA
classification

classification(Hemolysis
position)
extrac-
orpusc-
ular
intrac-
orpusc-
ular

1、A molecular defect:
hemoglobinopathy
enzymopathy
2、An abnormality in menbrane stucture and
function
3、An environmental factor :
physical— mechanical trauma,
immune-mediated— autoantibody
classification -----(etiology and pathogenesis)

正常红细胞球形红细胞椭圆形红细胞
口形红细胞靶形红细胞镰状红细胞
abnormality in menbrane stucture

• 1.Abnormality of RBC interior
a.Enzyme defect
b.Hemoglobinopathies
2.RBC menbrane abnormality
a.Paroxysmal nocturnal
hemoglobinuria
b.Spur cell anemia
3.Extrinsic factor
a.Hypersplenism
b.Antibody:immune hemolysis
c.Microangiopathic hemolysis
d.Infection,toxins,etc
Intracor-
puscular
Extracor-
puscular
Hereditary
Acquired

Chill, sore waist
vomiting,headache;
Hemoglobinuria;
anemia;
jaundice
Pallor ;Jaundice;
Anemia;
Splenomegaly;
Cholelithiasis(pigment
gallstone);
Aplastic crisis;
Folate defficiency;
1.Acute-- Intravascular 2.Chronic Extravascular
Clinical features

sore waist
jaundice
pallor

Pathogenesis

Normal red blood cell metabolism
RBC life span is 120d
apoptosis
RBC
The mononuclear
macrophage system
Unconjugated bilirubin
CB
urobilinogen
Blood
stercobilinogen

Red blood cell metabolism of HA
Introvascular HA Extravascular HA
UCB
Hemoglobinemia
con-hemoglobin-
globin
Hemoglobinuria
hemosiderin urine
urobilinogen
stercobilinogen
CB

0
0
0
fragments
↑
Erythroid hyperplasia
fragments
↑
Erythroid hyperplasia
Plasma or serum
Bilirubin
Plasma hemoglobin
LDH
↑,Unconjugated
N-↑
↑
Urine
Bilirubin
Hemosiderin
Hemoglobin
Hematologic
Routine blood film
Reticulocyte count
Bone marrow examination
↑,Unconjugated
↑↑
↑↑
0
＋
＋in severe case
Intravascular
Extravascular
Laboratory findings

1、Features of
increased red cell
breakdown
2.Features of increased
red cell production
3.damaged red cells
special test of each HA
screening test
(Hemolysis position)
special test
(etiology and differential diagnosis )
Laboratory findings

Screening Test
0
0
Plasma or serum
Bilirubin
Haptoglobin
Plasma hemoglobin
↑,Unconjugated
↓,Absent
N-↑
Urine
Hemosiderin
Hemoglobin
↑,Unconjugated
Absent
↑↑
＋
＋in severe case
Intravascular
Extravascular
1.Excessive destruction of red blood laboratory tests

Screening Test
a.Reticulocyte count:↑5%--20%
b.Peripheral bood:Nucleated Red Blood Cells↑, Red
blood cell fragments↑(Howell-Jolly and Cabot ring)
c.Bone marrow examination:Erythroid hyperplasia↑
2.Compensatory hyperplasia of erythropoiesis in
the bone marrow

reticulocyte：↑

Peripheral bood:Nucleated Red Blood Cells↑

Bone marrow：Erythroid hyperplasia ,especially late erythroblast

Howell-Jolly bodies

Cabot ring

Screening Test
3.Damaged red cells test:
a.Cell morphologe: micropherocyte, elliptocytos,
fragments, etc
b.Osmotic fragility, autohemolysis,etc
c.Heinz bodies
d.Shorten the life span of RBC :51Cr

Red blood cell fragments↑

Diagnose
Determine the
existence of HA
Determine the
cause of the HA
Identify the cause
of HA
51Cr study
Excessive destruction
of RBC
Erythroblast of bone
marrow hyperplasia
Introvascular
Extravascular
Patient history and
clinical examination
Diagnose of HA

Hereditary Spherocytosis
Definition
HS is characterized by spherical RBC, which menbrane
protein defect in the cytoskeleton resulting HA

Pathogenesis
Defective or absent spectrin molecule in the cytoskeleton of
RBC menbrane, lead to loss of menbrane , lead to spherocytosis
Increased osmotic fragility and dcreased deformability of cell，
occur to extravascular hemolysis in spleen

spherical RBC
normal RBC

band3
band4.2 anchor protein
α membrane contractile proteins
βmembrane contractile proteins
actin
band4.1
Blood protein C
membrane lipid bilayer
molecular
defect of
red cell
cytoskelet-
on
menbrane
protein
defects,Per-
meability
increased
influx of
Na+
increased
RBC
spherical,
spherocyto-
sis
Na-K-
ATPase
inhibition，
Dcreased
deformabili
ty of cell
hemolysis
in spleen HA

Clinical features
HS might occur at any age
1.Recurring anemia:
2.Splenomegaly:mostly,Varying degrees of splenomegaly
3.Intermittent Jaundice
4.Pigmented gallstones:50%
5.Aplastic crisis: severity

H
S
1.Biochemical examination:Bilirubin↑,
unconjugated ; urobilinogen and sterobilinogen ↑
1.Blood smear:microspherocytes >10%
reticulocytes increased:5%～10%↑
2.Bone marrow :Erythroid hyperplasia↑,especially
late erythroblast
3Special test:osmotic fragility test↑; glucose
test :autohemolysis test :positive; direct
antiglobulin test; 51Cr study
Laboratory findings

HS:spherixal RBC

Treatment
1.Splenectomy
age>10y
moderate or server HA( affect the
quality of life)
No surgical contraindications
2.Supportive
blood transfusion
supplementation with folic acid

Autoimmune Hemolytic Anemia
Definition
AIHA is an acquired disorder becouse of immune
regulating function abnormal in which an IgG or
IgM autoantibody is formed that bind to the RBC
menbrane.

AIHA
warm type:is most common form of AIHA, optimum
temperature is 37℃ ,common antibody is IgG
cold type:optimum temperature is 4℃, common
antibody is IgM
Classification

Pathogenesis
IgG is the incomplete antibody,adherence of RBC
menbrane, immune sensitization of RBC is prone to
destroyed by macrophages in spleen, lead to
extravascular HA.
---cold type of AIHA

Clinical features
1.Chronic, more common in adult women
2.Moderate to severe anemia rapid onset
3.Splenonmegaly and jaundice
4.Hemoglobinemia, hemoglobinuria,Spherocytosis
5.Fatigue, angina or congestive heart failure

Laboratory findings
A
I
H
A
1.Biochemicalexamination:Bilirubin↑,
unconjugated ; urobilinogen and stercobilinogen ↑
1.Blood smear: reticulocytes increased:5%～10%。
spherocytes, nucleated red cells↑
2.Bone marrow :Erythroid hyperplasia↑,especially
early erythroblast:80%
3Special test:deriect coombs antiglobin test:is the
major tool for diagnosing AIHA

＋
RBC
IgG antibody IgG-coated RBC
Anti-globulin antibody
Anti-globulin principle diagram
Agglutination positive
Direct response
Indirect response

Treatment
1.Remove the cause:SLE,Lymphomas,Infection....
2.Control of hemolysis :
a.Corticosteroids: prednisone(1.0mg/kg)
b.Splenectony:cannot tolerate or fail to respond
to corticosteroids
c.Immunosuppressive drugs:rituximab

Definition
PNH is an acquired red cell menbrane defect arising from
hemotopeitic stem cell gene mutation on the X-chromosome,is an
benign clonal disease.

P
N
H
☞ GPI anchor (Glycosyl phosphatidyl inosital)
biosynthesis obstacled.
☞Deficiency of the GPI anchored menbrane
protein :CD55,CD59
☞RBCs are more sensitive to the lytic effect of the
complement
☞Intravascular hemolysis
☞Disease involving multiple cell line
☞CD55:decay accelerating factor,
CD59:menbrane inhibitor of reactive lysis
Pathogenesis

RBC
PNH
RBC

Clinical features
1.Hemoglobinuria:25% ，company fatigue，fever
2.Deficient hemotopoiesis:
3.Venous thrombosis:mesenteric, hepatic vein
Different colors of
hemoglobinuria

Laboratory findings
P
N
H
☞1.Blood film:multiple cell line↓，reticulocyte↑;
blood smear: Nucleated Red Blood Cells and Red
blood cell fragments
☞2.Bone marrow:bone marrow may hyperplasia,
especially erythroid
☞3.Biochemical examination:Urine occult blood
test or hemosiderin urine test positive;Free heme↑
☞4.Diagnostic test:Ham test;Sucrose test;flow
cytometric assays:CD55,CA59↓

Nucleated Red Blood Cells
Red blood cell fragments

P
N
H
☞1.Supportive treatment:blood transfusion (washed
RBC) ; iron supplements:iron defficiency
☞2.Control hemolysis :Glucocorticoid: Prednisone
(moderate dose); NaHCO3 ; Anti-complement
monoclonal antibodies:Eculizumab
☞3.Pay attention to thrombogenesis:
Anticoagulant therapy
☞4.Allogeneic hematopoietic stem cell
transplantation(allo-HSTC)
Treatment

G6PD Deficiency
Definition
G6PD deficiency is a herediary enzyme defect that couse episodic
HA becouse of decreased ability of RBC to deal with oxidative
stressed.
Afican,Old world tropics and southern Chinese populations

H
S
X-linked，G6PD deficiency reduced NADPH and
GSH in RBC, after contact with oxidant, resulting in
direct oxidative damaged cell membranes, and
generate Heinz body which contain hematosin and
paraglobin.
The defitient RBC are prone to be swallowed by the
macrophages in the spleen.
Pathogenesis

Clinical features
1.Trigger by oxidant stess:drugs、fava beans;viral and
bacterium infection;
2.Experience an acute hemolytic crisis: hemoglobinuria
and peripheral vascular collapse in sever cases
3.Hemolytic crisis is uaually self-limited
----usually asymtomatic

Laboratory findings
1.Heinz bodies:>5%
2.G6PD enzyme activity:<40%normal average value

1.Avoid oxidant drugs and infection
2.Prompt treatment of infections
3.Supportive: blood transfusion ,glucocorticoids
4.Phototherapy and exchange transfusion --neonatal jaundice.
Treatment

Diagnose of HA
Determine
the cause of
the HA
Determine
the existence
of HA
clinical
evidence
Laboratory
evidence

• Chief omplaint:Female, 36, fatigue, pale face half a month
• Previous history:Half a month without reason progressive looking pale and
weak, can't do the work.Moving flustered, shortness of breath.urine showed
strong color , assay shuwed anemia (detail unknown), Since the onset of
disease ,there are no fever, no joint pain, no loss of hair, and light allergy; eat
and sleep a bit poor, defecate is normal.Always, body health, no cardiac,
liver, kidney disease, no toxic exposure history, no history of drug allergy, no
partial eclipse and tobacco habits, menstruation is normal, no similar patients
in the family.
• Physical Examination; T36.5℃，P96bpm，R16bpm Bp110/70mmHg，
• Anemia, no rash and bleeder, superficial lymph node untouched, sclera mild
yellow dye, lingual papilla is normal, thyroid (-), cardiopulmonary without
abnormally, abdomen flat soft, liver untouched, Splenomegaly under rib 1
cm, ascites sign (-), limbs unhepatomegaly.
Case Analysis

• Test:Blood: Hb68g/L, WBC6.4 x 109 / L, N72 %, L24 %, M4 %
， plt140 x 109 / L, ret18%；Blood smear:visible 2 late
erythroblast and basophilic stippling erythrocyte,；routine urine (-
), uric bilirubin (-), and urobilinogen strong positive, defecate
normal (-), occult blood (-), total bilirubin blood 41 umol/L, direct
bilirubin 5 umol/L, Coombs test (+).
• Q1、 The patient's diagnosis and the diagnosis basis?
• 2、What further test will do?
• 3、 The principle of treatment?

• Q1.Diagnosis and the diagnosis basis?
• A:Diagnosis :AIHAautoimmune hemolytic anemia (warm
type, primary)
• Diagnosis basis：
• ①、clinical features: fatigue, pale face, moving, flustered,
shortness of breath, such as anemia, splenomegaly；
• ②、laboratory test (blood indirect bilirubin, uric bilirubin
negative, uric bravery former strong positive) manifest it's
hemolytic jaundice.
• ③、 Blood：Hb, reticulocyte significantly higher 18%,
classification of late erythroblast and basophilic stippling
erythrocyte compensatory hyperplasia, Coombs test (+)
• ④、Haven't found a secondary reason

• Q 2、further test?
• A：①、 bone marrow examination and bone
• marrow iron stain
• ②、ANA, serum protein electrophoresis,
• serum IgG, IgA, C3 quantitatively
• ③、Liver function and B ultrasonic of
• abdomen, chest radiograph
Q3、Therapeutic principle?
A: ①. The preferred glucocorticoid
.②.The immune inhibitors or Splenectony

Case Analysis
• 女性，36岁，乏力、面色苍白半个月
• 半个月无原因进行性面色苍白、乏力，不能胜任工作，稍动则心慌、
气短，尿色如浓茶，化验有贫血(具体不详)，发病以来无发热、关节
痛、脱发、光过敏，进食和睡眠稍差，大便正常。既往体健，无心、
肝、肾、结核病史，无毒物接触史，无药物过敏史，无偏食和烟酒嗜
好，月经正常，家族中无类似患者。
• 查体：T36.5℃，P96次/分，R16次/分，Bp110/70mmHg，一般可，贫
血貌，无皮疹和出血点，全身浅表淋巴结未触及，巩膜轻度黄染，舌
乳头正常，甲状腺(-)，心肺无异常，腹平软，肝未及，脾肋下1cm，
腹水征(-)，双下肢不肿。
• 化验：血Hb68g/L, WBC6.4×109/L, N72%, L24%, M4%, 可见2个晚幼
红细胞，可见嗜碱性点彩红细胞，plt140×109/L,网织红细胞18%,
尿常规(-)，尿胆红素(-),尿胆原强阳性，大便常规(-)，隐血(-)，
血总胆红素41μmol/L，直接胆红素5μmol/L，Coombs试验(+)。

• 一、该患者的诊断及诊断依据？
• 二、应与哪些疾病鉴别诊断？
• 三、需做哪些进一步检查？
• 四、治疗原则?

• 一、诊断及诊断依据
(一)诊断自身免疫性溶血性贫
血（温抗体型，原发性）
(二)诊断依据
1.有乏力、面色苍白、动则心
慌，气短等贫血表现，脾大
2.巩膜轻度黄染，结合化验(血
间接胆红素增高，尿胆红素阴
性，尿胆原强阳性)为溶血性黄
疸
3.Hb低，网织红细胞明显增高
达18%，分类中晚幼红细胞和嗜
碱性点彩红细胞等骨髓代偿增
生的表现，Coombs试验(+)
4.未发现继发原因
• 二、鉴别诊断
1.继发性免疫性溶血性贫血(药
物，自身免疫病等)
2.急性黄疸性肝炎
• 三、进一步检查
1.骨髓检查及骨髓铁染色
2. ANA谱，血清蛋白电泳，血
清IgG、IgA、C3定量
3.其他有关溶血的检查
4.肝功能、乙肝两对半、胸片
、腹部B超和血糖检查
• 四、治疗原则
1.首选糖皮质激素
2.免疫抑制剂或切脾

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