Aplast Anemia (再生障碍性贫血)
陈进伟
Aplastic Anemia( 再生障碍性贫血)
Aplastic Anemia is a pancytopenia (全血
细胞减少) syndrome appearing as anemia,
infection and bleeding by multiple causes
that result in decrease or failure of hem
opoietic ( 造血) function of BM.
Etiology and pathogenesis
Cholormycine division quantity and/or
1.Drugs Sedative (-) synthesis of protein (-) quality abnormality of
anti-cancer mRNA stem cells
(Beed theory; defective
stem cell)
2.Chemical toxic Beyene
Substance inorganic arsenic (-)
3.Virus infection (+) antibodies resisting stem cells
(EB;hepatitis) self-immunition (+) IFN↑ (-)
(insect theory; disorder immunine function)
4.Physical factors copy of DNA (-) regeneration of hematopoietic
(X-ray,r-ray) (-) cells
damage microenviroment (-)hypoproliferation or failure of BM
(soil theory; defect of hemopoietic microenviroment)
Clinic appearance and classificationAAA(SAA-I;SAA-II) CAA (light AA)
onset Acute sharp Gradualoutstanding
manifestation
Bleeding(viscera 内脏 )Infection (serious; septicemia 败血症 )
Slight Bleeding(skin; mucosa 粘膜 ) Anemia
Blood pictureReticulocyte BM
prognosis
N<0.5×109/LPt<20×109/L<15×109/LHypoproliferation in many parts;non-hemopoietic cell↑
BadDead in 6-12 month by hemorrhage in brain and/or infection
N>0.5×109/L Pt>20×109/L >15×109/L Hypoproliferation orhyperproliferation non-hemopoietic cell↑
chronic procedure
Standuard of diagnosis:1. Pancytopenia ; decreased of re
ticularcytic absolute value (网织RBC绝对计数)
2. Usually unenlargement of liver and spleen
3. Bone marrow hypoproliferation(增生低下 ) of one site at least or hyperproliferation( 增生活跃) with megakaryocyte (巨核细胞) decreased
:
4. Increased of non-hematohistiololast (非造血组织细胞)
5. Being excepted other pancytopenia disease
6. Uneffect of usual anti-Aneamia treatment
Differential diagnosis1.Myelodysplastic syndrome(MDS;
骨髓增生异常综合症) normoblast (幼稚细胞) in blood p
icture
Morbid hemapoietsis ( 病态造血) 2.paroxysmal nocturnal hemoglobinur
ia (PNH; 阵发性睡眠性血红蛋白尿) Ham’s test , Rouse test (+)
3.Malignant histiocytosis( 恶性组织细胞病) jaundice (黄疸) ,and enlargement of lymphonodus (淋巴结) , liver and spleen.
Abnormal histiocyte (异常组织细胞) in BM
4. Aleukemic leukemia Blast cells ( 原始细胞) can be found in peripheral blood and/or BM
Treatment Principle of treatment
1. got rid of possible pathogeny
2. Classified and united treatment. AAA: immunsuppressive + BMT +cell factor CAA: male hormone mainly. immunosuppressive agent .sos 3. Early diagnosis,early treatment.
4.supportive therapy1) Individual and environment should be
kept clean
2). Control infection (控制感染 )
3). Stopping bleeding: prednison( 强的松)
4). Blood transfusion: Hb<60g/L. Compo
sition transfusion (成分输血)
druge 一 . Male hormone: (first selected for CAA)
(1) Effect a. directly stimulating renal EPO b. directly stimulating regeneration(增殖) and division (分裂) of stem cells. (2) Side effect: a. damage liver:
b. manly:
(3) Dosage (剂量) :
testosterone propionate (丙酸睾丸酮)
50-100mg im Qd or QOD stanozol (司坦唑;康力龙) 2-4mg
po tid danozol (哒那唑) 2.5-5mg po tid effective rate>75
Standard of BM restored
① restored to normality of Pt.
② Product rate of clony forming unit of bone marrow cell is Normality
二 .Immunosuppressive agent1.ALG/ATGa. effect: correcting immune disor
der and stimulating hematopoietic (造血) function of BM (effective rate 79%)
b. ALG/ATG 10-15mg/kg/ 日 + DXM 10mg + N.S 500ml / iv gtt . 5days/coures.
(First take skin test)
c. By-effect:
hypersensitivity (超敏反应) ;
serum-disease (血清病)
bleeding (出血)
2. McAb-T (Monoclonal Antibody-T ;T- 淋巴细胞单克隆抗体 )
OKT-3 5mg+NS 150ml / iv gtt .
QdΧ 7days.
(inhibiting IL-2,IFN secreted by TLC. indirectly stimulating hematopioetic function of BM) .
effective rate 75.8%
3. CsA (Cyclosporin A ;环胞菌素A ) CsA 0.4~ 5 mg/kg/day, Po , 3 weeks- 3months/course.
( inhibiting product IL-2 and secretion interferon of TLC).
effective 55±%
By-effect: damage function of liver and renal
4.Methylprednisolone( 甲基强的松龙) 20~30mg/kg by iv, QdΧ 3-14da
y.5.γ-Globulin 0.5-0.9g/kg,by iv QdΧ5
days
三 .cell factors:1. GM-CSF 8~60ug/kg/d . H. 14d/course .>3month 2. EPO 6000u /d. H. Q3W→Q2w→QW > 3 months effective rate 83.3% - 100%
3. IL-3:
250~500ug/M2/d . H. 15d/course
prompt development of pluripotent stem cell( 多能干细胞)
四 .Bone Marrow Transplantation (BMT)
There are there kinds of BMT Syn-BMT (同基因 BMT ) All-BMT (同种异基因 BMT ) ABMT (自体 BMT ) transfusion mounts of BM cell ar
e need o.9~ 14.2Χ 10.8/kg
The indication for BMT:
1.Younger patient (<40) with AAA/SAA
2.not or small blood transfusion, without any infection
3.There is donor’s HLA matching
to the patient
There are some diffcults:
1. Actually it is diffcult to get homogenic (同基因) BM although syn-BMT has high success
2. GVHD (Graft versus Host disease;移植抗宿主病) and GR (graft reject)
often occurs with Bleeding or infection.
3 .Money is too expansive(>200000yuan)
transplant of funicular blood stem cells
Transfusion of fetus liver cells
Prognosis( 预后 )
1/3~1/2 of AAA will died in intracranial hemorrhage (颅内出血) and/or septicemia (败血症) several months to 1 year after onset.
1/3~1/4 of CAA will delay for many years.
[Prevention] not abuse harmful drugs to BM
protection environment,
prevention from toxic substances