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Thalassemia (OVERVIEW AND TYPICAL PRESENTATIONS (Beta thalassemias (Beta…
Thalassemia
OVERVIEW AND TYPICAL PRESENTATIONS
Alpha thalassemias
過多 gamma and beta chains
時間: late gestation
有4個 alpha globin genes
adjacent pair on each chromosome
gene deletions
Hydrops fetalis and hemoglobin Barts
失去全部4個 alpha globin genes (--/--)
Severe anemia
從父母雙方 co-inheritance of alpha thalassemia-1 trait (aa/--)
只有
hemoglobin Barts
tetramers of gamma globin
不能傳遞氧氣給組織
affinity for oxygen 太高
(HbA 的10倍)
沒有 fetal hemoglobin (HbF): 6~8週 of gestation
沒有 adult hemoglobin (HbA)
hydropic state
massive total body edema
因為high-output heart failure
Fetal death
late-second ~ mid-third trimester
intrauterine transfusion可增加存活率
媽媽會 polyhydramnios (羊水過多)
Hemoglobin H disease
失去3個 alpha-chain genes
deletional (--/a-)
非洲, 亞洲
nondeletional (--/aat)
t代表 mutant
地中海
mild anemia
Hb: 9 to 11 g/dL
MCV : 62 to 77 fL
可產生 HbA 和 HbH
(tetramers of beta globin)
嚴重性多變
出生時 thalassemia intermedia
但可轉為 transfusion dependence
increased hemolysis
infection
pregnancy (with dilutional anemia)
aplastic crisis
因為 HbH 已經氧化
所以 RBCs are susceptible to
oxidant stress
(infection, oxidizing drugs)
co-inheritance of
cis-deletional form of alpha thalassemia
HbCS (--/aaCS)
更嚴重
Complication
ineffective erythropoiesis
extramedullary hematopoiesis
iron overload by adulthood
hepatosplenomegaly
gallstones, bone deformities, growth impairment, Leg ulcers
Alpha thalassemia minor or minima
Beta thalassemias
過多 alpha chains
時間: after the first six months of life
Hemolysis 會 overshadowed 因為 ineffective erythropoiesis
Beta thalassemia major
(Transfusion-dependent beta thalassemia)
又稱
Cooley's anemia, Mediterranean anemia
原因
homozygosity or compound heterozygosity
for beta0 thalassemia mutations
beta+ thalassemia mutations
with extremely low production of beta globin chains
compound heterozygosity for
hemoglobin E
(ie, HbE/beta thalassemia)
是beta+ type of mutation
late infancy (6~12月)
之前有 HbF (gamma chains)
症狀
hemolysis
jaundice
dark urine
pallor
severe anemia
high-output heart failure
failure to thrive
infection
extramedullary hematopoiesis
skeletal abnormalities
臉
長骨
hepatosplenomegaly
kidney enlargement
Late symptoms
iron overload
影響心臟,肝臟,內分泌器官
Anisopoikilocytosis
Mortality
不治療的話非常高
85% 5歲前死亡
心血管病灶
Beta thalassemia intermedia
(Non-transfusion-dependent beta thalassemia)
症狀
2~4歲出現
heterogenous of clinical presentations
症狀多變,每個人不一樣
原因
homozygosity
compound heterozygosity for a beta+ thalassemia mutation
heterozygosity for a beta0 thalassemia mutation
Beta thalassemia minor
(beta thalassemia trait)
原因
heterozygous for a beta+ or beta0 thalassemia mutation
asymptomatic carrier
但也可能會 lethargy, fatigue
microcytosis 被誤認成iron deficiency
2或1個 beta globin genes 產生 mutation
reduced expression (beta+)
complete absence of expression (beta0)
症狀於4~6個月時出現
因為
gamma globin (beta-like chain)
used in fetal and early infant hemoglobins
sickle-beta thalassemia
co-inherit
beta thalassemia mutation
sickle mutation
inherited hemoglobinopathies
減少 alpha or beta chains 生產
其用來assembly of the hemoglobin molecule
破壞 red blood cell RBC precursors 的發育
ineffective erythropoiesis
hemolytic anemia
Causes of variability in disease manifestations
之後補
MANAGEMENT
General aspects of anemia management
chronic transfusions
維持 Hb
減緩 anemia 症狀
抑制 extramedullary hematopoiesis
9 ~ 10 或
9.5 ~ 10.5
g/dL
alpha thalassemia major
出生前: intrauterine transfusion
出生後: chronic transfusion
beta thalassemia major
chronic transfusion (越早越好)
thalassemia intermedia
選擇 chronic transfusion regimen 或 periodic transfusions
thalassemia minor or minima
不用 transfusion
Dietary restrictions and supplements
folic acid
1 to 2 mg per day
增加 RBC turnover
避免 iron-containing supplements
因為 thalassemia 增加 iron absorption
茶可減少鐵吸收
若有 iron deficiency anemia 則例外
Regular transfusions
Decision to initiate regular transfusions
Thalassemia major
transfusion-dependent
防止 Hb 下降
9.5 to 10 g/dL
與病人體型及 Hb baseline 有關
early infancy 有症狀時
Thalassemia intermedia
erythropoietic stress
時
(Hb < 7 g/dL)
Infection, rapid growth, surgery, pregnancy
functional deterioration
cardiopulmonary compromise
extramedullary hematopoiesis
expanding bony masses
pathologic fractures
hypersplenism
考慮年齡, 併發症, iron store 增加
活動度, 生長發育, skeletal changes
Typical chronic transfusion regimen
Hb
9~10
9.5~10.5
g/dL
兩者之間取得平衡
抑制 hematopoiesis
減低 iron overload
higher level
heart disease
extramedullary hematopoiesis
suppressed bone marrow
back pain prior to transfusion
lower level
為了治療 anemia 而不是為了抑制 ineffective erythropoiesis
一天不超過 10 mL per kg of packed RBCs
pretransfusion hemoglobin: 9.5 to 10.5 g/dL
post-transfusion hemoglobin: 12 to 13 g/dL
每1~3天一次
小朋友避免 central venous catheter placement
extended crossmatching
避免 alloimmunization
leukocyte depletion
減少 febrile nonhemolytic reactions
Assessment of iron stores and initiation of chelation therapy
iron overload
造成 organ toxicity 和死亡
測定
serum ferritin
MRI
偵測心臟,肝臟 iron concentration
原因
increased distribution of iron to the
reticuloendothelial system
increased
intestinal absorption
Iron chelation
Initiation
開始 chronic transfusion 時
serum ferritin > 1000 ng/mL
liver iron concentration > 3 mg iron per g of dry weight
transfusion 20 to 25 units of RBCs 後
beta thalassemia major
6歲(2~4歲) 前開始 iron chelation
alpha or beta thalassemia intermedia
chronic transfusion 時(20~30歲) 開始使用 iron chelation
Reduction of alloimmunization and other complications of transfusion
