血液腫瘤科 廖浚凱 aug 15, 2012. outline anemia blood smear
TRANSCRIPT
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血液腫瘤科廖浚凱 Aug 15, 2012
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Outline
Anemia Blood smear
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Erythrocyte Development
EPO: 90% from kidney 10% from liver
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Hemoglobin
Fe + protoporphyrin α2β2 ↓ ↓ heme + globin ↓ Hb
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Two main approaches for anemia that are Two main approaches for anemia that are not mutually exclusive:not mutually exclusive:
1. Kinetic approach2. Morphological approach
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Kinetic approach of Anemia
Production? Survival/ Destruction?
The key test is the …..
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Reticulocyte Production Index— an estimate of marrow production relative to normalCorrected Ret= Ret(%) *Corrected Ret= Ret(%) *
Hct
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RPI=Corrected Ret
Maturation index
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RPI (kinetic approach)
RPI are the most helpful: extremely low (<0.1%)
AA/ PRCA are the first considerations
extremely high (>3%) Blood loss/ hemorrhage Hemolytic anemia (although 25% AIHA have normal RPI)
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Morphological Approach-1
MCV>115 Vit B12, Folate Drugs that impair
DNA synthesis (AZT, chemotherapy, azathioprine)
MDS
MCV 100 - 115 Ditto Reticulocytosis Hypothyroidism Alcoholism/ liver dz
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Morphological Approach-2
Normocytic (MCV 80-100)
Anemia of chronic disease (ACD)
Mixed deficiencies
Renal failure BM dz (ex AA,
MDS, MM…)
Microcytic (MCV<80)
Iron deficiency anemia
Thalassemia Anemia of chronic
disease (ACD, 30-40%)
Sideroblastic anemia Pb intoxification
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Distribution of Iron in Adults
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Storage iron Circulating iron RBC iron Tissue iron
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IDA Presentation
Presentation Diagnosis
Progressive MCV ↘ Progressive RBC ↘ Typically high RDW Typically high
MCV/RBC Typically mild PLT ↑
Ferritin: low (N=20-300)
Iron/TIBC <16% (N=~33%)
BM iron stain
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Causes of IDA
Increased iron requirement Inadequate iron supply
Hypermenorrhea
GI blood loss– hemorrhoid, PUD, GI cancer, angiodysplasia
Factitious removal
Hemolysis
Hemodialysis
Hookworm infestation
Rapid growth of teenage
Pregnancy and lactation
Poor nutritional intake
Malabsorption
Gastrectomy (may also has Vit B12 deficiency)
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Iron Supply
Oral: usually 3 months to restore iron storage Ferrum chewable (Fe 3+) 100mg/tab Hematonic (Fe 2+) 50mg/tab
IV Atofen (!! Risk of allergy and anaphylaxis—
0.6%)
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Harrison’s Principles of Internal Medicine 15th Ed. 2001
Hb Gene
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Thalassemia Presentation
Presentation Diagnosis
Constant low MCV Constant high RBC Typically low RDW Typically low MCV/RBC Typically iron storage
↗
Exclude IDA
Hb electrophoreis: Hb A2>3.5% or HbF>2% β-
thalassemia HbH(+) α-thalassemia with
¾ defect (HbH dz) HbA2 and HbF: N
α-thalassemia with ¼ or 2/4 defect
Gene diagnosis
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Gene Level of Thalassemia in Taiwan
α-thalassemia: Prevalence 4% --SEAα0 deletion -α3.7 deletion -α4.2 deletion HbQS or HbCS
β-thalassemia: Prevalence 2% Codon 41/42 TCTT deletion β0 IVS II 654 C-> T point-mutation β0 Codon 17 A-> T β0 Promoter 28 A-> G β+ HbE (Codon 26 G-> A) β+
??% α + β-thalassemia (Severity?)
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Hb H disease (黃疸 )
Hydrops fetalis (死胎 )
優生學的理由 β –Major (終身輸血 )
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Thalassemia Treatment
Mild: None
Severe: Folic acid RBC transfusions + iron chelators Allo-SCT
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Megaloblastic Anemia PresentationPresentation Diagnosis
High high MCV Pancytopenia Hypersegmented PMN Typically high RPI, hemolysis
(LDH ↗), indirect hyperbilirubinemia
Tinnitus or other neurological presentation
Vegetarism ( 奶 , 蛋 , 維他命 ) Gastrectomy or Pernicious
anemia
??Schilling test
Low Vit B12 or folic acid Vit B12: 270~400: empirical
try Vit B12< 270: definite
deficiency
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Remember Pancytopenia
P: PNH A: Asplatic anemia N: Neoplasm/ Near neoplasm (including
MDS) C: Cirrhosis/ Connective tissue disease Y: Vit B12/ Folic acid T: Toxin/ Drug O: Overwhelming sepsis
(Hemophagocytic syndrome)/ Others
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Vit B12/Folate Deficiency Anemia Treatment Vit B12 deficiency:
Vit B12 1 mg im qd *5 q1wk *4 q1m*3 q6m R/I pernicious anemia
(Anti-parietal Ab, anti-IF Ab and PES) Thyroid dz Gastric cancer
Folate deficiency: Improved diet, folic acid
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Harrison’s Principles of Internal Medicine 15th Ed. 2001
Usually rapid responseMost important F/U Reticulocyte, LDH
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Is there hemolysis? Damaged RBCs on smear
spherocytes (immune hemolysis, HS) RBCs fragments (microangiopathic anemias)
Marrow response to hemolysis polychromasia on smear reticulocytosis erythroid hyperplasia in marrow
Biochemical evidence of RBCs destruction Indirect hyperbilirubinemia increased LDH decreased/absent haptoglobin
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Extravascular vs Intravascular hemolysis
Extravascular IntravascularTest Hemolysis Hemolysis
LD
bilirubin
haptoglobin N to absent absent
hemoglobinuria absent present
free Hb in plasma absent present
urine hemosiderin absent present
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An approach to hemolytic anemia
Immune Non-immune
Congenital Acquired
Defects of: •Membrane/ skeleton (eg. Hereditary spherocytosis)
•Enzymes(eg. G6PD deficiency)
• Hemoglobinopathy
• PNH• Infections sepsis malaria
• Mechanical Prosthetic heart valve Microangiopathic HA (TTP, HUS, DIC)
•Hypersplenism
• Autoimmune
• Alloimmune
• Drug-induced
Hemolytic anemia
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D/D of AIHAWarm AIHA Cold AIHA
RBC’s coated with IgG, Fix complement poorly (usually C3 only)
RBC’s coated with IgM which fixes complement
Younger age Older age
extravascular hemolysis (Spleen is primary site of destruction)
Intravascular hemolysis (Liver is primary site of destruction)
Spherocytes on PB smear Agglutination on PB smear
70% associated with other illnesses 90% associated with other illnesses
Treatment: steroids, Splenectomy RituximabImmunosuppressants
Treatment: avoidance of coldPoor response to steroids,
splenectomyRituximabPlasmapheresis in refractory cases
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D/D of ACD and IDAD/D of ACD and IDA
Lab measure ACD IDA
Plasma Fe Reduced (normal) Reduced
Plasma transferrin Reduced (normal) Increased
Transferrin sat. Reduced (normal) Reduced
Plasma ferritin Increased (normal)* Reduced
Plasma TfR Normal Increased
TfR/log ferritin Low (<1) High (>4)
ACD may concurrently coexist with true iron deficiency(In this situation, iron/TIBC is more reliable than ferritin)
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貧血 分類:
依血球大小及形態: 紅血球偏小性貧血:海洋性貧血、缺鐵性貧血、慢性疾病相關之貧血 正常紅血球大小之貧血 紅血球偏大性貧血:維他命 B12 缺乏或葉酸缺乏性貧血、網狀紅血球增加之貧血
〈溶血急性出血〉 依製造功能
製造不足: 骨髓造血功能不足、再生不良性貧血、造血元素缺乏性貧血、缺鐵性貧血、純紅血球製造不
良、其他疾病合併骨髓侵犯 紅血球生成素〈 Erythropoietin 〉不足:腎衰竭、內分泌失調、營養 不良、 蛋白質不足
破壞或流失增加:溶血性貧血、出血、脾臟腫大性貧血
重要指標: 網狀性紅血球值〈 Reticulocyte count 〉 乳酸脫氫脢〈 LDH 〉 膽紅素〈 Bilirubin 〉 血紅素結合素〈 Heptoglobin 〉
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Burr cells
Altered lipid in cell membrane
artifact Uremia gastric CA transfused old
blood
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Elliptocytes/ovalocytes
Abnormal cytoskeletal proteins
Hereditary elliptocytosis
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Howell Jolly body Nuclear remnant -
DNA hemolytic anemia Absent or
hypofunction spleen
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Schistocyte/helmet cells
Fragmented (mechanical or phagocytosis)
DIC TTP HUS Vasculitis prosthetic heart valve severe burns
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Sickle cells
Molecular aggregation of Hgb-S
SS, SC, S-thal rarely S-trait
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NRBC
Common in newborn
severe degree of hemolysis
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Spherocyte
Absent central pallor look smaller Hereditary
spherocytosis immune hemolytic
anemia
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Target cells
Increased redundancy of membrane
hemoglobinopathies thalassemia liver disease
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Tear drop cells Distorted drop shaped Smear artifact myelofibrosis promyeloblastic
leukemia space occupying
lesions of marrow
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Rouleaux formation Increased serum
protein levels Multiple myeloma
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Red cell Agglutination
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血球成熟之變化性質 成熟之變化
細胞 大小 大->小 (megakaryoblas除外 )
細胞質 量 顏色 顆粒
少->多深藍->淡藍->橘紅 ( 如 RBC)多->少或消失
細胞核 染色質 顏色
圓,卵圓->內凹,變小->分葉->消失
細->粗紅紫->藍紫
核 / 質比 比例減少
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血球染色特徵細胞成分 顏色 細胞成分 顏色
核仁染色質紅血球
淡藍紫色粉紅色
網狀紅血球顆粒芽球細胞質血小板
灰藍色深藍色紫色
初級顆粒嗜中性顆粒嗜酸性顆粒嗜鹼性顆粒毒性顆粒
紅紫色紫色橘紅色黑紫色藍黑色
Auer 小體Cabot氏環Howell-Jolly小體Dohl小體
紫色紫色紫色鮮藍色
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WBC series
Granulocytes Neutrophil Eosinophil Basophil
Monocyte Lymphocyte
T cell, B cell
Neutrophil Blast Promyelocyte Myelocyte Metamyelocyte Band Segment
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Granulocyte
0-5% 50-65%
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Pancytopenia withmacrocytic anemia
Causes megaloblastic anemia aplastic anemia acute leukemia myelodysplastic syndrome chronic liver disease (esp.
liver cirrhosis) Work-up
Serum VitB12 & folic acid reticulocytes bone marrow study
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Macrocytic anemia withunmeasurable RBC
RBC & Hct : unmeasurable RBC agglutination
Causes : autoimmune hemolytic anemia, mixed type or cold type
Work-up peripheral blood smear serum bilirubin (T/D), AST,
LDH, haptoglobin, urine analysis, reticulocytes
Coombs’ test (direct and indirect)
ANA, VDRL, cold hemagglutinin antibody
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有獎徵答
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檢驗項目 檢驗值 單位 H/L 參考值 =======================================================
WBC 3.0 1000/CMM L M3.9-10.6 F3.5-11
RBC 2.06 MILON/CMM L M4.5-5.9 F4.0-5.2
HGB 8.5 g/dL L M13.5-17.5 F12-16
HCT 25.8 % L M41-53 F36-46
MCV 125.2 FL H 80-100
MCH 41.3 pg/Cell H 26-34
MCHC 32.9 g/dL 31-37
RDW-SD 97.0 % H 38-45
PLATELET 443 1000/CMM H 150-400
RDW-CV 24.8 % H 11.0-14.0
SEGMENT 41.5 % L 42-74
LYMPHOCYTE 51.5 % 20-56
MONOCYTE 5.3 % 0-12
EOSINOPHIL 1.7 % 0-5
BASOPHIL 0.0 % 0-1
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IDA
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Leukoerythroblastosis Immature RBC
(nucleated RBC) and myeloid cells in peripheral blood
Causes Bone morrow disorders :
Infiltrative disorders or hematologic malignancy
Peripheral disorders : Severe infection, major
stress or operation, acute blood loss
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Thrombocytosis
Primary: Bone marrow disease Myeloproliferative disease
Secondary (Reactive) Malignancy Inflammation or infection Connective tissue disorder Blood loss or anemia Splenectomy
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THANKS