義大醫院兒童醫學部 1 目錄 1 Orientation 2 兒科病房常用藥物 4 兒童心臟科 12 兒童內分泌 30

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兒童血液腫瘤科

陳式瑜醫師/楊詠甯醫師

Anemia

1. 1 Anemia的定義是RBC volume或hemoglobin concentration在正常值以下，根據年齡的不同而有不同的正常值 (參考table 1)

1.2 Infant的生理性貧血: 足月兒在8~12個星期大時hemoglobin會降到最低點，約9~11 g/dL；早產兒在3~6個星期大時hemoglobin會降到最低點，約7~9 g/dL
1.3首先check blood smear (RBC morphorlogy), MCV (mean corpuscular volume)及 RPI (reticulocyte production index)可先將anemia大致分成幾類 (table 2)
註: RPI 的算法

* 其中μ指的是reticulocyte在週邊血液存在的天數，和anemia的程度有關，anemia越嚴重μ值越大(參考 fig 1)

1.4再根據history taking, blood smear, MCV, RPI的結果，選擇性的check以下項目:

(血清，特殊蛋白): ferritin, transferrin, haptoglbin,

(重金屬): serum iron & TIBC, Pb, aluminum

(血液特殊檢查): G6PD quantitative

(血清，電泳): Hemoglobin electrophoresis (Hb EP)

(核醫，抽血，內分泌): Vitamin B12, Folic acid

1.5 Iron deficiency anemia (IDA): 純母乳哺育的infant，在4個月大之後會補充鐵劑。足月兒在6個月大之前，很少因為單純鐵質缺乏而發生貧血，而通常是發生在9~24個月的孩子。青少年因快速成長，經血流失，加上飲食不均衡，所以也是iron deficiency anemia好發的年齡。Lab方面可見到: ferritin, serum iron, transferrin saturation降低，transferrin升高。IDA的 RBC count通常減少，RDW ( RBC distribution width)升高，platelet count有時也會升高；相反的，thalassemia的RBC count通常升高。
1.6幾乎所有兒童的megaloblastic anemia都是由於缺乏folic acid或vitamin B12造成，以上兩者在Lab及blood smear的finding類似: 有大的RBC，有large and hypersegmented neutrophil (很多netrophil都有4~5葉以上的lobes)，高的LDH activity(代表無效造血)。Megaloblastic anemia的好發年紀是4~7個月，比IDA早。

Folic acid在體內的儲存量不多，若飲食中完全不含folic acid，則在2~3個月就會造成megaloblastic anemia。攝取量不足較常發生在vitamin需要量增加時(如: 懷孕、infant成長期、慢性溶血)。Breast milk, cow’s milk, and infant formula都含有足夠的folic acid，羊奶的folic acid量則不足，以羊奶為主食的兒童，則需要額外添加folic acid。Chronic diarrhea、腸道手術、抗痙攣藥物(phenytoin, primidone, Phenobarbital)可因folic acid的吸收不足(decreased absorption)而引起megaloblastic anemia。Folic acid level的正常值: 5~20 ng/mL。

大小孩及成人體內vitaminB12的儲存量通常可提供3~5年的使用，且許多食物都含有vitaminB12，所以dietary deficiency很少見。若low vitaminB12 stores媽媽生的小孩，可能在4~5個月大就會出現vitaminB12缺乏的症狀。和folic acid缺乏不同的是，vitaminB12缺乏會有neurologic symptoms (包括: paresthesias, sensory deficits, hypotonia, seizures, developmental delay/ regression, and neuropsychiatric changes)。另外，Schilling test測試的是absorption of vitaminB12，可診斷缺乏intrinsic factor等vitaminB12吸收的問題。
1.7 具有G6PD deficiency的病人通常在接觸有oxidant properties的物質24~48小時後，會產生溶血的症狀。其中藥物包括：aspirin, sulfonamides, and antimalarials，其他如蠶豆、hepatitis也可引起hemolysis。診斷是測RBC的G6PD activity （＜10% of normal），在剛發生溶血後，周邊血液以reticulocytes and young RBCs 為主，young RBCs有比older RBCs更高的enzyme activity，因此，發生溶血後數星期再測enzyme activity較能得到正確的診斷。
Reference: Nelson textbook of pediatrics 17^th and 18^th edition

Table 1 Hematologic Values During Infancy and Childhood

	HEMOGLOBIN (G/DL)		HEMATOCRIT (%)		RETICULOCYTES (%)	MCV (FL)
AGE	Mean	Range	Mean	Range	Mean	Lowest	Mean
Cord blood	16.8	13.7–20.1	55	45–65	5.0	110	18,000
2 wk	16.5	13.0–20.0	50	42–66	1.0		12,000
3 mo	12.0	9.5–14.5	36	31–41	1.0		12,000
6 mo–6 yr	12.0	10.5–14.0	37	33–42	1.0	70–74	10,000
7–12 yr	13.0	11.0–16.0	38	34–40	1.0	76–80	8,000
Adult
Female	14	12.0–16.0	42	37–47	1.6	80	7,500
Male	16	14.0–18.0	47	42–52		80

Fig 1 Number of days for maturation of reticulocytes to mature erythrocytes in the marrow and blood. The duration of maturation as blood reticulocytes is taken as μ.

Table 2 differential diagnosis of anemia in children

兒童輸血準則：
1. RBC及PLT輸血標準

_{常用成份血之適應症及其標準：}

_{新鮮冷凍血漿} (FFP)	_{1. 血漿蛋白缺乏造成之血栓栓塞症。} _{2. 凝固因子缺乏造成之出血傾向時。} _{3. 栓塞性血小板減少性紫斑。} _{4. 免疫球蛋白缺乏者。} _{5. 血漿蛋白缺乏者。} _{6. 血漿交換治療。} _{7. 可作為循環血液量補充劑。} _{8. 大量輸血時。} _{*不能用於補給營養或傷口癒合；最好照會血液科後使用}
_{冷凍沈澱品} (Cryoprecipitate)	_{1. 第十三因子缺乏者。} _{2. 擴散性血管內凝固症(DIC)。} _{3. A 型血友病患。} _{4. von-Willebrand 氏病。} _{5. 纖維蛋白原缺乏或異常者。} _4.
_全血	_{1. 病人在 24 小時內出血喪失其總血量 30%以上時。} 2. 外傷或開刀病人失血大人達 1000–1500 mL，小孩達體重的 30%以上者。 _{3. 交換輸血。}

Indications for washed RBC

2.3.1 Frequent transfusion, such as thalassemia major, SAA

2.3.2 Frequent transfusion reaction

2.3.3 SAA, pre-BMT transfusion

2.3.4 Post - BMT ( dependent on donor-recipient blood type )
2.4 Indication for irradiation

2.4._{1. Neonates}

2.4._2._{接受子宮內輸血治療的胎兒}

2.4._3._{先天或後天性}_{immunodeficiency}

2.4._4._{器官移植病患}₍_{器官含有淋巴球}₎

2.4._5._{化療或放射治療期間，特別是}_A_L_C_(ab_s_olute_l_y_m_phoc_y_te_c_o_u_n_t)_<500/m_m³

2.5. Indications for leukocyte filter

2.5._1._需降低_CMV_{感染機率時}₍_{例如早產兒、免疫力低下者}₎

2.5._2._{血液或骨髓移植術後}

2.5._{3. SAA}_患者_的_pre-BMT_transfusion

2.5._4._{曾發生兩次以上輸血反應}
_{2.6. 計算輸血量及預期血球上昇值}

^PRBC、WRBC

10–15 mL/kg

Hb  2–3 g/dL

PLT

5–10 mL/kg

PLT  50–100

Granulocyte

10–15 mL/kg

1–210⁹PMN/kg

_{Cryoprecipitate}

_{1–2 U/10 kg}

_{Fibrinogen  30–50 mg/dL}

血小板輸血無效(platelet transfusion refractoriness)的D.D.：

_{輸完血一小時後，抽血計算 CCI (corrected PLT count increment)：}

每袋血小板的細胞數：PLT concentration 1 U 為 0.27

Single donor PLT：12 U 則為 3.3

CCI <7,500  血小板輸注無效：血小板損耗(如出血、DIC、肝脾腫大)、藥物(化療的骨髓抑制、vancomycin、AmB)、血品因素(血小板收集與儲存品質等)

Lymphadenopathy
1. . Lymph node在正常孩童常可觸摸到。Cervical or axillary nodes超過1 cm，inguinal nodes 超過1.5 cm才被認為是enlarged lymph nodes。

Adenopathy分為local及generalized。Generalized adenopathy的定義是:在兩個以上不連續的區域都有enlarged lymph nodes。Generalized or local adenopathy的鑑別診斷分別在table1及table2。

Acutely infected nodes常有壓痛，且在overlying skin有紅、熱等現象。

和腫瘤有關的lymph nodes常是硬的(firm)、無壓痛，且和週邊組織緊密相連( fixed to the skin or underlying structures)。

若懷疑bacterial infection 引起，使用的抗生素則至少須cover streptococci及 staphylococci。

Lymph nodes的size未在14天內減少，考慮進一步evaluation，包括: CBC/DC, Epstein-Barr virus ( EB-VCA IgG, IgM) , cytomegalovirus (CMV IgG, IgM), Toxoplasma (Toxoplasma IgG, IgM) , cat-scratch disease titer; antistreptolysin O; tuberculin skin test; and chest radiograph.

以下情況考慮作biopsy: persistent or unexplained fever, weight loss, night sweats, hard nodes, fixation of the nodes to surrounding tissues, 2星期內nodes的size增大，6星期內nodes的size沒有減少的跡象，12星期內nodes的size尚未恢復正常，或有新症狀出現。

TABLE 1 -- Differential Diagnosis of Systemic Generalized Lymphadenopathy

TABLE 2 -- Sites of Local Lymphadenopathy and Associated Diseases

CERVICAL

Oropharyngeal infection (viral or group A streptococcal, staphylococcal)

Scalp infection

Mycobacterial lymphadenitis (tuberculosis and nontuberculous mycobacteria)

Viral infection (EBV, CMV, HHV-6)

Cat-scratch disease

Toxoplasmosis

Kawasaki disease

Thyroid disease

Kikuchi disease

Sinus histiocytosis

Autoimmune lymphoproliferative disease

ANTERIOR AURICULAR

Conjuctivitis

Other eye infection

Oculoglandular tularemia

Facial cellulitis

POSTERIOR AVRICULAN

Otitis media

Viral infection (especially rubella, parvovirus)

SUPRACLAVICULAR

Malignancy or infection in the mediastinum (right)

Metastatic malignancy from the abdomen (left)

Lymphoma

Tuberculosis

EPITROCHLEAR

Hand infection, arm infection^[

Lymphoma

Sarcoid

Syphilis

INGUINAL

Urinary tract infection

Venereal disease (especially syphilis or lymphogranuloma venereum)

Other perineal infections

Lower extremity suppurative infection

Plague

HILAR (NOT PALPABLE, FOUND ON CHEST RADIOGRAPH OR CT)

Tuberculosis

Histoplasmosis

Blastomycosis

Coccidioidomycosis

Leukemia/lymphoma

Hodgkin disease

Metastatic malignancy

Sarcoidosis

Castleman disease

AXILLARY

Cat-scratch disease

Arm or chest wall infection

Malignancy of chest wall

Leukemia/lymphoma

Brucellosis

ABDOMINAL

Malignancies

Mesenteric adenitis (measles, tuberculosis, Yersinia, group A streptococcus)

Idiopathic thrombocytopenia purpura（ITP）

Clinical manifestations.
1. most common cause of acute onset of thrombocytopenia
2. 1–4 wk after exposure to a common viral infection  autoimmune

4.1.3 特微

血小板數量小於100000/mm3
血小板壽命減短
血漿中有抗血小板的抗體產生
骨髓中的megakaryocytes 增加。

4.1.4 1–4 yr old child，70–80% of children who present with acute ITP, spontaneous resolution occurs within 6 mo
Lab: CBC/DC, CRP, if needed virus survey, PT, PTT
*** Indications for bone marrow aspiration include an abnormal WBC count or differential or unexplained anemia as well as findings suggestive of bone marrow disease on history and physical examination.

4.2 Treatment

4.2.1 類固醇療法：1–4 mg/kg/24 hr

4.2.2 IVIG：0.8–1.0 g/kg/day for 1–2 days

以下請consult Hematology

4.2.3 免疫抑制劑

4.2.4 Danazole

4.2.5 splenectomy

Reference: Nelson textbook of pediatrics 17^th and 18^th edition

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