⾎液期末整理

1.Hemostatis凝⾎：相關⾎管壁、凝⾎因⼦、⾎⼩板
⾎管壁:內⽪細胞-選擇性通透、防⽌凝⾎的因⼦ex.PGI2、⽣成結締組織
fribinolytic:纖維蛋⽩溶解/ fribinolysis:纖維蛋⽩合成
A.⾎管壁受損：肌⾁收縮減少⾎流、內⽪細胞thrombogenic(分泌vWF、⾎⼩板活化、collagen、
plaminogen activator inhibitor 阻⽌纖維蛋⽩溶解）
Inherited Acquired

Hereditary hemorrhagic telangiectasis Senile purpura

遺傳性出⾎性⽑細⾎管擴張症 老年性紫癜

Connective tissue disorders Scurvy

(Ehlers-Danlos syndrome)無法凝⾎ 壞⾎病

Cushing’s syndrome
Henoch-Schonlein syndrome
*⾎⼩板介紹：活10天、store（腎臟）& circulate總量⼀樣、正常值15萬到40萬、前⾝巨核細胞
（megakaryocytes）、Thrombopoietin簡稱TPO促⾎⼩板⽣成素肝臟分泌

活化⾎⼩板

修復⾎管

＊Platelet glycoproteins

Ib -⾎⼩板與 vWF 的初始附著

-Defective in Bernard-Soulier syndrome

Ia 促進⾎⼩板與膠原蛋⽩的粘附
IIb -platelet-platelet aggregation by vWF and brinogen
-Defective in Glanzman’s thrombasthenia

*vWF:(a)⾎漿 FVIII 載體蛋⽩(b)配體結合Ib＆IIb (c)Prolonged APTT and BT

Factor XIII
Fribin polymer

說明

Prothrombin（凝⾎酶原）：Factor2.7.9.10+Protein S&C

Extrinsic activation factor X催化為Xa Prothrombin test (PT) - tissue factor outside
需VII參與 the blood vessels
- Clotting faster
Intrinsic activation factor X催化為Xa Activated partial - Clotting slow
需factor Xll,XI,IX thromboplastin test
(aPTT)
Common pathway Prothrombin變thrombin
需要V

HEMOSTASIS
• ⾎管壁完整性
• ⾜夠的⾎⼩板
• 正常運作的⾎⼩板
• ⾜夠⽔平的凝⾎因⼦
• 纖維蛋⽩溶解通路的正常功能
PLATELET DISORDERS
1.THROMBOCYTOPENIA⾎⼩板減少症:骨髓衰竭、脾腫⼤、紫斑、出⾎
fi
(A)Produce減少：megakaryocyte減少、化療、HIV、慢性肝炎
(B)破壞增加：特發性⾎⼩板減少性紫癜 (ITP)、輸⾎後紫癜 (HPA-1a)、⾎栓性⾎⼩板減少性
紫癜 (TTP)、溶⾎性尿毒症綜合徵 (HUS)、彌散性⾎管內凝⾎ (DIC)
2.THROMBOCYTOPATHY⾎⼩板增多症：尿毒症、遺傳性疾病、骨髓增⽣性疾病
3.TMA (Thrombotic microangiopathy)⾎栓性微⾎管病:⾎⼩板低下加上Microangiopathic
Hemolytic anemia (MAHA)。並至少要有以下其中⼀種症狀：神經學症狀、腎臟侵犯、 腸胃
道症狀。
*Renal Microvascular disease包括STEC-HUS、Atypical HUS、TTP。要先驗Shiga toxin，排除
STEC-HUS，再測ADAMTS13判斷是Atypical HUS 或TTP，如果ADAMTS13< 5 %，較像TTP
4.⾎友病：Factors VIII and IX de ciencies,治療⽤Emicizumab
5.DIC:Activation of both coagulation and brinolysis
6.Lupus phospholipid syndrome:後天⾃體免疫⾎栓、vascular thrombosis,recurrent流產,
thrombocytopenia.
7.動脈⾎栓：graywhite and friable
靜脈⾎栓：red in color
8.後天⾎栓因⼦：術後靜脈⾎栓形成、抗磷脂綜合徵
9.Deep vein thrombosis:臥床休息、⼝服避孕藥
10.PE肺栓塞：治療⽤heparin

Anticoagulant drugs
常⽤靜脈栓塞、易出⾎！！

heparin IV 快速 改良後LMW heparin只抑制XA

需要antithrombin III（抑制XA跟2A） protamine為解藥
highly acidic glycosaminoglycan
Fondaparinux 更優於LMW

Warfarin⼝服 blocks vitamin K‐dependent metabolized by the liver

γ‐carboxylation of glutamate residue 會有交互作⽤：
long half‐life (about 40 h)較長不適合 carbamazepine cimetidine,
緊急狀況 ethanol, metronidazole
解藥：phytomenadione(VITK)

Dabigatran IIa抑制物 Idarucizumab 解藥

Rivaroxiban Xa抑制物

Antiplatelet drugs reduce the risk of myocardial infarction

常⽤動脈栓塞 ⾎⼩板活化的關鍵事件是cytoplasmic calcium聚集
減少⾎⼩板聚集 ADP /TXA2會使cytoplasmic calcium升⾼
PGI2會使cytoplasmic calcium降低

Aspirin inhibition of platelet TXA2 synthesis by

irreversibly inhibiting cyclo‐oxygenase

Clopidogrel irreversibly blocking ADP used in patients in whom

aspirin is contraindicated
fi
fi
 Antiplatelet drugs reduce the risk of myocardial infarction
常⽤動脈栓塞 ⾎⼩板活化的關鍵事件是cytoplasmic calcium聚集
減少⾎⼩板聚集 ADP /TXA2會使cytoplasmic calcium升⾼
PGI2會使cytoplasmic calcium降低

Prasugrel and ticagrelor ADP inhibitors acting on P2Y12

Epti batide, tiro ban binding to the glycoprotein IIb/IIIa 常同時施予aspirin and heparin
and abciximab receptors ⽤IV

Dipyridamole increasing cAMP

Fibrinolytic drugs IV can rapidly lyse thrombi by activating plasminogen to form

常⽤在coronary artery disease plasmin
side‐e ects: bleeding, nausea, vomiting,allergic
近年常⽤PCI⼿術治療

Streptokinase binds to circulating plasminogen Allergic

to form an activator complex that
converts further plasminogen to
plasmin

Alteplase does not cause allergic Streptokinase替代⽅案

reactions

2.Anemia drugs
病 成因 副作⽤ 藥

Iron 缺乏會有⼩球性貧⾎ • chronic blood loss ⼝服鐵：GI不適 Oral

• pregnancy ⼩孩易Acute toxicity Ferrous xxxxxx
absorbed in the • abnormalities of 解藥：
duodenum and the gut desferrioxamine Parental
proximal jejunum • premature birth 鐵常以⾎紅素for Iron xxxxxxxx
nonstorage iron

Store as ferritin
and haemosiderin

Vit B12 缺乏會有⼤球性貧⾎ • lack of intrinsic ⼝服效果差直接注射

factor (惡性貧⾎) vitamin B12
CNS degeneration • 縮胃⼿術 (no
intrinsic factor) Hydroxocobalamin
需要 intrinsic factor • in various small
才能吸收 bowel diseases in Methylcobalamin＆
which absorption is deoxyadenosylcobala
會有神經性病變 impaired min are the active
forms of the vitamin

Folic acid 缺乏會有⼤球性貧⾎ • pregnancy

• malabsorption

＊不確定成因不要單獨給葉酸治療
fi
ff
fi
EPO缺乏 epoetin alfa ⽪下注射糾正慢性腎功能衰竭患者
epoetin beta 的貧⾎
還⽤於治療含鉑引起的貧⾎抗癌
藥。

Neutropenia Neutropenia caused by anticancer drugs can

be shortened in duration by treatment with
recombinant human granulocyte colony‐
stimulating factor (lenograstim）

Cancer drugs
1.MDR:transmembrane protein (P-glycoprotein for “permeability” glycoprotein

說明

Alkylating agents readily form covalent bonds

prevent cell division by cross‐linking the two strands of the double helix.
長期⽤會有⽣育問題
與非淋巴細胞⽩⾎病發⽣率增加有關

Cyclophosphamide haemorrhagic cystitis

Cytotoxic antibiotics

Doxorubicin inhibits DNA and RNA synthesis, High cumulative doses are
probably by an action on cardiotoxic
topoisomerase II.
 Vinca alkaloid 影響M phase
destroy spindle

Vincristine toxic e ects on peripheral and

autonomic nerves

Vinblastine 骨髓抑制強less neurotoxic

taxanes 影響M phase

stabilize spindle

Paclitaxel 卵巢癌常併⽤cisplatin or carboplatin會有腎功能障礙

Pretreatment with dexamethasone

and antihistamines is necessary to
prevent sensitivity reactions.

Antimetabolites 影響Ｓ phase

inhibit purine or pyrimidine
synthesis.

Folic acid antagonists Methotrexate

Antipyrimidines Fluorouracil inhibits thymidylate synthetase

Monoclonal antibodies react with antigen speci cally

expressed on cancer cells
皆IV

Trastuzumab human epidermal growth factor 適⽤early breast cancer and

receptor 2(HER2/neu) metastatic breast cancer

Rituximab lyses B‐cell lymphocytes by On IV 且毒性⾼

attaching to a surface
protein (CD20)

Bevacizumab inhibitor of vascular endothelial

growth factor VEGF

Hormones and
hormone antagonists

Glucocorticoids inhibit cell Removal of the gland producing

division by interfering with DNA the hormone
synthesis.

tamoxifen oestrogen antagonist treatment of postmenopausal

雌激素拮抗劑 metastatic breast cancer

anastrozole and Aromatase inhibitors 阻斷周圍組織中雄激素轉化雌激素，

letrozole 但不阻斷卵巢中的雄激素轉化。
停經前婦女不適⽤

Gonadorelin prostatic cancer

ff
fi
 Hormones and
hormone antagonists

utamide initial increase in LH may cause the tumour to grow.

Immunosuppressants and antirheumatoid drugs

Immunosuppressant
攻Th1 IL2 MAC Corticosteroids prednisolone inhibit cytokines IL

inhibiting transcription
factors e.g. NF‐κB and
AP‐1

Calcineurin inhibitors Ciclosporin⼝服 not cytotoxic

no myelotoxic e ects
預防和治療移植器官的排斥
Nephrotoxicity＆
hepatotoxicity

Tacrolimus 同上但更有效

Monoclonal AB Basiliximab Severe hypersensitivity

reactions

Cytokine modulators -mab Monoclonal AB

antiTNF agents
(bind TNF‐α ) Etanercept recombinant molecule
usually in combination
常⽤在治療RA病⼈且
with methotrexate.
已對DMARDS無效
副作⽤：肺結核復
發、hypersensitivity Anakinra anti‐IL‐1 antibody

攻Th2 IL4 B cell Antiproliferative methotrexate

immunosuppressants
azathioprine prevent tissue rejection
in transplant
surgery and in
autoimmune disease

main side‐e ect:bone

marrow suppression

Mycophenolate 預防急性排斥反應
mofetil
副作⽤包括胃腸道紊亂和骨
髓抑制
fl
ff
ff
 Immunosuppressant
DMARDS Methotrexate as early as possible
Rheumatoid arthritis rst‐line DMARD
(RA)：循環⾃⾝抗體
associated with bone
marrow
suppression,
hepatotoxicity and
pneumonitis

-salazine 細菌在結腸中分裂產⽣
sulfapyridine
adverse e ects:rash! GI不
適、⾎液異常

Gold as sodium IM
aurothiomalate rashes, blood disorders
多被methotrexate and proteinuria
取代

Penicillamine Adverse e ects：nausea,

vomiting, rashes,
proteinuria and blood
disorders

Hydroxychloroqui 作為其他 DMARD 的輔助

ne 藥物
可能發⽣視網膜⾊素變性⾊
素性視網膜炎

＊When at least two DMARDs have failed, anti‐TNF‐α agents are used.

蘇part
1.Neutrophilia中性球上升：bacterial infection, drugs, stress
2.淋巴球上升：⼩孩、viral infection
3.Infectious mononucleosis=lymphocyte上升
4.monocytosis:marrow recover,原蟲立克次體感染
5.嗜酸性球上升：過敏、parasite
6.⼩⼼：leukoerythroblastosis骨髓異常危急,hemolysis,
7.LAP score:算⽩⾎球顆粒，正常值
8.Neutropenia:WBC too low,
fi
ff
ff
9.COVID腳⾎栓、淋巴球⾎⼩板下降！嗜中性球上升！！肺栓塞、凝⾎時間增加、⾎栓多！可⽤
ddimer測（缺氧、細胞激素活化、內⽪細胞活化）重症可以預防性給抗凝⾎劑、spleen 出⾎

10.⾎液幹細胞HSC在骨髓內、周邊⾎液、臍帶⾎
骨髓幹細胞在腸股胸股
11.骨髓移植與⾎型無關需配對HLA
12.周邊幹細胞移植副作⽤：肌⾁痠痛、疲勞、發燒
13.
腸骨捐贈 周邊⾎捐贈

術後需補充⾎可⾃備 先施打G-CSF

補充鐵劑跟葉酸 解熱鎮痛劑

復原兩週 ⼀天復原

全⾝⿇醉 動脈抽取可局部⿇醉