경희대학교 의과대학·의학전문대학원

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Blood Coagulation Tests

Lee Woo In, MD, PhD

Department of Laboratory Medicine

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Homeostasis ( 항상성 )

Procoagulant

Regulatory

Endothelium

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NL Endothelial Cell

NL Endothelial Cell :

Anti-thrombotic state

- 항혈소판

,

- 항응고

,

- 섬유소용해

Damaged Vessel :

Thrombotic state

-Platelet activation

-Adhesion

-Prothrombotic

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Primary Hemostasis

• Platelet plug :key

Platelet plug :

–

혈관수축

–

혈소판

adhesion,

aggregation

–

작은 혈관손상의 지혈

• Function of platelet

– Adhesion

– Release

– Aggregation

– Coagulant activity

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Secondary Hemostasis

• Fibrin clot :key

–

응고인자 활성화

–

큰 혈관손상

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Three factors for Hemostasis

• Vascular factors

– local vasoconstriction (immediate reaction)

– compression of injured vessels by blood

extravasated into surrounding tissues

• Platelet factors

– adhere to the site & form aggregates

(

hemostatic plugs

)

– release factors to augment vasoconstriction

– vessel wall repair (platelet-derived growth

factor)

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Plasma Coagulation factors

• Factor I: fibrinogen

• Factor II: prothrombin

• Factor III: tissue thromboplastin (tissue factor & phospholipid) • Factor IV: ionized calcium

• Factor V: occasionally called labile factor or proaccelerin • Factor VI: unassigned

• Factor VII: occasionally called stable factor or proconvertin • Factor VIII: anti-hemophilic factor

• Factor IX: plasma thromboplastin component, Christmas factor • Factor X: occasionally called Stuart-Prower factor

• Factor XI: occasionally called plasma thromboplastin antecedent

• Factor XII: Hageman factor

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Coagulation Cascade

E x tr in s ic p a th w a y In tr in s ic p a th w a y

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Regulatory mechanisms

• Normally prevent activated

coagulation reactions

– local thrombosis or DIC

• Antithrombin III, protein C, protein S,

etc

• Fibrinolytic system

• Plasmin-plasminogen system

• etc

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Coagulation Tests

Tests for Hemostatic plug(Primary hemostasis)

1. Bleeding time

Vessel contraction & primary hemostasis 혈소판질환, 폰빌레브란트 병

2. Platelet count

3. Platelet function test

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2) Aggregation test

; ADP, collagen,

thrombin, epinephrine,

ristocetin

 응집률 , 속도

3) 혈소판 기능과

아스피린 저항성 검사

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Tests for fibrin plug (2ndary hemostasis)

1. Prothrombin time(PT)

–

환자혈장

+ tissue thromboplastin + 칼슘

Factor VII activation Fibrin clot 시간 측정

–

I, II, V, VII, X 인자 (NL 30% 이어도 PT 정상 )

–

Report 단위 : sec, %, INR

• INR : Vit K dependent factor(II, VII, IX, X) 길항제인 coumarin(warfarin) 복용 환자의 치료 농도

monitoring 에 이용

• INR(international normalized ratio)= ( 환자의 PT/ 참고치 PT)ISI (internaltional sensitivity index)

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2. aPTT

– Factor XII, XI 응고인자에 대한 활성제 (kaolin,

ellagic acid, celite), 혈소판 대용 물질인 인지질 첨가

– VIII, IX, X,

XII, prekallikrein, HMWK

• I, II, V, X 은 공통 이나 문제 발생하면 PT 가 연장

– 헤파린

• 오염 • 헤파린 치료 ( 정상 aPTT 의 1.5 ~ 2.5 배 ) – LMWH, 헤파린유사 항응고제 등은 anti-Xa 법으로 검사

– lupus anticoagulant

3. Mixing test( 혈장혼합검사 )

– 감별 : 응고인자 결핍 vs. 응고억제인자

– 정상범위로 교정되면

• 응고인자 억제인자 , anti-phospholipid ab.,anti-prothrombin

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4. Activated clotting time(ACT)

– aPTT 와 유사 , , 헤파린 치료 모니터링

5. Thrombin time

– Hypofibrinogenemia, 섬유소기능이상 , 과섬유소원증 , 섬유소 로 전환되는 것을 억제하는 인자 여부 ( 헤파린 , FDP)

6. Fibrinogen

– Acute phase reactant

– DIC, 간질환 , 혈전용해치료 등에서 증가

7. Coagulation factor assay

8. von Willebrand factor

subendothelial cell, megakaryocyte 에서 생성되어 platelet adhesion

- factor VIII 과 복합체를 이루며 순환

- Ristocetin cofactor assay … vWF 의 기능 검사 - Ristocetin 에 의한 혈소판응집정도

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Laboratory markers of Fibrinolysis

• Fibrinolysis

– Fibrin clot 이 다시 용해되는 과정

– Key : plasmin

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FDP test ( fibrinogen/fibrin degradation product) ; 섬유소용해 선별검사 DIC screening, hyperfibrinolysis, thromboembolic disease 증가 D-dimer fibrin clot 이 있었음을 의미 섬유소용해 확진 검사 (-): thrombosis 진단을 배제 Plasminogen Alpha-2 antiplasmin

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