Hematology 6 Blood Coagulation Tests Lee Woo In
Hematology 6 Blood Coagulation Tests Lee Woo In, MD, Ph. D Department of Laboratory Medicine
Homeostasis (항상성) Procoagulant Regulatory Coagulation proteins Endothelium Platelets
NL Endothelial Cell : Damaged Vessel : Anti-thrombotic state -항혈소판, -항응고, -섬유소용해 Thrombotic state -Platelet activation -Adhesion -Prothrombotic
Primary Hemostasis • Platelet plug : key : –혈관수축 –혈소판 adhesion, aggregation –작은 혈관손상의 지혈 • Function of platelet – Adhesion – Release – Aggregation – Coagulant activity
Secondary Hemostasis • Fibrin clot : key –응고인자 활성화 –큰 혈관손상 –견고한 haemostatic plug
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) • Plasma factors
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 • Factor XIII: fibrin-stabilizing factor
Coagulation Cascade Extrinsic pathway Intrinsic pathway
Regulatory mechanisms • Normally prevent activated coagulation reactions – local thrombosis or DIC • Antithrombin III, protein C, protein S, etc • Fibrinolytic system • Plasmin-plasminogen system • etc
Coagulation Tests for Hemostatic plug(Primary hemostasis) 1. Bleeding time Vessel contraction & primary hemostasis 혈소판질환, 폰빌레브란트 병 2. Platelet count 3. Platelet function test 1) Adhesion test … v. WD, Bernard Soulier, uremia
2) Aggregation test ; ADP, collagen, thrombin, epinephrine, ristocetin 응집률, 속도 3) 혈소판 기능과 아스피린 저항성 검사
Tests for fibrin plug (2 ndary 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) 길항제 인 coumarin(warfarin) 복용 환자의 치료 농도 monitoring에 이용 • INR(international normalized ratio)= (환자의 PT/ 참고치 PT)ISI (internaltional sensitivity index) • Therapeutic range 2 ~ 3
4. Activated clotting time(ACT) – a. PTT와 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, megakaryocyte에서 생성되어 platelet adhesion - factor VIII 과 복합체를 이루며 순환 - Ristocetin cofactor assay … v. WF의 기능 검사 - Ristocetin에 의한 혈소판응집정도 혈장의 v. WF의 활성도와 비례
Laboratory markers of Fibrinolysis • Fibrinolysis – Fibrin clot이 다시 용해되는 과정 – Key : plasmin
FDP test ( fibrinogen/fibrin degradation product) ; 섬유소용해 선별검사 DIC screening, hyperfibrinolysis, thromboembolic disease 증가 D-dimer fibrin clot이 있었음을 의미 섬유소용해 확진 검사 (-): thrombosis 진단을 배제 Plasminogen Alpha-2 antiplasmin
Acquired inhibitor • VIII 응고인자 항체 • VIII 응고인자 일정량을 불활성화 시키는 inhibitor activity • Pt plasma + Normal plasma residual activity of factor VIII 측정 • 1 Bethesda unit: 1 m. L내의 응고억제인자가 응고인자 VIII 활성도를 50% 로 감소시키는 양 • Lupus anticoagulant – 항인지질 항체(antiphospholipid antibody, APA)의 일종 – 자가면역성, 동종면역성 면역글로블린 • Antiphospholipid Antibody – SLE, autoimmune disease, lymphoprolierative disease – Anticardiolipin antibody
Natural Anticoagulants • Anti-thrombin – Factor Xa, thrombin 억제 – Heparin에 의해 활성도 증가 – 유전, 간질환, DIC, oral contraceptive, preeclampsia • Protein C – Thrombin에 의해 활성화, factor Va, VIIIa을 억제 • Protein S – Protein C의 coenzyme • -2 macroglobulin, heparin cofactor II – Thrombin 억제
Tests for Hypercoagulation states 1. 유전성 혈전성향의 원인 Natural anticoagulant 기능소실 응고인자의 기능항진 2. 복합적 요인에 의한 과응고 상태 3. 후천적 과응고 상태 Tests Primary antithrombin activity C protein activity S protein antigen activated protein C resistance Lupus anticoagulant Anticardiolipin Ab Secondary Leiden V 인자 prothrombin G 20210 A fibrinogen, homocysteine, factor VIII
- Slides: 21