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Overview of primary hemostasis. 진단검사의학과 안정열. I. The mechanism of blood coagulation : 혈관벽 손상시 vascular system 내에 blood 가 fluid state 로 잘 유지되도록 하는 과정 * Vasoconstriction -> PLT aggregation -> coagulation * Effectiveness of hemostatic mechanism
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Overview of primary hemostasis 진단검사의학과 안정열
I. The mechanismof blood coagulation :혈관벽 손상시 vascular system내에 blood가 fluid state로 잘 유지되도록 하는 과정 * Vasoconstriction -> PLT aggregation -> coagulation * Effectiveness of hemostatic mechanism - type and degree of injury - ability of vasoconstriction - PLT availability & activity - blood factor & relation to function - absence of inhibitors, circulating anticoagulants and antagonists * Fibrinolysis : the process of dissolution of the clot * Homorrhage or thrombosis
II Primary hemostasis : The vascular system The platelets 1. Vascular system * a thin layer of endothelial cells : thromboresistant surface * vascular damage -> vasoconstriction -> immediate reduced blood flow * vasoactive substance (serotonin, thromboxane A2 , endothelin) 2. Platelets * 2-4um in diameter, * are produced in BM from a megakaryocyte, which produces about 2000 PLT * 70-80% circulate in blood, 20-30% pool in the spleen * life span is 7 to 10 days
1) PLT number Vs function* PLT function is more relevant than PLT numbers* ex) > 150만 : bleeding can be caused by dysfunctional PLT < 5만 : often not bleed < 1만 : spontaneous bleeding may occurs but young PLT will correct for the defects2) PLT kinetics* Adhesion : - adhere to collagen -> undergo a shape change from discs to spheres - primary aggregation and is reversible
* Release : - dense granules ( ADP, ATP, ionized calcium, magnesium, epinephrin, phosphate, and serotonin) - alpha granules ( fibrin, PDGF, PAI, fibronectin, albumin, PF3, PF4, vWF, fibrinogen, ßthromboglobulin, and factor V)- secondary aggregation , is irreversible * Aggregation : PLTs cohere to other PLTs * Stabilization of the clot : - thrombus formation- release factor V and expose PF 3 to accelerate the coagulation cascade and promote activation of cloting factors -> stabilze the PLT plug with a fibrin clot
III. Evaluation of bleeding in primary hemostasis1. Abnormalities of the vascular endothelium : Hereditary or Acquired vascular disorders* Ehlers-Danlos, Homocystinuria* Allergic purpura, Henoch-Schölein purpura ** Normal vessel walls provide - a surface resistant to the formation of thrombi - if disrupted, provide the initial stimuli for thrombus formation - inhibitors for PLT activity, activators for clearance of thrombus
2. Evaluation of PLT abnormalities1) Thrombocytopenia - PLTs are low in number but normal in function - immunologic, ITP - infection, viral ect - drugs (aspirin)2) Thrombocytopathia - poor PF3 activity : PLT count normal, poor in function - too little PF3, due to systemic disease (uremia, scurvy, hepatic dz) - failure or release PF3 - deficiency of plasma factor- vWF
3) Thrombocytosis - PLTs are increased in number, normal in function- acute hemorrhage, hemolysis, postsplenectomy • 4) Thrombocythemia • - PLTs increased in number, large, and bizarre forms, • bleeding time prolonged, poor clot retraction • - myeloproliferative disorders
VI. Teststo evaluate a bleeding disorder of primary hemostasis (1) 출혈 시간 (Bleeding time) * 피하 혈관에 작은 절개 후 출혈이 멈출때 까지의 시간을 측정 *혈관의 수축 및 혈소판의 부착과 응집에 의한 일차성 지혈 기능 반영 *Duke법: puncture in the ear lobe 절개부위의 크기와 깊이를 일정, 정상인의 경우 1~4분7일 이내 aspirin 복용 history 없어야 *혈소판 감소증, 기능이상, vWD 및 혈관장애시 연장 *혈소판 수가 정상, 출혈시간 연장 : 혈소판 기능 장애, vWD 의심 afibrinogenemia, severe hypofibrinogenemia
(2) PLT aggregation test* PLT rich plasma 에 aggregating agents를 넣으면 PLT 모양의 변화 와 aggregation 유발 => aggregometer로 percent transmittance를 측정 * Aggregation agents : ADP, EPI, Collagen, Ristocetin, Arachidonic acid * 7일 이내 aspirin 복용 history 없어야 * Interpretation : - primary curve ; aggregating agent와 PLT의 직접반응으로 PLT shape and small aggregates 생성- secondary wave; complete aggregation
* ADP : Glanzmann’s thrombasthenia * Collagen : Glanzmann’s thrombasthenia, aspirin-like release disorder, storage pool disorder, uremia * Ristocetin : vWD, Bernard-Soulier syndrome
(3) Capillary fragility test( = tourniquet test , vascular disorder) * Tourniquet test ; upper arm에 cuff를 놓고 diastolic 과 systolic pressure의 중간압으로 5분간 압력을 주고 풀어준 후 수 분 안에 petechiae 발생 여부를 확인 * 5개 이상, 3cm이상일 때 양성으로 판독(4) Clot retraction time* fibrin formation, from the inspection of the clot * clot retraction occurs by the interaction between PLT psuedopods and fibrin strands. * occurs within 60 minutes, and the colt occupies 50% of total volume of blood.