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Q TRÌNH ÂÄNG MÁU L cå chãú bo vãû cuớa cồ thóứ, chọỳng laỷi tỗnh traỷng mỏỳt maùu täøn thỉång thnh mảch Nụt tiãøu cáưu nhanh chọng âỉåüc cng cäú båíi hãû thäúng såüi fibrin khäng tan Sỉû tảo thnh fibrin l kãút qu ca chùi phn æïng men liãn quan âãún caïc yãúu täú âäng maïu huút tỉång Nhỉỵng phn ỉïng ny xy trãn bãư màût tãú bo näüi mä, lm cho âäng mạu l hiãûn tỉåüng chè khu trụ åí vãút thỉång thnh mảch Ngoi ra, hiãn tỉåüng hoảt hoạ ngỉåüc tråí lải lm cho dng thạc phn ỉïng âäng mạu tỉû khúch âải v cå chãú bo vãû ca cå thãø phaùt huy hóỳt khaớ nng Quaù trỗnh õọng maùu âỉåüc âiãưu ho tảo trảng thại thàng bàịng Nãúu sỉû thàng bàịng ny bë phạ våỵ, s cọ nguy cå chy mạu hay huút khäúi CẠC ÚU TÄÚ THAM GIA Yãúu täú âäng maïu - Caïc yãúu täú hoảt hoạ tiãúp xục: úu täú XII, XI, HMWK v prekallikrein - Cạc úu täú phủ thüc vitamin K: úu täú II, VII, IX, X (nhọm PPSB) v hai cháút ỉïc chãú sinh l (protein C v protein S) - Cạc úu täú dãù bë hu úu täú V v VIII dãù bë hu nháút Hm lỉåüng (mg/dl) Chỉïc nàng Nỉía âåìi säúng Phủ thüc vitamin K Cọ huyãút 150-400 Cå cháút ÂM 90 giåì Khäng Khäng II (prothrombin) 10-15 Zymoge n 60 giåì Cọ Khäng V (proaccelerin) 0.5-1 Âäưng úu täú 12- 36 giåì Khäng Khäng 0,1 Zymoge n 4- giåì Cọ Cọ VIII (chäúng hemophilia A) < 0.01 Âäưng úu täú 12 giåì Khäng Khäng IX (chäúng hemophilia B) 3,5 Zymoge n 24 giåì Cọ Cọ 0.75 Zymoge n 24 giåì Cọ Cọ XI 1,2 Zymoge n 40 giåì Khäng Cọ XII (Hageman) 0.4 Zymoge n 48- 52 giåì Khäng Cọ XIII (äøn fibrin) 2.5 Chuyãøn amidase 3- ngaìy Khäng Khäng 0.3 Zymoge 48- 52 Khäng Coï Yãúu täú I (fibrinogen) VII (proconvertin) X (Stuart) Prekallikrein âënh BLOOD PRO-CLOTTING FACTORS: synthesized in liver* Factor I Fibrinogen Factor II Factor III Prothrombin Tissue Factor Factor V Factor VII Factor VIII Factor IX Cofactor With TF Activate X & IX Cofactor Christmas - Activates X Factor X Stuart-Prower - Converts prothrombin Factor XI Activates IX Factor XII Prekallikrein Hageman - Activates XI Fletcher - Activates XII HMWKininogen Cofactor *vWF is an exception Cháút æïc chãú âäng maïu sinh lyï Cháút æïc chãú Nåi täøng håüp Näưng âäü huút tỉång (mg/dl) Chỉïc nàng Nhọm 1: cạc cháút ỉïc chãú ca serin protease hay serpin -Antithrombin -2Macroglobulin -1anti trypsin -Cháút ỉïc chãú C1 -Âäưng yãúu täú heparin Tãú Tãú Tãú Tãú Tãú baìo baìo baìo baìo baìo gan gan gan gan gan 24  215  290  4.5 24   2.6 ỈÏïc chãú thrombin, XIIa, kallikrein ỈÏïc chãú thrombin, ỈÏïc chãú thrombin, ỈÏïc chãú kallikrein, ỈÏïc chãú thrombin Xa, IXa, XIa, kallikrein kallikrein, XIa XIa, XIII Nhoïm 2: hãû thäúng protein C - Protein C -Thrombomodulin -Protein S Tãú bo gan våïi sỉû cọ màût ca vit K Tãú bo näüi mảc Tãú bo gan våïi sỉû cọ màût ca vit K 5.0 25 Lm thoại hoạ Va v VIII:Ca Cng våïi thrombin âãø hoảt hoạ protein C L âäưng úu täú ca protein C, thục âáøy sỉû thoại hoạ Va v VIII:Ca úu täú täø chỉïc L mäüt glycoprotein cọ háưu hãút cạc täø chỉïc, âàûc biãût no v phäøi.Liãn kãút chàût ch våïi phospholipit mng Phỉïc håüp úu täú täø chỉïc phospholipit tråí thnh mäüt âäưng úu täú, hoảt hoạ úu täú VII Tiãøu cáưu Khi bë hoảt hoạ, TC l bãư màût tiãúp xục, âãø cạc úu täú âäng mạu gàõn vo Cung cáúp bãư màût âiãûn têch ám âãø hoảt hoạ cạc úu täú tiãúp xục Näüi mảc maỷch maùu - traỷng thaùi bỗnh thổồỡng, nọỹi maỷc mảch mạu khäng thãø tảo huút khäúi - Näüi mảc tham gia âiãưu ho âäng mạu CÅ CHÃÚ ÂÄNG MẠU Âỉåìng âäng mạu näüi sinh - Giai âoản tiãúp xục Cạc úu täú XII, XI, kallikrein, HMWK cäú âënh vo mäüt bãư màût âiãûn têch ám + úu täú XII thnh XIIa (hoảt hoạ) + XIIa xục tạc chuøn prekallikrein thnh kallikrein qua trung gian ca HMWK Kallikrein quay lải xục tạc chuøn úu täú XII thnh XIIa nhiãưu hån + XIIa xục tạc chuøn XI thnh XIa XIa vaì Ca++ chuyãøn yãúu täú IX thaình IXa + IXa + VIIIa + Ca++ v phospholipid xục tạc chuøn yãúu täú X thaình Xa Intrinsic Pathway Contact (Eg: with glass) XII XIIa XIa XI IXa IX VIIIa PL Ca++ X Xa Clotting factors: the Phospholipid-Calcium dimension Several clotting factors are bound, with the aid of calcium ions, to phospholipids of the membranes of endothelial cells or platelets For example: VIIa TF X VIIa-TF Phospholipid Xa Ca 2+ VIIa TF VIIa Ca 2+ The membrane tethering localises activities to where they are needed, brings components together, structures catalytic activation, and keeps events under some cellular control Clotting factors: Cofactors to augment action I The incorporation of activated cofactors into some of the complexes greatly increases the action of the primary enzyme, e.g., Factor V in prothrombinase complex Prothrombin/ Factor II X VIIa-TF Xa Va Factor V Thrombin Fibrinogen/ Factor I Fibrin monomer Prothrombinase complex Factor V in the prothrombinase complex acts, along with phospholipid tethers and Cacium ion, greatly to accelerate Factor Xa’s cleavage of prothrombin Prothrombin/ Factor II X VIIa-TF Xa Va Thrombin Prothrombinase complex Xa Prothrombin Phospholipid Va Ca 2+ Factor V Thrombin activation: Intrinsic The initiating process is more complicated, involving: Prekallikrein/PK Kininogen XII Pre-kallikrein Kininogen XI Intrinsic Pathway & Factor XII/ Hageman factor XIIa and then proceeds on the surface of platelets, with the assistance of Calcium ions IX XIa Prothrombin/ Factor II X IXa Xa Thrombin Fibrinogen/ Factor I Factor XIII Fibrin monomer Thrombin Factor XIII activated Clotting factors: Cofactors to augment action II The incorporation of activated cofactors into some of the complexes greatly increases the action of the primary enzyme, e.g., Factor VIII in intrinsic X-ase complex XII Pre-kallikrein Kininogen XI Intrinsic Pathway XIIa IX XIa Factor VIII VIIIa Prothrombin X IXa Thrombin X-ase complex IXa X Phospholipid VIIIa Ca 2+ Xa Fibrinogen/ Factor I Fibrin monomer Clinical Manifestations of DIC Microscopic findings in DIC    Fragments Schistocytes Paucity of platelets Hemostasis: Coagulation & Clot Stabilization      Prothrombin Ca++ Fibrinogen Fibrin Polymerization Figure 16-13: The coagulation cascade Stable adhesion Rolling activation/aggregation GpIb/VWF GpIIb/IIIa + GpVI/Collagen Initial adhesion Shear Flow GpIb/VWF VWF VWF VWF collagen collagen VWF VWF collagen VWF collagen VWF VWF VWF VWF collagen collagen VWF collagen VWF collagen Blood Flow VWF VWF VWF VWF collagen collagen VWF collagen VWF collagen XII XIIa XI + XIa IX IXa VIIIa +PL +Ca X Xa Va +PL +Ca Prothrombin Tissue Factor/VIIa Fibrinogen Thrombin Fibrin VWF VWF VWF VWF collagen collagen VWF collagen VWF collagen Blood Flow VWF VWF VWF VWF collagen collagen VWF collagen VWF collagen VWF VWF VWF VWF collagen collagen VWF collagen VWF collagen Blood Flow VWF VWF VWF VWF collagen collagen VWF collagen VWF collagen XII XIIa XI Protein S XIa IX IXa Protein C Protein S VIIIa+Ca+Pl X Xa Va+Ca+Pl TF / VIIa TFPI II Fibrinogen IIa/Thrombomodulin interaction IIa Fibrin Fibrinolysis VIIIa Protein S APC Anticoagulant Protein C Protein S Va IIa Thrombin IIa + Thrombomodulin