抗凝和溶栓英文版

Defective in Common pathway
Intrinsic Pathway
Blood Vessel Injury XII XI IX X Factors affected By Heparin Prothrombin Fibrinogen XIII XIIa XIa IXa Xa
Extrinsic Pathway
Diagnosis of coagulation defects
Prolonged APTT No change in PT Defective Intrinsic Pathway
No change in APTT Prolonged PT
Defective Extrinsic Pathway
Prolonged APTT Prolonged PT
Anticoagulants and Thrombolytics
S. Ramakrishnan
Objectives
To learn how Blood Clots are formed. How the blood clots are broken down ? What drugs can be used to regulate clotting ? How to rectify clotting deficiencies
Platelets and Thromboemolism
Arteries : White Thrombus Platelets adhere Release ADP More adhesion/ aggregation Reduced blood flow (stasis) Fibrin clot Veins low pressure : Red thrombus is formed Especially in valve pockets Contains a long tail of fibrin Can detach and form emboli
Myocardial infarction (MI), stroke, heart valve replacement and shunts
Other antiplatelet drugs are - Dipyridamole, sulfinpyrazone and Ticlopidine
Mechanism of action
XIIa
Inactive XI
Active XIa
+
Thrombosis
Arterial Thrombosis :
Adherence of platelets to arterial walls - White in color - Often associated with MI, stroke and ischemia
Thromboembolism
Classes of Drugs
Prevent coagulation Dissolve clots Prevent bleeding and hemorrhage Hemostatic Overcome clotting deficiencies ( replacement therapies)
Heparin mechanism of action
Heparin Antithrombin III
Thrombin
Oral anticoagulants : warfarin, dicumarol
Coumarins - warfarin, dicumarol Isolated from clover leaves Structurally related to vitamin K Inhibits production of active clotting factors Absorption rapid - binds to albumin Clearance is slow - 36 hrs Delayed onset 8 - 12 hrs Overdose - reversed by vitamin K infusion Can cross placenta - do not use during late pregnancies
Activated partial thromboplastin time (APTT)
Blood sample + EDTA or Citrate No clot ( recalcification will result in clot in about 2 - 4 min) Add calcium Mix with negatively charged phospholipid Kaoline (aluminum silicate) Determine clotting time Generally clotting occurs in 26 to 33 seconds Used to detect defects in the intrinsic pathway
Blood Clotting
Vascular Phase Platelet Phase Coagulation Phase Fibrinolytic Phase
Vascular Phase
Vasoconstriction Exposure to tissues activate Tissue factor and initiate coagulation
Intrinsic Pathway All clotting factors are within the blood vessels Clotting slower Activated partial thromboplastin test (aPTT)
Extrinsic Pathway Initiating factor is outside the blood vessels - tissue factor Clotting - faster - in Seconds Prothrombin test (PT)
Anticoagulant Warfarin Decrease synthesis of Oral Clotting factors Antiplatelet drugs Thrombolytic Drugs Aspirin Decrease platelet aggregation
Streptokinase Fibinolysis
Anticoagulant drugs to treat thromboembolism
Drug Class Anticoagulant Parenteral Prototype Heparin Action Inactivation of clotting Factors Effect Prevent venous Thrombosis Prevent venous Thrombosis Prevent arterial Thrombosis Breakdown of thrombi
Tissue Factor
Platelet phase
Non-nucleated - arise from magakaryocytes blood vessel wall (endothelial cells) prevent platelet adhesion and aggregation platelets contain receptors for fibrinogen and von Willebrand factor after vessel injury Platelets adhere and aggregate. Release permeability increasing factors (e.g. vascular permeability factor, VPF) Loose their membrane and form a viscous plug
Blood clots - Thrombus Thrombus dislodge from arteries and veins and become an embolus. Venous emboli can block arterioles in the lung and pulmonary circulation
agulation Phase
Two major pathways
Intrinsic pathway Extrinsic pathway
Both converge at a common point 13 soluble factors are involved in clotting Biosynthesis of these factors are dependent on Vitamin K1 and K2 Most of these factors are proteases Normally inactive and sequentially activated Hereditary lack of clotting factors lead to hemophilia -A
Heparin
Sulphated carbohydrate Purified from bovine lungs Different size Active in vitro and in vivo Administration - parenteral- Do not inject IM only IV or deep s.c. Half-life 1 - 5 hrs - monitor aPTT Adverse effect - hemorrhage - antidote protamine sulphate
Tissue Injury Tissue Factor Thromboplastin
VIIa X Thrombin
VII
Fribrin monomer Fibrin polymer
Vit. K dependent Factors Affected by Oral Anticoagulants
Activation
Aspirin inhibits cyclooxygenase (COX) COX is a key enzyme involved in the synthesis of thromboxane 2 (prostaglandins) Inhibits platelet aggregation
Prophylactic use of Aspirin
Venous Thrombosis :
Develops in areas of stagnated blood flow (deep vein thrombosis), Red in color- Associated with Congestive Heart Failure, Cancer, Surgery.
Mechanism of action
Descarboxy Prothrombin Prothrombin
Reduced Vitamin K Oxidized Vitamin K
NAD NADH
Warfarin
Antiplatelet drugs
Aspirin Prevents platelet aggregation /adhesion Clinical use - prevents arterial thrombus
Prothrombin time (PT)
Tissue Thromboplastin factor III Mix with phospholipid extract Add calcium and blood sample Determine clotting time
Generally 12 - 14 seconds Used to detect defects in extrinsic pathway