Comprehensive Overview of Coagulants and Anticoagulants in Blood Clotting

Comprehensive Overview of Coagulants and Anticoagulants in Blood Clotting

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  COAGULANTS AND ANTICOAGULANTS COAGULANTS •Coagulantsare drugs or substances that promote blood clotting. •They are also called: Haemostatics ANTICOAGULANTS •Anticoagulants are substances or drugs that prevent blood clotting. •They decrease the ability of blood to clot and are commonly referred to as: Blood Thinners HAEMOSTASIS •Haemostasis is a sequence of responses that: Stops Bleeding and Prevents Further Blood Loss •It occurs when a blood vessel is damaged or ruptured.
• 3.
  MECHANISM OF BLOODCOAGULATION •Haemostasis involves three main steps. I. Vascular Spasm •The smooth muscles of the blood vessels contract. •This reduces blood loss due to the release of substances from activated platelets. II. Platelet Plug Formation •A thin platelet plug is formed at the site of the damaged blood vessel. •This temporarily seals the damaged blood vessel. III. Blood Coagulation / Clotting •During coagulation: Fibrin is formed •Fibrin forms a network or mesh. •The fibrin clot traps: RBCs & Other blood components and seals the damaged blood vessel. •Fibrin is an insoluble protein. •The coagulation process involves approximately thirteen clotting factors.
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  COAGULATION PATHWAYS Blood coagulationinvolves: •Intrinsic pathway •Extrinsic pathway •Common pathway Both intrinsic and extrinsic pathways lead to the activation of: Factor X → Activated Factor Xa COMMON PATHWAY Activated Factor X (Xa) ↓ Conversion of Prothrombin to Thrombin ↓ Conversion of Fibrinogen to Fibrin ↓ Fibrin Clot Formation ↓ Traps RBCs and Seals the Damaged Blood Vessel
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  INTRINSIC PATHWAY The intrinsicpathway involves factors and components such as: •Prekallikrein •High molecular weight kininogen (HMWK) •Factor XII •Factor XI •Factor IX •Factor VIII These ultimately participate in activation of: Factor X EXTRINSIC PATHWAY •The extrinsic pathway is initiated by: Tissue Factor / Thromboplastin •It ultimately leads to activation of: Factor X
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  Factor Name /Source / Pathway I Fibrinogen – Liver – Common pathway II Prothrombin – Liver – Common pathway III Tissue factor / Thromboplastin – Damaged tissues and platelets – Extrinsic IV Calcium ion (Ca² ) – Diet, bones and plasma – All ⁺ V Proaccelerin – Liver and platelets VII Proconvertin – Liver – Extrinsic VIII Antihaemophilic factor – Liver – Intrinsic IX Christmas factor / Plasma thromboplastin component – Liver – Intrinsic X Stuart-Prower factor – Liver – Intrinsic and extrinsic XI Plasma thromboplastin antecedent (PTA) BLOOD COAGULATION FACTORS
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  LOCAL COAGULANTS /STYPTICS Local coagulants or styptics are used to control bleeding from a local and approachable site. Examples include: Tooth extraction , Nasal bleeding Drugs include: •Thrombin powder obtained from bovine plasma •Fibrin sheet obtained from human plasma •Thromboplastin powder •Astringents, etc. VITAMIN K Vitamin K is a natural coagulant. Available in various forms •Vitamin K₁ •Phytonadione •Vitamin K₂ •Menaquinone •Vitamin K₃ •Menadione – Synthetic Vitamin K is fat-soluble. It is required for the synthesis of clotting factors: Prothrombin , Factor VII , Factor IX, Factor X
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  DAILY REQUIREMENT OFVITAMIN K •The notes mention approximately: 3–10 µg/day CAUSES OF VITAMIN K DEFICIENCY •Liver disease •Malabsorption •Dietary deficiency •Prolonged antimicrobial therapy •Overdose of oral anticoagulants MECHANISM OF ACTION OF VITAMIN K Vitamin K stimulates the liver for the synthesis of clotting factors such as: •Prothrombin •Factor VII •Factor IX •Factor X Vitamin K ↓ Increased Synthesis of Clotting Factors ↓ Increased Blood Clotting
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  USES OF VITAMINK Prophylaxis and prevention of bleeding To increase blood clotting Dose:- Approximately: 5–10 mg/day ANTICOAGULANTS Anticoagulants are drugs that: •Prevent blood coagulation •Decrease the ability of blood to clot •Are also called blood thinners Unwanted blood clotting may be harmful and can result in: •Blockage of blood vessels •Reduced blood supply Anticoagulants are therefore used in conditions involving abnormal or excessive clot formation
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  CLASSIFICATION OF ANTICOAGULANTS A.PARENTERALANTICOAGULANTS 1. Indirect Thrombin Inhibitors •Heparin •Danaparoid •Fondaparinux B. ORALANTICOAGULANTS 1. Vitamin K Antagonist •Warfarin 2. Direct Thrombin Inhibitors •Lepirudin •Argatroban •Dabigatran etexilate 3. Direct Inhibitor of Activated Factor X •Rivaroxaban
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  HEPARIN Heparin is obtainedmainly from animal tissues. It is a mixture of: Mucopolysaccharides Its molecular weight is approximately: 10,000–20,000 Heparin is found in the mast cells of: Lungs, Liver, Intestinal mucosa Commercial heparin is commonly obtained from: Ox lungs, Pig intestinal mucosa MECHANISM OF ACTION OF HEPARIN Heparin ↓ Plasma Antithrombin III ↓ Heparin–Antithrombin Complex ↓ Binding and Inactivation of Clotting Factors The complex inhibits clotting factors such as: Thrombin (IIa), Xa, Ixa, Xia, XIIa This results in: Reduced Blood Clotting
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   PHARMACOKINETICS OFHEPARIN •Heparin is not absorbed orally •It is administered intravenously •It does not cross the placenta •Metabolism occurs mainly in the liver by heparinase •Excretion occurs through urine ADVERSE EFFECTS OF HEPARIN •Bleeding •Osteoporosis during long-term use •Hypersensitivity reactions •Thrombocytopenia ANTAGONIST OF HEPARIN:- Protamine Sulphate DIRECT THROMBIN INHIBITORS These drugs bind directly to thrombin and inactivate it. This inhibits: Formation of Fibrin and reduces clotting. Prothrombin ↓ Thrombin ↓ Fibrinogen → Fibrin  Direct thrombin inhibitors block thrombin and therefore reduce fibrin formation.  Examples: Lepirudin , Argatroban
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  ORALANTICOAGULANTS – WARFARIN Warfarinis a synthetic derivative of: Coumarin It acts only in vivo. MECHANISM OF ACTION OF WARFARIN Warfarin interferes with vitamin K-dependent synthesis of clotting factors in the liver. It acts by blocking: Vitamin K Reductase This reduces the synthesis of vitamin K-dependent clotting factors. The affected factors include: Factor II (Prothrombin) Factor VII Factor IX Factor X
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  VITAMIN K CYCLEAND WARFARIN The notes indicate that warfarin blocks the recycling of vitamin K through inhibition of the vitamin K reductase system. Vitamin K ↓ Vitamin K-dependent Clotting Factor Synthesis Warfarin: Blocks Vitamin K Reductase ↓ Reduced Active Vitamin K ↓ Reduced Synthesis of Clotting Factors ↓ Anticoagulant Effect PHARMACOKINETICS OF WARFARIN Completely absorbed orally Slow onset of action Onset may take approximately 1–3 days Metabolized by glucuronide conjugation, as noted in the source
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  ADVERSE EFFECTS OFWARFARIN •Bleeding •Warfarin poisoning •Can cross the placenta during pregnancy DIRECT INHIBITOR OF ACTIVATED FACTOR X •Rivaroxaban: It is used in deep vein thrombosis ORAL DIRECT THROMBIN INHIBITOR •Dabigatran Etexilate It acts as a direct thrombin inhibitor. USES OF ANTICOAGULANTS Anticoagulants are used to: Prevent the Extension of Thrombus •Deep vein thrombosis •Myocardial infarction •Unstable angina •Rheumatic heart disease General Treatment Concept Heparin → Rapid effect / initial treatment Warfarin → Slow onset / maintenance treatment