Haemostatic agents
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This document provides an overview of haemostatic agents for medical students. It defines key terms related to haemostasis and classifies haemostatic agents into categories including coagulants, local haemostatics, and antifibrinolytics. Vitamin K and its role in coagulation factor synthesis is described in detail. Specific agents are explained within each category, along with their mechanisms of action, indications for use, and important adverse effects.
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Haemostatic agents
- 1. Haemostatic Agents Dr. Pravin Prasad M.B.B.S., MD Clinical Pharmacology Lecturer, Lumbini Medical College June 6, 2018 (Jestha 23, 2075), Wednesday
- 2. By the end of the class, MBBS Semester II students will be able to: Classify drugs used as haemostatic agents Describe the pharmacology of Vitamin K List the agents used for local haemostasis Describe the pharmacology of antifibrinolytic drugs
- 3. Lets Brain storm! Define: Haemostasis Haemophilia How is haemostasis achieved?
- 5. Classification Coagulants Fresh whole blood/ plasma Vitamin K: K1 , K3 Miscellaneous: Fibrinogen, Antihaemophilic factor Local Haemostatics Styptics: fibrin, thrombin, vasoconstrictors, astringents Sclerosing agents Anti-fibrinolytics Epsilon amino-caproic acid (EACA), Tranexamic acid
- 6. Contains all the factors necessary for coagulation Acts immediately Indications: Reversal of warfarin effect Factor deficiency states Must be ABO compatible Stored at -18OC Thawed before administration Fresh Whole Blood/Plasma
- 7. Vitamin K K1: Phytonadione, Phylloquinone Plant source, Fat soluble K3: Synthetic Fat soluble: Menadione, acetomenaphthone Water soluble: Menadione sod. bisulphite, menadione sod. diphosphate
- 8. Vitamin K Co-factor for synthesis of coagulation proteins by liver Coagulation protein precursors (factor II, VII, IX, X) Coagulation protein (factor II, VII, IX, X) γ glutamyl carboxylase Vitamin K Can bind to Ca2+ and phospholipid surface
- 9. Vitamin K Absorption Fat soluble: lymphatics of intestine, bile salts required Water soluble: portal blood Distribution: Temporarily stored in liver Metabolism: Liver (side chain cleavage and glucuronidation) Excretion: bile and urine
- 10. Vitamin K: Uses Newborn baby Prevent/treat haemorrhagic disease of the newborn Overdose of oral anticoagulants Phytonandione Prolonged high dose salicylate therapy
- 11. Vitamin K: Uses Dietary deficiency Prolonged antimicrobial therapy Obstructive jaundice Malabsorption syndromes Sprue, Regional ileitis, Steatorrhoea Liver disease
- 12. Vitamin K: Adverse effects Oral, intra-muscular injection: Safe Intra-venous injection: severe anaphylactoid reaction by emulsified preparation Menadione, Water soluble K3: Haemolysis in dose-dependent manner Kernicterus in newborn
- 13. Miscellaneous Fibrinogen: Fraction of human plasma Indications: Haemophilia Anti-haemophilic globulin (AHG) deficiency Acute afibrinogenemic states Intra-venous infusion, 0.5 gm
- 14. Miscellaneous Anti-haemophilic factor(AHG): Concentrated human AHG Short lasting action Indications: (along with human fibrinogen) Haemophilia AHG deficiency Intra-venous infusion, 5-10U/kg, every 6-12 hrs
- 15. Miscellaneous Desmopressin: Acts on V2 receptors (vascular endothelium) Releases factor VIII and von Willebrand’s factor from vascular endothelium Also induces platelet aggregation Indications: Haemophilia von Willebrand’s disease
- 16. Miscellaneous Ethamsylate: Exerts anti-hyaluronidase action, corrects abnormalities of platelet adhesion Controls capillary bleeding with adequate platelets Indications: capillary bleeding states Side effects: nausea, rash, headache, fall in BP (on i.v. injection)
- 17. Miscellaneous Uncertain efficacy Adrenochrome monosemicarbazone: Probably acts by reducing capillary fragility Control oozing from raw surface, prevent micro-vessel bleeding Rutin: Plant glycoside Reduces capillary bleeding
- 18. Local Haemostatics (Styptics) To control bleeding from approachable sites Non-pharmacological treatment Fibrin (sheet or foam) Prepared from human plasma Gelatin foam, oxidised cellulose Thrombin powder Bovine source
- 19. Local Haemostatics (Styptics) Oxidised Cellulose sheet
- 20. Local Haemostatics (Styptics) Fibrin (sheet or foam), Gelatin foam, oxidised cellulose, Thrombin powder Acts by: Providing meshwork activates clotting mechanism Gets absorbed in 1-4 weeks Indication: To stop oozing of blood: tooth socket, abrasions, etc
- 21. Local Haemostatics (Styptics) Astringents Tannic acid, metallic salts (Alum) Precipitates proteins toughens the surface Bleeding gums, bleeding piles Vasoconstrictors Adrenaline 0.1%
- 22. Local Hemostatics (Styptics) Sclerosing agents Sodium tetradecyl sulfate, Polidocanol Irritants Inflammation coagulation fibrosis Injected locally Haemorrhoids (piles), varicose vein mass
- 23. Antifibrinolytic Drugs Epsilon amino-capric acid (EACA), Tranexamic acid Binds to lysine binding site of plasminogen and plasmin Plasminogen Plasmin Fibrin (insoluble) Fibrin (soluble) EACA, Tranexamic acid (-)
- 24. Antifibrinolytic drugs EACA-Indications: Counteract the overt action of fibrinolytic drugs Specific antidote for fibrinolytic drugs Adjunctive role in haemophiliacs undergoing tooth extraction, prostatectomy, trauma Hematuria (establish fibrinolysis prior using EACA)
- 25. Antifibrinolytic drugs EACA-Adverse effects: Rapid i.v. injection: Hypotension, bradycardia, arrhythmia Intravascular thrombosis Ureteric obstruction when used in hematuria Myopathy
- 26. Antifibrinolytic drugs Tranexamic acid 7 times more potent than EACA Preferred over EACA Uses: Menorrhagia, especially due to intra uterine contraceptive device Recurrent epistaxis, peptic ulcer, hyphema due to ocular trauma
- 27. Antifibrinolytic drugs Tranexamic acid-Adverse effects: Nausea and diarrhoea Thrombophlebitis of injected vein Thromboembolic events, disturbed colour vision, allergic reactions
- 28. Conclusion Haemostatic agents facilitate or checks degradation of fibrin Phytonadione (Vitamin K1) is commonly used preparation Given oral intra-muscular Styptics are used locally to achieve haemostasis Tranexamic acid is preferred over Epsilon Amino Capric Acid (EACA)
- 29. Questions??
- 30. Thank you!
Editor's Notes
- Hemostasis is the cessation of blood loss from a damaged vessel. Hemophilia is a group of sex-linked inherited blood disorders, characterized by prolonged clotting time. However, the bleeding time is normal. Usually, it affects the males, with the females being the carriers. Whenever a vessel is severed or ruptured, hemostasis is achieved by several mechanisms: (1) vascular constriction, (2) formation of a platelet plug, (3) formation of a blood clot as a result of blood coagulation, and (4) eventual growth of fibrous tissue into the blood clot to close the hole in the vessel permanently.
- Prothrombin, Stable Factor, Plasma thromboplastin component (Christmas factor), Stuart-Prower factor
- Dose: 0.3mcg/kg diluted in 50mL saline and infused i.v. over 30 mins
- Capillary bleeding states: menorrhagia, post-abortion, PPH, epistaxis, malena, hematuria, post tooth extraction
- ? Thromboplastin
- ? Thromboplastin
- Hyperplasminemic states associated with excessive intra-vascular fibrinolysis resulting in bleeding
- Intravascular thrombosis- pt is in hypercoaguable state