Haemostatic agents

MBBS Sem II Class, Lumbini Medical College

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?

4. Let’s Brain storm!

5. Classification Coagulants Fresh whole blood/ plasma Vitamin K: K 1 , K 3 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 -18 O C Thawed before administration Fresh Whole Blood/Plasma

7. Vitamin K K 1 : Phyton adione, Phylloquinone Plant source, Fat soluble K 3 : 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 Ca 2+ 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 V 2 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 K 1 ) 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!