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Haemostatic Agents
Dr. Pravin Prasad
M.B.B.S., MD Clinical Pharmacology
Lecturer, Lumbini Medical College
June 6, 2018 (Jestha 23, 2075), Wednesday
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
Lets Brain storm!
 Define:
Haemostasis
Haemophilia
 How is haemostasis achieved?
Let’s Brain storm!
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
 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
Vitamin K
 K1:
Phytonadione, Phylloquinone
Plant source, Fat soluble
 K3:
Synthetic
Fat soluble: Menadione, acetomenaphthone
Water soluble: Menadione sod. bisulphite,
menadione sod. diphosphate
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
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
Vitamin K: Uses
 Newborn baby
Prevent/treat haemorrhagic disease of the
newborn
 Overdose of oral anticoagulants
Phytonandione
 Prolonged high dose salicylate therapy
Vitamin K: Uses
 Dietary deficiency
 Prolonged antimicrobial therapy
 Obstructive jaundice
 Malabsorption syndromes
Sprue, Regional ileitis, Steatorrhoea
 Liver disease
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
Miscellaneous
 Fibrinogen:
Fraction of human plasma
Indications:
Haemophilia
Anti-haemophilic globulin (AHG) deficiency
Acute afibrinogenemic states
Intra-venous infusion, 0.5 gm
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
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
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)
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
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
Local Haemostatics (Styptics)
Oxidised Cellulose sheet
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
Local Haemostatics (Styptics)
 Astringents
Tannic acid, metallic salts (Alum)
Precipitates proteins  toughens the
surface
Bleeding gums, bleeding piles
 Vasoconstrictors
Adrenaline 0.1%
Local Hemostatics (Styptics)
 Sclerosing agents
Sodium tetradecyl sulfate, Polidocanol
Irritants
Inflammation  coagulation  fibrosis
Injected locally
Haemorrhoids (piles), varicose vein mass
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
(-)
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)
Antifibrinolytic drugs
 EACA-Adverse effects:
Rapid i.v. injection:
Hypotension, bradycardia, arrhythmia
Intravascular thrombosis
Ureteric obstruction when used in hematuria
Myopathy
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
Antifibrinolytic drugs
 Tranexamic acid-Adverse effects:
Nausea and diarrhoea
Thrombophlebitis of injected vein
Thromboembolic events, disturbed colour
vision, allergic reactions
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)
Questions??
Thank you!

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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
  • 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)

Editor's Notes

  1. 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.
  2. Prothrombin, Stable Factor, Plasma thromboplastin component (Christmas factor), Stuart-Prower factor
  3. Dose: 0.3mcg/kg diluted in 50mL saline and infused i.v. over 30 mins
  4. Capillary bleeding states: menorrhagia, post-abortion, PPH, epistaxis, malena, hematuria, post tooth extraction
  5. ? Thromboplastin
  6. ? Thromboplastin
  7. Hyperplasminemic states associated with excessive intra-vascular fibrinolysis resulting in bleeding
  8. Intravascular thrombosis- pt is in hypercoaguable state