overview of hemostatic agents

1. Chemical haemostatic agents

2. In this lecture…
• A brief history of haemostatic agents
• The role players
• Local agents
• Systemic agents

3. History
• Egyptians used very high temperature cautery
combined with waxes and poultices on wounds to
stem bleeding
• Native Americans used scrapings from the inside of
animal hides applied to wounds to attain
haemostasis
• Hippocrates used caustics to achieve haemostasis
• At the end of the eighteenth century, Carnot
introduced the use of gelatin as a haemostatic.

4. Morawitz presented a model for
blood coagulation in which
prothrombin is converted in the
presence of Calcium ions to active
thrombin , in 1905
WWI Fibrin patches and tampons
used –discontinued due to a high
rate of failure

5. History continued…
• Oxidized cellulose(OC) in 1942
• Oxidized regenerated cellulose (ORC) was
developed in 1960
• Gelatin foam(GF) in 1945
• Microfibrillar collagen (MFC) was developed in
1970 by Hait
• Chitosan based agents was approved by FDA in
2003

6. History continued…
• The newest mineral based agent has been
introduced by US Army Institute of Surgical
Research in 2007

7. The players
• Platelets
• Vessels
• Coagulation factors
• Inhibitors of coagulation
• Fibrinolytic system

8. A brief overview of a complex system

9. Local agents
• Porcine gelatin
• Oxidized regenerated cellulose
• Microfibrillar collagen
• Topical thrombin
• Tissue sealants
▫ Fibrin glues

10. Gelfoam in a wound

11. Porcine Gelatin
• Eg. Gelfoam, Surgifoam, Spongistan
• No intrinsic haemostatic action
• Absorb 45 times their weight in blood
• Provides a scaffold on which platelets come into
close contact, initiating the release of clotting
mech
▫ Need to have functioning clotting factors in order
for this to help clot formation

12. Porcine gelatin
• Absorbed within 4-6 weeks
• Liquefies within 2-5 days when used on the nasal
mucosa

13. Surgicell

14. Oxidized and regenerated cellulose
• Eg. Surgicell, Oxycell
• Been around since the 1940s
• Derived from alpha cellulose
• Surgicel
▫ Fibers in knit form
▫ Solid fibers
• Oxycell
▫ Microfibrillar form
▫ Hollow fibers

15. Oxidized and regenerated cellulose
• Low pH=bactericidal properties
• Achieves haemostasis via
▫ Denaturation of blood proteins
▫ Mechanical activation of clottin cascade
▫ Local vasoconstriction
• Need functional clotting factors to work
• Needs to be applied dry
• Takes 6-8 weeks to be reabsorbed

16. Ativene –microfibrillar collagen

17. Microfibrillar collagen
• Derived from bovine collagen
• Provides a binding site for platelets
▫ Degranulation
▫ Release of coagulation factors
• Available in a variety of forms
▫ Powder
▫ Sheets
▫ Loaded syringes
• Absorbed by the body over time

18. Topical thrombin

19. Topical thrombin
• Can be supplied as a liquid and sprayed onto
oozing sites
• Cannot be used in combination with ORC

20. FloSeal

21. Gelatin matrix/Thrombin sealants
• Eg. FloSeal
• Thrombin + Gelatin matrix
• Thrombin:
▫ Sterile freeze dried powder
▫ Reconstituted with saline and mixed with gelatin matrix in
theater
• Gelatin matrix:
▫ manufactured by extracting collagen from bovine corneal
tissue
▫ collagen gelatinized and ground to 500-600um particles

22. FloSeal mechanism of action
• Components work independently and
synergistically to promote clot formation
• Granular nature of compound conforms to
wound shape
• Granules swell 10 to 20 percent-tamponade in
wound bed on contact with blood/other fluid

23. FloSeal mechanism of action
• Thrombin
▫ Activates platelets
▫ Factors:V,VII,XII
▫ Fibrinogen to Fibrin
• Fibrin traps the granular matrix –stability of
complex
• Absorbtion of the complex 6-8 weeks after
application
• Requires the presence of blood at it’s application
site in order to function

24. FloSeal risks
• BSE
• Thromboembolic events if directly injected into
medium to large blood vessels
• Immunologically induced coagulopathy
▫ Anti thrombin Abs
▫ Anti factor V Abs
• IgE mediated anaphylaxis

25. FloSeal

26. Tissue sealants

27. Tissue sealants
• “fibrin glues”
• Eg. Tisseel
▫ Combination of: human thrombin,fibrinogen and
aprotinin
• Manufactured from single- or multiple donors
• 2 vial system
• Preparation time 15 min

28. Tissue sealants
• Available for use for 4 hours
• Applied with a double-barrel syringe to a dry
tissue bed
• Once applied the wound must be free of
mechanical stress for at least 3 minutes

29. Tissue sealants
• Fibrinogen -Fibrin
• Factor XIII activated
• Haemostasis even with defects in other parts of
the pathway
• Clot formed by sealant degrades physiologically

30. Tissue sealants -Thromboseel
• Eg. Thromboseel
• Produced by SANBS
• Two component preparation
▫ Human platelet rich plasma
▫ Human Thrombin
• Prp obtained by apheresis from a single regular
platelet apheresis donor
• Thrombin prepared by calcium chloride
activation of an euglobulin fraction of plasma
obtained from a single regular plt donor

31. Tissue sealants -Thromboseel
• Pharmacological action:
▫ Thrombin +Prp =fibrin and platelet components
released into the coagulum
▫ Formed fibrin adheres to wound surface
▫ Gains in strength over the next two hours
following administration
• Indications:
▫ Used to achieve haemostasis and accelerate
wound healing in surgical procedures on
haemostatically compromised patients

32. Chitosan based dressing

33. Chitosan based dressings
• Chitosan :
▫ biodegradable,nontoxic,complex carbohydrate
derived from chitin(a naturally occuring substance
from zeolites)
• mucoadhesive activity
• Positively charged –attrackt negatively charged
platelets and RBC
• The freeze-dried dressing augments its sealing
action
• antibacterial barrier

34. Chitosan based dressings
• It should be applied with pressure for 3 minutes
• Can be left on the wound for 48 h ; easily
removed by saline without disturbing the clot
• Suitable for high flow ,high pressure bleeding
• Sizing is important

35. Mineral based haemostatic agents

36. Mineral based haemostatic agents
• WoundStatTM
is a 5.5 ounce package of non-
metallic clay mineral (smectite) composed of
hydrated sodium, calcium, aluminum & silicate.
• This product swells when exposed to water or
blood and forms a clay-like material with high
plasticity and tissue adhesiveness.
• Haemostasis lasts for up to 3 hours

38. Systemic agents
• DDAVP
• Conjugated estrogens
• Anti-fibrinolytic amino acids
• Ethamsylate

39. Desmopressin

40. Desmopressin
• Used to treat patients with Haemophillia A or
vWD for te first time in 1977
• Synthetic analogue of Vasopressin
▫ Increases the level of factor8 and vWF in healthy
people
▫ BUT
 Causes little or no vasoconstriction
 No increase in BP
 No contraction of the uterus or GIT

41. Desmopressin
• Mechanism of action
▫ Shortens aPTT and bleeding time
▫ No effect on Plt count or aggregation
▫ Enhances Plt adhesion to the vessel wall
▫ Acts on storage sites of vWF and F8 via V2
receptors
▫ Patients treated repeatedly with Desmopressin
may become less responsive because of depletion
of their stores

42. Desmopressin
• Should be given when an immediate effect on
haemostasis is required
▫ Eg. Acute bleeding
▫ Prevent bleeding during emmergency surgery

43. Desmopressin

44. Conjugated estrogens

45. Conjugated estrogens
• Shorten bleeding times in uremic patients
• Single daily infusion of 0.6mg/kg for 4-5 days,
shortens the bleeding time by 50% for at least two
weeks
• Longer duration of effect on bleeding time than
DDAVP
• Should be given when long lasting haemostasis is
required
▫ Eg. Elective surgery
▫ Treatment of recurrent episodes of GIT or Nasal
bleeding

46. Antifibrinolytic amino acids

47. Antifibrinolytic amino acids
• Eg. Tranexamic acid
• Lysine analogue
• Works by binding reversibly to plasminogen
• Enters the extravascular space and accumulate
in tissues –inh tissue fibrinolysis and
consequently stabilizes clots

48. Copyright restrictions may apply.
Mahdy, A. M. et al. Br. J. Anaesth. 2004 93:842-858; doi:10.1093/bja/aeh227
Mechanism of action of lysine analogues

49. Antifibrinolytic amino acids

50. Antifibrinolytic amino acids