1. Surgical Secondary
Hemostasis in Wound Healing
Dr. Milan D Choksey

2. "An area of increasing concern is lethal hemorrhage
from sites that are not suitable for application of
tourniquets or compression dressings."
Hasan B. Alam. "Hemorrhage control in the battlefield: Role of new
hemostatic agents." Military Medicine, 170(1):63-69.

3. Hemostasis

4. Biology of Hemostasis
Injury to a vessel
Platelet factors
Platelet plug
Vascular factors
Vasoconstriction
Plasma/blood factors
Fibrin clot
Stable Hemostatic clot
Synergy of Factors contributing to normal hemostasis

5. Phases of Hemostasis
• Primary hemostasis
– Arteriolar vasoconstriction
– Formation of platelet plug
• Secondary hemostasis
– Activation of coagulation cascade
– Formation of permanent fibrin plug

8. Types of bleeding during Surgery
• Arterial bleeding:
– Pulsating
• Venous bleeding
– Oozes
Adapted with permission from: Samudrala S. Topical hemostatic agents in surgery: a surgeon’s perspective. AORN J. 2008;88(3): S2-S11

9. Factors influencing Surgical bleeding
Type of procedure
Patient position
Surgical incisions
Exposed bone
Large surfaces of exposed
capillaries
• Unseen sources of bleeding
• Tissues that cannot be sutured or
low-pressure suture lines
• Adhesions stripped during surgery
• Specific anatomical considerations
• Medications (eg. Anticoagulants)
• Coagulopathies
Procedural
factors
Patient
factors
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• Platelet dysfunction or deficiency
• Fibrinolytic activity
• Coagulation factor deficiencies
• Medical conditions
• Nutritional status
Adapted with permission from: Samudrala S. Topical hemostatic agents in surgery: a surgeon’s perspective. AORN J. 2008;88(3): S2-S11

10. Adverse effects of Surgical bleeding
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Visual obstruction of the surgical field
Need for blood transfusions
Reduction in core temperature
Thrombocytopenia
Hypovolemic shock
Economic consequences
Adapted with permission from: Samudrala S. Topical hemostatic agents in surgery: a surgeon’s perspective. AORN J. 2008;88(3): S2-S11

11. Characteristics of an Ideal hemostatic
agents for prehospital/battlefield use:
(1) capability to stop large vessel arterial and venous
bleeding within minutes of application when applied to an
actively bleeding wound through a pool of blood;
(2) no requirement for mixing or pre-application
preparation;
(3) simplicity of application by wounded victim, buddy, or
medic;
(4) light weight and durable;
(5) long shelf life in extreme environments;
(6) safe to use with no risk of injury to tissues or
transmission of infection;
(7) cost-effective

12. Methods of Hemostasis
Mechanical methods
. Direct pressure
. Fabric pads/sponges/gauzes
. Sutures/staples/ligating clips
Thermal/energy based methods
. Electrosurgery
. Monopolar
. Bipolar
. Bipolar vessel sealing device
. Argon enhanced coagulation
. Ultrasonic device
. Laser
Chemical methods
. Pharmacological agents
. Epinephrine
. Vitamin K
. Protamine
. Desmopressin
. Lysine analogues
. rFVIIa
Adapted with permission from: Samudrala S. Topical hemostatic agents in surgery: a surgeon’s perspective. AORN J. 2008;88(3): S2-S11

13. . Topical hemostatic agents
. Passive (mechanical) agents
. Active agents
. Others
. Collagen based agents
. Cellulose
. Gelatin
. Polysaccharide spheres
. Thrombin products
. Flowables
. Sealants
. Fibrin sealants
. Polyethylene glycol (PEG)
polymers
. Albumin and glutaraldehyde
. Cyano-acrylate
Adapted with permission from: Samudrala S. Topical hemostatic agents in surgery: a surgeon’s perspective. AORN J. 2008;88(3): S2-S11

14. Mechanical methods
Direct pressure
• Simplest & fastest
• Surgeon’s first choice
• Arterial bleeding better controlled than venous
Fabric pads/gauzes/sponges
• Application of direct pressure
• Packaging of body cavity
• No. of sponges used during surgery needs to be counted
• Temporary measures
Sutures/staples/ligating clips
• Sutures and ties used as ligatures to tie off blood vessels
• Chances of FB reaction, tissue reaction, injury & allergic reactions
• For staples, stapling device required
• Efficient method when diving tissue
• Ligating clips – quick & easy to apply
• Applicator required
• Site of application should be clearly visible
Adapted with permission from: Samudrala S. Topical hemostatic agents in surgery: a surgeon’s perspective. AORN J. 2008;88(3): S2-S11

15. Thermal/energy based methods
Electro-surgery
• Use of high frequency (radio) alternating current for cutting, coagulating and
vaporizing tissues
• Potential risks – patient injuries, user injuries, fires & electromagnetic interference
• Monopolar – most frequently used
• Bipolar – better on delicate tissues/small anatomical structures
• Bipolar vessel sealing device – applies heat with high compression. Capable of
simultaneously sealing and transecting vessels upto 7 mm diameter, large tissue
pedicles, vascular bundles
• Argon enhanced coagulation technology
Ultrasonic devices
• Converts electrical energy to mechanical energy
• Simultaneously cuts & coagulates
• Less thermal damage to tissues
Lasers
• Laser energy delivered to target site can be reflected, scattered, transmitted or
absorbed
Adapted with permission from: Samudrala S. Topical hemostatic agents in surgery: a surgeon’s perspective. AORN J. 2008;88(3): S2-S11

16. Monopolar Electrosurgical Unit
Bipolar Electrosurgical Unit
Bipolar Vessel Sealing device

17. Chemical methods – pharmacological agents
Chemical agents enhance the natural coagulative mechanisms
Epinephrine
• Causes direct vasoconstriction & increases heart rate
• Can be applied topically or injected with local anesthesia
Vitamin K
• Administered pre-operatively to reverse effects of warfarin
& to avoid need of transfusion of FFP
• Reversal of raised INR takes app. 24 hours
Protamine
• Only agent with ability to reverse heparin anticoagulation
• Can cause anaphylaxis, acute pulmonary
vasoconstriction, right ventricular failure

18. Desmopressin
• Stimulates release of von Willebrand factor
(vWF) & enhances primary hemostasis
Lysine analogues
• Aminocaproic acid, tranexamic acid
• Are antifibrinolytic and competitively inhibit
activation of plasminogen
• Variable effect & published data is limited
Adapted with permission from: Samudrala S. Topical hemostatic agents in surgery: a surgeon’s perspective. AORN J. 2008;88(3): S2-S11

19. Historical background of Chemical hemostatic agents
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Hippocrates used caustics to achieve hemostasis.
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At the end of the eighteenth century, Carnot introduced gelatin.
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In 1886 Horsley developed a mixture of beeswax, salicylic acid, and
almond oil, thus leaving his legacy of “antiseptic wax.”
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Oxidized cellulose(OC) in 1942
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Oxidized Regenerated Cellulose (ORC) was developed in 1960
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Gelatin foam(GF) in 1945
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Microfibrillar collagen (MFC) was developed in 1970 by Hait
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Chitosan based agents was approved by FDA at 2003
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The newest mineral based agent has been introduced by US Army
Institute of Surgical Research in 2007
•
A Plant extract agents was registered in Turkey in 2007

20. Topical hemostatic agents
• Two primary categories: passive and active
Passive
Act passively thru contact with
bleeding sites and promotion of
platelet aggregation
Active
Acts biologically on the clotting
cascade
Eg collagens, cellulose, gelatins and Eg thrombin and products in which
polysacchride spheres
thrombin is combined with a passive
agent
• Two more categories: flowables & sealants
Adapted with permission from: Samudrala S. Topical hemostatic agents in surgery: a surgeon’s perspective. AORN J. 2008;88(3): S2-S11

21. Topical agents – passive
Provides a physical, lattice like matrix that adheres to bleeding site
Matrix activates the extrinsic clotting pathway
Platelets aggregate and form a clot
Passive agents rely on fibrin production and hence can be used only in a patient
with intact coagulation cascade
Passive agents can absorb several times its weight in fluid. However, this
expansion of the agent can cause complications like compression of
surrounding tissues.
Adapted with permission from: Samudrala S. Topical hemostatic agents in surgery: a surgeon’s perspective. AORN J. 2008;88(3): S2-S11

22. Collagen based products
Activated on contact with bleeding. Provide stable matrix for clot
formation, enhance platelet aggregation, degranulation and release of clotting
factors
Derived from either bovine tendon or bovine dermal collagen
Microfibrillar collagen hemostat
• Derived from purified bovine dermal collagen
• Effective agents when there is capillary, venous or small arterial
bleeding
• Potential adverse events: allergic reaction, adhesion formation,
inflammation, FB reaction, potentiation of infection and abscess
formation
Absorbable collagen hemostat sponge
• Derived from purified and lyophilized bovine flexor tendon
• Collagen sponge gets absorbed into 8 to 10 weeks
Adapted with permission from: Samudrala S. Topical hemostatic agents in surgery: a surgeon’s perspective. AORN J. 2008;88(3): S2-S11

23. Oxidized regenerated cellulose
• ORC reacts with blood, increases in size and forms a gelatinous
mass and promotes clot formation
• Potential AEs: encapsulation of fluid and FB reaction, stenosis of
vascular structures, burning or stinging sensations, headaches
, etc
Gelatins
• Derived from purified bovine gelatin solutions
• Can be used in dry or wet form
• Conforms easily to wounds and therefore can be used for irregular
wounds
Polysacchride hemospheres
• Derived from vegetable starch
• Contains no human or animal component
Adapted with permission from: Samudrala S. Topical hemostatic agents in surgery: a surgeon’s perspective. AORN J. 2008;88(3): S2-S11

24. Topical agents – active
Have biological activity
Participate directly at the end of coagulation cascade
Stimulate fibrinogen at the bleeding site to produce a clot
Thrombin acts at the end of the clotting cascade, action of agent is not affected by
clotting factor deficiencies or platelets malfunction.
Can also be given to patients receiving anti-platelets/anti-coagulation
Active topical agents provide hemostasis within 10 minutes and they are
more effective in controlling bleeding than passive agents
Adapted with permission from: Samudrala S. Topical hemostatic agents in surgery: a surgeon’s perspective. AORN J. 2008;88(3): S2-S11

25. Thrombin products
Bovine thrombin
• Applied using a pump or spray kit, or in a saturated, absorbable
gelatin sponge
• AEs: antibody formation to bovine thrombin can lead to
coagulopathy, allergic reactions, death
Pooled human plasma thrombin
• Delivered via saturated, absorbable gelatin sponge
• Has potential risk of viral or prion disease transmission
Recombinant thrombin
• Reduced risk of antibody formation and eliminates risk of viral
or prion disease transmission
Adapted with permission from: Samudrala S. Topical hemostatic agents in surgery: a surgeon’s perspective. AORN J. 2008;88(3): S2-S11

26. Flowable hemostatic agents
• Combine passive and active hemostatic agents into a single
application product
• Work by blocking blood flow & actively converting fibrinogen into
fibrin
• Two types of products:
– Absorbable bovine gelatin + pooled human thrombin
– Absorbable porcine gelatin + either of the 3 thrombin types
• Both the products do not contain fibrinogen. Hence direct contact
with blood is necessary
• Both products are indicated for all types of surgeries except
ophthalmic surgeries
• AEs: anemia, arrhythmia, arterial thrombosis, atelectasis, atrial
fibrillation, hemorrhage, infection, pleural effusion, right heart failure
Adapted with permission from: Samudrala S. Topical hemostatic agents in surgery: a surgeon’s perspective. AORN J. 2008;88(3): S2-S11

27. Sealants
Sealants work by forming a barrier that is impervious to the flow of most liquids
Fibrin sealants
• Consists of conc fibrinogen and thrombin which upon mixing with blood
create a fibrin clot
• Increases rate of clot formation by providing higher conc of both fibrinogen
& thrombin at bleeding site
• 3 types: pooled human plasma, individual human plasma with bovine
collagen and bovine thrombin, pooled human plasma and equine collagen
• Fibrin sealants control local as well as diffuse bleeding
• Do not control vigorous bleeding
• Fibrin sealants can be used in patients with coagulopathies
• Also in patients receiving heparin
• Clinical concerns: difficulty of reconstitution, time taken for surgeon to learn
application
• AEs: viral or prion disease transmission, antibody formation with bovine
thrombin, swelling associated with collagen use
Adapted with permission from: Samudrala S. Topical hemostatic agents in surgery: a surgeon’s perspective. AORN J. 2008;88(3): S2-S11

28. Polyethylene glycol polymers
Adapted with permission from: Samudrala S. Topical hemostatic agents in surgery: a surgeon’s perspective. AORN J. 2008;88(3): S2-S11

29. Albumin-glutaraldehyde
• Contains 10% glutaraldehyde sol and 45% bovine serum
albumin
• Glutaraldehyde cross-links the residual proteins in
albumin to cell proteins at wound site and forms a tough
scaffold to which clot can adhere
• Commonly used for sealing holes around suture or
staple lines in complex CV procedures and in peripheral
vascular procedures
• AEs: tissue injury, muscle necrosis, emboli, delayed
pseudoaneurysm formation, sensitivity to glutaraldehyde
Adapted with permission from: Samudrala S. Topical hemostatic agents in surgery: a surgeon’s perspective. AORN J. 2008;88(3): S2-S11

30. Cyano-acrylates
• Consists of 2 cyanoacrylate monomers
– 2-octyl cyanoacrylate
– Butyl lactoyl cyanoacrylate
• Product to be used as a sealant and not as a substitute
for sutures, staples, or other methods of mechanical
closure
Adapted with permission from: Samudrala S. Topical hemostatic agents in surgery: a surgeon’s perspective. AORN J. 2008;88(3): S2-S11

31. Key considerations in the selection of topical agent
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Rapidly and effectively control bleeding
Effectively contact the bleeding surface
Work reliably
Be handled easily
Be prepared easily
Be available in multiple delivery options
Be compatible with patient’s physiology
Be safely used
Be cost effective
Adapted with permission from: Samudrala S. Topical hemostatic agents in surgery: a surgeon’s perspective. AORN J. 2008;88(3): S2-S11

32. Thank you