Surgical Secondary Hemostasis in Wound Healing

Dr. Milan D Choksey

"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.

Hemostasis

Biology of Hemostasis

Injury to a vessel

Platelet factors Vascular factors Plasma/blood factors

Stable Hemostatic clot

Fibrin clotVasoconstrictionPlatelet plug

Synergy of Factors contributing to normal hemostasis

Phases of Hemostasis

• Primary hemostasis – Arteriolar vasoconstriction – Formation of platelet plug

• Secondary hemostasis – Activation of coagulation cascade – Formation of permanent fibrin plug

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

Factors influencing Surgical bleeding

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

Adverse effects of Surgical bleeding

• 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

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

Methods of HemostasisMechanical 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

. Topical hemostatic agents . Passive (mechanical) agents

. Active agents

. Collagen based agents

. Cellulose

. Gelatin

. Polysaccharide spheres

. Thrombin products

. Others . 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

Mechanical methods

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

Thermal/energy based methods

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

Monopolar Electrosurgical Unit

Bipolar Electrosurgical Unit

Bipolar Vessel Sealing device

Chemical methods – pharmacological agents

Chemical agents enhance the natural coagulative mechanisms

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

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

Historical background of Chemical hemostatic agents

• Hippocrates used caustics to achieve hemostasis.

• At the end of the eighteenth century, Carnot introduced gelatin.

• In 1886 Horsley developed a mixture of beeswax, salicylic acid, and almond oil, thus leaving his legacy of “antiseptic wax.”

• 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 at 2003

• 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

Topical hemostatic agents

• Two primary categories: passive and active

• Two more categories: flowables & sealants

Passive Active

Act passively thru contact with bleeding sites and promotion of platelet aggregation

Acts biologically on the clotting cascade

Eg collagens, cellulose, gelatins and polysacchride spheres

Eg thrombin and products in which thrombin is combined with a passive agent

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

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

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

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

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

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

Thrombin products

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

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

Sealants Sealants work by forming a barrier that is impervious to the flow of most liquids

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

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

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

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

Key considerations in the selection of topical agent

• 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

Thank you