Hemostatic Agents in Surgery

Hemostasis

To understand patient management and stabilization during bleeding, the mechanisms of hemostasis and thrombosis must be known. Hemostasis can be defined as a regulated and complex process that maintains the blood flow and simultaneously activates a thrombotic response when tissue damage occurs.

The main factors in maintaining hemostasis are the vessel wall, platelets, and the coagulation and fibrinolytic systems.

Hemostasis can be divided into:

• Primary hemostasis: It starts when endothelial disruption occurs, a local contraction of vascular smooth muscle appears and the blood flow is reduced which allows platelet adhesion and activation. The Von Willebrand factor attaches to thebsubendothelium at the site of injury and adheres to the platelets. After this a soft plug of aggregated platelets and fibrinogen is formed.

• Secondary hemostasis: Secondary hemostasis is defined as the formation of insoluble, cross-linked fibrin by activated coagulation factors, specifically thrombin. Fibrin stabilizes the primary platelet plug, which makes it possible to stop the hemorrhage, particularly in larger blood vessels where the platelet plug alone is insufficient. It is also known as the clotting cascade.

When performing a surgery excessive blood loss is associated with increased mortality, morbidity, and intensive care stay.

Surgical bleeding is usually due to technical factors but in some cases acquired or congenital coagulopathies may favor, if not directly cause, surgical hemorrhage.

Uncontrolled bleeding leads to a combination of hemodilution, hypothermia, consumption of clotting factors, and acidosis, which in turn worsen the clotting process, further exacerbating the problem in a vicious bloody circle.

In surgery, there are different methods to maintain hemostasis - mechanical, thermal or chemical. Usually, when bleeding occurs the first option is to apply pressure or mechanical techniques to stop it.

Other mechanical methods, including sutures, staples, and ligating clips, are useful if the source of bleeding is easily identifiable and can be sealed but it is not always easy to identify the bleeding source so this may fail as a hemostatic technique.

When bleeding occurs, surgeons can use various hemostatic products to help control it. These agents range from absorbable hemostats, such as gelatins and collagens, through biologically active topical hemostats, such as thrombin and combined agents, to systemically delivered agents, such as coagulation factors used for more extensive bleeding.

It depends also on the procedure and the location of the bleeding, as it may sometimes be impossible to use mechanical or thermal techniques. In those cases, using topical hemostatic agents may be useful.

These agents are applied directly to the bleeding site and may prevent continuous bleeding during the entire procedure and also in the postoperative period.

When talking about hemostatic topical agents, they can be divided into passive and active:

• Passive: They provide a physical structure around which platelets can aggregate so a clot can form.
• • Collagen-based products interacting with blood promote platelet aggregation. They can be applied as a powder, paste or sponge.
  • Cellulose-based products contain regenerated oxidized cellulose which initiates clotting via contact activation.
  • Gelatins: When held in place swollen gelatin particles restrict blood flow and provide a stable matrix around which a clot can form.
• Active: They have biological activity and participate directly in the coagulation cascade including thrombin or combinations of products containing thrombin. As it appears at the last stages of the clotting cascade it is less susceptible to coagulopathies.

Characteristics of the ideal topical hemostatic agent

• Effective
• Easy to use
• Rapid effect
• Ability to make effective contact with the bleeding surface
• Simple to prepare
• No side effects

Some surgical scenarios and different options and costs:

Large artery bleeding/repair

• Bioglue (approved in USA for large vessel repair in Cardiovascular surgery) $$$$

Needle hole bleeding in vessel adventitia or in vascular graft material:

• Microporous polysaccharide spheres (Arista) ($)
• Thrombin-soaked gelatin foam (Gelfoam, Surgifoam) ($)
• Oxidized regenerated cellulose (Surgicel) ($)
• Gelatin matrix-thrombin combination (FloSeal, Surgiflo) ($$)
• Spray fibrin sealant (Tisseel, Evicel, Hemaseel APR, Crosseal) ($$$$)

Pulsatile external exsanguinating hemorrhage (preoperative setting):

• Compression with external agents, Kaolin based ($) or Chitosan based ($$)
• Pack with dry fibrin sealant dressing ($$$$+)

Spleen, liver, kidney parenchymal surface post-trauma or partial resection:

• Oxidized regenerated cellulose (Surgicel) ($) or microfibrillar collagen (Avitene Ultrawrap) ($$$) with or without suture fixation.
• Microporous polysaccharide spheres (Arista) ($) and holding the sponge for several minutes.
• Spray with thrombin ($).
• Gelatin matrix-thrombin combination (FloSeal, Surgiflo) ($$).
• Spray fibrin sealant (eg, Tisseel, Evicel, Hemaseel APR, Crosseal) ($$$$).

Venous or capillary oozing from area of dissection or deserosalization:

• Oxidized regenerated cellulose Surgicel Nu-Knit, Surgicel Fibrillar) with sponges and hand pressure ($ to $$).
• Microporous polysaccharide spheres (eg, Arista) and holding sponge pressure for several minutes ($ to $$).
• Spray with thrombin ($).
• Spray with fibrin sealant (eg, Tisseel, Evicel, Hemaseel APR, Crosseal) ($$$$).

Cavity or potential space, nerve or other tissue not amenable to cautery, need to avoid compression of nerve:

• Apply microporous polysaccharide spheres (eg, Arista) and holding sponge pressure for several minutes. Irrigate remaining powder away ($).
• Avitene Flour, EndoAvitene (OK to leave in place) ($$).
• Spray with fibrin sealant (eg, Tisseel, Evicel, Hemaseel APR, Crosseal) ($$$$).

Take home messages

• Intraoperative bleeding can be life threatening so a fast and effective blood management plan incorporating topical hemostatic agents is essential.
• The use of topical hemostatic agents improves blood conservation, reduces overall procedure time, and contributes to faster patient recovery times.
• Hemostatic agents provide rapid and effective hemostasis, are available in multiple delivery forms, and need to be known to surgeons in order to use in the operating room.
• Appropriate use of these products improves outcomes for patients, the surgical team, and health care facilities.