Surgical Hemostatic Agents

For More Reading: CO 812

Clotting Cascade: An Overview

• Listen to the podcast for more, but the most important steps to know are:

  • Trauma leads to extrinsic pathway and intrinsic pathway (more extrinsic activation)

  • Both lead into the common pathway, where:

    • Factor X → Xa

    • Prothrombin → Thrombin by action of Xa

    • Fibrionogen → Fibrin by action of Thrombin

    • Fibrin monomers → polymers → clot by action of factor 13, platelets, and other molecules.

How bad is the bleeding?

• Topical agents should be used in places where electrosurgery or sutures are not ideal or safe for the situation -- i.e., near structures like ureters or nerves.

• These agents are not ideal for widespread bleeding or use for prophylaxis against bleeding!

• Slow, venous bleeding is most adept for these agents -- fast/pumping arterial bleeders, or large areas, are not going to be solved by use of these agents.

Assuming you need one of these, there are three categories of topical agents:

• Caustic

• Physical

• Biologic

Caustic Hemostatic Agents

• These agents coagulate proteins leading to tissue necrosis and eschar formation. 

• Examples -- aluminium chloride, ferric subsulfate 20% (aka Monsel’s solution), silver nitrate, and zinc chloride paste.

• These agents are great for topical bleeding, particularly at the cervix or vagina.

  • They are NOT for intraabdominal use -- they can cause tissue damage and toxicity.

Physical Hemostatic Agents

• These products use some sort of substrate to form a matrix at the site of bleeding, providing a scaffold for clot formation via the extrinsic pathway.

  • Some of the substrates are made of cellulose, gelatin, starch, or collagen.

• Because these only provide a matrix to build a clot upon, they are not ideal in patients who have a concern for a coagulation cascade issue -- you need an intact cascade for these to work!

• Options in this category:

  • Gelatin-based (Gelfoam, Gelfim, Surgifoam) - 

    • Available as powder or sponge

    • Absorbs over 4-6 weeks 

    • Porcine-derived

    • Absorbs surrounding blood and fluid to increase its size and weight -- great to “apply some pressure” too! But be careful near areas that have fragile structures that shouldn’t be compressed, like near nerves.

  • Cellulose-based (Surgicel) 

    • Available as powder or knit mesh -- great for using in laparoscopy since you can trim the mesh to size! 

    • Absorbs over 1-2 weeks

    • Plant-derived

    • Acidic pH purportedly provides antibacterial properties, and enhances natural thrombosis.

      • However, this acidic pH will inactivate topical thrombin products, so don’t use these in combination.

• Polysaccharide hemospheres (Arista)

  • Powder

  • Plant derived

  • Absorbs within 48 hours -- may be less likely to cause foreign body reaction or form a nidus for infection compared to other physical agents 

  • Absorbs water, allowing platelets and other proteins to accelerate clot formation

  • Also, this is the only topical agent approved for arterial bleeding!

• Microfibrillar collagen (Avitene)

  • Powder or foam

  • Bovine-derived

  • Absorbed in 8-12 weeks

  • Facilitates platelet aggregation and thrombus formation

Biologic Hemostatic Agents

• These bypass the extrinsic/intrinsic pathways to get right to the point of the common pathway, providing a “bolus” of material to promote clotting.

• In patients with an impaired coagulation cascade, depending on the step, these may have a more favorable profile than physical agents.

• Options in this category:

  • Topical thrombin (Thrombin-JMI, Recothrom, Evithrom)

    • Many of these agents are bovine-derived.

      • Evithrom is derived from pooled human plasma, and thus is considered a blood product.

      • Recothrom is recombinant, and interestingly should not be used if patients have allergies to snakes or hamsters!

    • These agents provide thrombin directly, which in turn can go straight to fibrinogen→fibrin activation and clot formation.

      • If fibrinogen is severely deficient, then these will not work well!

    • Often topical thrombin is turned into a combination agent with physical hemostatic agents to create a topical gel.

      • The most well known of this is likely Floseal, which is a combination of bovine-derived gelatin and human-derived thrombin (also a blood product!). Compared to other products and given its combination action, it is more expensive overall. 

  • Fibrin sealants (Tisseel, Evicel)

    • These are another combination solution that combines human-derived thrombin solution with human fibrinogen solution and can be applied to a bleeding site, forming a clot on the spot! 

      • These are great in that they can be used in patients with coagulopathy, as you are supplying the fibrinogen!

      • These have to be kept at special temperatures, and often take at least 10-20 minutes to thaw and prepare -- and not surprisingly, these are also quite expensive. 

  • Topical tranexemic acid (TXA)

    • TXA can be mixed with sterile water and applied directly to bleeding surfaces, and the systemic absorption when performed this way is quite low (<10% of IV form).

      • This may help abate concerns regarding use of IV TXA in patients who may be prone to thrombosis, but this question needs further study. 

Risks and Contraindications to Use

Fortunately, many of these items are well tolerated. But they shouldn’t be used carelessly, for a variety of reasons beyond expense. As we’ve gone through their nature, we should make mention generally of some risks/complications of their use:

• The physical agents may be associated with infection.

  • For physical or combination agents, these are foreign bodies, with varying absorption times. While it’s hard to tease out whether a complex surgery or the agent’s presence led to an infection, it’s worth noting that all of these products have the potential to be a nidus for infection at their site of use.

  • Confusing things further, these agents often may appear like an abscess or collection on postoperative imaging -- so don’t forget to dictate if and where you used them! 

• Many of these products are bovine or porcine derived.

  • Notably, religious leaders from around the world do support use of these animal-derived products if no alternatives are available, or in an emergent situation. 

  • However, being aware of culturally appropriate care is important, and patients who are concerned about this in preoperative counseling should be heard and offered alternatives.

• Animal products also have risk of significant allergic reactions!

  • For instance, there have been reports of severe antibody mediated reactions resulting in catastrophic bleeding on re-exposure to bovine-derived thrombin products. This resulted in a US FDA black box warning for these products.

    • If used during surgery, patients should be counseled about the use and the potential risks of reexposure with future surgery.

• Human-derived samples can be considered blood products, so it’s worth discussing their use in advance with patients who object to use of blood products in surgery. 

  • Human samples also have a theoretical risk of viral contamination and transmission of infections such as HIV or hepatitis. These risks are thought to be very small, however; with the risk of this estimated to be 1 in 10^15 for both thrombin and fibrinogen, and higher for parvovirus (as high as 1 in 500k). 

  • Immunologic events can also rarely occur with use of human products and development of antibodies against human-derived biologic agents; however, this occurs at a much lower incidence compared to bovine-derived thrombin.