Topical hemostatic agents for managing bleeding

Agent	Source	How supplied	Trade names in United States	Absorption time^[1]	Adverse effect*^[2]	Relative expense^¶[1,3]
Physical agents
Wax-based
Bone wax	Beeswax	Stick form	Not applicable	Indefinite	Impaired bone healing	¢
Ostene (soluble copolymer implant material)	Synthetic alkaline oxide copolymers	Stick form	Ostene	48 hours		¢
Dry matrix
Absorbable gelatin (gelatin matrix)	Porcine	Sponge, powder	Gelfilm, Gelfoam, Surgifoam, Gelfoam hemostasis kit (also contains human thrombin)	4 to 6 weeks	Infection, abscess or granuloma formation, fibrosis, clot disruption if sponge is removed^[1]	$
Oxidized regenerated cellulose	Plant	Mesh	Surgicel (Nu-Knit, Fibrillar, SNoW)	1 to 2 weeks^Δ	Foreign body reaction, infection, adhesions^[1]	$
Microfibrillar collagen (collagen hemostat)	Bovine	Sheets	Actifoam, Avitene (Ultrafoam), Endo Avitene, Instat MCH, Helistat Helitene, Syringe Avitene	>8 weeks	Granuloma formation, allergenic	$$
Microfibrillar collagen (collagen hemostat)	Bovine	Powder	Avitene Flour	>8 weeks	Granuloma formation, allergenic	$$
Microporous polysaccharide spheres (MPH)	Synthetic	Powder	Arista AH	24 to 48 hours	Use of >50 g can alter glucose load in patients with diabetes	$
External agents
Chitosan	Biodegradable complex carbohydrate derived from chitin	Adhesive dressing	HemCon bandage (Chitoflex)	Not applicable	Training needed to ensure proper application	¢
Kaolin-impregnated sponge	Aluminosilicate mineral	Gauze sponge	Quikclot	Not applicable	Possible clot disruption when sponge removed	¢
Hemafiber	Cellulose and silica	Dressing, surgical pad, elastic wrap	NuStat OTC, NuStat Trauma Pad XR, NuStat Flex	Not applicable	Possible clot disruption when pad removed	$
Biologically active agents
Topical thrombin	Bovine	Liquid	Thrombin-JMI	Not applicable	Intravascular application leads to thrombosis Antibody formation against bovine thrombin can inhibit coagulation and prolong prothrombin time/INR	$$
	Human		Evithrom
	Recombinant human (rHuman)		Recothrom
Fibrin sealant (human fibrinogen and human thrombin)^◊	Human	Liquid	Artiss, Tisseel (also contains synthetic aprotinin), Evicel, TachoSil, Evarrest, Vistaseal	Immediate	Potential exposure to blood-borne viruses	$$$
	Human autologous	Liquid	CryoSeal Fibrin Sealant System Vitagel (autologous fibrinogen and bovine thrombin)	Immediate		Not available
	Human	Powder (spray and direct application; for use with absorbable gelatin sponge)	Raplixa	(Refer to Absorbable gelatin sponge, above)		Not available
Dry Fibrin Sealant Dressing (DFSD)^§	Freeze-dried fibrinogen and thrombin applied to gauze substrate	Dressing	Not applicable	Not applicable		$$$$
Bovine albumin-glutaraldehyde tissue adhesive	Bovine	Liquid	Bioglue		Antibody formation against bovine thrombin can inhibit coagulation and prolong prothrombin time/INR	$$$$
Combination preparations
Thrombin/gelatin	Bovine or porcine	Liquid	Floseal (bovine), Surgiflo (porcine)	6 to 8 weeks	Antibody formation against bovine thrombin can inhibit coagulation and prolong prothrombin time/INR	$$$
Thrombin/collagen	Bovine	Liquid	Costasis	4 weeks	Antibody formation against bovine thrombin can inhibit coagulation and prolong prothrombin time/INR	$$$

INR: international normalized ratio.
* Although rare, use of protein-containing topical hemostatics and fibrin sealants can be associated with severe hypersensitivity reactions and formation of antibodies; such reactions may be seen especially after repeated application.
¶ The cost of topical hemostatics is highly variable in United States and subject to institutional contracting. Price range (US dollars): ¢: less than 50 dollars; $: 50 to 100 dollars; $$: 101 to 300 dollars; $$$: 301 to 500 dollars; $$$$: 501 to 750 dollars.
Δ The low pH of the oxidized regenerated cellulose can inhibit proteases and elastase, which can delay resorption for more than two weeks.
◊ Thrombin and fibrinogen concentrations vary. Fibrinogen concentrations are higher for commercial preparations. As an example, Tisseel, Evicel, and Vistaseal have fibrinogen concentrations of 70, 55 to 85, and 80 mg/mL, respectively, compared with 2.5 to 25 mg/mL for cryoprecipitate (unmanipulated). When rapid clot formation (5 to 10 seconds) is desired, thrombin concentrations of 500 to 1000 NIH units should be used (eg, Tisseel, 500 IU/mL; Evicel, 800 to 1200 IU/mL).^[4,5,6]
§ Investigational.

References:

Duenas-Garcia OF, Goldberg JM. Topical hemostatic agents in gynecologic surgery. Obstet Gynecol Surv 2008; 63:389.
Gabay M, Boucher B. An essential primer for understanding the role of topical hemostats, surgical sealants, and adhesives for maintaining hemostasis. Pharmacotherapy 2013; 33:935.
Hong YM, Loughlin KR. The use of hemostatic agents and sealants in urology. J Urol 2006; 176:2367.
TISSEEL VH Kit. Available at: https://www.fda.gov/downloads/biologicsbloodvaccines/bloodbloodproducts/approvedproducts/licensedproductsblas/fractionatedplasmaproducts/ucm072968.pdf (Accessed on October 27, 2017).
EVICEL Fibrin Sealant. Available at: https://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM270787.pdf (Accessed on October 27, 2017).
VISTASEAL Fibrin Sealant. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a8708417-2f74-4dfa-b6f9-ef88f902e0fc (Accessed on December 15, 2021).

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Topical hemostatic agents for managing bleeding