World J. Surg. 25, 1573–1577, 2001DOI: 10.1007/s00268-001-0152-y WORLD

Journal ofSURGERY© 2001 by the Societe

Internationale de Chirurgie

Potential Uses of Absorbable Fibrin Adhesive Bandage for Genitourinary Trauma

John G. Anema, M.D.,1 Allen F. Morey, M.D.,1 Richard Harris, D.V.M.,1 Martin MacPhee, Ph.D.,2

Rhonda L. Cornum, M.D., Ph.D.1

1Urology Service and Institute of Surgical Research, Brooke Army Medical Center, 3581 Roger Brooke Drive, Bldg. 3600, Fort Sam Houston,Texas 78234, USA2American Red Cross, Holland Laboratory, 15601 Crabbs Branch Way, Rockville, Maryland 20855, USA

Published Online: October 22, 2001

Abstract. Fibrin sealants have become increasingly popular in nearly allsurgical specialties. The absorbable fibrin adhesive bandage (AFAB) is anovel, potentially revolutionary product made from dried fibrinogen andthrombin. The AFAB appears to have excellent efficacy in producing rapidhemostasis in a variety of experimental major renal trauma models. TheAFAB also appears to enhance healing of the urinary collecting system.Further study is essential to explore new urologic applications of thisexciting technology.

Although many great technologic advances have dramaticallychanged the practice of urology (the cystoscope, lithotripsy, lapa-roscopy, lasers), the technology available to control hemorrhage(tourniquet, pressure bandages, ligatures) has remained largelyunchanged for the last 2000 years [1]. The application of fibrinsealant products now offers the potential to revolutionize surgicalpractice in both traumatic and routine applications.

Fibrin Sealant Products: Background

Fibrin sealant products replicate and amplify the body’s naturalclotting cascade [2]. Activated fibrin sealant is the final step in thecoagulation system. Thrombin catalyzes the conversion of fibrin-ogen to fibrin monomers by cleaving fibrinopeptides A and B.These monomers then condense to form fibrin polymer. Thetensile strength of the clot depends on the concentration of fi-brinogen.

Liquid fibrin sealant has been in use in Europe and the UnitedStates for several limited clinical applications but unfortunatelyhas not proved effective for major hemorrhage. Liquid fibrin gluesare limited by the poor solubility of ethanol- or salt-precipitatedthrombin and fibrinogen and the low fibrin concentration of theresulting clots [2]. The use of dried powders of fibrinogen andthrombin overcomes these limitations, producing a clot much

stronger than natural clot because of the higher concentration ofthe fibrinogen/thrombin at the injured tissue interface [3].

Development of the Absorbable Fibrin Adhesive Bandage

Attempts to use dry fibrin sealants are not new. World War Isurgeons created “homemade” prepolymerized fibrin sheets andpowders for use as hemostatic agents [4]. Such products were latermass-produced for use during World War II by a joint military/American Red Cross program [5]. These products were not activehemostatic agents, however (i.e., not capable of creating newclots), and were withdrawn from use and forgotten when theywere discovered to transmit hepatitis [6].

Long after appropriate technology to render pooled humanfibrinogen safe from communicable diseases had been developed,a ready-to-use dry fibrin bandage was developed independently atthe U.S. Army’s Letterman Institute of Research and the Amer-ican Red Cross (ARC). The first in vivo test of a dry fibrinbandage was performed by the Letterman group using powderedfibrinogen and thrombin on a gauze dressing [7]. Following this,the U.S. Army and the ARC manufactured a dressing of pow-dered fibrinogen and thrombin on a removable silicone gel back-ing. They successfully tested this product in a goat major ballistictrauma model [8]. The latest iteration of this product substitutedabsorbable polyglactin mesh backing for the silicone gel and isnow known as the absorbable fibrin adhesive bandage (AFAB)(Fig. 1).

The AFAB consists of a concentrated mixture of lyophilizedfibrinogen and thrombin deposited on a polyglactin backing. Itsadvantages over liquid delivery systems include ease of use, con-venient storage, and enhanced hemostatic capability owing to thehigh concentration of clotting factors attainable. The AFAB isstable and inert when dry; but when placed in contact with mois-ture, such as blood, it forms a dense, gelatinous clot almostimmediately.

The AFAB has shown effectiveness in controlling hemorrhagein several animal models including both resuscitated and coagu-lopathic grade 5 liver laceration swine models [9, 10]. Applications

The views expressed in this article are those of the authors and do notreflect the official policy of the Department of Defense or other Depart-ments of the US government.

Correspondence to: A.F. Morey, M.D., e-mail: allen.morey@cen.amedd.army.mil

of the earlier generation silicone gel bandage showed effectivenessin a porcine femoral artery injury model [11].

Urologic Applications of the AFAB

Our laboratory at Brooke Army Medical Center Institute of Sur-gical Research has been actively seeking appropriate urologicapplications of this technology. Urologic uses of these productsmust account for unique concerns specific to the urinary tract:specifically, not only how well the AFAB controls hemorrhage butalso what effects it has on sealing the urinary collecting system andany potential long-term complications such as stone formation.

Radical Prostatectomy. The first urologic specific application ofthe AFAB was in a prostatectomy model. Prostatectomy is acommonly performed urologic procedure with a known risk ofsignificant hemorrhage. Cornum et al. [12] developed a canineprostatectomy model and applied an AFAB experimental proto-col as follows. After the canine prostate was removed with asurgical technique identical to that of a human retropubic pros-tatectomy, one of four treatments was applied to effect hemosta-sis. The AFAB application entailed laying the AFAB onto theprostatic bed and applying pressure. This method was comparedin a blinded fashion with an inert look-alike bandage, with liquidfibrin sealant, and with conventional surgical management forcontrolling hemorrhage. The AFAB bandage required less thanone-half the time compared to the other treatment arms toachieve hemostasis and showed significantly decreased blood loss(p � 0.5). Importantly, no differences were discovered with regardto anastomotic integrity or continence compared to conventionalmanagement [12]. The success of this application led to the de-velopment of models with clear urologic trauma applications.

Partial Nephrectomy. A porcine partial nephrectomy model wasdeveloped in which female pigs (n � 18) underwent left nephrec-

Fig. 1. Absorbable fibrin adhesivebandage (AFAB) is comprised oflayered fibrinogen and thrombin ona Vicryl mesh backing.

Fig. 2. A 40% lower pole right partial nephrectomy was done, clearlyexposing the renal pelvis.

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tomy and a 40% (by length) right lower pole partial nephrectomy(Fig. 2). One of three treatments was immediately applied.

1. Conventional—closure of the collecting system, ligation ofvisible segmental vessels, application of an oxidized regeneratedcellulose (Surgicel; Ethicon, Somerville, NJ, USA) bandage withbolstering sutures to the renal capsule.

2. AFAB—application of up to two 4 � 4 inch AFABs heldunder pressure for 60 seconds.

3. Placebo—application of a hemostatically inert Vicryl (Ethi-con) bandage, visually identical to the AFAB.

Blood loss and ischemic and total operative times were re-corded; and abdominal computed tomography (CT) was per-formed on postoperative day 6. Animals were sacrificed at 6 weeksto evaluate the remaining renal mass histologically.

Compared with conventional therapy, use of the AFAB re-sulted in significantly less bleeding (13 vs. 68 ml, p � 0.001) andlower operative (7.2 vs. 16.3 minutes, p � 0.001) and ischemictimes (3.4 vs. 7.8 minutes, p � 0.001). Postoperative CT andhistologic sectioning showed that the AFAB produces a stable,durable clot and that healing is at least as successful as withconventional treatment. Use of the AFAB facilitated performanceof partial nephrectomy by reducing blood loss and ischemic andtotal operative times. Again, the AFAB appeared equivalent toconventional surgery in terms of its ability to seal the collectingsystem [13].

Renal Stab Wound. Given the success of the partial nephrectomymodel in which hemorrhage from a major injury was easily con-trolled, we wondered what utility the AFAB may have in control-ling hemorrhage from a major penetrating renal injury. Penetrat-ing renal trauma poses a challenging surgical problem; significantinjuries require exploration and can result in major hemorrhageor nephrectomy.

We developed a porcine stab wound model by producing areproducible, potentially lethal, grade IV renal laceration. Specif-ically, a 3.5 cm sagitally oriented, centrally located, through-and-through stab wound was produced into an in vivo pig kidney (Fig.3). Treatments were then applied in a randomized fashion toinclude: (1) no treatment—suture closing the overlying perito-neum and then releasing the renal artery clamp; (2) conventionaltreatment—reconstructing the capsular defects with Gelfoam(Pharmacia & Upjohn, Kalamazoo, MI, USA) and horizontalmattress sutures; (3) liquid fibrin sealant; or (4) AFAB—twolayers of AFAB applied as sole therapy and pressure held for 60seconds. In all arms the sponges were weighed at the start and endof each operation to measure acute blood loss. Renal CT wasperformed on postoperative day 3, and serial samples for hemat-ocrit determinations were collected to assess for delayed bleeding.The animals were sacrificed at 6 weeks and the creatinine clear-ance from each kidney determined.

Compared to conventional repair, liquid fibrin sealant, and no

Fig. 3. Renal stab wound model consisted of a central, sagittal 3.5 cm, through-and-through laceration with an autopsy blade.

Anema et al.: Absorbable Fibrin Adhesive Bandage for Genitourinary Trauma 1575

treatment, the AFAB dramatically enhanced hemostasis. CTscans of the AFAB-treated pigs uniformly showed a small devi-talized segment lateral to the stab wounds with no urinary extrav-asation (Fig. 4). Moreover, compared to conventional repair, theAFAB required significantly less time for repair compared toconventional repair. No significant differences between the groupswere noted with regard to urinary leaks, delayed hemorrhage, orrenal function [14].

Discussion

The AFAB is a promising, potentially revolutionary product. Itshandling characteristics are adequate although not ideal. In its dryinert form the bandage is brittle and rigid, but when moistened itsoftens rapidly. Because firm direct pressure is required forproper application, the dense gelatinous clot produced by theAFAB can be difficult to disengage from the surgeon’s glovedhand. Saline irrigation obviates this problem. Safety of the AFABdoes not appear to be an issue. Current production techniqueshave virtually eliminated any risk of viral transmission, and sys-temic coagulopathic or hypotensive effects have not been ob-served [15].

The partial nephrectomy and renal stab wound models areimportant additions to the growing list of potential applicationsfor the AFAB. Potential clinical applications in humans are easilyinferred. With greater benefits being attributed to “damage con-trol” surgery, this technology could have multiple and significantapplications to the management of various renal injuries.

We believe that many trauma nephrectomies are performedunnecessarily, simply because renal reconstruction after deep lac-eration or significant acute parenchymal loss is labor-intensive,time-consuming, and potentially risky. In the trauma setting, thesurgeon often does not have the luxury of performing a meticu-

lous renal reconstruction. Trauma patients are often cold, coagu-lopathic, anemic, and hypotensive. Such patients could benefitsignificantly, however, if nephron salvage were both efficient andreliable. The AFAB has been shown to function equally well inhypothermic, hemodiluted pigs subjected to liver laceration [9,10].

Conclusions

The AFAB shows promise for facilitating renal salvage, whetherfor trauma or malignancy. It is simple to use and remarkablyeffective in achieving rapid hemostasis. Technical modifications ofbandage application should be studied further, as should otherindications. Potential applications in the prehospital setting, theoperating theater, and on the battlefield are limitless.

Résumé. L’utilisation de colles à base de fibrine est devenue de plus enplus populaire dans pratiquement toutes les spécialités chirurgicales.L’adhésive de fibrine résorbable (AFR) est un produit relativementnouveau, potentiellement révolutionnaire, fabriqué à partir defibrinogène et de thrombine séchées. L’AFR semble être extrêmementefficace, assurant une hémostase rapide, dans tous les modèles detraumatismes rénaux. L’AFR potentialise la cicatrisation de l’appareilurinaire. D’autres études sont nécessaires pour explorer cette nouvelletechnologie dans d’autres applications urologiques.

Resumen. Los sellantes de fibrina se han vuelto crecientemente popularesen la práctica de casi todas las especialidades quirúrgicas. El peganteabsorbible de fibrina (PAF) es un novel y potencialmente revolucionarioproducto hecho a base de fibrinógeno seco y trombina. El PAF parecetener tremenda eficacia en cuanto a hemostasia rápida en una variedadde modelos experimentales de trauma renal mayor. También pareceestimular la cicatrización en el sistema colector urinario. Se requierenestudios adicionales para determinar nuevas aplicaciones urológicas deesta excitante tecnología.

Fig. 4. Postoperative computedtomography (CT) scan on day 3after the right renal stab woundwith AFAB treatment reveals asmall, stable perirenal hematomaand a central renal defect.

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