Baxter International Inc.

develops, manufactures and markets products that save

and sustain the lives of people with hemophilia, immune disorders, infectious
diseases, kidney disease, trauma, and other chronic and acute medical
conditions. As a global, diversified healthcare company, Baxter applies a unique
combination of expertise in medical devices, pharmaceuticals and biotechnology
to create products that advance patient care worldwide.

Baxter's Biosurgery products are biologically active products and are used to
facilitate hemostasis and tissue sealing in surgery. The company's fibrin sealants,
for example, are made up of human fibrinogen and human thrombin, which when
mixed, replicate the start of the tissue sealing process to stop bleeding in certain
surgical procedures. Baxter is also developing products to facilitate the
regeneration of soft and hard tissue, including bone.

Control of bleeding is important in every surgical procedure, even minimally

invasive ones. The extent of intra-operative bleeding depends on a number of
factors, including the type of procedure and types of medicine given intra-
operatively. One other factor is the method of hemostasis the surgeon uses
during the procedure. Not all products work the same. For example, cardiac
patients are often placed on anti-coagulant medicines during surgery and may
experience a significant amount of bleeding.

Wounds must be effectively closed and bleeding controlled to ensure the

success of surgical procedures. Failure to close surgical wounds completely can
result in serious or possibly life-threatening complications, including blood loss,
tissue damage, infection and excessive scarring. If bleeding persists during a
difficult operation, a blood transfusion may be required.

The information contained in this page is intended for U.S. healthcare

professionals only.

BioSurgery
• ACTIFUSE [Bone Graft Substitute] Silicate Substituted Calcium
Phosphate
ACTIFUSE is a bone void filler intended for orthopedic applications as a
filler for gaps and voids that are not intrinsic to the stability of the bony
structure. ACTIFUSE is also intended to fill, augment, and/or reconstruct
maxillofacial osseous bone defects, including periodontal, oral, and
craniomaxillofacial applications.

ACTIFUSE is indicated to be packed gently into bony voids or gaps of the

skeletal system, i.e. extremities, pelvis and spine including use in
posterolateral spinal fusion procedures with appropriate stabilizing
hardware. These defects may be surgically created osseous defects or
osseous defects created from traumatic injury to the bone. The product
 provides a bone void filler that resorbs and is replaced by bone during the
healing process.

• ADEPT® Adhesion Reduction Solution [4% Icodextrin]

ADEPT Adhesion Reduction Solution is indicated for use intraperitoneally
as an adjunct to good surgical technique for the reduction of post-surgical
adhesions in patients undergoing gynecologic laparoscopic adhesiolysis.

• ARTISS [Fibrin Sealant (Human)]

ARTISS is indicated to adhere autologous skin grafts to surgically
prepared wound beds resulting from burns in adult and pediatric
populations. ARTISS is not indicated for hemostasis.

• COSEAL [Surgical Sealant]

COSEAL is indicated for use in vascular reconstructions to achieve
adjunctive hemostasis by mechanically sealing areas of leakage.

• FLOSEAL Hemostatic Matrix

FLOSEAL is indicated in surgical procedures (other than opthalmic) as an
adjunct to hemostasis when control of bleeding by ligature or conventional
procedures is ineffective or impractical.

• GELFOAM PLUS Hemostasis Kit

GELFOAM PLUS Hemostasis Kit is intended as a hemostatic device for
surgical procedures when control of capillary, venous, and arteriolar
bleeding by pressure, ligature, and other conventional procedures is either
ineffective or impractical. Thrombin (Human) used without the Gelfoam
Sterile Sponge is not indicated for hemostasis.

• TISSEEL [Fibrin Sealant]

Hemostasis: TISSEEL is indicated for use as an adjunct to hemostasis in
surgeries involving cardiopulmonary bypass and treatment of splenic
injuries due to blunt or penetrating trauma to the abdomen, when control
of bleeding by conventional surgical techniques, including suture, ligature,
and cautery, is ineffective or impractical. TISSEEL is a satisfactory
hemostatic agent in fully heparinized patients undergoing cardiopulmonary
bypass.

Sealing: TISSEEL is indicated as an adjunct to prevent leakage from

colonic anastomoses following the reversal of temporary colostomies
ACTIFUSE [Bone Graft Substitute]
Silicate Substituted Calcium
Phosphate
ACTIFUSE [Bone Graft Substitute] Silicate Substituted Calcium Phosphate
is a 100% synthetic, osteostimulative bone graft substitute. It is an autograft
alternative without the complications of a secondary surgery site2,8. The
ACTIFUSE family of products has been designed to provide control of bone graft
placement throughout the surgery. Effective in a variety of surgical procedures.

Family of Products: ACTIFUSE MIS System; ACTIFUSE ABX; ACTIFUSE

Shape; ACTIFUSE Granules and ACTIFUSE Mocrogranules

Indications & Usage

ACTIFUSE is a bone void filler intended for orthopedic applications as a filler for
gaps and voids that are not intrinsic to the stability of the bony structure.
ACTIFUSE is also intended to fill, augment, and/or reconstruct maxillofacial
osseous bone defects, including periodontal, oral, and craniomaxillofacial
applications.

ACTIFUSE is indicated to be packed gently into bony voids or gaps of the

skeletal system, i.e. extremities, pelvis and spine including use in posterolateral
spinal fusion procedures with appropriate stabilizing hardware. These defects
may be surgically created osseous defects or osseous defects created from
traumatic injury to the bone. The product provides a bone void filler that resorbs
and is replaced by bone during the healing process.

ACTIFUSE has not been cleared for use in vertebroplasty.

Features
• ACTIFUSE accelerates bone growth by combining an interconnected
macro- and micro- porous structure with osteostimulative chemistry
created through a patented silicate substitution process to attach and
stimulate osteoprogenitor cells (OPCs) and mesenchymal stem cells
(MSCs).1,2,9
• ACTIFUSE mimics the composition of human bone with the optimal 0.8%
silicon by weight, which is similar to the level identified in naturally-growing
bone3, enhancing osteoblast and hMSC attachment, and protein
adsorption.2,4
 • ACTIFUSE has a physiologically appropriate resorption rate: like human
bone, ACTIFUSE is remodeled via osteoclastic resorption rather than
chemical dissolution.1
• ACTIFUSE provides a stable scaffold for as long as the bone healing
process requires it.1
• ACTIFUSE is a purely synthetic, sterile, and consistent bone graft,
mitigating disease transmission.
• The ACTIFUSE Family of Products includes a variety of formulations
designed for surgical control.
• ACTIFUSE resists irrigation and compression5,6
• ACTIFUSE is ready to use, no mixing or preparation required7
No special storage required7
• ACTIFUSE can be clearly viewed on x-ray8

Important Risk Information

ACTIFUSE is contraindicated where the device is intended as structural/load-
bearing support in the skeletal system.

ACTIFUSE has not been cleared for use in vertebroplasty.

Other conditions representing contraindications include: severe vascular or

neurological disease; uncontrolled diabetes; severe degenerative disease;
uncooperative patients who cannot or will not follow post-operative instruction,
including individuals who abuse drugs and/or alcohol; hypercalcemia, abnormal
calcium metabolism; existing acute or chronic infections, especially at the site of
the operation; inflammatory bone disease such as osteomyelitis; malignant
tumors; severely impaired renal function.

Attempts should not be made to modify the size of the granules or to change
their shape. It is important to maximize contact between existing bone and the
implant to ensure proper bone regeneration.

The graft must be secured to prevent potential migration and should only
be used in surgical procedures where bone grafts are adequately
contained. Do not overfill or attempt to pressurize the bony defect site, as
this may lead to extrusion of the product beyond the site of its intended
application and damage the surrounding tissues, or may lead to fat
embolization or embolization of the device into the bloodstream. The effect
of mixing ACTIFUSE with substances other than sterile saline/water,
autologous blood, or bone marrow aspirate is unknown.
ADEPT ® Adhesion Reduction
Solution [4% Icodextrin]
ADEPT® is an icodextrin solution that keeps the peritoneal surfaces apart for 3 to
4 days during the critical post-surgery period when the patient is at greatest risk
of adhesion formation following laparoscopic gynecologic adhesiolysis.1,2

Indications & Usage

ADEPT® Adhesion Reduction Solution [4% Icodextrin] is indicated for use
intraperitoneally as an adjunct to good surgical technique for the reduction of
post-surgical adhesions in patients undergoing gynecological laparoscopic
adhesiolysis.

Features
• ADEPT® provides a temporary separation of peritoneal surfaces by
hydroflotation as a result of maintaining a fluid reservoir. Icodextrin
functions as a colloid osmotic agent. This colloidal osmotic action of
icodextrin allows the retention of a reservoir of fluid within the peritoneal
cavity for 3-4 days.1,3
• ADEPT® minimizes tissue apposition during the critical period of fibrin
formation and mesothelial regeneration following surgery, thereby
providing a barrier to adhesion formation.1

Easy To Use
• Requires no significant change to surgical routine2
• Does not impair tissue handling and visibility of the surgical field2

Important Risk Information

ADEPT is for direct intraperitoneal administration only. NOT for intravenous (IV)
administration. Adept is contraindicated in patients with known or suspected
allergy to cornstarch based polymers e.g. icodextrin, or with maltose or
isomaltose intolerance, or with glycogen storage disease. ADEPT is
contraindicated in laparotomy, in cases involving bowel resection or repair, or
appendectomy and in surgical cases with frank abdomino-pelvic infection.

There have been rare reports of sterile peritonitis following the use of icodextrin.
Leakage of ADEPT from port sites may lead to wound healing complications;
meticulous fascial closure may reduce leakage through laparoscopic port sites
post-operatively. There have been rare reports of hypersensitivity reactions,
pulmonary edema, pulmonary effusion and arrhythmia. Anaphylaxis has been
reported in a few patients. Maltose metabolites of icodextrin may interefere with
blood glucose measurement in diabetic patients who use rapid blood glucose
systems that are not glucose specific.

In the pivotal study, the most frequently occurring treatment-related adverse

events between surgeries were post procedural leaking from port sites, labial,
vulvar or vaginal swelling and abdominal distention.

ARTISS [Fibrin Sealant (Human)]

ARTISS [Fibrin Sealant (Human)], Vapor Heated, Solvent Detergent Treated,
(ARTISS) is a two-component fibrin sealant made from pooled human plasma.
When combined, the two components, Sealer Protein (Human) and Thrombin
(Human), mimic the final stage of the blood coagulation cascade.

Indications & Usage

ARTISS is indicated to adhere autologous skin grafts to surgically prepared
wound beds, resulting from burns in adult and pediatric populations.

ARTISS is not indicated for hemostasis.

Features
• ARTISS provides full surface adhesion of the graft to the wound bed,
closing the space that exists when grafts are attached using point fixation
techniques such as staples1
• ARTISS sets in approximately 60 seconds, and is specifically designed for
use in burn surgery allowing the surgeon time to manipulate and position
the graft prior to polymerization2
• ARTISS does not require staple fixation of donor graft, eliminating need
for applying and removing staples1

Applications
The aerosolized sealant should be applied to the wound in a painting motion from
side to side to achieve a single thin application.
The wound bed will glisten in the area to which fibrin sealant has been applied.
Any areas not covered by fibrin sealant will be clearly visible.

The wound bed should be as dry as possible before application

Important Information when applying ARTISS:

For Topical Use Only.

• Do not inject directly into the circulatory system; thromboembolic events

can occur.
• Air or gas embolism has occurred with the use of spray devices employing
pressure regulator to administer fibrin sealants. This event appears to be
related to the use of the spray device at higher than recommended
pressures and in close proximity to the surface of the tissue.
• Apply only as thin layer.
• Use caution when applying ARTISS with pressurized gas.

Mechanism of Action
Upon mixing Sealer Protein (Human) and Thrombin (Human), soluble fibrinogen
is transformed into fibrin that adheres to the wound surface and to the skin graft
to be affixed. Due to the low thrombin concentration, polymerization of ARTISS
will take approximately 60 seconds.

ARTISS Safety Profile

Adverse reactions occuring in greater than 1% of patients treated with ARTISS
were skin graft failure and pruritus.

Important Risk Information

For Topical Use Only. Do not inject ARTISS directly into blood vessels.
Intravascular application of ARTISS may result in life-threatening
thromboembolic events.

Do not use ARTISS in individuals with a known hypersensitivity to aprotinin

and/or hypersensitivity to any of the active or excipients.

Hypersensitivity or allergic/anaphylactoid reactions may occur with the use of

ARTISS. Symptoms associated with allergic anaphylactic reactions include:
flush, urticaria, pruritus, nausea, drop in blood pressure, tachycardia or
bradycardia, dyspnea, severe hypotension and anaphylactic shock. Such
reactions may also occur in patients receiving ARTISS for the first time.
Discontinue administration of ARTISS in the event of hypersensitivity reactions.

Apply as a thin layer. Excessive clot thickness may negatively interfere with the
product's efficacy and the wound healing process.

Air or gas embolism has occurred with the use of spray devices employing a
pressure regulator to administer fibrin sealants. This event appears to be related
to the use of the spray device at higher than recommended pressures and in
close proximity to the tissue surface.

When applying ARTISS using a spray device, be sure to use the pressure within
the pressure range recommended by the spray device manufacturer.

Exposure to solutions containing alcohol, iodine or heavy metals may cause

ARTISS to be denatured. If any of these substances have been used to clean the
wound area, the area must be thoroughly rinsed before the application of
ARTISS and made as dry as possible.

ARTISS is made from human plasma. It may carry a risk of transmitting

infectious agents, e.g., viruses, and theoretically, the Creutzfeldt-Jakob disease
(CJD) agent.

Adverse reactions occurring in greater than 1% of patients treated with ARTISS

were skin graft failure (5 events of 138 patients treated) and pruritus (2 events of
138 patients treated).

COSEAL [Surgical Sealant]

The information contained in this page is intended for U.S. healthcare
professionals only.

COSEAL is a completely synthetic hemostatic sealing agent for peripheral

vascular reconstructions.

Indications
COSEAL is indicated for use in vascular reconstructions to achieve adjunctive
hemostasis by mechanically sealing areas of leakage.

Features
 • Sealing capability within 60 seconds and does not require any human
blood products or bovine components to inhibit bleeding 1,3
• Immediate anastomotic sealing [median time to complete sealing 16.5
seconds]1
• No refrigeration required; use directly from shelf [approximately 25°C] to
sterile field2
• To suit your needs, COSEAL has four applicator options- including our
Hand-Controlled SpraySet system: 7cm and 22cm Flex Direct Tip;
Extended Flex Direct Tip for uniform coverage and control
• Flexible, gel-like seal that remains intact at the site of application 3

Safety
• COSEAL is 100% synthetic and avoids risk of patient hypersensitivities to
bovine components or glutaraldehyde contributed from the use of a
sealant4

Important Risk Information

COSEAL is not to be used in place of sutures, staples, or mechanical closure.

COSEAL swells up to four times its volume within 24 hours of application

and additional swelling occurs as the gel resorbs. Therefore, surgeons
should consider the maximum swell volume and its possible effect on
surrounding anatomic structures potentially sensitive to compression.

Apply only as a thin layer.

Use caution when applying with pressurized gas.

Do not place devices or other objects on top of tissue where COSEAL has been
applied, until the material is fully polymerized (non-tacky).

Do not apply COSEAL over any devices or objects that will need to be removed.
COSEAL must not be used as a mechanism of adherence, even temporarily, for
any object.

Do not inject COSEAL into vessels.

In vivo testing demonstrated a mild skin sensitization response in an animal

model. Similar testing in humans has not been conducted.
FLOSEAL Hemostatic Matrix
FLOSEAL is an an effective adjunctive hemostatic agent that stops bleeding in 2
minutes (median time to hemostasis). 1

Indications & Usage

FLOSEAL is indicated in surgical procedures (other than ophthalmic) as an
adjunct to hemostasis when control of bleeding by ligature or conventional
procedures is ineffective or impractical.

Features
• FLOSEAL Hemostatic Matrix is a proprietary combination of two
independent hemostasis-promoting agents1,2
• FLOSEAL is effective for all degrees of bleeding, from oozing to spurting1,2
• Works on wet, actively bleeding tissue1,2
• Conforms to irregular wound surfaces and is easy to deliver to hard-to-
reach surfaces2,3
• Proven effective on hard and soft tissue3
• FLOSEAL Hemostatic Matrix consists of patented bovine-derived gelatin
granules coated in human-derived thrombin that work in combination to
form a stable clot at the bleeding site1,4
• All-in-one package with human thrombin and no refrigeration required1
• FLOSEAL granules expand approximately 20% within about 10 minutes,
giving predictable control during and after surgery
• Only excess product not incorporated in clot should always be removed 1
• FDA approved since 19995

Safety and Efficacy

• FLOSEAL is proven to stop bleeding in two minutes (median time to
hemostasis) in patients undergoing cardiac, vascular, or spinal/orthopedic
surgery1
• FLOSEAL stops bleeding 97% of the time within 6-10 minutes, 93% of the
time within 3-6 minutes (first lesion; per protocol analysis)1
• FLOSEAL Hemostatic Matrix was efficacious 89% of the time in fully-
heparinized patients undergoing cardiac surgery1,2
• FLOSEAL is resorbed by the body within 6-8 weeks, consistent with the
time frame of normal wound healing4

Important Risk Information

Do not use FLOSEAL in patients with known allergies to materials of bovine
origin.

Do not use FLOSEAL in the closure of skin incisions because it may interfere
with the healing of the skin edges.

FLOSEAL must not be injected into blood vessels, or allowed to enter blood
vessels. Do not apply in the absence of active bleeding. Extensive intravascular
clotting and even death may result.

FLOSEAL is made from human plasma. It may carry a risk of transmitting

infectious agents, e.g., viruses, and theoretically, the Creutzfeldt-Jakob disease
(CJD) agent.

FLOSEAL is not intended as a substitute for meticulous surgical technique and

the proper application of ligatures or other conventional procedures for
hemostasis.

Excess FLOSEAL (material not incorporated in the hemostatic clot) should

always be removed by gentle irrigation from the site of application.

The maximum swell volume of approximately 20% is achieved within about 10

minutes.

FLOSEAL should not be used in conjunction with methylmethacrylate or other

acrylic adhesives. Do not use FLOSEAL on bone surfaces where adhesives will
be required to attach a prosthetic device.

RX Only: For safe and proper use of this device, please refer to full device
Instructions For Use.

GELFOAM PLUS ® Hemostasis Kit

GELFOAM PLUS is the only hemostasis kit that contains the Gelfoam
brand...plus Baxter's Human Thrombin.

Indications
GELFOAM PLUS is intended as a hemostatic device for surgical procedures
when control of capillary, venous, and arteriolar bleeding by pressure, ligature,
and other conventional procedures is either ineffective or impractical.
Thrombin (Human) used without the Gelfoam Sterile Sponge is not indicated for
hemostasis.

Features
• Offered in a convenient kit that contains: 1 Gelfoam sterile sponge (size
100), thrombin (human) dried powder, saline solution and a sterile 10 mL
syringe with needle
• Provides up to 20 mL of volume to saturate the Gelfoam sterile sponge
• Can provide cost savings compared to items purchased separately1
• Allows easy management of thrombin use
• Can help consolidate inventory of multiple products
• Can be stored at room temperature (15-25°C)

Clinical Study
• In an animal study*, Gelfoam with human thrombin at 125 IU/mL was
associated with an acceleration of hemostasis and a reduction in the
amount of bleeding compared to Gelfoam and saline2

* In a porcine model, the rate of bleeding was scored at various time intervals.
Data collected and analyzed on four animals. Twenty lesions were created in
each animal (10 control and 10 treatment) allowing for a total of 80 lesions.

The treated group was Gelfoam Plus, and the control group was Gelfoam and
saline.

Important Risk Information

• GELFOAM PLUS should not be used in closure of skin incisions, because
it may interfere with the healing of the skin edges. GELFOAM PLUS
should not be placed intravascularly, because of the risk of embolization.
• GELFOAM PLUS is not recommended for use other than an adjunct for
hemostasis.
• GELFOAM PLUS contains thrombin, which is made from human plasma.
It may carry the risk of transmitting infectious agents, e.g., viruses, and
theoretically the Creutzfeldt-Jakob disease (CJD) agent.
• While packing a cavity for hemostasis is sometimes surgically indicated,
GELFOAM PLUS should not be used in this manner unless excess
product not needed to maintain hemostasis is removed. Whenever
possible, GELFOAM PLUS should be removed after use in laminectomy
procedures and from foramina in bone, once hemostasis is achieved. This
is because GELFOAM Plus may swell to its original size on absorbing
fluids, and produce nerve damage by pressure within confined bony
spaces.
 • GELFOAM PLUS is not recommended in the presence of infection. There
have been reports of fever associated with the use of Gelfoam Sterile
Sponge, without demonstrable infection.

TISSEEL [Fibrin Sealant]

TISSEEL consists of a two-component fibrin sealant that offers concentrated
human fibrinogen as an adjunct for sealing in the closure of colostomies and to
stop diffuse bleeding in surgeries involving cardiopulmonary bypass and
treatment of splenic injuries.

Indications
Hemostasis: TISSEEL is indicated for use as an adjunct to hemostasis in
surgeries involving cardiopulmonary bypass and treatment of splenic injuries due
to blunt or penetrating trauma to the abdomen, when control of bleeding by
conventional surgical techniques, including suture, ligature, and cautery, is
ineffective or impractical. TISSEEL is a satisfactory hemostatic agent in fully
heparinized patients undergoing cardiopulmonary bypass.

Sealing: TISSEEL is indicated as an adjunct to prevent leakage from colonic

anastomoses following the reversal of temporary colostomies.

Features
• Pre-filled syringe can be ready in a few minutes if thawed and warmed in
advance 1. Please see PI for complete information.
• Upon mixing Sealer Protein (Human) and Thrombin (Human), soluble
fibrinogen is transformed into fibrin, forming a rubber-like mass that
adheres to the wound surface and achieves hemostasis and sealing or
gluing of tissues1
• Fibrinogen is converted to fibrin strands that join into net-like matrices2

Safety and Efficacy

• Manufactured using processed, screened pooled human plasma,
(collected at US licensed collection centers), a vapor heating process, and
a solvent detergent process1
• Satisfactory for use in fully heparinized patients undergoing
cardiopulmonary bypass1
Tisseel is made from human plasma. It may carry a risk of transmitting infectious
agents, e.g., viruses, and theoretically, the Creutzfeldt-Jakob disease (CJD)
agent.

Important Risk Information

For Topical Use Only. Do not inject TISSEEL directly into the circulatory
system. Intravascular application of TISSEEL may result in life-threatening
thromboembolic events. Caution should be exercised to minimize any risk of
inadvertent intravascular application.

Do not use TISSEEL in individuals with a known hypersensitivity to aprotinin.

Do not use TISSEEL for the treatment of severe or brisk arterial bleeding. In
these situations, TISSEEL will be washed away in the flow of blood before
hemostasis can be attained.

Hypersensitivity or allergic/anaphylactoid reactions may occur with the use of

TISSEEL. Symptoms associated with allergic reactions include: flush, urticaria,
pruritus, nausea, drop in blood pressure, tachycardia or bradycardia, dyspnea,
severe hypotension and anaphylactic shock. Such reactions may also occur in
patients receiving TISSEEL for the first time.

Discontinue administration of TISSEEL in the event of hypersensitivity reactions.

Apply as a thin layer. Excessive clot thickness may negatively interfere with the
product's efficacy and the wound healing process.

Air or gas embolism has occurred with the use of spray devices employing
pressure regulator to administer fibrin sealants. This event appears to be related
to use of the spray device at higher than recommended pressures and in close
proximity to the tissue surface.

When applying fibrin sealants using a spray device, be sure to use the pressure
within the pressure range recommended by the spray device manufacturer.

Exposure to solutions containing alcohol, iodine or heavy metals may cause

TISSEEL to be denatured. If any of these substances have been used to clean
the wound area, the area must be thoroughly rinsed before the application of
TISSEEL.

The safety and effectiveness of TISSEEL used alone or in combination with

biocompatible carriers in neurosurgical procedures or other surgeries involving
confined spaces have not been evaluated; its use in this setting is not FDA
approved.
There have been reports of serious adverse events such as paralysis and other
compressive complications possibly related to the use of fibrin sealant in
combination with resorbable hemostatic agents.

TISSEEL is made from human plasma. It may carry a risk of transmitting

infectious agents, e.g., viruses, and theoretically, the Creutzfeldt-Jakob disease
(CJD) agent.