Article published in Dentistry Today
March 2005, pages 62 – 65
(with permission of authors)
Review of Hemostatic Agents Used in Dentistry
Dentists perform a variety of surgical
procedures frequently requiring the need for a
hemostatic agent. Exodontia, tissue biopsies,
placement of endosseous implants, and
periodontal surgery are just some examples
where hemostatic agents may be beneficial. Not
only are these agents useful for specific
procedures, but they also are valuable for
certain patient groups, specifically those with
coagulation defects. These defects may be
genetic or acquired (Table). A comprehensive
review of this topic is beyond the scope of this
article. Nevertheless, dentists performing
surgery should be familiar with these defects
and their clinical manifestations. Figure 1
demonstrates a schematic diagram of the
cascade of events leading to the formation of a
fibrin clot. These steps are initially divided into
intrinsic and extrinsic pathways, leading into a
common pathway of coagulation.
This article is a review of perioperative
hemorrhage, certain available hemostatic
agents, and an introduction to a new agent with
good potential for application in the oral cavity.
PERIOPERATIVE HEMORRHAGE
The best management of perioperative
hemorrhage is prevention. This includes a
thorough preoperative patient history, necessary
medical consults, familiarity with managing
patients with possible bleeding diathesis,
meticulous intra-operative technique, and
appropriate post-operative instructions, care,
and follow-up. Although these are easily listed,
application in practice can be challenging.
Multiple obstacles may prevent the
implementation of the management steps listed.
Some of these hurdles include treating patients
with an undisclosed or undiagnosed medical
condition, improper information retrieval, or
difficult surgical conditions. Poor patient
compliance with medication or postoperative
instructions also are factors to be considered.
If an intraoperative bleeding episode is
encountered, the clinician should consider
several steps. A quick mental review of the
patient's medical history is first. If the
hemorrhagic episode is difficult to manage,
injection of 1/50,000 solution of epinephrine
into the area may be needed. This will likely
provide temporary reduction of bleeding as a
result of local vasoconstriction. The site may
need to be packed, and the clinician will need to
consider the seriousness of the event. If very
serious, a call to an emergency service (911)
may be necessary. Further, if the dentist is
properly, trained starting an intravenous line to
initiate fluid resuscitation may be advisable.
The process of immediate delivery of the
patient to a medical facility for possible
transfusions, anticoagulant reversal, and general
life support measures can be initiated.
However, a careful clinician will rarely
encounter such an event in an outpatient office
setting. More commonly, dentists confront
patients with inconvenient, nonemergent
bleeding events that require a response.
During oral surgical procedures,
persistent minor oozing of blood is
common, although occasionally a bleeding
episode prevents the continuation of the
procedure and requires immediate
attention. The usual sources for this
intraoperative complication are incision
into an area of granulomatous tissue,
vessels in the periosteum or mucosa, or
encountering nutrient arteries in the
alveolar bone. Identification of the source
of the bleeding requires good illumination,
adequate retraction, and thorough
suctioning. Once identified, the bleeding
site should be packed, clamped,
cauterized, burnished, debrided, and/or
sutured for control. Topical hemostatic
agents should be available, and if
necessary, applied.
The dentist should be familiar with
the range of methods, techniques,
materials, and their application during
different types of bleeding episodes.
Having a broad knowledge of the
management approaches will allow the
clinician to know when to apply a
particular approach. Unfortunately, some
of the most useful preventive measures
and management techniques are not
utilized because of a lack of understanding
of the coagulation process and/or the
approaches and materials that are
available.
One of the more common methods
of intraoperative hemorrhage control
involves the use of a topical hemostatic
agent. This article reviews some of the
more common hemostatic agents and
introduces ActCel (MedSpring Group), a
hemostatic agent that has recently become
available.
TOPICAL HEMOSTATIC AGENTS
Hemostatic Collagen
These products (eg, CollaPlug,
CollaTape, and Helistat [Integra
LifeSciences]) are soft, white, pliable,
nonfriable, coherent, sponge-like
structures. They are fabricated from
bovine collagen (usually from deep flexor
tendons) and are nontoxic and
nonpyrogenic. The products are highly
absorbent and able to hold many times
their own weight of fluid. Their
indications are for wound protection and
for control of oozing or bleeding from
clean oral wounds. As for application,
these products should be held in place for
approximately 2 to 5 minutes to achieve
hemostasis and then may be removed,
replaced, or left in situ. All of these
collagen materials are completely
resorbed within 14 to 56 days.1
In addition to serving as a
mechanical obstruction to bleeding, these
materials affect the coagulation process.
In contact with blood, collagen causes
Figure 1. Coagulation cascade. (Reprinted
from Handbook for Anesthesia and Co-
Existing Disease, Vol 1, Robert K. Stoelting,
MD, and Stephen F. Dierdorf, MD, page 256,
1993, with permission from Elsevier.)
aggregation of platelets, which bind in large
numbers to the collagen fibrils.
The aggregated platelets degranulate,
releasing factors such as thromboxane A22 that
assist in the formation of a clot. The sponge also
provides a 3-D matrix for strengthening the blood
clot.3
As with most hemostatic agents, collagens
are not to be used in infected or contaminated
wounds. The agents may serve as a nidus for
abscess formation and may potentiate bacterial
growth. Possible adverse reactions are formation
of adhesions, allergic reactions, foreign body
reactions, and subgaleal seroma formation3
(subgaleal seroma is an accumulation of blood
serum beneath the scalp). In an animal model,
incision sites inoculated with Staphylococcus
aureus demonstrated more infection when collagen
was used as compared to a control.3 Such results
are similar to what has been reported for other
hemostatic agents.3
Besides sponges and plugs, these products
are available in microfibrillar form. This form is
generally less useful for oral surgical procedures.
Gelatin
(eg, Gelfoam)
Gelfoam (Pharmacia) is one of the more
commonly employed agents for the control of
minor bleeding, It is a porous, pliable sponge made
from dried and sterilized porcine skin gelatin.
Gelfoam's mode of action is not completely
understood, but unlike collagen, it is believed to be
related to formation of a mechanical matrix that
facilitates clotting4-7 rather than affecting the
blood-clotting mechanism. This agent can retain in
its interstices 45 times its weight in blood.8
Gelfoam liquefies in one week and is completely
resorbed in 4 to 6 weeks.
Its use is not associated with excessive scar
formation.8-12 Reported adverse reactions are giant
cell granuloma and hematoma formation, foreign
body reactions, excessive fibrosis, toxic shock
syndrome, fever, and failure of absorption.13
Bone Wax
Bone Wax (Ethicon) is a sterile mixture of
 evaluate the extrinsic
pathway. These tests
measure different phases of
early aspects of the
coagulation process
(intrinsic and extrinsic
pathways), but all measure
the common pathway and
Figure 5. Preoperative Figure 6. In the process of formation of end
radiograph of tooth No. 32- removing bone with a bur on the products.25 Research has
a partial bony impaction. disto-buccal aspect of this tooth
The patient is a 32-year-old (see x-ray in Figure 5), a nutrient demonstrated that in vitro,
male and is healthy with no canal (artery) was cut. Some PTT is decreased (resulting
Figures 2a and 2b. Left: A 1 x 1-inch piece of hemostatic gauze. known bleeding problems. spurting of blood ensued. The
Right: The same piece of gauze that has been placed for a few vessel was localized by the use of in enhanced clotting) with
seconds into water. Upon saturation with water or blood, the gauze suction, and bone surrounding the the presence of ActCel in
starts to convert to a resorbable, gel-like state. In a fresh bleeding source was compressed
extraction socket, it serves to promote hemostasis and stabilize a into the site with a periosteal
the wound.24 (The
blood clot. elevator. Bleeding lessened but still procedure consists of
continued. The next step was to
burnish Bone Wax into the bleeding
placing defined weight, or a
bony orifice. Again, the magnitude surface area equivalent, of
of bleeding diminished but did not
stop. Note the amount of blood
test material in contact with
collected on 4 x 4-inch gauze citrated plasma, incubation,
sponges during this period of time.
and then adding a PTT
reagent and calcium
chloride. Time required for
organisms, and it does not clotting is then determined
enhance infection under After an injury,
platelets are activated, for the test sample and the
experimental conditions.16- control, which has no
19
Nevertheless, it is still changing from a discoid to
spherical shape and device contact. A minimum
Figure 3. The cotton plier is Figure 4. The gauze is placed in recommended to avoid its of 6 tests were performed,
grasping a 1 x 1-inch piece of and out of the socket until it is extending pseudopodia.
hemostatic gauze. It is ready to be totally saturated with blood.
use in contaminated averaged, and statistically
placed in a lower third molar socket.
When saturated, it can be left in wounds where persistent Platelets release factors
The purpose of the gauze is to help
the socket, since it readily such as thromboxane A22 analyzed using analysis of
stabilize the clot and prevent a dry
converts to glucose and saline
drainage is desired. variance.) These data
socket. It has been lightly coated that stimulate other
with tetracycline. (Approximately 20 within 1 to 2 weeks. One or Encapsulation of fluid and support the role of ActCel
1 x 1-inch pieces of the gauze were more sutures can then be placed foreign body reactions have platelets to activate.
placed in a sterile container to which superiorly to close the wound.
Platelets have receptors that in modifying the intrinsic
the contents of one 250-mg capsule been reported,20-22 and a pathway.
of tetracycline was added. The promote their adhesion to
container was then shaken to coat burning sensation has been Additionally, many
each piece uniformly with a small
noted when the product is blood vessel linings,
amount of tetracycline powder.) As
collagen, and other of the previously
the gauze enters the socket, it is placed in unanesthetized mentioned enzyme-
easily controlled and manipulated
with the cotton pliers. nasal passages. 15 platelets.2 It has been
demonstrated that the mediated reactions within
ActCel is a new the clotting cascade are
topical hemostatic agent fabric-like and solid texture
of ActCel slows blood flow calcium dependent. One
beeswax, paraffin, and that is made from treated study has demonstrated that
isopropyl palmitate (a and sterilized cellulose and and reduces the time for
Cellulose ActCel adheres to calcium
softening agent) that is available in similar fabric thrombin to be released
(eg, Surgicel, ActCel)
into the wound.24 This ions,23 making calcium
packaged in individual foil meshwork as Surgicel, more available for the
envelopes. It is useful when although it is slightly more increases platelet adhesion
Surgicel (Johnson clotting cascade. Further,
bleeding is from a friable. It is an FDA- (similar to platelet
& Johnson) is a resorbable since the material's surface
visualized local vascular approved material aggregation at a damaged
oxidized cellulose material area increases as it
channel within bone, indicated for the control of blood vessel wall or at
and is an expensive but dissolves, the area available
commonly referred to as a bleeding from open wounds exposed collagen), thereby
useful option in oral for the coagulation process
"bone bleeder," at the and body cavities (eg, reducing the time to
surgery. It is prepared as a also increases.
surgical site. This occurs mouth, ears, nose, throat, establish the clot.
sterile fabric meshwork. Its Another special
commonly during the and vagina). The material Subsequently,
mechanism of action is not characteristic of this
extraction of mandibular does not contain chemical coagulation progresses
completely understood, but material is its bacteriostatic
third molars, and if not additives, thrombin, or through a cascade of events
appears to be physical properties.24
This is
adequately addressed collagen, and is hypo- with the relatively unstable
rather than involve an especially important in
during surgery can be a allergenic. In contact with platelet plug being replaced
alteration of the clotting contaminated wounds or in
reason for postoperative blood, it expands to 3 to 4 with a stronger, more
mechanism. After it is fully body cavities in which it is
bleeding. The wax is times its original size and is resilient clot. This cascade
absorbed with blood, it difficult or impossible to
pliable enough to be placed almost immediately involves a series of
swells into a maintain a sterile field.
within a vascular channel, converted to a gel. interdependent, enzyme-
brownish/black gelatinous
immediately tamponading Complete dissolution of the mediated reactions that are
mass that aids in clotting. Dry Socket Prevention
the vascular source. product takes place within initiated by the
Excessive amounts of the
Bone Wax is 1 to 2 weeks.23 Because of degranulation of platelets
material should be removed Localized alveolar
nonresorbable, and due to its purity and the fact that it or the release of activated
if possible to prevent osteitis is the most common
its possible adverse effect degrades rapidly into tissue thromboplastin from
delayed healing. complication in extractions,
on osteogenesis,14 caution biocompatible end products damaged blood vessels.
Specific dental with a prevalence of 1.9%
should bee used where (glucose, water), it does The fundamental reaction is
indications include use as to 31.2% following
regeneration of bone is not adversely affect wound the generation of thrombin
an adjunct to control removal of mandibular
expected (eg, a future healing. ActCel's and fibrin from
bleeding in exodontia and third molar teeth.26-28 A
implant site). Mild mechanisms of action are prothrombin and
other oral surgical variety of theories exist as
inflammatory reactions multiple, enhancing the fibrinogen, respectively.
procedures.15 This material to its etiology, although it
have been reported in coagulation process Clinically, the blood tests
may be more useful in soft- certainly involves an
tissues adjacent to the site biochemically by performed to detect
tissue procedures due to its interruption of the
of Bone Wax enhancing platelet abnormalities within this
shape, consistency, and healing process. This
implantation,14 and this aggregation and physically series of events are partial
interference with condition is a significant
agent may prevent the by 3-D clot stabilization thromboplastin time (PTT)
osteogenesis. problem for both the
clearing of bacteria from (Figure 2). to assess the intrinsic
Surgicel has been clinician & the patient, as
infected sites.1 pathway or prothrombin
found to be bacteriocidal in 45% of patients who
time (PT) and international
vitro against many develop alveolar
normalized ratio (INR) to
osteitis require at least 4 additional
postoperative visits.29 Several
methods have been found to reduce
the incidence of alveolar osteitis,
including the use of both topical30-32
and systemic agents. 33-35
Preliminary results examining the
use of ActCel and tetracycline in
mandibular impacted extraction
sites have reduced alveolar osteitis
(personal observation).
Randomized controlled trials are
needed to substantiate these
observations.
Indications for the use of
ActCel are the control of bleeding
or protection of a wound in the oral
cavity. This includes minor oozing
that may require additional
hemostatic assistance, routine use
in mandibular third molar
extraction sites to decrease the
occurrence of alveolar osteitis, or
as an adjunct for control of arterial
bleeding (first stopping the arterial
bleed with other methods and then
assisting in stabilizing the clot by
placement of ActCel). ActCel, as
previously noted, should not be
placed in areas that are not in
communication with the external
environment or placed in infected
sites (Figures 3 to 8).
CONCLUSION
Hemostatic agents are used
in dentistry for hemorrhage control
and wound protection. This
article has reviewed
different hemostatic agents, their
mechanisms of action, and their
clinical indications and
contraindications. ActCel, a new
hemostatic agent, was reviewed.
References
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Table. Categories Of
Coagulation Disorders
Hereditary
------------------------------------------
hemophilia A
hemophilia B
von Willebrand's disease
afibrinogenemia
factor V deficiency
factor XIII deficiency
hereditary hemorrhagic
telangiectasia
protein C deficiency
antithrombin III deficiency
Acquired
------------------------------------------
vitamin K deficiency
drug induced hemorrhage
massive blood transfusion
postcardiopulmonary bypass
disseminated intravascular
coagulation
drug induced platelet dysfunction
idiopathic thrombocytopenic
purpura
catheter induced
thrombocytopenia
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Figure 7. Since bleeding was not
yet completely controlled
(continued from Figures 5 and 6),
1 x 1-inch pieces of hemostatic
gauze were placed in the socket
one-by-one until the bleeding
totally stopped. A total of 8 pieces
were placed. After a few minutes,
3 sutures were tied to
approximate soft tissue over the
socket. This helped contain the
gauze and protect it from
dislodgement. After 30 minutes of
observation, the patient was
allowed to leave the office.
23. Zhang Qin shang Xu Qing zhong. Application
of S 99 soluble styptic gauze to wounds. Beijing
Xuan Wu Hospital, Departments of Pathology and
Stomatology. Beijing, China. December 31, 1982:
personal communication.
24. Data on file. Nelson Laboratories, Inc; Salt
Lake City, Utah; Telephone: (801) 963 2600.
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JR, Zieve PD eds. Principles of Ambulatory
Medicine 5th ed. Baltimore, W. Williams &
Wilkins; 1999:641.
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27. Swanson AE. Prevention of dry socket: an
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A prospective study of complications related to
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34. Krekmanov L, Nordenram A. Postoperative
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Figure 8. The immediate
postextraction socket of tooth No. 5
in an 82-year-old woman who was
taking Coumadin. She had an INR of
3.0. Preoperatively, her physician was
consulted over the phone. It was
decided that with her stroke history
and the limited nature of the oral
surgery, it would be best to use local
measures to control expected
intraoperative and possible
postoperative hemorrhage. At the
surgery appointment, the tooth was
removed atraumatically. Following the
extraction, one 1 x 1-inch piece of
hemostatic gauze was placed in the
socket. A figure-8 suture was tied
over the socket to better approximate
buccal and lingual gingival and to
prevent hemostatic gauze
dislodgement. As a precaution, food
was limited to a liquid diet that day.
Food was chewed on the other side of
the mouth for the following few days.
William L. McBee, DDS
Dr. McBee is an oral and maxillofacial
surgeon who graduated from dental
school at the University of Tennessee
and then completed his residency at
the University of Minnesota. He
currently practices oral and
maxillofacial surgery in Provo, Utah,
and can be reached at (801) 375-4707
or mcbee0006@msn.com.
Disclosure: Dr McBee is a member of
the MedSpring Group Medical Advisory
Board. He does not receive financial
remuneration for any product
mentioned in this article.
Karl R. Koerner, DDS, MS
Dr. Koerner has taught more than 500
didactic and hands-on courses to
dentists in the United States and
abroad. He has contributed to 2
volumes of Dental Clinics of North
America. Since 2002, he has been a
clinician and lecturer for Clinical
Research Associates in Provo, Utah.
He is past president of the Utah
Dental Association and Utah Academy
of General Dentistry. He is a general
dentist and practices in Salt Lake City,
Utah, and can be reached at (801)
502-8585 or krkoerner@comcast.net.
Disclosure: Dr Koerner is a member of
the MedSpring Group Medical Advisory
Board. He does not receive financial
remuneration for any product
mentioned in this article.