Efficacy of Hemostatic Agents in Improving
Surgical Hemostasis
David Green, Cynthia A. Wong, and Przemyslaw Twardowski
URTAILING operative bleeding has always
C been a surgical priority. Perioperative hemor-
rhage, and the need for blood product transfusions,
increases morbidity, mortality, and cost. The driest
fields are usually attributed to the most skillful
surgeons. However, despite excellent surgical skill
there may be increased bleeding under a variety of
circumstances. These include extensive operations
versus limited ones, deep dissections versus super-
ficial ones, and reoperations versus primary proce-
dures. Furthermore, other factors over which the
surgeon has little or no control may increase
surgical hemorrhage. Examples include patient
diseases affecting the liver or kidney; recent expo-
sure to medications such as aspirin or anticoagu-
lants; and operations requiting extracorporeal circu-
lation. To control blood loss under these conditions,
physicians have turned to a variety of topical and
systemic agents thought to have hemostatic proper-
ties. In this article, we will examine the safety and
efficacy of some of these agents. Plasma, platelets,
and specific clotting factors will be excluded be-
cause a discussion of these blood components is
beyond the scope of this article.
Table 1 lists some of the hemostatic agents that
have been used at one time or another to control
operative bleeding. Many of the topical agents
listed are believed to be useful in surgical practice,
but most have not been subjected to rigorous
clinical trials. Seaweed extracts (Alginate) are used
for the arrest of capillary hemorrhage. Styptic
pencils can diminish bleeding by cauterizing small
vessels. Bismuth subgallate, an analogue of ellagic
acid, activates factor XII and may be applied to the
tonsillar fossae along with epinephrine to stem
bleeding. 1 Collagen and microcrystalline collagen
(Avitene) enhance platelet adhesion and aggrega-
tion. They have found widespread use in cardiovas-
cular, orthopaedic, and plastic surgery. 2 Gelatin
sponges and oxidized cellulose are applied to the
bleeding surface, compress severed vessels, absorb
fluid, and provide a scaffold for fibrin formation.
Russell's viper venom (Stypven) very rapidly clots
shed blood and has been used topically to staunch
bleeding from lacerations in hemophiliacs. Throm-
bin, usually of bovine origin, is applied alone or
Transfus'on Medicine Reviews, Vol X, No 3 (July), 1996: pp 171-182
with other topical agents to promote hemostasis.
However, the most popular use of thrombin is in
combination with fibrinogen to form fibrin glue.
Between 1990 and 1995, 318 articles described the
preparation, use, and adverse effects of this hemo-
static material, and a review was published in these
pages in 1993. 3 Some of the salient points about
fibrin glue are summarized below.
FIBRIN GLUE
Fibrin glue is prepared from a mixture of cryopre-
cipitated plasma, calcium, thrombin, and may in-
clude an inhibitor of proteolysis such as aprotinin.
The cryoprecipitated plasma provides factor XIII,
fibronectin, and plasminogen in addition to fibrino-
gen. The cryoprecipitate may be obtained from
either ACD or CPDA-1 donor plasma, although the
fibrinogen concentration is higher in the latter. 4
Because there is concern about viral transmission
from a product made from pooled homologous
blood, fibrin glue may be prepared from autologous
blood collected either preoperatively or intraopera-
tively. 5 The cryoprecipitate and concentrated bo-
vine thrombin are applied separately to the surgical
target, mixed, and allowed to set. The speed of
formation of the seal is proportional to the throm-
bin concentration, and its thickness and bonding
power are dependent on the concentrations of
fibrinogen, factor XIII, and fibronectin in the
cryoprecipitate.
Major benefit from fibrin glue is reported in
those situations where the use of sutures or adhe-
sive dressings would be associated with an inferior
result. Examples include dissecting aortic aneu-
rysms, where suturing through the aorta may
induce bleeding and skin grafting, where the glue
serves as a sealant and enhances graft adherence. 6,7
Other applications include sealing the dura in
patients undergoing neurosurgery, and preventing
leakage and fistulas from the pancreatic duct after
From the Departments" of Medicine and Anesthesiology,
Northwestern University Medical School, Chicago, 1L
Address reprint requests' to David Green, MD, PhD, 345 E
Superior St-Rm 1407, Chicago, 1L 60611.
Copyright 9 1996 by W.B. Saunders Company
0887- 7963/96/1003-000253.00/0
171