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© Alexander V. Plotkin, Evgeniy Zh. Pokrovsky, Galina V. Voronova, Kseniya A. Menglet, 2015
UDC 615.273.5
EFFICACY EVALUATION OF THE MEDICINAL SUBSTANCE
HAEMOBLOCK HEMOSTATIC EFFECT IN THE COURSE OF OPEN
AND LAPAROSCOPIC SURGERY. MULTICENTER CLINICAL TRIALS
ALEXANDER V. PLOTKIN, M.D., Professor, Head of the Moscow Regional Scientific-andResearch Blood Institute, Moscow, Russia
EVGENIY ZHANOVICH POKROVSKIY, D.M., A.P., Head of the Chair of the Hospital Surgery of
the State Budget Educational Institution of Higher Professional Education Ivanov State Medical
Institution of the Ministry of Health of Russia, Ivanovo, Russia
GALINA VYACHESLAVOVNA VORONOVA, Deputy Chief Doctor for Clinical Care of the Regional
Budgetary Institution of Health Kineshemskaya Central District Hospital, doctor-endoscopist,
Kineshma, Russia
KSENIYA ALEXANDROVNA MENGLET, leading research associate of the Moscow Regional
Scientific-and- Research Blood Institute, Moscow, Russia
Abstract. Objective - results of a multi-center clinical trial conducted in 4 medical centers from different
regions of the Russian Federation were summarized. The trial refers to the evaluation of the efficacy of
Haemoblock as a hemostatic agent for local topical use in the course of various surgical procedures.
Materials and methods. The total of 89 people were operated. In 31 cases the medicinal substance was
applied to the bleeding surface in the course of videolaparoscopic surgery by a gauze pad well
permeated with haemoblock delivered through a 5 mm tube; in 35 cases the drug was applied to the
wound surface by a wetted gauze in the course of open surgery, and in 23 cases the drug was delivered
in
a
laparoscopic
way
by
targeted
irrigation
via
a
catheter
introduced
through
ezophagogastroduodenoscope. Results. Sustainable hemostasis was recorded in the course of all types
of surgery in various cases of pathology. Thus, the haemoblock proved to be a highly efficient topical
hemostatic agent.
Keywords: haemoblock, capillary bleeding, parenchymal hemorrhage, hemostatic agent.
T
he effective intraoperative arrest of hemorrhage and
mitigation of risk of infectious complications in the
postoperative period is a challenging issue, and in this
regard the new topical hemostatic agent haemoblock with a
bactericidal function is of considerable interest.
The medical substance Haemoblock is a topical
hemostatic agent registered in the Russian Federation as a
medical product. Its formula includes partial silver salt of
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polyacrylic acid, containing silver nanoparticles, which
determines a marked bactericidal and bacteriostatic effect of
haemoblock. The substance is applied topically in cases of
parenchymal and capillary hemorrhage. Sterile cotton wool
or gauze tampons are soaked with the substance and
applied to the bleeding, preliminarily dried up surface of the
wound. In case of vast wound surfaces the substance is
used in a form of spray. The hemostatic effect is achieved
within 12 minutes.
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Since haemoblock forms a clot with plasma proteins
(mainly, albumin) the hemostatic effect is achieved. Recent
studies conducted in the laboratory of the Moscow Regional
Scientific-and-Research Blood Institute showed that the
mode of haemoblock action does not depend on
concentration of blood clotting proteins in plasma, but on
albumin content mainly.
At the first stage of the medical substance action, a
polyacrylic matrix structure is formed which contains albumin
molecules in the cells of polyacrylic matrix. This is a primary
structure and its life cycle is not too long, since polyacrylate
anion does not create strong connections with protein
molecules and is sustained only due to weak bonds. But this
structure is a primary organizer of a sustainable film.
At the next stage silver ions are reduced by albumin
molecules, thus forming a steady complex: polyacrylate
anions form a strong bond with positively charged protein
molecules. Such structure is packed in several micro-layers,
creating a strong polymethacrylate film on the wound
surface. Provided that the reduced metal like silver in
complex with proteins is a potent bactericidal factor that
ensures absence of wound infection when using
haemoblock. At a later stage the haemoblock-protein surface
structure
is replaced by fibrin. Whereas the polyacrylate matrix is
plasmolyzed within 24 hours.
The objective of this trial is to evaluate the hemostatic
effect of the medicinal substance haemoblock in the course
of open and laparoscopic surgeries.
Materials and methods. A multi-center trial was
conducted in order to evaluate the efficacy of local
hemostasis when using the Haemoblock medicinal
substance. The study covered 89 patients who underwent
treatment in four medical treatment facilities of the Russian
Federation:
1. Hospital Surgery Clinic of the Regional Budgetary
Institution of Health “City Clinical Hospital No. 4” of the city
of Ivanovo.
2. The Surgical center of NGHCI Central Clinical
Hospital No1 of Russian Railways, Moscow
3. The Endoscopy Department of the State Budgetary
Institution of Health
“Chelyabinsk regional clinical hospital No. 3”
4. The Endoscopy Department of the Central District
Hospital, the City of Kineshma, the Ivanovo region.
Patients were subdivided into 3 groups. Each group was
characterized by the way of
Haemoblock delivery to the wound surface.
1. 31 patients underwent the surgical treatment in
regard to destructive cholecystitis. The operations were
conducted by a videolaparoscopic method. Haemoblock was
applied to the bleeding surface by a well-wetted gauze pad
delivered to the wound surface through the 5 mm tube.
2. 35 patients with acute surgical pathology of
abdominal organs, major vessels and skeleton bones
underwent
the abdominal surgery (open surgery) of different types.
Haemoblock was applied to the open bleeding surface by a
well-wetted gauze pad.
3. 23 patients with various surgical and cancer
pathologies were operated by the laparoscopic method.
Haemoblock was delivered to the bleeding surface in a
laparoscopic way by targeted irrigation via a catheter
introduced through ezophagogastroduodenoscope.
Trial progress.
1. The Hospital Surgery Clinic of the Regional
Budgetary Institution of Health “City Clinical Hospital
No. 4”, Ivanovo, the group led by Evgeniy Z.
Pokrovskiy, D.M., A.P., Head of the Chair of the
Hospital Surgery of the State Budget Educational
Institution of Higher Professional Education “Ivanovo
State Medical Institution of the Ministry of Health of
Russia”, Ivanovo, Russia
An open, prospective study involved 39 patients. The
medicinal substance was used in cases of diffusive
(capillary) bleedings from the liver tissue in patients who
underwent surgical treatment of acute surgical pathology.
The basic group of immediate causes comprised the
acute calculous destructive cholecystitis (79.5%) and focal
lesions of liver (intrahepatic abscesses - 7.7%; metastatic
lesions - 12.8%).
Surgical treatment of the acute destructive cholecystitis
was performed urgently, in all cases videolaparoscopical
cholecystectomy was used. In the course of surgery in this
group of patients the diffusive bleeding from the gallbladder
bed was the most frequent case. The antibacterial effect of
haemoblock is an important aspect of its usage, critical in
cases of destructive cholecystitis. As it is known, additional
and excessive coagulation of a gallbladder bed during
surgery often does not provide an adequate hemostatic
effect. An additional area of coagulation necrosis is formed,
whereas this area itself can be a source of hyperthermia and
a substrate for purulent processes in the postoperative
period.
Mass lesions of liver diagnosed during examination or
intraoperatively sometimes require atypical resections of the
liver which are also accompanied by diffuse bleeding. In our
cases of extensive purulent processes the surgery was
performed using LigaSure device, whereas the biopsy
materials were taken traditionally. It should be noted that in
the studies conducted, even LigaSure did not always provide
stable hemostasis on the liver surface. First of all, it is
determined by the following device feature: closure of two
jaws of clips and exclusion of the surface fragments with
small vessels from the zone of action of the device. The
more detailed characteristic of the underlying disease is
presented in Table 1.
Most patients were diagnosed with coexisting
cardiovascular
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Table 1
The nature of underlying disease of the patients examined
The number of patients
Underlying disease
Abs.
%
Choledocholithiasis Acute calculous destructive cholecystitis
11
28.2
Choledocholithiasis Acute calculous destructive cholecystitis Gallbladder empyema
12
30.7
Choledocholithiasis Acute calculous destructive cholecystitis
6
15.6
Acute phlegmonous noncalculolis cholecystitis
1
2.5
Acute phagedenic noncalculolis cholecystitis
1
2.5
Hepatic abscess
3
7.7
Gallbladder cancer with liver metastases
1
2.5
Metastatic lesions of liver (cancer of the cecum, ovarian cancer)
4
10.3
Total
39
100
Pathology: hypertension (80.5%) and coronary heart disease
(75.4%). Among females high incidence of chronic
gynecological diseases of inflammatory origin and
myomatous lesions of the uterus (84.8%) was registered, as
for males the high incidence of benign prostatic hyperplasia
was observed (46.9%). In general the comorbidity structure
reflects the level and nature of morbidity of population in the
service area where a high percentage of diabetes, chronic
diseases of lower limb veins (varicose veins, chronic venous
insufficiency), and chronic respiratory diseases (chronic
obstructive pulmonary disease, chronic bronchitis, bronchial
asthma) is observed.
There were 1.7 times as many females as males. The
bulk of the patients were people of active working age. The
most part of the observations concerns the patients of
elderly and senile age - 33.6%.
The application methodology of the medicinal substance
was the following: during the open surgery a dry gauze pad
was imposed on the wound for a short moment,
Fig 1. Diffuse bleeding during liver biopsy
Fig. 2. The bleeding was stopped by the Haemoblock medicinal substance.
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immediately followed by an average sized gauze pad soaked
in 25-50 ml of Haemoblock. The exposition lasted for 2-3
min. In all cases the stable hemostasis was achieved (fig. 1
and 2).
Clinical examples
Surgical report, patient B.
Operation as of January 17, 2014 Resection of liver
segment VI. Plugging the subhepatic space with a tampon.
Surgical Procedure The abdomen was opened in layers
in the right hypochondrium by Fedorov’s incision. There is no
effusion. In the sixth liver segment a destructive process in
the form of detritus is detected (possibly tumor), no other
seedings in the liver are observed. Taking into account the
localization and the character of affection, the resection of
liver segment VI was performed using LigaSure. A gauze
plug with Haemoblock was used. The laparotomy incision
was closed in layers, followed by iodine and gauze dressing
application.
Tissue specimen: a fragment of liver tissue with detritus
for histopathological examination.
Post-surgical diagnosis: Abscess (tumor destruction?) of
liver segment VI.
Surgical report, patient M.
Operation dd. March 31, 2014 Enucleation of a giant
cyst in the left hepatic lobe. Drainage and tamponing of
abdominal cavity.
Surgical Procedure The skin and subcutaneous tissue
were intersected by an incision in the right upper quadrant
(with excision of an old post-operative scar) with transition to
the left upper quadrant. Hemostasis. Abdomen opening.
Abdominal exploration. Due to an adhesive process in the
subhepatic space and in the area of surgical approach the
full abdominal exploration is impossible. No signs of severe
pathology are observed. Right and left hepatic lobes,
gallbladder and extrahepatic bile ducts are located. Blunt
dissection helped to move away from the choledoch,
hepaticus, right and left hepatic ducts. A liver cyst is located
in the left hepatic lobe, on the border with the right lobe and
a fragment of normal liver tissue, over the diaphragmatic
surface leftwards. The cyst size is about 12 to 14 cm. Taking
into consideration its large size and previous oncotomy, a
radical cystectomy and the fibrous capsule removal are
required. Enucleation of the cystic lesion was performed
using the LigaSure device, though its spontaneous opening
with pyorrhea with sweetish odor could not be avoided. The
cyst was removed within healthy tissues. Loose interrupted
stitches are put in the gallbladder bed involving the
gastrocolic omentum and a tampon with Haemoblock. The
haemostatic swab is applied over the liver, drainage is
placed into the subhepatic area. Sanitation. Control of
hemostasis. The incision is closed in layers around drainage
and tampons, followed by iodine and gauze dressing
application.
Tissue specimen: a cyst of the hepatic left lobe sized
about 12 to 14 cm in diameter, the wall is about 2 to 3 mm.
The cavity contains several subcavities, sent for
histopathological examination.
Post-surgical diagnosis: Infected multilocular cyst of the
hepatic left lobe.
During the videolaparoscopic operation the technique
was slightly different. Irrigation of the gallbladder bed was
performed with 5% chlorhexidine, the fluid was aspirated,
and then through a pre-attached 5 mm tube a gauze pad
soaked in Haemoblock (20-25 ml) was introduced to the
gallbladder bed by a clamp and held it there for about 2 - 3
minutes. In all cases a stable hemostasis was achieved.
It may be noted that as a result of Haemoblock
application no recurrent bleeding occurred. At the same
time, one can note a certain reduction in complications such
as infiltration of the gallbladder area, subhepatic abscess
and coagulative hyperthermia.
2. The Surgical Center of NGHCI Central Clinical
Hospital No1 of Russian Railways, Moscow, a group
led by M.V. Lysenko, Doctor of Medical Sciences,
Professor, Honoured Doctor of the Russian Federation.
Haemoblock was used in 27 patients aged from 30 to 76
years. 16 people among them suffered from cancer
pathology (advanced cancer), 11 patients had the acute
surgical pathology of abdominal organs, major vessels and
skeleton bones.
As a result of clinical trials, in 23 cases a stable
hemostatic effect was achieved, in 2 cases recurrent
bleeding occurred: one of the patients required the repeated
surgical intervention, whereas in another case a repeated
application of Haemoblock with an exposure of 5 minutes
was used. Haemoblock was ineffective twice: one patient
had septic shock against the background of chronic
cholangitis, with low and unstable blood pressure, the
bleeding continued from abdominal adhesions, it was
arrested by application of Tachocomb plates and gauze
tampons. And another patient had the bleeding from ureter
continued despite the introduction of 10 ml of Haemoblock
(with the 5 min. exposure) to the ureter, as the ureter was
connected with aortic aneurysm. Consequently nephrectomy
and patch graft aortoplasty were performed [1].
3. The Endoscopy Department of the State
Budgetary Institution of Health “Chelyabinsk regional
clinical hospital No 3” , O.Y. Sitnikova, E.A.
Tryasenogova, V.Y. Podshivalov
In modern endoscopic practice the techniques of
endoscopic arrest and prevention of gastrointestinal
bleedings are broadly demonstrated. They include electro
coagulation, argon plasma coagulation, injection therapy,
ligation, and clipping. All of them are indicated in the
presence of local, specific source of bleeding (erosion,
ulcers, arteriovenous fistula, etc.).
The disadvantages of these methods include the high
cost of equipment and the difficulties in localizing the source
of bleeding in less accessible areas.
In the everyday endoscopic practice there are cases with
sufficiently large area of lesions in the form of capillary,
diffuse bleeding (Forrest IB bleeding), consequently the
above-mentioned techniques of endoscopic hemostasis
cannot be applied (hemorrhagic gastropathy, chemical burn
of the esophagus, chemical burn of stomach etc.) or when
the source of bleeding is covered by a blood clot (Forrest IIB
bleeding).
The easiest and the most accessible endoscopic
manipulation method in regard to such areas of
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bleeding is irrigation with hemostatic agents. Due to the
interaction of hemostatic agent with blood the blood clot is
formed and tightly fixed to the wall of the organ. This method
is effective in cases of continuous capillary bleeding and
arrested bleeding.
Currently in clinical practice there is a new hemostatic
agent of topical application - Haemoblock - which has a nonspecific mechanism of action. It interacts with blood proteins
(mainly albumin) and forms a polymer complex that arrests
bleeding.
The possibility of using this hemostatic agent in
endoscopy in cases of Forrest IB and IIB bleedings was
evaluated.
To this end, the irrigation of hemostatic agent through a
catheter to the area of bleeding was applied to in 11 patients
using a gastroduodenoscopic method. A bleeding site or
blood clots were irrigated with 20 ml of Haemoblock.
All patients were males aged 44 to 77 years.
Characteristics of sources and types of bleeding, effect of
Haemoblock are presented in Table 2.
With IIB type of bleeding we used the hemostatic agent if
fresh, friable blood clots were present only. During their
irrigation the color change and size reduction of the clot due
to its compression were observed.
As data in the Table 2 show in all the cases of
Haemoblock application no recurrent bleeding occurred.
Conclusions:
1. The technique of endoscopic application of
Haemoblock is easy to perform and does not require any
specific equipment.
2. The presence of bleeding of I B or II B type is one of
the indications for irrigational endoscopic therapy with
Haemoblock [2].
4. The Endoscopy Department of the Central
District Hospital, the City of Kineshma, the Ivanovo
region, a group led by G.V. Voronova, Deputy Chief
Doctor for Clinical Care of the Regional Budgetary
Institution of Health Kineshemskaya Central District
Hospital , a doctor-endoscopist
The evaluation of Haemoblock effect in endoscopy and
its comparison with hemostatic agent Caprofer were
performed. Targeted irrigation was performed via a catheter
inserted through ezophagogastroduodenoscope. 30 ml of
Haemoblock solution was used for irrigation of bleeding
sites. Endoscopic hemostasis was performed in 24 patients
with diffuse capillary bleeding and the presence of a blood
clot on the bleeding source.
The study included male patients aged 44 to 77 years.
The characteristics of sources and types of bleeding, results
of Haemoblock application are presented in Table 3.
In cases of irrigation with Haemoblock reduction of blood
clots size and change in their color were observed, while in
case of Caprofer usage the size of clots increased. As it can
be seen in Table 3, in all cases of Haemoblock usage no
recurrent bleeding occurred.
It is shown that in all patients of the 1st group (31
people) hemostasis occurred within 1 - 3 minutes. Secondary
hemorrhage and suppuration were not fixed.
In 31 patients of the 2nd group hemostasis occurred for
1-3 minutes. Secondary hemorrhage and suppuration have
not been recorded. In 2 patients of the 2nd group recurrent
bleeding required repeated application of the hemostatic
agent, in 2 patients of the 2nd group the hemostatic agent
was ineffective.
Table 2
The results of endoscopic hemostasis
Type of bleeding
IB
IIB
The number of patients
The presence of recurrent bleeding
Acute duodenal ulcer
Diagnosis
2
—
Chemical burn of the esophagus
1
—
Acute gastric ulcer
1
—
Erosive esophagitis
—
—
Chemical burn of the esophagus
2
—
Mallory-Weiss syndrome
1
—
Chronic peptic ulcer
1
—
Acute duodenal ulcer
1
—
11
—
Total
Table 3
The results of endoscopic hemostasis
Caprofer
The presence of recurrent
bleeding
Haemoblock
The presence of recurrent
bleeding
Acute duodenal ulcer
2
—
2
—
Acute gastric ulcer
2
—
2
—
Chemical burn of the esophagus
1
—
1
—
Erosive esophagitis
2
—
2
—
Mallory-Weiss syndrome
3
1
3
—
Stomach cancer
2
1
2
—
Total
12
2
12
—
Diagnosis
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In the third group in all 23 patients, reliable hemostasis
with exposure up to 2 minutes was observed. In all cases no
suppuration occurred.
Conclusions Haemoblock is an effective topical
hemostatic agent regardless of the method of application to
the wound surface and anamnesis. This hemostatic agent
produced effect in 95% of open surgery cases and in 100%
cases of laparoscopic surgery.
bleedings / O.Y. Sitnikova, E.A. Tryasenogova, V.Y. Podshivalov
// Topical issues of endoscopy: IV All-Russia Scientific-Practical
Conference (with international participation): theses, St.
Petersburg, Russia, March 27-28, 2014. - SPb., 2014.
REFERENCES
1.
2.
REFERENCES
1.
2.
Pfaf, V.F. Experience of clinical application of Haemoblock, the
new hemostatic agent in surgical practice / V.F. Pfaf; edited. Pfaf
V.F. - М., 2014. — 56 p.
Sitnikova, O.Y. The first experience of Haemoblock usage in
endoscopy of gastrointestinal
Pfaf,
V.F.
Opyt
klinicheskogo
primeneniya
novogo
gemostaticheskogo sredstva «Gemoblok» v hirurgicheskoi
praktike / V.F. Pfaf; pod red. V.F. Pfaf. — M., 2014. — 56 s.
Sitnikova, O.Yu. Pervyi opyt ispol'zovaniya preparata gеmoblok
v endoskopii zheludochno-kishechnyh krovotechenii / O.Yu.
Sitnikova, E.A. Tryasenogova, V.Yu. Podshivalov // Aktual'nye
voprosy endoskopii: IV Vseros. nauch.-prakt. konf. s
mezhdunarodnym uchastiem: tez. dokl., Sankt-Peterburg,
Rossiya, 27— 28 marta 2014. — SPb., 2014.
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