中华劳动卫生职业病杂志
2022
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Chin J Ind Hyg Occup Dis
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2022
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702-710
702
Evaluation of the homeostasis system before and after tooth extraction in patients with viral
hepatitis
O.U.Rakhmatullaeva, K.E. Shomurodov, M.M.Fozilov, I.A.Eshmamatov,
Sh.Sh Ikramov
.
Tashkent State Dental Institute
https://doi.org/10.5281/zenodo.7148125
Abstract:
The purpose of this study was to assess the state of hemostatic homeostasis in the
postoperative period after tooth extraction in patients with viral hepatitis. 58 patients with chronic
viral hepatitis were examined. The indicators of the hemostasis system before and after the tooth
extraction operation were studied. It was revealed that the indicators of vascular-platelet and
fibrinolytic links of the hemostasis system in viral hepatitis have a compensatory and adaptive
orientation and contribute to maintaining homeostasis at different levels, but are closely related to
the number and functional state of platelets.
Keywords:
viral hepatitis. tooth extraction, vascular-platelet and fibrinolytic links of the hemostasis
system.
One of the most frequent operations in surgical dentistry is the removal of teeth, which leads to
the appearance of defects in the dentition, which require orthopedic treatment. It has been
established that the main causes leading to complications and unsatisfactory quality of dental
treatment after tooth extraction include: imperfection and insufficient information content of both
clinical and instrumental laboratory methods of examination of patients, reduction in the
perioperative period of complications caused by disorders of the hemostasis system. As is known,
damage to the endothelium of a blood vessel during tooth extraction is an incentive to start the
formation of a blood clot. The process of blood clot formation is closely related to liver function.
Parenchymal liver cells produce most of the factors of the coagulation and fibrinolytic systems, as
well as thrombopoietin, which is responsible for the production of platelets from megakaryocytes.
In addition, the reticuloendothelial system of the liver provides clearance of activated forms of
hemostatic factors. Changes in liver function in acute and chronic diseases initiate hemostatic
abnormalities predisposing to the manifestation of bleeding or thrombosis.
Various aspects of hemostasis disorders associated with chronic liver diseases have been actively
discussed in the scientific literature of the last decade. The reason for this is that the compensatory
abilities of the blood clotting system are noticeably weakened in liver diseases. The opinion is
expressed about the frequent predisposition of patients with liver pathology to hypercoagulation and
thrombosis. At the same time, there are practically no works devoted to the study of the predictive
role of hemostatic parameters in tooth extraction in patients with viral hepatitis. In this regard, the
study of the clinical pathogenetic and prognostic significance of hemostatic homeostasis disorders
during tooth extraction in chronic liver pathology is of undoubted theoretical and practical interest,
since, on the one hand, it will clarify the features of hemostasis disorders and establish their
relationship with the clinical manifestations of chronic liver diseases, and, on the other, enrich the
arsenal of dentists with new criteria, which can be used to improve differential diagnostic and
treatment programs and to form risk groups for the unfavorable course of liver pathology in surgical
patients.
The purpose of this study was to assess the state of hemostatic homeostasis in the postoperative
period after tooth extraction in patients with viral hepatitis.
Material and methods of research
58 patients with chronic viral hepatitis were examined. The
studies were conducted in strict accordance with the requirements of biomedical ethics in
accordance with the Geneva Convention on Human Rights (1997) and the Helsinki Declaration of
the World Medical Association (2000) on the basis of the permission of the local ethics committee.
In the group with chronic hepatitis, patients were distributed by gender as follows: men — 58%,
women - 42%, the average age of patients was 35.6 ± 10.7 years. All patients received written
voluntary informed consent to participate in the study. Inclusion criteria: verified diagnosis of
中华劳动卫生职业病杂志
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chronic viral hepatitis B and C detected by polymerase chain reaction (PCR) using a test system,
patients who did not receive antiviral therapy. Exclusion criteria: patients under 18 years of age
with concomitant viral hepatitis D or other diseases that cause liver damage, HIV infection, a
history of pulmonary tuberculosis, autoimmune, oncological diseases, as well as pregnant women.
In order to determine the control values of the studied parameters of the hemostasis system, 16
practically healthy individuals aged 25 to 45 years who gave informed consent to the examination,
who did not differ from patients by gender and age, who did not have a history, the results of
biochemical and serological studies of viral hepatitis, as well as other liver diseases, were
examined. The work uses: instrumental studies: ultrasound examination of abdominal organs,
clinical and laboratory methods. HCV-PHK indication, virus genotype determination, viral load
level by polymerase chain reaction (PCR). A complete clinical and special examination of patients
with HCV was carried out on an outpatient basis before surgery.
The examination included an analysis of complaints, anamnesis, objective research data; standard
laboratory and instrumental studies were conducted. The number of platelets in the hematological
analyzer was calculated in all examined patients, the adhesive and aggregation properties of
platelets using an ADP inductor were determined visually using a phase contrast microscope
according to Shitikova T.A. (1997). Determination of activated recalcification time (AVR) in
plasma by the Clauss method was carried out according to a unified technique on the DiaMed CD 4
apparatus (Switzerland). Antithrombin-Sh (AT-Sh) was studied on an automatic digital photometer
at a wavelength of 405 nm. [Barkagan Z.S. 2001]. Coagulometric method was used to determine the
duration of prothrombin time, APTT using reagents of NPO RENAM (Russia). The platelet
content was determined on an automatic analyzer "HT-2000i fSusmeh" (Japan).
Statistical processing of the obtained results was carried out using the applied analysis package of
the Mi-crosoft Excel 2002 tabular editor. The sample mean and the mean error (M ± m) were
calculated. The reliability of the differences for dependent and independent samples between the
two averages was assessed by the Student's f-criterion. Differences in the compared indicators were
taken as reliable results at p < 0.05
Research results and their discussion
After tooth extraction in patients with viral hepatitis, a hemostatic sponge and polycapran were used
to stop bleeding. At the same time, it was found that after tooth extraction in the I-group of patients
in 18 (45%) cases, bleeding from the hole of the removed tooth stopped within the next 10 minutes,
and in the II-group of patients in 22 (55%) cases, bleeding occurred, which lasted for the first hour
after tooth extraction. At the same time, thrombocytopenia (less than 100x109/l) was noted in group
II patients, as well as an elongation of the onset of VSC to 5 minutes despite the use of a hemostatic
sponge as a local hemostatic agent. In these cases, we replaced the hemostatic sponge with a
polycapran, after which the bleeding from the hole of the removed tooth stopped within the next 10
minutes. Consequently, the use of a hemostatic sponge proved effective only when the level of
platelets in peripheral blood was above 180x109/, whereas with thrombocytopenia (less than
100x109/l), the hemostatic sponge was replaced by polycapran.
As is known, viral liver damage leads to complex complex disorders in the hemostasis system, but
at the same time a balance is maintained between the coagulation and anticoagulation systems with
a reduced reserve, and this balance is easily disturbed in one direction or the other, therefore,
patients with chronic liver disease of viral etiology may develop not only bleeding, but also
thrombosis. Therefore, we decided to assess the state of the vascular-platelet, plasma and
fibrinolytic links of the system in the examined patients against the background of the use of a
hemostatic sponge and polycapran, which will allow us to introduce in outpatient settings as
prognostic tests to assess hemostatic homeostasis in the postoperative period during tooth extraction
in patients with viral hepatitis.
中华劳动卫生职业病杂志
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I Evaluation of the vascular-platelet link of the hemostasis system after tooth extraction in two
groups of patients with viral hepatitis
Considering that many of the studied factors of the coagulation system are synthesized in the
endothelium and liver, we decided to study the effect of endothelial damage during tooth extraction
on the parameters of the vascular-platelet link of the hemostasis system in patients with viral
hepatitis
To do this, we studied the nature of changes in blood platelet content and activity, the level of
activated recalcification time (AVR), a hemolysataggregational test evaluating the functional
activity of platelets relative to the ADP inducer, as well as the activity of Willebrand factor and the
content of antithrombin III in patients with viral hepatitis after tooth extraction.
As is known, about one third of patients with chronic liver diseases have thrombocytopenia (less
than 100 • 109/l). They often have a reduced platelet aggregation capacity, which is due to a
violation of the signal transduction mechanisms. As can be seen from the results of the study
(table), the concentration of antithrombin III (AT III) synthesized by the liver and endothelium in
the examined patients of group 2 after the manipulation decreases due to a decrease in synthesis
and/ or an increase in consumption with hyperfibrinolysis, which is more pronounced in patients of
group 2. At the same time, increased adsorption of platelets to the site deprived of endothelial
lining, during tooth extraction in patients with viral hepatitis is accompanied by an increase in
active forms of blood plates. The observed dynamics of the sum of active forms of platelets in
patients with chronic viral hepatitis combined with tromocytopenia tended to increase by an average
of 1.9 times relative to the indicators of healthy individuals with intact periodontal disease. A
significant number of active platelets are located not only in the lumen of the vessels of the oral
mucosa, but also in the gum mucosa itself. This is one of the reasons for the activation of the
atherogenic process at the site of destruction of the endothelium after tooth extraction in patients
with viral hepatitis. After appropriate use in patients of group 2 of polycapran, it was possible to
reduce the level of active forms of platelets.
Table 1
Indicators of the vascular-platelet link of the hemostasis system in patients with viral hepatitis
before and after therapy
Indicators
Healthy
n=16
Patients with viral
hepatitis I-group
n=18
Patients with viral
hepatitis II-group
n=22
before
after
before
after
The sum of active
forms of platelets
(%)
12,42±0,79
18,13±1,74*
16,57±1,13
20,13±1,34*
13,11±1,24
Platelet aggregation to
ADP inducer
Tma%
34,18±2,47
42,31±3,48*
39,14±3,03
47,69±3,53*
36,12±2,78
Activated
recalcification time
(sec)
57,81± 5,21
64,76±5,15
62,74± 5,43
72,07±6,13*
64,76±7,15
Antithrombin-III
(%)
88,35±6,12
80,14±5,71
81,79±6,68
74,23±5,66
79,67±5,71
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The Willebrand Factor
(%)
81,37±4,56
88,59±7,13
85,73±7,04
92,89±7,84*
83,02±7,15
Note: *-the reliability of differences P 0.05 relative to healthy individuals
At the site of surgery, there is also an effusion of red blood cells and its destruction, which leads to
the release of platelet ADP-inducer from the erythrocyte, which enhances platelet aggregation. In
patients with viral hepatitis, an increase in platelet aggregation activity on the effect of the ADP
inducer (Tma) was noted by 1.5 times. Also, the therapy performed using polycapran contributed to
a decrease in the aggregation properties of platelets to the ADP inducer. The observed prolongation
of the activated recalcification time (AVR) by 1.4 times in patients with group 2 viral hepatitis
indicates a deficiency of plasma factors (XII,XI,XIII) of the blood coagulation system and the
process of hypocoauguration. Against this background, fibrinogen consumption coagulopathy is
observed.After appropriate therapy, taking into account the platelet level, led to a reduction in the
time of the activated recalcification time.
As is known, antithrombin-III is a specific protein of the blood coagulation system, which is
synthesized in the vascular endothelium and in the liver. Its main function is to inactivate several
major coagulation factors, including thrombin, and prevent the increased formation of blood clots-
blood clots. In patients with viral hepatitis, especially in the second group, as shown in Table 1,
there is a statistically significant decrease in the activity of antithrombin III compared to the control
group, which reflects a decrease in its release by endothelial cells, as well as the index of
anticoagulant activity of the vascular endothelium. Usually, antithrombin III helps regulate this
process by slowing down the action of several coagulation factors, including thrombin, as well as
factors X, IX and XI, designed to prevent the formation of excess blood clots. At the same time, a
decrease in the level of antithrombin III, as shown in our studies, indicates the consumption of this
anticoagulant, due to the activation of the hemostasis system. The use of polycapran in group 2
patients contributed to an increase in the level of antithrombin-III in the blood plasma of the
examined individuals after surgery. Thus, the obtained research results indicate that tooth extraction
in the examined patients, especially with combined thrombocytopenia, requires the use of
polycapran instead of a hemostatic sponge, and at the same time, the diagnostic marker is an
assessment of not only the number of platelets, but also the functional property of the blood plate.
II Evaluation of the fibrinolytic link of the hemostasis system
after tooth extraction in patients with viral hepatitis
All proteins involved in the process of fibrinolysis; protein C, alpha-2-macroglobulin,
antithrombin-III and representatives of the kallikrein system are synthesized in the liver. At the
same time, the kallikrein-kinin system (KCS) plays a central role in regulating the activity of
cascade proteolytic systems – kininogenesis, blood clotting, fibrinolysis, complement, renin-
angiotensive system – and providing the processes of adaptation and protection of the div. This
system, together with the renin-angiotensin-aldosterone system, regulates local microcirculation. In
blood plasma, the activity of kallikrein is controlled by a2-macroglobulin and antithrombin III.
Activation of precallikrein occurs due to its cleavage by activated Hageman factor (XIIa) on the
surface of the damaged endothelium. This system activates fibrinolysis by converting plasminogen
into plasmin, and also increases the secretion of IL-1, TNFa, IL-8, prostaglandins and leukotrienes.
In our study, which is presented in Table 2, reliable signs of activation of the kallikrein-kinin
system were revealed. The high activity of kallikrein in combination with a significant decrease in
the blood content of its precursor, precallikrein, testified to the activation of the kallikrein—kinin
system of the blood in patients with chronic viral hepatitis, which is often accompanied by a
significant increase in fibrinolytic activity in the blood. Thus, the activity of kallikrein was
increased by 1.7 times and the level of precallikrein was reduced by 10%. The use of polycapran in
patients with viral hepatitis b after the surgical period allowed to reduce the level of kallikrein and
increase precallikrein.
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Table 2
Indicators of the fibrinolytic link of the hemostasis system in patients
with viral hepatitis before and after tooth extraction
Note: *-the reliability of differences P 0.05 relative to healthy individuals
We found a regular coordinated activation of proteinase systems and a decrease in the level of the
main kallikrein inhibitor -alpha2-macroglobulin, the value of which was increased by 99% before
surgery compared with the norm in most of the examined patients. It should be noted that the
observed prolongation in time of the APTT index in blood plasma before surgery in patients of
group 2 indicates a violation of the activity of plasma hemostasis, due to the activation of the
plasmin system.
Thus, the indicators of the vascular-platelet and fibrinolytic links of the hemostasis system in
viral hepatitis have a compensatory and adaptive orientation and contribute to maintaining
homeostasis at different levels, but are closely related to the number and functional state of
platelets. At the same time, it is possible that the main influence on changes in hepatic blood flow in
patients with chronic viral hepatitis has an increased level of kallikrein. The latter is one of the
causes of excessive expansion of the precapillary bed, which contributes to slowing down blood
flow in tissues and organs and exacerbates the state of hypoxia and hypoxemia. These are the
pathogenetic basis for the occurrence of liver dysfunction. Consequently, patients with chronic
viral liver pathology have a variety of hemostatic defects that affect all parts of the hemostasis
system. Such patients have a narrow band of maintaining hemostatic balance, and the existing
balance can easily be transformed into hypo- or hypercoagulation. This group of patients with
surgical placement in the dental system may be one of the causes of the disorder, which is
accompanied by increased bleeding, but in some patients the development of intravascular
coagulation syndrome can lead to thrombotic episodes. Only comprehensive studies prior to
surgical placement in the dental system, including simultaneous diagnosis of the main components
of fibrinolysis and thrombosis of the blood clotting system, are able to give a general picture of the
state of hemostasis and carry out preventive measures to prevent complications in this contingent of
patients. In this situation, coagulological support for tooth extraction in patients with viral hepatitis
should be differentiated, taking into account not only the indicators of the hemostasis system, but
also the study of the activity of blood plasma platelets. It should be noted that timely laboratory
detection of existing defects of the hemostasis system helps to prevent both hemorrhagic and
thrombotic complications, improve the quality of life of patients and the results of treatment of
Indicators
Healthy
n=16
Patients with viral
hepatitis I-group
n=18
Patients with viral
hepatitis II-group
n=22
before
after
before
after
Kallikrein
nmol / min / ml
71,56 ± 5,68
123,1 ± 9,27
108,1 ±8,75
126,18 ± 9,27*
83,15 ± 7,27
Precallikrein
nmol/min / ml
358,2± 13,45
321,3 ±11,49
334,2 ±11,68
319,35 ± 12,37
351,12 ±10,6
Alpha-2-
macroglobulin
(mg/dl)
147,83±7,51
281,91±9,39*
267,5±8,11*
284,91±9,15*
162,54±8,23
Activated partial
thromboplastin
time (sec)
30,56 ± 2,78
28,32 ± 2,14
32,12 ± 2,19
35,78 ± 2,53
30,14 ± 2,05
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pathology of the dental system. It must be remembered that infection can be a trigger factor in the
development of bleeding in this contingent of patients after tooth extraction.
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