International Journal of Medical Sciences And Clinical Research
65
https://theusajournals.com/index.php/ijmscr
VOLUME
Vol.05 Issue05 2025
PAGE NO.
65-68
10.37547/ijmscr/Volume05Issue05-14
A Modern View Of Hemostasis Pathology In The Aspect
Of Medical Biology
M.M. Shertaev
Candidate of Biological Sciences, Associate Professor of Medical Biology and Genetics Tashkent State Medical University. Tashkent,
Uzbekistan
Received:
29 March 2025;
Accepted:
25 April 2025;
Published:
30 May 2025
Abstract:
In our work, we analyzed the problems of hemostasis disorders based on literature analysis.
Keywords:
Aspects, evolution, disorders, organism, enzymes.
Introduction:
The
hemostasis
system
is
an
evolutionarily developed, multi-component protective
device of the div. It ensures the processes of
formation of a fibrin clot and maintaining blood in a
liquid state.
Physiological clot formation and lysis is a series of well-
regulated and balanced interactions between plasma
factors, enzyme cofactors, their regulators, and various
blood cells, as well as the vascular endothelium.
The main mechanism of activation of hemostasis
components is limited proteolysis, in which an active
enzyme is formed from an inactive precursor,
catalyzing the process of blood clotting or lysis of the
fibrin clot.
When
compensatory-adaptive
hemocoagulation
mechanisms
fail,
the
process
of
blood
microcoagulation is triggered, which accompanies
many pathological conditions, in particular, thermal
burns.
Disorders of the hemostasis system occur as
disseminated
intravascular
coagulation
(DIC
syndrome), the development of which leads to
progression, a sharp aggravation, and often an
unfavorable outcome of the pathological process.
DIC syndrome is always secondary to a general
disturbance of homeostasis. It is characterized by
excessive activation of the hemostasis system, leading
to excessive thrombin generation (thrombinemia),
accelerated intravascular fibrin synthesis with
subsequent blockade of microcirculation in target
organs. (lungs, kidneys, liver, gastrointestinal tract,
brain). In this case, hypoxia, acidosis, and intoxication
with various metabolites of protein, lipid, and
carbohydrate metabolism develop in the div. DIC
syndrome is accompanied by a decrease in
anticoagulant potential, depression of fibrinolysis,
which leads to the accumulation of fibrin microclots in
the bloodstream and the development of multiple
organ failure.
The study of DIC syndrome under the influence of a
thermal agent on the div began in the 1960-1980s.
The data obtained allowed researchers to conclude
that DIC syndrome in severe burns is related to
disorders in the lungs, kidneys, gastrointestinal tract,
etc.).
However, the main methods for studying the
hemostasis system in those years were such as
determining blood clotting according to Lee and White,
prothrombin
time,
thrombin
time,
plasma
recalcification time, fibrinogen content, and total
fibrinolytic activity.
The earliest possible diagnosis of DIC syndrome is a
critical task, the successful solution of which is the key
to a favorable outcome of the pathological process.
Rapid correction of hemostasis normalizes blood
supply in parenchymatous organs, restores their
function and biosynthesis of biologically active
compounds that regulate the coagulation and
anticoagulation systems.
Changes in hemostasis system parameters can precede
the clinical picture of DIC syndrome by 1-1.5 days,
which allows it to be diagnosed at an early preclinical
stage. Laboratory tests, on the basis of which the
diagnosis of DIC syndrome is made, must meet the
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International Journal of Medical Sciences And Clinical Research (ISSN: 2771-2265)
following criteria: informativeness, efficiency and
accessibility for clinical practice, as well as the
comparative simplicity of the method.
To date, the following tests meet these requirements.
1/. Study of the activity of antithrombin III - the main
biological regulator of the hemostasis system, one of
the most powerful natural blood anticoagulants, the
main physiological inhibitor of thrombin.
Its level in the bloodstream determines the direction of
the pathological process in extreme conditions.
Determination of AT III activity is a key test for diagnosis
and monitoring of therapy of patients with DIC
syndrome. 2/. Analysis of the activity of HPA-
dependent fibrinolysis. The most "vulnerable" already
at the early stages of the formation of DIC syndrome.
3/. Counting the number of platelets, the degree of
reduction of which reflects the severity of disseminated
intravascular coagulation. 4/. Determination of the
content of soluble fibrin-monomer complexes - a
marker of activation of intravascular blood coagulation,
allowing quantitative determination of the level of
thrombinemia. 5/. Identification of fragmented
erythrocytes, which contribute to the activation of the
coagulation system and are of great importance for the
diagnosis of DIC syndrome.
However, in the literature we studied, we did not find
any works devoted to a systematic and in-depth study
of the dynamics of the indicators of the coagulation and
anticoagulation systems of the blood during thermal
exposure to the div during shock and acute toxemia
using modern research methods.
A comparative analysis of the diagnostic value of each
laboratory test for characterizing various links of the
hemostasis system has not been conducted. A set of
effective laboratory studies sufficient for establishing a
diagnosis of DIC syndrome based on the results of
blood sample analysis has not been identified.
At present, there are no algorithms for comprehensive
diagnostics and assessment of the state of various links
in
the
hemocoagulation
system,
endogenous
anticoagulants and fibrinolysis based on laboratory
analysis of blood samples.
Further analysis of the literature showed that the task
of the hemostasis system in humans is to prevent blood
loss when the integrity of the circulatory system is
compromised. The plasma coagulation link is one of the
important components of this system, the task of which
is to form a gel at the site of damage to prevent fluid
leakage.
More than 30 proteins are involved in blood plasma
coagulation, interacting with each other to form a huge
network of biochemical reactions.
Such a complex system requires appropriate
regulation. This leads to the fact that even small
disturbances in the delicate balance of pro- and
anticoagulant reactions can lead to serious
consequences for the div: thrombosis and bleeding.
Hemophilia - the disease of "royalty" - is an old but still
relevant disease.
It is noted in the literature that hemophilia is one of the
diseases known since ancient times. The first known
descriptions of symptoms similar to the manifestations
of hemophilia were made in Hebrew in the 2nd century
BC.
The authors of literary sources noted the fact that the
biblical sages, thanks to the tradition of meticulously
tracking genealogies, penetrated into the essence of
hemophilia more deeply than doctors and biologists of
the early 20th century. Thus, hemophilia as a
hereditary disease was described in the Talmud in the
5th century CE, where a description of cases of death
of boys from ritual circumcision is given.
A detailed description of hemophilia was made by John
Conrad Otto, a researcher from Philadelphia. In 1803,
he published his scientific work on the topic of
excessive bleeding. While studying the genealogy of
one of the families in detail, Otto concluded that there
is a hereditary tendency to excessive bleeding in boys.
Later, the famous scientist Johann Lukas Schonlein
called this disease "hemorrhage", which in Latin means
"tendency to bleed". It is assumed that the students
who listened to Schonlein's lectures "christened" the
disease with a more euphonious, but meaningless
name "hemophilia".
However, it is still generally accepted that the term
"hemophilia" was proposed in 1828 by F. Hopff. As an
independent disease, hemophilia was described only in
1874 by V. Fordyce. In Russia, a detailed description of
this disease belongs to the privat-docent of Moscow
University A.P. Poletaev, who in 1913 in the book
"Hemorrhagic diseases" described the features of its
inheritance and clinical symptoms. A steady increase in
the number of patients with hemophilia is noted, which
is associated with progress in treatment, patients
reaching reproductive age, as well as an increase in the
frequency of spontaneous mutations, leading to an
increase in the number of patients and carriers of
hemophilia.
It is currently known that the genes of hemophilia A
and B are localized in the sex X chromosome.
Statistical data have shown that the frequency of
hemophilia A in the population is 1 in 10,000, and
hemophilia B - 1 in 60,000 births. It is important to note
that all other hemorrhagic diathesis are much less
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International Journal of Medical Sciences And Clinical Research (ISSN: 2771-2265)
common - 1:500,000.
Hemophilia is a hereditary disease that manifests itself
as a deficiency of blood clotting factors VIII (hemophilia
type A) or IX (hemophilia type B). This trait is inherited
along the X chromosome. Women are carriers of the
pathological gene, while it is mainly men who suffer
from the disease.
In a woman with hemophilia, both her parents have the
abnormal gene in their X chromosome. In a sick man,
all sons will be healthy, and all daughters will be
carriers. A carrier woman and a healthy father have a
50% chance of having both an affected son and a carrier
daughter.
Experts have noted that hemophilia is caused not only
by inherited genetic abnormalities, but also by
spontaneous mutations. If the disease appears in a
family with no history of hemophilia, this variant is
called sporadic. The frequency of occurrence of
sporadic "new" cases of hemophilia can reach 1/3 of all
cases of the disease.
The gene responsible for hemophilia A or B is located
on the X chromosome. Hemophilia A is caused by a
deficiency or molecular abnormality of
the
procoagulant portion of factor VIII (antihemophilic
globulin) with a recessive, X-linked inheritance pattern.
Hemophilia B is a hereditary coagulopathy caused by a
deficiency in factor IX activity (the plasma component
of thromboplastin). Like hemophilia A, it is transmitted
in an X-linked recessive manner.
To date, the genes controlling the synthesis of factors
VIII or IX and responsible for the development of
hemophilia have been mapped. It has been established
that the gene encoding the synthesis of factor VIII is
located on the long arm of the X chromosome in the Xq
28 locus and consists of 26 exons and 25 introns (the
mature protein contains 2332 amino acids), and the
factor IX gene is located in the Xq 27 locus of the long
arm of the X chromosome and consists of 8 exons and
7 introns.
The factor VIII gene is large in size and contains about
186 thousand base pairs of DNA. Defects of this gene
can be of different nature: duplications, deletions,
frame shifts, inclusions of new bases. In more than half
of the cases, nucleotide sequence inversion occurs. The
factor IX gene has a size of about 34 thousand base
pairs. The incidence of hemophilia type B is 3-5 times
lower than type A.
Hemophilia type C, associated with a deficiency of
factor XI (PTA factor) of blood coagulation, is also
distinguished. It has an autosomal nature of
inheritance and is manifested by a mild or moderate
tendency to bleeding, but is often asymptomatic.
Hemophilia A is often called the "royal" (less often -
"crowned") disease. This is due to the fact that the
most famous carrier of hemophilia in history was
Queen Victoria. It is assumed that a de novo mutation
occurred in her genotype, since hemophiliacs were not
registered in the families of her parents. Queen Victoria
passed on the mutated gene to her son Leopold (Duke
of Albany) and some of her daughters.
This led to the spread of haemophilia in the royal
families of Europe, including the royal families of Spain,
Germany and Russia. The Queen's grandsons and great-
grandsons, born to daughters or granddaughters,
suffered from haemophilia, including the Russian
Tsarevich Alexei, son of the Russian Emperor Nicholas
II.
Hemophilia B as a separate disease was identified only
in 1952. This form is often called "Christmas disease"
after the name of the first sick boy, in whom its
presence was confirmed during examination. There are
two types of hemostasis - vascular-platelet (primary)
and coagulation. The enzymatic cascade of coagulation
hemostasis has internal (contact) and external
activation pathways.
Both pathways are closed by the formation of the
prothrombinase complex, consisting of factors X
(Stewart-Prower) and V (proaccelerin), calcium ions
and phospholipid matrices. The external pathway is
initiated by tissue thromboplastin (factor II) entering
the blood. In laboratory diagnostics, this pathway is
assessed using the prothrombin (thromboplastin) test.
Other hemostasis tests that should be performed in
individuals suspected of having hemophilia and related
disorders include prothrombin time (PT), activated
partial thromboplastin time (APTT), bleeding time, and
platelet count.
In hemophilia, only APTT will be elevated. It should be
remembered that, especially in mild cases of the
disease, all laboratory parameters may be normal. This
is primarily characteristic of stressful situations
(operations, injuries), since back in 1772 it was noted
that blood taken after stress clots faster.
Thus, summing up the literature review, it can be said
that the above methods allow only a rough
identification of gross violations in the blood
coagulation system. They do not provide an
opportunity to assess the level of thrombinemia, the
content of components of the fibrinolytic system, the
activity of individual physiological anticoagulants,
changes in which underlie microthrombosis.
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