Thrombophilia tests are done to detect a genetic predisposition (GP) to blood clots in patients. The practical importance of laboratory methods is very important - they make it possible to find out the causes of blood clotting disorders, predict the development of thrombotic complications and thereby reduce the frequency of the most common diseases such as thrombosis, thrombophlebitis, etc. Timely detection is especially important. Knowing the patient's diagnosis, the doctor will be able to provide her with competent medical support until the very birth.
Causes and symptoms
The main cause of the disease is the lack of regulatory mechanisms that limit the formation of blood clots.
Blood clots are formed during blood clotting to restore damaged vessels as a result of biochemical reactions between special cells (platelets) and proteins (clotting factors), which are responsible for regulating the processes of hemorheology and hemostasis. When these processes are disturbed, blood clots begin to form for no apparent reason and block blood flow to surrounding tissues. This tendency toward increased blood clot formation is called hematogenous thrombophilia.
If a patient has thrombophilia, the clinical manifestations will depend on the location of the clots, the degree of circulatory disorders, concomitant pathology, age and gender of the patient. The main symptom is the frequent formation of blood clots, soreness in the place of their localization, and increasing swelling. The development of the disease can be provoked by genetic and environmental factors, therefore thrombophilic anomalies are divided into hereditary and acquired.
Disease types
Hereditary thrombophilia
The genetic defect causes a large number of blood clots to form in young people. The main signs are the occurrence of multiple thrombosis in relatively young people for no apparent reason. Hereditary thrombophilia is caused by genetic defects that are present from birth. The greatest predisposition to congenital form appears when both parents are carriers of the defective genes. The most common anomalies are:
- deficiency of antithrombin III and protein C and S, which are responsible for increased clot formation;
- factor V Leiden, which prevents free blood flow.
Acquired thrombophilia
It occurs in older age and results from autoimmune disorders, hormonal imbalances and diseases that lead to a decrease in blood flow through the veins and arteries. Abnormal clotting can appear after major operations, vascular catheterization, prolonged immobilization, during pregnancy and the use of hormonal oral contraceptives.
When are tests needed?
Screening and testing for genetic thrombophilia should be done under circumstances such as:
If the pregnancy is proceeding with complications, then the woman needs additional examination. - re-thrombosis;
- single or multiple thrombosis at a relatively young age;
- planning pregnancy;
- complications that have arisen when carrying a child;
- oncological and systemic ailments;
- consequences of complex operations, severe injuries, infections.
What analyzes are performed?
For the study, venous blood is taken, which contains genetic markers of thrombophilia, information about the composition, viscosity, and coagulability. For this, the patient undergoes a coagulogram - a basic blood test for thrombophilia, which allows diagnosing problems with hemostasis and hemorheology. It includes the definition of parameters such as:
- blood clotting time;
- APTT;
- prothrombin index;
- thrombosed time;
- fibrinogen concentration;
- fibrinolytic activity;
- activated recalcification time;
- the period of lysis (dissolution) of the euglobulin clot;
- antithrombin activity;
- clotting factors;
- D-dimer, etc.
To identify a gene mutation, it is necessary to additionally be examined. A separate examination is prescribed if there is a suspicion of a genetic mutation in order to identify gene polymorphism and confirm an innate predisposition to the disease. This requires the performance of specific analyzes. Determining the form of genetic characteristics makes it possible to choose a treatment strategy for patients who have a gene mutation. The analysis for hereditary thrombophilia includes the detection of the most commonly inherited polymorphisms:
- blood coagulation genes - F2, factor V-Leiden, F7, F13, etc.
- mutation of antithrombin 3;
- deficiency of proteins C and S;
- the MTHFR gene;
- the gene of the plasminogen activator inhibitor PAI-1 4G / 5G, etc.
Analyzes can be passed in laboratories where there are all conditions for studying the material. In large medical centers, pathology is diagnosed using a special test system "Cardiogenetics of thrombophilia". When planning a pregnancy, screening tests are performed. The main requirement for preparation is abstinence from food for 8 hours before the analysis. Differential diagnosis is sometimes necessary to distinguish the disease from hemophilia.
Deciphering the analysis, norms and deviations
Gene polymorphism is not an indispensable criterion for the development of a disease, but it causes a greater risk of its development, especially when exposed to various external factors.
The study can be positive. The genotype of polymorphism in a patient can be represented by the following options:
- GG is the norm;
- A / A - homozygote;
- G / A - heterozygote.
Thrombophilia test results indicate the presence or absence of the mutation. A blood test can show the following results:
- No mutations have been identified.
- Homozygous - indicates the presence of two genes with an altered structure, so the likelihood of the manifestation of the disease is high.
- Heterozygous. It means that the patient is a carrier of one altered gene, and the likelihood of the disease is low.
The decoding of the gene polymorphism analysis is shown in the table:
A specialized doctor should evaluate the data obtained during the blood test. Based on these data, a prognostic conclusion is formed about a person's genetic predisposition to the development of thrombophilia and the degree of risk of thrombosis. When examining blood in the laboratory, different methods are used, so the indicators may differ slightly. Evaluation of the results should be carried out in accordance with the guidelines of the individual laboratory by a hematologist. The rate of individual indicators of blood coagulation is shown in the table.
“To know in order to foresee;
foresee in order to act;
act to warn. "
Auguste Comte.
Pro et contra of genetic examination of pregnant women.
We call childless women unhappy. Never to experience the feeling of motherhood is a huge ... HUGE MOUNTAIN. We, doctors, inevitably become witnesses of other people's suffering. But today we can say no to this trouble. Now the doctor can really help, prevent, heal the disease, restore the joy of existence.
In this article we will discuss a serious problem of our days - thrombophilia, its contribution to obstetric complications, genes that predetermine the development of thrombophilia in a woman, the consequences of this disease, methods of prevention and treatment.
Why are we discussing this topic? Because there is no greater miracle in the world than the miracle of birth. We are amazed at the beauty of the sunset and the northern lights, we admire the heavenly scent of a blossoming rose. But all the wonders and mysteries of our planet, all the secrets of nature and the secrets of the world bow their heads before birth: A miracle with a capital letter. We must, we can make a woman's life a fairy tale with a happy ending, not a tragedy like the life of NN. So, dear doctor, your attention is given the key to the treatment of infertility, miscarriages, developmental anomalies and much more. To save the life of a woman and an unborn child is now a feasible task. New life is in our hands!
Thrombophilia (TF) is a pathological condition characterized by increased blood clotting and a tendency to thrombosis and thromboembolism. According to numerous studies, this disease is the cause of obstetric complications in 75%.
Classically, two types of TF are distinguished - acquired (antiphospholipid syndrome, for example) and hereditary1. This article will focus on hereditary TF and polymorphic genes2 (polymorphisms) that cause it.
Genetic polymorphism does not necessarily lead to a disease state, most often provoking factors are needed: pregnancy, postpartum period, immobilization, surgery, trauma, tumors, etc.
Taking into account the peculiarities of the physiological adaptation of the hemostasis system to pregnancy, the vast majority of genetic forms of thrombophilia are clinically manifested precisely during the gestational process and, as it turned out, not only in the form of thrombosis, but also in the form of typical obstetric complications. During this period, the restructuring of the coagulation, anticoagulation and fibrinolytic system occurs in the mother's body, which leads to an increase in blood coagulation factors by 200%. Also, in the third trimester, the blood flow velocity in the veins of the lower extremities is halved due to the partial mechanical obstruction of the venous outflow by the pregnant uterus. The tendency to blood stasis in combination with hypercoagulability during physiological pregnancy predisposes to the development of thrombosis and thromboembolism. And with preexisting (genetic) TF, the risk of thrombotic and obstetric complications increases tens and hundreds of times!
What kind of harm are we talking about? How is TF related to obstetric complications? The thing is that full-fledged placental blood circulation depends on a balanced ratio of procoagulant and anticoagulant mechanisms. Hereditary TF leads to a disturbance of this balance in favor of procoagulant mechanisms. With TF, the depth of trophoblast invasion decreases, and implantation is incomplete. This is the cause of infertility and early pre-embryonic loss. A violation of the uteroplacental and fetal-placental blood flow due to the development of vascular thrombosis is a pathogenetic cause of complications such as infertility of unknown origin, recurrent miscarriage syndrome, detachment of a normally located placenta, preeclampsia, intrauterine growth retardation, fetal loss syndrome (undeveloped pregnancy, stillbirth) , neonatal mortality as a complication of premature birth, severe gestosis, placental insufficiency), HELLP syndrome, unsuccessful IVF attempts.
Prevention (general provisions)
* Prevention of obstetric complications in thrombophilia should be started before pregnancy.
* Relatives of the patient with the same defects should receive appropriate prophylaxis.
* Specific prophylaxis for a specific mutation (see sections on polymorphisms)
Treatment (general provisions)
* Anticoagulant therapy regardless of the mechanism of thrombophilia: low molecular weight heparin (does not cross the placenta, creates a low risk of bleeding, no teratogenic and embryotoxic effect). In women at highest risk (genetic TF, history of thrombosis, recurrent thrombosis), anticoagulant therapy is indicated throughout pregnancy. On the eve of childbirth, therapy with low molecular weight heparin is recommended to be canceled. Prevention of thromboembolic complications in the postpartum period is resumed after 6-8 hours and is carried out for 10-14 days.
* Multivitamins for pregnant women
* Polyunsaturated fatty acids (omega-3 - polyunsaturated fatty acids) and antioxidants (microhydrin, vitamin E)
* Specific treatment for a specific mutation (see sections on polymorphisms)
Criteria for the effectiveness of therapy:
* Laboratory criteria: normalization of the level of thrombophilia markers (thrombin-antithrombin III complex, P1 + 2 prothrombin fragments, fibrin and fibrinogen degradation products), platelet count, platelet aggregation
* Clinical criteria: absence of thrombotic episodes, preeclampsia, placental insufficiency, premature placental abruption
At-risk groups:
* pregnant women with a burdened obstetric history (severe forms of preeclampsia, eclampsia, recurrent miscarriage and other obstetric pathologies)
* patients with recurrent thrombosis or episode of thrombosis in history or in this pregnancy
* patients with a burdened family history (the presence of relatives with thrombotic complications under the age of 50 - deep vein thrombosis, pulmonary embolism, stroke, myocardial infarction, sudden death)
Let us dwell in detail on the polymorphisms that are the instigators of TF:
Clotting genes
prothrombin gene (factor II) G20210A
gene 5 factor (Leiden mutation) G1691A
fibrinogen gene FGB G-455A
glycoprotein Ia gene (integrin alpha-2) GPIa C807T
platelet fibrinogen receptor gene GPIIIa 1a / 1b
polymorphisms responsible for the deficiency of proteins C and S, antithrombin III
Protein S receptor gene PROS1 (large deletion)
Genes "thick-blooded"
plasminogen activator inhibitor gene PAI-1 4G / 5G
Genes for vascular tone disorders
NO synthase gene NOS3
ACE angiotensin-converting enzyme gene (ID)
gene GNB3 С825T
Metabolic genes
methylenetetrahydrofolate reductase gene MTHFR C677T
Prothrombin gene (factor II) G20210A
Function: encodes a protein (prothrombin), which is one of the main factors of the coagulation system
Pathology: the replacement of guanine for adenine at position 20210 occurs in an unreadable region of the DNA molecule, therefore, changes in prothrombin itself do not occur in the presence of this mutation. We can detect an increase in one and a half to two times the amount of chemically normal prothrombin. The result is a tendency towards increased thrombus formation.
Polymorphism data:
* frequency of occurrence in the population - 1-4%
* frequency of occurrence in pregnant women with a history of venous thromboembolism (VTE) - 10-20%
4
Clinical manifestations:
* unexplained infertility, gestosis, preeclampsia, premature detachment of a normally located placenta, recurrent miscarriage, fetal-placental insufficiency, intrauterine fetal death, fetal growth retardation, HELLP syndrome
* venous and arterial thrombosis and thromboembolism, unstable angina pectoris and myocardial infarction.
A mutation in the prothrombin gene is one of the most common causes of congenital thrombophilia, but functional tests for prothrombin cannot be used as complete screening tests. It is necessary to carry out PCR diagnostics in order to identify a possible defect in the prothrombin gene.
Clinical relevance:
GG genotype - normal
The presence of a pathological A-allele (GA, GG-genotype) - an increased risk of TF and obstetric complications
* Small doses of aspirin and subcutaneous injections of low molecular weight heparin before pregnancy
When taking oral contraceptives, the risk of thrombosis increases hundreds of times!
Factor gene 5 (Leiden mutation) G1691A
Function: encodes a protein (factor V), which is essential
a component of the blood coagulation system.
Pathology: Leiden mutation of the coagulation factor V gene (replacement of guanine for adenine at position 1691) leads to the replacement of arginine for glutamine at position 506 in the protein chain, which is a product of this gene. The mutation leads to resistance (resistance) of factor 5 to one of the main physiological anticoagulants - activated protein C. The result is a high risk of thrombosis, systemic endotheliopathy, microthrombosis and placental infarction, disorders of uteroplacental blood flow.
Polymorphism data:
* frequency of occurrence in the population - 2-7%
* frequency of occurrence in pregnant women with VTE - 30-50%
* autosomal dominant inheritance
Clinical manifestations:
* unexplained infertility, gestosis, preeclampsia, premature detachment of a normally located placenta, recurrent miscarriage, fetal-placental insufficiency, intrauterine fetal death, fetal growth retardation, HELLP syndrome,
* venous and arterial thrombosis and thromboembolism. 3
Clinical relevance:
GG genotype is normal. Pathological A-allele (GA, GG-genotype) - increased risk of TF and obstetric complications.
It should be remembered that the combination of the Leiden mutation with pregnancy, the use of hormonal contraceptives, an increase in the level of homocysteine, the presence of antiphospholipid antibodies in the plasma increases the risk of developing TF.
Indications for testing:
* History of repeated VTE
* First episode of VTE before age 50
* First episode of VTE with unusual anatomical localization
* The first episode of VTE developed in connection with pregnancy, childbirth, taking oral contraceptives, hormone replacement therapy
* Women with spontaneous abortion in the second and third trimester of unknown etiology
Complementary therapy and prevention:
* In the case of a heterozygote (G / A), relapses rarely occur, therefore, long-term anticoagulant therapy in them is carried out only with a history of repeated thrombosis
* Small doses of aspirin and subcutaneous injections of low molecular weight heparin even before pregnancy, throughout pregnancy and six months after delivery.
Gene methylenetetrahydrofolate reductase MTHFR C677T
Function: Encodes the enzyme methylenetetrahydrofolate reductase, which is a key enzyme in the folate cycle and catalyzes
reaction of conversion of homocysteine to methionine.
Pathology: Normal plasma homocysteine levels are low during pregnancy. This can be seen as a physiological adaptation of the mother's body, aimed at maintaining adequate blood circulation in the placenta.
Substitution of cytosine for thymine at position 677 leads to a decrease in the functional activity of the enzyme to 35% of the average value.
The result is an increase in blood homocysteine levels, which causes endothelial dysfunction during pregnancy.
Polymorphism data:
* the frequency of occurrence of homozygotes in the population - 1o-12%
* the frequency of occurrence of heterozygotes in the population - 40%
* frequency of occurrence in pregnant women with VTE - 10-20%
* autosomal recessive inheritance
Clinical manifestations:
* gestosis, premature detachment of a normally located placenta, intrauterine growth retardation, antenatal fetal death
* defect in the development of the neural tube of the fetus (spina bifida), anencephaly, mental retardation of the child, "cleft lip", "cleft palate"
* premature development of cardiovascular diseases (atherosclerosis!), arterial and venous thrombosis.
It should be remembered that this polymorphism alone is capable of causing resistance of factor 5 to activated protein C due to the binding of homocysteine to activated factor 5.
This means that it can cause all clinical manifestations of the Leiden mutation (see above).
Complementary therapy and prevention:
* folic acid (4 mg / day) in combination with vitamin B6, B12
* adding folic acid to the diet: found in large quantities in the leaves of green plants - dark green vegetables with leaves (spinach, lettuce, asparagus), carrots, yeast, liver, egg yolk, cheese, melon, apricots, pumpkin, avocado , beans, whole wheat and dark rye flour.
Plasminogen activator inhibitor gene PAI-1 4G / 5G
Function: encodes a protein inhibitor of plasminogen activator, which plays an essential role in the regulation of fibrinolysis, and is also an integral component in the process of implantation of the ovum.
Pathology: the presence of 4 guanines instead of 5 in the structure of the plasminogen activator inhibitor gene leads to an increase in its functional activity.
The result is a high risk of thrombosis.
Polymorphism data:
* the frequency of occurrence in the heterozygote 4G / 5G population - 50%
* frequency of homozygote 4G / 4G - 26%
* frequency of occurrence in pregnant women with TF - 20%
* autosomal dominant inheritance
Clinical manifestations:
* early and late miscarriages, development of early and late gestosis, premature detachment of a normally located placenta, feto-placental insufficiency, preeclampsia, eclampsia, HELLP syndrome
* thromboembolic complications, arterial and venous thrombosis, myocardial infarction, stroke, oncological complications
Clinical relevance:
5G / 5G genotype is the norm
Pathological 4G allele (4G / 4G, 4G / 5G - genotype) is a high risk of developing TF and obstetric complications.
Complementary therapy and prevention:
* low doses of acetylsalicylic acid and low doses of low molecular weight heparin
* low sensitivity to aspirin therapy
* vitamins antioxidants C, E
* clean drinking water 1.5-2 l / day
Fibrinogen gene FGB G455A
Function: encodes the protein fibrinogen (more precisely one of its chains), produced in the liver and converted into insoluble fibrin - the basis of a blood clot in blood clotting.
Pathology: the replacement of guanine for adenine in position 455 leads to increased gene performance, the result of which is hyperfibrinogenemia and a high risk of developing TF, the formation of blood clots.
Polymorphism data:
The frequency of occurrence of the heterozygote (G / A) in the population is 5-10%
Clinical manifestations:
* strokes, thromboembolism, deep vein thrombosis of the lower extremities,
* habitual miscarriage, habitual abortions, placental insufficiency, insufficient supply of nutrients and oxygen to the fetus
Clinical relevance:
GG genotype - normal
The presence of a pathological A-allele - an increased risk of hyperfibrinogenemia, and hence the pathology of pregnancy
It should be remembered that hyperhomocysteinemia (MTHFR C677T) also causes hyperfibrinogenemia.
The main therapy and prevention of obstetric complications in this case will be adequate treatment with anticoagulants (low molecular weight heparin).
Gene platelet fibrinogen receptor GPIIIa 1a / 1b (Leu33Pro)
Function: Encodes the beta-3 subunit of the integrin complex of the surface platelet receptor GPIIb / IIIa, also known as glycoprotein-3a (GPIIIa). It ensures the interaction of platelets with blood plasma fibrinogen, which leads to rapid aggregation (adhesion) of platelets and, thus, to the subsequent arrest of the damaged surface of the epithelium.
Pathology: a nucleotide substitution in the second exon of the GPIIIa gene, which leads to the substitution of leucine for proline at position 33.
* There is a change in the structure of the protein, which leads to an increase in the aggregation ability of platelets.
* The second mechanism - a change in the structure of a protein leads to a change in its immunogenic properties, an autoimmune reaction develops, which in turn is the cause of blood clotting disorders.
Polymorphism data:
* frequency of occurrence in the population - 16-25%
Clinical manifestations:
* Arterial thrombotic complications
* Exacerbates the action of other polymorphisms, such as the Leiden mutation.
Clinical relevance:
Leu33 Leu33 - genotype - normal
Pro33 allele - increased risk of arterial thrombosis
Adjunctive therapy and prevention
* New generation antiplatelet drugs - IIb / IIIa receptor antagonists - pathogenetic therapy
Gene GNB3 C825T
F function: is a secondary carrier of the signal from the receptor on the cell surface to the nucleus
Pathology: a point mutation in the G-protein gene - the replacement of cytosine (C) with thymine (T) at position 825 leads to a dysfunction of this secondary carrier. As a result, the signals cease to enter the nucleus, and the humoral regulation of platelet aggregation is disrupted.
Clinical relevance: the polymorphism itself does not play a large role in the pathogenesis of thrombophilia, however, only if it is present, the manifestation of the GPIIIa 1a / 1b polymorphism described above is possible.
NO synthase gene NOS3 (4a / 4b)
Function: encodes nitric oxide synthase (NOS), which synthesizes nitric oxide, which is involved in vasodilation (relaxation of vascular muscles), affects angiogenesis and blood clotting.
Pathology: the presence of four repeats of the nucleotide sequence (4a) instead of five (4b) in the nitric oxide synthase gene leads to a decrease in the production of NO, the main vasodilator that prevents tonic contraction of vessels of neuronal, endocrine or local origin.
Polymorphism data:
The frequency of occurrence in the population of homozygote 4a / 4a - 10-20%
Clinical manifestations:
Endothelial dysfunction.
Polymorphism contributes to the development of preeclampsia, preeclampsia, fetal hypoxia, and intrauterine growth retardation.
Also, this polymorphism determines the development of metabolic syndrome, which negatively affects the hormonal background of a woman, which can also adversely affect the course of pregnancy.
Clinical relevance:
4b / 4b - normal variant of polymorphism in homozygous form; 4b / 4a - heterozygous form of polymorphism; 4a / 4a - mutant variant of polymorphism associated with an increased risk of disease, in a homozygous form
Additional treatment and prevention:
There is currently no pathogenetic treatment. However, it should be remembered that this polymorphism aggravates the clinical picture of other polymorphisms that increase the risk of thrombotic complications.
It is possible to prescribe vasodilators to improve the blood supply to the fetus, but research on this issue has not yet been conducted.
For the prevention of metabolic syndrome and in the presence of overweight, insulin resistance, dyslipidemia in a pregnant woman, it is necessary to prescribe a diet - normal-calorie balanced and normal-calorie unbalanced in salt. Polymorphism predetermines the development of arterial hypertension in a person, therefore, it is useful to prescribe physical activity - cardio training - not only during, but always after pregnancy.
Glycoprotein Ia gene (integrin alpha-2) GPIa C807T
Function: glycoprotein Ia is a subunit of the platelet receptor for collagen, von Willebrand factor, fibronectin and laminin. The interaction of platelet receptors with them leads to the attachment of platelets to the wall of the damaged vessel and their activation. Thus, glycoprotein Ia plays an important role in primary and secondary hemostasis.
Pathology: replacement of cytosine with thymine at position 807 leads to an increase in its functional activity. There is an increase in the rate of platelet adhesion to type 1 collagen.
The result is an increased risk of thrombosis, stroke, myocardial infarction
Polymorphism data:
* frequency of occurrence in the population - 30-54%
Clinical manifestations:
* cardiovascular diseases, thrombosis, thromboembolism, myocardial infarction,
* mild thrombotic tendency (increased action of other polymorphisms that predispose the body to thrombophilia)
Clinical relevance:
CC genotype is the norm
T-allele - increased risk of blood clots and pregnancy pathology
Additional treatment and prevention:
To date, no pathogenetic treatment has been developed.
ACE angiotensin-converting enzyme gene (ID)
Function: conversion of an inactive form of angiotensinogen to angiotensin
Pathology: deletion D and insertion I of the nucleotide sequence in the angiotensin-converting enzyme gene. If a person has a D allele, the risk of developing endothelial dysfunction increases.
Endothelial dysfunction determines the thrombotic tendency of the body.
Clinical manifestations:
Venous thrombosis and thromboembolic complications, premature birth, fetal loss syndrome
Clinical relevance:
II-genotype - the norm
D-allele - increases the risk of developing endothelial dysfunction, which is the basis of all the above-described obstetric complications.
Additional treatment and prevention:
Pathogenetic therapy has not been developed. However, it should be remembered that the D-allele of this gene enhances the pathological manifestations of other polymorphisms predisposing to thrombophilia.
You also need to know that this polymorphism (D-allele) is a genetic component of metabolic syndrome, the presence of which disrupts the hormonal background of a woman. This, of course, can adversely affect the course of pregnancy. Therefore, to prevent the development of metabolic syndrome or if a woman is overweight, insulin resistance, dyslipidemia, a normocaloric diet unbalanced in lipids and adequate physical activity (swimming, yoga, etc.) should be prescribed to such a patient.
Polymorphisms responsible for protein C deficiency
Function: protein C is a major inhibitor of thrombosis. Together with other components, they form a complex that prevents excessive thrombus formation.
Pathology: to unregulated progression of the coagulation cascade and excessive thrombus formation.
Protein C Deficiency Data:
* frequency of occurrence in the population - 0.2-0.4%
Clinical manifestations:
* thrombosis, thromboembolism (pulmonary artery in particular), superficial recurrent thrombophlebitis
* microthrombosis of the placenta and corresponding disorders of fetoplacental blood flow
* neonatal, coagulopathy; syndrome of neonatal fulminant purpura (manifested by ecchymosis around the head, trunk, extremities, often accompanied by cerebral thrombosis and heart attacks; numerous skin ulcerations and necrosis) 5
Clinical relevance:
There are many known polymorphisms that predetermine protein C deficiency, but polymorphisms that determine pathology with a high probability are unknown. Therefore, the leading method for detecting pathology is a biochemical blood test.
Concentration 0.59-1.61 μmol / l - normal
Concentration 30-65% of the norm (less than 0.55 μmol / L) - heterozygous protein C deficiency
Complementary therapy and prevention:
* infusion of protein C concentrate or activated protein S
* with a deficiency of protein C, relapses rarely occur, therefore, long-term anticoagulant therapy is carried out in them only with a history of repeated thrombosis
* possible development of necrosis of the skin and subcutaneous fatty tissue when taking indirect anticoagulants
* Simultaneously with warfarin, it is necessary to use low molecular weight heparin
Polymorphisms responsible for protein S deficiency
Function: protein S is a major inhibitor of thrombosis. Together with other components, they form a complex that prevents excessive thrombus formation.
Pathology: Loss of interaction between this antithrombotic complex and factors of the coagulation cascade leads to to unregulated progression of the coagulation cascade and excessive thrombus formation
There are three types of protein S deficiency: a decrease in the antigenic level of protein S, both total and free, a decrease in the activity of protein S (type 1), a decrease in the activity of protein S with its normal antigen level (type 2), a normal total antigenic level of protein S with a decrease activity (type 3)
Protein S Deficiency Data:
* frequency of occurrence in pregnant women with VTE - 2-10%
* autosomal dominant type of examination
Clinical manifestations:
* superficial thrombophlebitis, deep vein thrombosis, pulmonary embolism, arterial thrombosis
* spontaneous abortion, intrauterine fetal death
Clinical relevance:
Today, many mutations are known that predispose the body to protein S deficiency, but it is not yet possible to isolate the leading polymorphism from them.
More recently, a polymorphism has been discovered that causes type I protein S deficiency in 95% of cases. This is a mutation in the PROS1 protein S receptor gene (large deletion). However, the role of this mutation in the development of obstetric pathology is not yet clear enough.
To identify this pathology, a biochemical blood test should be performed.
Complementary therapy and prevention:
* with a deficiency of protein S, relapses rarely occur, therefore, long-term anticoagulant therapy is carried out in them only with a history of repeated thrombosis
* taking warfarin can cause necrosis of the skin and subcutaneous fatty tissue
Polymorphisms responsible for antithrombin III deficiency
Function: antithrombin III is the main inhibitor of thrombosis. Together with other components, it forms a complex that prevents excessive thrombus formation.
Pathology: Loss of interaction between this antithrombotic complex and factors of the coagulation cascade leads to to unregulated progression of the coagulation cascade and excessive thrombus formation.
Hereditary deficiency of antithrombin III can be manifested either by a decrease in the synthesis of this protein (type I), or by a violation of its functional activity (type II)
Antithrombin III deficiency data:
* frequency of occurrence in the population - 0.02%
* frequency of occurrence in pregnant women with VTE - 1-5%
* autosomal dominant inheritance
Clinical manifestations:
* deficiency of antithrombin in a newborn - a high risk of developing respiratory distress syndrome, intracranial hemorrhage
* deep vein thrombosis of the lower extremities, renal veins and retinal veins
* microthrombosis of the placenta; violation of placental blood flow
Clinical relevance:
At the moment, a large number of mutations have been identified that determine the deficiency of antithrombin III. However, for their manifestation, their combination is necessary. Today, there is no known mutation that would determine antithrombin III deficiency with a very high probability. Therefore, the diagnosis of this mutation is carried out according to biochemical parameters (biochemical blood test).
Complementary therapy and prevention:
1) infusion of antithrombin III concentrate;
2) it should be remembered that in patients with such a mutation, thrombosis recur very often, and therefore, after the first manifestation of TF, they should receive anticoagulant therapy for life.
Laboratory signs:
* platelet aggregation is normal
* bleeding time is normal
* global coagulation tests are not changed
* low immunological level of antithrombin III
* low level of biological activity
* lack of adequate lengthening of APTT with heparin therapy
* tests for fibrinolysis are normal
Especially dangerous combinations of polymorphisms:
* A-allele of factor 5 gene (Leiden G1691A mutation) + A-allele of prothrombin gene (G20210A)
* A allele of factor 5 gene (Leiden G1691A mutation) + A allele of prothrombin gene (G20210A) + T allele of MTHFR gene (C677T)
* A-allele of factor 5 gene (Leiden G1691A mutation) + deficiency of protein C or protein S
* A allele of factor 5 gene (Leiden G1691A mutation) + deletion in the PROS1 gene
* T-allele MTHFR (C677T) + A-allele FGB (G455A)
* 4G / 4G in the PAI-1 gene + T-allele MTHFR (C677T)
* Pro33-allele GPIIIa + T-allele of gene GNB3 (C825T)
Output:
genetic testing will allow you
1.to identify a woman's predisposition to the development of thrombophilia during pregnancy
2. to prescribe pathogenetic therapy that is most effective in each specific case
3.Avoid most obstetric complications, including infertility and intrauterine fetal death
4. to prevent thrombotic complications in a woman in the postpartum period and in subsequent years of life
5.Prevent thrombotic complications in a newborn
6.Prevent the teratogenic effects of thrombophilia (avoid spina bifida e.s.)
7. make a woman's life happy and fulfilling.
Genetics is capable of helping you, dear doctor, in fulfilling your holy duty. Contact us, we are waiting for you.
1. There is a more complex clinical classification based on the clinical manifestations of TF:
1) Hemorheological forms characterized by polyglobulia, an increase in hematocrit, an increase in blood and plasma viscosity in combination with hyperthrombocytosis or without it (screening - measurement of blood and plasma viscosity, determination of the number of cells and hematocrit)
2) Forms caused by disorders of platelet hemostasis, caused by an increase in platelet aggregation function (spontaneous and under the influence of the main agonists), the level and multimeric nature of von Willebrand factor, (screening (c) - counting the number of platelets, measuring their aggregation under the influence of low doses of FLA and ristomycin)
3) Forms associated with a deficiency or abnormalities of plasma coagulation factors: (c - abnormalities in the protein C system, thrombin and ancistronic clotting times, determination of fibrin lysis time) factor 5a abnormality and its resistance to activated protein C, factor 2 abnormality, thrombogenic dysfibrinogenemia
4) Forms associated with deficiency and / or abnormalities of primary physiological anticoagulants (determination of the activity of antithrombin III, screening for disorders in the protein C system) of proteins C and S, antithrombin III
5) Forms associated with impaired fibrinolysis (c - determination of the time of spontaneous and streptokinase-induced lysis of euglobulins, 12- kallikrein-dependent fibrinolysis, cuff test)
6) Forms associated with increased activity and insufficient inactivation of factor 7
-Autoimmune and infectious-immune (c - definition of lupus anticoagulant)
-Paraneoplastic (Trousseau syndrome)
-Metabolic forms of diabetic angiopathy, hyperlipidemic forms, thrombophilia in homocysteinemia
-Iatrogenic (including medication) when taking hormonal contraceptives, heparin thrombocytopenia, fibrinolytic therapy, when treating with L-asparaginase.
2. Polymorphism is a variant of a gene formed from a point adaptive mutation and fixed in several generations and occurs in the population for more than 1-2 percent.
3. A recent study has shown that in carriers of the Leiden mutation, the success rate of embryo implantation during IVF is about 2 times higher than among patients who are not carriers of this mutation. These curious data indicate that, despite the increased likelihood of complications, the fertility of patients with the Leiden mutation (the likelihood of pregnancy in each cycle) may be higher.
4. inheritance: it can be dominant and recessive (this article does not talk about inheritance linked to the sex, that is, to the sex chromosome). The dominant one will manifest itself in a child if there is a corresponding gene for hot in one of the parents, and the recessive one requires genes that are the same for this trait in both parents.
5. the syndrome is described in people who are twice homozygous for type 1 (quantitative and functional deficiency of protein C) and type 2 (qualitative deficiency of protein C); the syndrome is refractory to therapy with heparin or antiplatelet agents. If the patient does not have clinical and laboratory data for irreversible damage to the brain or organ of vision, then the optimal therapy would be the use of a concentrate of activated protein C, protein C or fresh frozen plasma in combination with heparin.
The tendency to develop thrombosis (often venous), which is associated with gene defects, is called hereditary thrombophilia. It is manifested by the pathological formation of blood cells and coagulation factors. In patients, there is a blockage of blood clots of vessels of various localization. During pregnancy, the first signs of the disease are possible with complications in the form of premature birth.
📌 Read in this article
Risk factors for thrombophilia
With a hereditary predisposition to increased blood clotting, a deficiency is most often noted. They reduce the formation of blood clots, so when they are deficient, there is an accelerated formation of a blood clot. In addition, patients may have structural abnormalities of fibrinogen and other coagulation factors.
Many of these disorders remain undiagnosed and do not show clinical signs until provoking factors arise:
- prolonged stay in a static position (bed rest, immobilization after injury, surgery);
- professional activities associated with prolonged sitting or standing on legs, carrying heavy loads;
- sedentary lifestyle;
- obesity;
- pregnancy;
- surgical interventions, extensive tissue damage during trauma, connecting a venous catheter to the central vein;
- loss of fluid during treatment with diuretics, diarrhea, or vomiting;
- malignant tumors;
- diseases of the heart and blood vessels;
- hormonal contraception.
An increase in the synthesis of the amino acid homocysteine is also one of the variants of the familial form of thrombophilia. A high concentration of this compound in the blood has a traumatic effect on the vessel wall, the result of which is the appearance of a blood clot. An increase in homocysteine concentration is considered one of the disease markers:
- and the brain;
- venous thrombosis.
During pregnancy, an increased level of this amino acid is a sign of fetal oxygen starvation due to insufficient blood flow through the placenta, it is often combined with impaired metabolism of folic acid, vitamins B6 and B12, and leads to developmental defects in the child.
Gene disorders can occur not only with hereditary thrombophilia, mutations can also affect the chromosomal apparatus due to external factors:
- ionizing radiation;
- poisoning with chemicals;
- contamination of food and water with pesticides;
- contact with petroleum products;
- the use of medicines;
- eating food with preservatives and dyes, genetically modified foods.
Screening for hereditary thrombophilia
Indications for the determination of blood coagulation factors and concomitant thrombophilia of biochemical parameters may be needed in the following cases:
Blood test
In order to determine the increased threat of thrombus formation, patients are assigned a comprehensive blood test, which includes determining:
Markers
To study the genetic predisposition to thrombophilia, an analysis of venous blood and scraping of the epithelium of the oral mucosa is performed. The data obtained reflects the identified mutation and gene diversity (polymorphism). These abnormalities can increase the risk of blood clots in adverse conditions. Several genes are examined:
- coagulation factors - prothrombin (F2), fifth, seventh, thirteenth (F13A1), fibrinogen (FGB);
- antagonist of plasminogen activator PAI-1 (serpin);
- platelet receptors for collagen ITGA2 or ITGB3 (alpha and beta integrin).
Hereditary thrombophilia and pregnancy
When mutations are found in genes during pregnancy, the risk of blood clots increases. This is dangerous for bearing a child, since in women during this period there is a physiological increase in the coagulation system to protect the body from blood loss during childbirth. Therefore, with genetic abnormalities, blockage of placental vessels often occurs, which leads to adverse consequences:
- early miscarriage;
- premature birth;
- insufficient blood supply to the fetus;
- delay in the development of organs in a child;
- detachment of the placenta;
- venous thrombosis and cerebrovascular accident in the expectant mother;
- habitual miscarriage.
Treatment for hereditary thrombophilia
If a disease is detected, then first of all it is recommended to observe the following rules:
- exclude a long stay in a motionless position (pause for a light warm-up), lifting weights;
- swimming;
- , stockings (especially during pregnancy and childbirth);
- carry out self-massage with the application of venotonic gels (, Hepatrombin);
- correctly build a diet.
For drug therapy of thrombophilia, use:
- anticoagulants - Heparin, Fraxiparin,;
- antiplatelet agents (Tiklid, acetylsalicylic acid, Dipyridamole, Wessel Douay F);
- venotonics -, Aescin, Phlebodia, Troxevasin, Eskuzan, Vasoket.
Diet with a tendency to thrombosis
Foods that increase blood viscosity must be completely excluded from the diet. These include:
- fatty meats, offal, lard, meat broths, jellied meat;
- coffee, black tea, chocolate;
- hard cheese, whole milk;
- spinach and leafy celery;
- all spicy and fatty foods;
- semi-finished products, canned food.
To thin the blood, the menu must include:
- lingonberry, cranberry or viburnum fruit drink;
- compotes with black chokeberry, prunes, dried apricots;
- seaweed, mussels, shrimps;
- ginger;
- pomegranate juice;
- buckwheat, barley and oatmeal porridge;
- dates.
Blood thinning products Hereditary thrombophilia occurs when the body has defects in genes involved in the formation of coagulation factors or substances with anticoagulant activity. The symptoms of the disease are recurrent blockages of the venous vessels. This pathology is especially dangerous for pregnant women due to the increased threat of premature birth and fetal malformation.
Individuals from risk groups are recommended to undergo an examination, including a lipid profile and coagulogram, as well as tests for markers of genetic thrombophilia. Dosed physical activity, medication and an antithrombotic diet are recommended for the treatment and prevention of complications.
Useful video
Watch the video about thrombophilia and pregnancy:
Read also
A torn off blood clot is a fatal threat to humans. Prevention of venous and vascular thrombosis can reduce the risk of a fatal threat. How can thrombosis be prevented? What are the most effective remedies against it?
Head of
"Oncogenetics"
Zhusina
Yulia Gennadevna
Graduated from the pediatric faculty of the Voronezh State Medical University named after V.I. N.N. Burdenko in 2014.
2015 - internship in therapy on the basis of the Department of Faculty Therapy of V.G. N.N. Burdenko.
2015 - Certification course in the specialty "Hematology" on the basis of the Hematological Scientific Center in Moscow.
2015-2016 - physician therapist, VGKBSMP No. 1.
2016 - the topic of the dissertation for the degree of candidate of medical sciences "study of the clinical course of the disease and prognosis in patients with chronic obstructive pulmonary disease with anemic syndrome" was approved. Co-author of over 10 publications. Participant of scientific and practical conferences on genetics and oncology.
2017 - advanced training course on the topic: "interpretation of the results of genetic studies in patients with hereditary diseases."
Since 2017, residency in the specialty "Genetics" on the basis of the RMANPO.
Head of
"Genetics"
Kanivets
Ilya Viacheslavovich
Kanivets Ilya Vyacheslavovich, geneticist, candidate of medical sciences, head of the genetics department of the Genomed medical and genetic center. Assistant of the Department of Medical Genetics of the Russian Medical Academy of Continuing Professional Education.
He graduated from the medical faculty of the Moscow State University of Medicine and Dentistry in 2009, and in 2011 - his residency in Genetics at the Department of Medical Genetics of the same university. In 2017 he defended his thesis for the degree of candidate of medical sciences on the topic: Molecular diagnostics of variations in the number of copies of DNA regions (CNVs) in children with congenital malformations, phenotype abnormalities and / or mental retardation when using SNPs of high-density oligonucleotide microarrays "
From 2011-2017 he worked as a geneticist at the Children's Clinical Hospital named after N.F. Filatov, scientific advisory department of the Federal State Budgetary Scientific Institution "Medical Genetic Research Center". From 2014 to the present, he has been the head of the genetics department at MGC Genomed.
The main areas of activity: diagnostics and management of patients with hereditary diseases and congenital malformations, epilepsy, medical and genetic counseling of families in which a child was born with hereditary pathology or developmental defects, prenatal diagnostics. During the consultation, clinical data and genealogy are analyzed to determine the clinical hypothesis and the required amount of genetic testing. Based on the results of the survey, the data are interpreted and the information received is explained to the consultants.
He is one of the founders of the School of Genetics project. Speaks regularly at conferences. Gives lectures for doctors, geneticists, neurologists and obstetricians-gynecologists, as well as for parents of patients with hereditary diseases. She is the author and co-author of more than 20 articles and reviews in Russian and foreign journals.
The area of professional interests is the introduction of modern genome-wide studies into clinical practice, the interpretation of their results.
Reception time: Wed, Fri 16-19
Head of
"Neurology"
Sharkov
Artem Alekseevich
Sharkov Artyom Alekseevich- neurologist, epileptologist
In 2012, he studied under the international program "Oriental medicine" at the Daegu Haanu University in South Korea.
Since 2012 - participation in the organization of a database and an algorithm for the interpretation of genetic tests xGenCloud (https://www.xgencloud.com/, Project Manager - Igor Ugarov)
In 2013 he graduated from the Pediatric Faculty of the Russian National Research Medical University named after N.I. Pirogov.
From 2013 to 2015, he studied in clinical residency in neurology at the Scientific Center of Neurology.
Since 2015 he has been working as a neurologist, research assistant at the Academician Yu.E. Veltischev N.I. Pirogov. He also works as a neurologist and doctor of the video-EEG monitoring laboratory in the clinics “Center for Epileptology and Neurology named after V.I. A.A. Kazaryan "and" Epilepsy Center ".
In 2015, he studied in Italy at the “2nd International Residential Course on Drug Resistant Epilepsies, ILAE, 2015” school.
In 2015, advanced training - "Clinical and molecular genetics for practicing doctors", RCCH, RUSNANO.
In 2016, advanced training - "Fundamentals of Molecular Genetics" under the guidance of bioinformatics, Ph.D. Konovalova F.A.
Since 2016 - the head of the neurological department of the Genomed laboratory.
In 2016, he studied in Italy at the San Servolo international advanced course: Brain Exploration and Epilepsy Surger, ILAE, 2016 school.
In 2016, advanced training - "Innovative genetic technologies for doctors", "Institute of laboratory medicine".
In 2017 - the school "NGS in Medical Genetics 2017", Moscow State Scientific Center
Currently, he conducts scientific research in the field of epilepsy genetics under the guidance of Professor, MD. Belousova E.D. and professors, d.m.s. Dadali E.L.
The topic of the dissertation for the degree of candidate of medical sciences "Clinical and genetic characteristics of monogenic variants of early epileptic encephalopathies" was approved.
The main areas of activity are the diagnosis and treatment of epilepsy in children and adults. Narrow specialization - surgical treatment of epilepsy, epilepsy genetics. Neurogenetics.
Scientific publications
Sharkov A., Sharkova I., Golovteev A., Ugarov I. "Optimization of differential diagnosis and interpretation of the results of genetic testing by the XGenCloud expert system in some forms of epilepsy." Medical genetics, no. 4, 2015, p. 41.
*
Sharkov A.A., Vorobiev A.N., Troitsky A.A., Savkina I.S., Dorofeeva M.Yu., Melikyan A.G., Golovteev A.L. "Epilepsy surgery for multifocal brain lesions in children with tuberous sclerosis." Abstracts of the XIV Russian Congress "INNOVATIVE TECHNOLOGIES IN PEDIATRICS AND PEDIATRIC SURGERY". Russian Bulletin of Perinatology and Pediatrics, 4, 2015. - p. 226-227.
*
Dadali E.L., Belousova E.D., Sharkov A.A. "Molecular genetic approaches to the diagnosis of monogenic idiopathic and symptomatic epilepsies". Thesis of the XIV Russian Congress "INNOVATIVE TECHNOLOGIES IN PEDIATRICS AND PEDIATRIC SURGERY". Russian Bulletin of Perinatology and Pediatrics, 4, 2015. - p. 221.
*
Sharkov A.A., Dadali E.L., Sharkova I.V. "A rare variant of early type 2 epileptic encephalopathy caused by mutations in the CDKL5 gene in a male patient." Conference "Epileptology in the System of Neurosciences". Collection of conference materials: / Edited by: prof. Neznanova N.G., prof. Mikhailova V.A. SPb .: 2015. - p. 210-212.
*
Dadali E.L., Sharkov A.A., Kanivets I.V., Gundorova P., Fominykh V.V., Sharkova I, V ,. Troitsky A.A., Golovteev A.L., Polyakov A.V. A new allelic variant of type 3 myoclonus epilepsy caused by mutations in the KCTD7 gene // Medical genetics. -2015.- v. 14.-No. 9.- p. 44-47
*
Dadali E.L., Sharkova I.V., Sharkov A.A., Akimova I.A. "Clinical and genetic features and modern methods of diagnosing hereditary epilepsies." Collection of materials "Molecular biological technologies in medical practice" / Ed. Corresponding Member RAYEN A.B. Maslennikov. - Issue. 24.- Novosibirsk: Akademizdat, 2016.- 262: p. 52-63
*
Belousova E.D., Dorofeeva M.Yu., Sharkov A.A. Epilepsy in tuberous sclerosis. In "Diseases of the brain, medical and social aspects" edited by Gusev EI, Gekht AB, Moscow; 2016; pp. 391-399
*
Dadali E.L., Sharkov A.A., Sharkova I.V., Kanivets I.V., Konovalov F.A., Akimova I.A. Hereditary diseases and syndromes accompanied by febrile seizures: clinical and genetic characteristics and diagnostic methods. // Russian Journal of Pediatric Neurology.- T. 11.- №2, p. 33- 41.doi: 10.17650 / 2073-8803- 2016-11- 2-33- 41
*
Sharkov A.A., Konovalov F.A., Sharkova I.V., Belousova E.D., Dadali E.L. Molecular genetic approaches to the diagnosis of epileptic encephalopathy. Collection of abstracts "VI BALTIC CONGRESS ON CHILD NEUROLOGY" / Edited by Professor Guzeva V.I. St. Petersburg, 2016, p. 391
*
Hemispherotomy for pharmacoresistant epilepsy in children with bilateral brain damage Zubkova N.S., Altunina G.E., Zemlyansky M.Yu., Troitsky A.A., Sharkov A.A., Golovteev A.L. Collection of abstracts "VI BALTIC CONGRESS ON CHILD NEUROLOGY" / Edited by Professor Guzeva V.I. St. Petersburg, 2016, p. 157.
*
*
Article: Genetics and differential treatment of early epileptic encephalopathy. A.A. Sharkov *, I.V. Sharkova, E. D. Belousova, E.L. Dadali. Journal of Neurology and Psychiatry, 9, 2016; Issue 2doi: 10.17116 / jnevro 20161169267-73
*
Golovteev A.L., Sharkov A.A., Troitsky A.A., Altunina G.E., Zemlyansky M.Yu., Kopachev D.N., Dorofeeva M.Yu. "Surgical treatment of epilepsy in tuberous sclerosis" edited by M. Dorofeeva, Moscow; 2017; page 274
*
New international classifications of epilepsy and epileptic seizures of the International League Against Epilepsy. Journal of Neurology and Psychiatry. C.C. Korsakov. 2017.Vol. 117.No. 7.P. 99-106
Head of
"Prenatal diagnosis"
Kievskaya
Yulia Kirillovna
In 2011 she graduated from the Moscow State University of Medicine and Dentistry. A.I. Evdokimova with a degree in General Medicine She studied in residency at the Department of Medical Genetics of the same university with a degree in Genetics
In 2015, she graduated from an internship in the specialty of Obstetrics and Gynecology at the Medical Institute for Advanced Training of Doctors of the FSBEI HPE "MGUPP"
Since 2013, he has been conducting a consultative reception at the State Budgetary Healthcare Institution "Center for Family Planning and Reproduction" DZM
Since 2017, he has been the head of the Prenatal Diagnostics department of the Genomed laboratory
Speaks regularly at conferences and seminars. Gives lectures for doctors of various specialties in the field of reproduction and prenatal diagnostics
Conducts medical and genetic counseling for pregnant women on prenatal diagnostics in order to prevent the birth of children with congenital malformations, as well as families with presumably hereditary or congenital pathologies. Interprets the results of DNA diagnostics.
SPECIALISTS
Latypov
Arthur Shamilevich
Latypov Artur Shamilevich - doctor geneticist of the highest qualification category.
After graduating from the medical faculty of the Kazan State Medical Institute in 1976, for many years he worked first as a doctor in the office of medical genetics, then as the head of the medical genetics center of the Republican Hospital of Tatarstan, chief specialist of the Ministry of Health of the Republic of Tatarstan, teacher of the departments of Kazan Medical University.
Author of over 20 scientific papers on problems of reproductive and biochemical genetics, participant in many national and international congresses and conferences on problems of medical genetics. Introduced methods of mass screening of pregnant women and newborns for hereditary diseases into the practical work of the center, carried out thousands of invasive procedures for suspected hereditary diseases of the fetus at different stages of pregnancy.
Since 2012 she has been working at the Department of Medical Genetics with a course of prenatal diagnostics at the Russian Academy of Postgraduate Education.
Research interests - metabolic diseases in children, prenatal diagnostics.
Reception time: Wed 12-15, Sat 10-14Reception of doctors is carried out by appointment.
Doctor-geneticist
Gabelko
Denis Igorevich
In 2009 he graduated from the medical faculty of KSMU named after SV Kurashova (specialty "General Medicine").
Internship at the St. Petersburg Medical Academy of Postgraduate Education of the Federal Agency for Healthcare and Social Development (specialty "Genetics").
Internship in therapy. Primary retraining in the specialty "Ultrasound diagnostics". Since 2016, he has been an employee of the Department of Fundamental Foundations of Clinical Medicine of the Institute of Fundamental Medicine and Biology.
Sphere of professional interests: prenatal diagnostics, the use of modern screening and diagnostic methods to identify the genetic pathology of the fetus. Determination of the risk of recurrence of hereditary diseases in the family.
Participant of scientific and practical conferences on genetics and obstetrics and gynecology.
Work experience 5 years.
Consultation by appointmentReception of doctors is carried out by appointment.
Doctor-geneticist
Grishina
Kristina Alexandrovna
Graduated in 2015 from the Moscow State Medical and Dental University with a degree in General Medicine. In the same year she entered the residency in the specialty 30.08.30 "Genetics" at the Federal State Budgetary Scientific Institution "Medical Genetic Research Center".
She was hired to work at the Laboratory of Molecular Genetics of Difficult Inherited Diseases (headed by A.V. Karpukhin, Doctor of Biological Sciences) in March 2015 as a research laboratory assistant. Since September 2015, she has been transferred to the position of a research assistant. He is the author and co-author of more than 10 articles and abstracts on clinical genetics, oncogenetics and molecular oncology in Russian and foreign journals. Regular participant of conferences on medical genetics.
Field of scientific and practical interests: medical and genetic counseling of patients with hereditary syndromic and multifactorial pathology.
A consultation with a geneticist allows you to answer the questions:
whether the child's symptoms are signs of a hereditary disorder
what research is needed to identify the cause
determining an accurate forecast
recommendations for the conduct and assessment of the results of prenatal diagnostics
everything you need to know when planning a family
IVF planning consultation
on-site and online consultations
She took part in the scientific and practical school "Innovative genetic technologies for doctors: application in clinical practice", the conference of the European Society of Human Genetics (ESHG) and other conferences dedicated to human genetics.
Conducts medical and genetic counseling for families with presumably hereditary or congenital pathologies, including monogenic diseases and chromosomal abnormalities, determines indications for laboratory genetic studies, interprets the results of DNA diagnostics. Consults pregnant women on prenatal diagnostics in order to prevent the birth of children with congenital malformations.
Geneticist, obstetrician-gynecologist, candidate of medical sciences
Kudryavtseva
Elena Vladimirovna
Geneticist, obstetrician-gynecologist, candidate of medical sciences.
Specialist in the field of reproductive counseling and hereditary pathology.
Graduated from the Ural State Medical Academy in 2005.
Residency in Obstetrics and Gynecology
Internship in Genetics
Professional retraining in the specialty "Ultrasound diagnostics"
Activities:
- Infertility and miscarriage Vasilisa Yurievna
She is a graduate of the Nizhny Novgorod State Medical Academy, the Faculty of General Medicine (specialty "General Medicine"). She graduated from the clinical residency at the Moscow State Scientific Center for Genetics. In 2014, she completed an internship at the clinic for mothers and children (IRCCS materno infantile Burlo Garofolo, Trieste, Italy).
Since 2016 he has been working as a consultant physician at Genomed LLC.
Regularly participates in scientific and practical conferences on genetics.
Main areas of activity: Consulting on clinical and laboratory diagnostics of genetic diseases and interpretation of results. Management of patients and their families with presumably hereditary pathology. Consulting in planning pregnancy, as well as in pregnancy on prenatal diagnostics in order to prevent the birth of children with congenital pathology.
In their work, obstetricians-gynecologists of the CIR constantly answer the questions: what is thrombophilia? What is genetic thrombophilia? What kind of thrombophilia test should be taken in order to exclude hereditary factors? How are thrombophilia, pregnancy and polymorphisms related? And many others.
What is thrombophilia?
Thrombus (clot) + philia (love) = thrombophilia. This is such a love for a blood clot, or rather an increased tendency to thrombosis- the formation of blood clots in vessels of different diameters and localization. Thrombophilia is system malfunction.
Hemostasis is a mechanism that provides correct blood reaction to external and internal factors. The blood should flow through the vessels quickly, without lingering, but when it becomes necessary to reduce the flow rate and / or form a clot, for example, to “repair” an injured vessel, the “correct” blood should do this. Further, making sure that the thrombus has done its job and is no longer needed, dissolve it. And run on)
Of course, not everything is so simple, and the coagulation system is a very complex multicomponent mechanism that is regulated at different levels.
A bit of history ...
1856 - German scientist Rudolf Virchow asked about the pathogenesis of thrombus formation, conducted a number of studies and experiments in this regard, and formulated the basic mechanism of thrombus formation. Any medical student when mentioning the "Virchow triad" is obliged to report - trauma to the inner wall of the vessel, a decrease in the speed of blood flow, an increase in blood coagulation. In fact, the great Virchow was the first to solve the riddle "why the same blood can flow freely, but can clog a vessel."
1990 - The British Committee for Hematological Standards defined the concept of "thrombophilia" as a congenital or acquired defect of hemostasis, leading to a high degree of susceptibility to thrombosis.
1997 - the outstanding scientist-hematologist A.I. described "hypercoagulable syndrome", that is, a certain condition of the blood with increased readiness for clotting.
Is the blood clot dangerous?
The answer is yes. Except for physiological necessity, thrombosis is certainly bad. Because blockage of any vessel is dangerous. The larger the vessel, the more significant it is, the more dangerous the complications. The vessel should not have blocked blood flow. This immediately or gradually entails a decrease in oxygen delivery to the tissues (hypoxia) and triggers a series of pathological changes. It may be imperceptible and not as scary as I described, but it can be very painful, and it can be fatal. Thrombosis entails a significant damage to the function of one or another organ, and sometimes the body as a whole. Thrombosis is pulmonary embolism, heart failure (including acute coronary), lesions of the legs (deep vein thrombosis), intestines (mesenteric), etc.
How is thrombophilia related to pregnancy?
Pregnancy is a special "test" period, revealing the carriage of genetic thrombophilia, and most women first learn about the polymorphism of hemostasis genes during pregnancy.
As for obstetric complications, the problem of increased thrombus formation primarily concerns the organ that consists entirely of vessels. This is the placenta. In great detail and with pictures - here:
In all women, physiological hypercoagulation occurs during pregnancy, that is, the blood normally slightly increases its coagulability. This is a normal physiological mechanism aimed at preventing blood loss after the end of pregnancy - in childbirth or with possible pathological outcomes (early termination of pregnancy, placental abruption, etc.).
But if a woman has a carriage of a defective hemostasis gene (or several), then, contrary to the mathematical rule, minus by minus will give an even greater minus - it will significantly increase the risk of blood clots in the vessels of the placenta, which can cause many complications.
What types of thrombophilia are there?
Thrombophilia are divided into hereditary and acquired, there are also mixed types.
Acquired (non-genetic) thrombophilia
Acquired forms of thrombophilia are realized under certain "special" conditions. This happens when the body is going through tough times; rather serious pathological changes entail "over" - the reaction of the coagulation system. For example, oncological diseases accompanied by chemotherapy, severe infectious, autoimmune, allergic processes, liver and kidney diseases, cardiovascular pathologies, connective tissue diseases - systemic lupus erythematosus, various vasculitis, etc. In such cases, the thrombus formation cascade can be triggered and without carrier defective genes for hemostasis. Prolonged and persistent dehydration, physical inactivity, obesity, pregnancy, taking hormonal drugs, etc., can become predisposing factors.
To be continued. In the next release of the blog -.
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