Thrombophilia is a change in the balance of the blood coagulation system, manifested by an increased tendency to the process of thrombosis. Thrombophilia is characterized by a prolonged course and sudden manifestations of complications - phlebothrombosis , thromboembolism.
The main function of the blood coagulation system is to maintain the liquid state of the blood and, if necessary, the formation of a "hemostatic plug" when the vessel is damaged. Hemostasis is nothing more than a chain of chemical reactions in which substances called coagulation factors take part.
The process of thrombosis is dynamic and depends on the state of the epithelium of the vessel wall, the dynamics of blood flow and the haemostatic components of the blood. If there is a disturbance in the balance between these components, the risk of an increased or decreased level of thrombosis increases.
It should be taken into account that not always thrombophilia is accompanied by thrombosis and thromboembolism, but in patients with thrombophilia the risk of thrombosis of different localization increases.
People with thrombophilia have an increased protein content, which increase thrombosis and reduce the level of anti-clotting proteins, which tends to create thrombotic masses in the lumen of the vessels.
Any person may have signs of thrombophilia, but the degree of their manifestation will be different depending on the presence of a set of risk factors for this pathology. Recently there has been a progressive increase in the number of patients with genetic and acquired forms of thrombophilia, which is explained by the deterioration of the ecological situation, untimely diagnosis and treatment of chronic pathologies, and the global "aging" of the population.
All thrombophilia are divided into two main groups according to the etiological principle: hereditary and acquired.
The hereditary risk factors for thrombophilia include: lack of antithrombin III, deficiency of prothrombin S and C, mutations of factor V and prothrombin genes, disfibrinogenemia, increased level of lipoproteins in the blood, sickle cell anemia and thalassemia. This group also includes congenital anomalies of the vessels, which are often accompanied by an increased risk of thrombosis.
Acquired factors rarely become the root cause of thrombophilia, but with their combination conditions are created for the formation of thromboembolic complications. This group includes: prolonged catheterization of veins, dehydration accompanied by polycythemia, autoimmune diseases, heart defects, oncological diseases requiring massive chemotherapy.
The age of the patient is of great importance in the development of thrombophilia. So, even in the neonatal period, the children lack the system of fibrinolytic activity because of the lack of natural anticoagulants. In older children, among the causes of thrombophilia, the leading position is occupied by catheterization of the system of the superior vena cava. In adulthood, there is often enough one factor to initiate thrombus formation processes.
The commonly recognized etiopathogenetic classification of thrombophilia distinguishes three main types of disease:
- hematogenous thrombophilia, caused by changes in coagulation, anticoagulation and fibrinolytic properties of blood;
- hemodynamic thrombophilia, caused by a violation in the circulatory system.
Very often people suffering from thrombophilia do not make any complaints and do not notice any changes in the state of health, since this pathology is characterized by the duration of the course and the smoothness of the increase in clinical manifestations. Sometimes, the period of the unfolded clinical picture comes several years after the diagnosed thrombophilia according to laboratory indicators.
Bright clinical symptoms appear in patients only when there is a clot formation and the severity of the manifestation of symptoms depends on the location of the thrombus and the degree of obturation of the lumen of the vessel.
Signs of arterial thrombosis due to the appearance of blood clots in the lumen of blood vessels of the arterial bed are: ischemic stroke and attacks of acute coronary insufficiency in young people, multiple miscarriages and fetal death during the formation of a thrombus in the lumen of the placental vessels.
Venous thrombosis of the lower extremities is characterized by a wide range of clinical manifestations: a feeling of heaviness in the lower extremities, the appearance of pain in the region of the legs in the projection of the location of the vascular bundle, pronounced swelling of the lower extremities and trophic changes in the skin. If the thrombus is localized in the mesenteric vessels, then there are signs of mesenteric thrombosis of the intestine: acute daggerache without clear localization, nausea, vomiting and loosening of the stool.
Thrombosis of the hepatic veins is manifested by intense pain in the epigastric region, indomitable vomiting, edema of the lower extremities and anterior abdominal wall, ascites and hydrothorax (Badd-Chiari syndrome).
Thus, the main consequences of thrombophilia include: ischemic heart attacks and strokes, thrombosis of various locations and thromboembolism of the pulmonary trunk.
Hereditary or genetic thrombophilia is a tendency to the increased formation of blood clots, inherited from parents to their children. The signs of inherited thrombophilia appear in childhood.
Congenital thrombophilia is characterized by the presence in the patient of one or another defective gene, causing violations in the hemostasis system. Defective genes of thrombophilia the child can inherit from one of the parents. If both parents have a thrombophilia gene, then the child may have serious disorders of the blood coagulation system.
The frequency of occurrence of genetic thrombophilia is on the average 0.1-0.5% of the whole population and 1-8% among patients with thromboembolism.
Among the hereditary thrombophilia, the following forms should be noted:
- genetically determined deficiency of antithrombin III, which is characterized by an autosomal dominant type of inheritance. If both parents have a dominant gene, the risk of stillbirth in such a family reaches 90%. The frequency of this pathology is 0.3% in the population;
- congenital deficiency of proteins C and S, inherited by the dominant type. Signs of thrombophilia appear during the neonatal period in the form of fulminant purpura (the appearance of ulcers and foci of necrosis on the skin), and in homozygous individuals 100% lethality;
- Defect factor Leiden significantly increases the risk of thrombosis at any age, and during pregnancy is considered one of the most common causes of abortion;
- mutation of the prothrombin gene is the cause of thrombophilia in young people and the appearance of signs of thrombosis of placental vessels in pregnant women;
- congenital hyperhomocysteinemia, accompanied by intrauterine defects of the nervous system in the future fetus.
Thrombophilia in pregnancy
Many women with a tendency to increased thrombosis can easily tolerate a healthy child, but such women are at risk of developing varicose veins, phlebothrombosis and other complications during pregnancy.
During pregnancy, in the body of every woman there are enormous compensatory changes, including changes in the blood coagulation system, aimed at limiting blood loss at the time of delivery.
However, world statistics prove the leading role of thrombophilia in the development of pulmonary embolism in pregnant women (50% of cases), while pulmonary embolism is the main cause of maternal mortality.
Critical periods for the manifestation of signs of thrombophilia in pregnant women is the tenth week of pregnancy and the third trimester, when complications occur.
The main complications of thrombophilia during pregnancy are:
- Multiple miscarriages in late pregnancy;
- stillbirth in the third trimester;
- placental abruption accompanied by massive, prolonged bleeding, threatening the life of the mother and child;
- premature birth ;
- lag in the development of the fetus due to malnutrition, as in the placental vessels there are thrombi that prevent the normal flow of blood;
The main criteria for additional examination of a pregnant woman for the presence of genetic thrombophilia are:
- presence in the anamnesis of relatives of thrombophilia episodes;
- thrombosis of a recurrent nature not only in a pregnant woman, but also in her immediate relatives;
- Early pre-eclampsia, cases of stillbirth and repeated miscarriages in the anamnesis.
Women suffering from hereditary forms of thrombophilia and planning pregnancy should observe a number of measures aimed at preventing possible complications. Such mandatory preventive conditions include: modification of the way of life (refusal to lift heavy objects and work associated with prolonged standing), normalization of eating behavior (exclusion of fatty and spicy food), use of objects of compression medical jersey, regular exercise of exercise exercises.
With the established diagnosis of "thrombophilia", a pregnant woman should be treated not only by a gynecologist, but also by a geneticist with a hematologist. In addition to drug therapy should adhere to a special dietary diet. As food products, preference should be given to seafood, dried fruits and ginger, as they contribute to a decrease in blood coagulability.
Modern approaches to conducting pregnancy, burdened with thrombophilia, imply premature delivery at a period of 36-37 weeks to avoid thromboembolic complications. Provided that all recommendations of doctors and adequate preventive therapy are followed, the prognosis for thrombophilia during pregnancy can be favorable.
The main method of diagnosing thrombophilia is a blood test. Blood for thrombophilia is investigated in two stages. The first stage is screening and its main goal is to detect pathology in a specific link of the coagulation system by performing nonspecific blood tests. The second stage allows differentiating and concretizing the problem by conducting specific analyzes.
Even during screening tests, the following forms of thrombophilia can be determined:
- Increased blood viscosity, hyperthrombocytosis and increased hematocrit allows you to suspect hemorheological forms of thrombophilia;
- determination of the level and multimerity of von Willebrand factor, hyperthrombocytosis and increased aggregation ability of platelets indicate the presence of thrombophilia in a patient due to a violation of platelet hemostasis;
- screening tests that determine changes in the protein C and S system, as well as the determination of antithrombin III, are performed for the purpose of diagnosing thrombophilia due to a lack of primary natural anticoagulants;
- calculation of the time of fibrin lysis, the determination of thrombin clotting time and changes in the system of proteins C and S are directed to identify thrombophilia associated with plasma clotting disorders;
- screening tests such as "cuff test", determination of tissue plasminogen activator deficiency and overestimated indices of its inhibitors, calculation of the euglobulin lysis time, allow to judge the presence of thrombophilia caused by a violation of the fibrinolysis system;
- the presence of lupus anticoagulant is indicative of autoimmune thrombophilia.
If the patient has the following indicators, one should think about the possible development of thrombophilia and its consequences in the form of thrombosis: erythrocytosis , polycythemia, decreased ESR, increased hematocrit, isolated hyperthrombocytosis. In addition, an isolated change in the size and shape of red blood cells can cause thrombosis.
Absolute indications for examining a patient for signs of thrombophilia are: episodes of thromboembolism at a young age, diagnosed thrombosis of mesenteric vessels and cerebral vessels, the presence of symptoms of purpura in a newborn, the presence of thromboses in the immediate family, repeated miscarriages and a delay in fetal development.
The treatment of patients with thrombophilia is carried out by specialists in various fields of medicine - the hematologist deals with the study and correction of blood composition changes, the phlebologist treats phlebothrombosis and thrombophlebitis, and in the absence of the effect of conservative treatment, surgical treatment methods that are used by vascular surgeons come to the fore.
Treatment of patients with diagnosed thrombophilia should be complex and individual. First of all, it is necessary to take into account the etiopathogenetic mechanisms of thrombophilia development, since it is impossible to achieve good results from treatment without eliminating the root cause of the disease. In addition to the pathogenetic direction in the treatment of all patients, a conventional scheme of thrombosis therapy in therapeutic and prophylactic doses is conducted. When thrombophilia is not prescribed any specific therapy and treatment of this condition is similar to that of thrombosis.
Common recommendations for dietary nutrition should be considered: the restriction of fried and fatty foods, the complete exclusion of foods with high cholesterol (meat by-products, fatty meats and fish, fats of animal origin). In large quantities, fresh herbs, raw vegetables and fruits and dried fruits should be consumed, which contribute to the rapid utilization of low-density lipoproteins, which provoke the formation of atherosclerotic plaques in the lumen of the vessels.
Thus, with thrombophilia associated with hemorrhagic changes and polycythemia, good results are achieved by the method of prescribing disaggregants (Aspirin 100 mg once a day, Curantil 1 tablet in the evening) and the selection of an individual anticoagulation regimen (Warfarin 2.5 mg once a day orally) . Appropriate additional techniques in this situation are: hemodilution and therapeutic bloodletting.
Indications for the appointment of anticoagulant therapy are: the presence of a thrombus, confirmed by instrumental research, a combination of more than three risk factors for thrombosis, the first 6 weeks after delivery.
The forms of thrombophilia due to a lack of coagulation factors and antithrombin III require a replacement transfusion of large volumes of freshly frozen plasma (up to 900 ml per day intravenously), which should be combined with heparinization.
Hyperaggregational thrombophilia, accompanied by a sharp deficit of fibrinolytic blood components (thrombocytopenic purpura, Moshkovich disease), it is necessary to combine massive plasmapheresis and jet-drop introduction of fresh frozen plasma.
In the case of hereditary thrombophilia due to congenital deficiency of antithrombin III, substitution therapy comes first in the treatment. As a rule, in this situation heparin therapy does not have a proper positive result, and vice versa, in the case of the introduction of hemopreparations together with Heparin, it is possible to provoke hemorrhagic complications. In this regard, the introduction of drugs containing antithrombin III 3 hours after the last dose of Heparin is recommended.
The effectiveness of therapy is controlled by laboratory tests. So, a positive result of treatment is an extension of the coagulation time by 3 times.
In order to accurately determine the dose of fresh-frozen or fresh plasma necessary for infusion, it is necessary to take into account the degree of antithrombin III deficiency and the clinical form of thrombophilia. In the first 2 days after massive thrombosis of the lumen of the main vessels, 400 ml of plasma should be administered three times a day, then go on to supportive substitution therapy - 400 ml per day every other day.
Easy thrombophilia, provided there are no risk factors for thromboembolic complications, is treated with the combined use of intravenous injection of 200 ml of lyophilized plasma and 5000 units of Heparin 4 times a day subcutaneously. The analog of lyophilized plasma is a dry donor plasma, which is used in the absence of the first one.
Currently, as a substitute therapy, complex preparations of antithrombin III are successfully used, which are administered intravenously, previously dissolved in isotonic sodium chloride solution.
In situations where there is a diagnosis of severe thromboembolism , the use of not only direct anticoagulants, but also fibrinolytic drugs (Streptokinase 200,000 units per hour for the first 6 hours, followed by 100,000 units per hour, followed by a transition to intravenous drip Heparin for 10 000 units each). The best effect from the application of fibrinolytic therapy can be achieved if the drug is administered directly at the level of the clogged vessel with a catheter with simultaneous mechanical destruction of thromboembol.
As a prophylactic treatment for patients suffering from thrombophilia, before carrying out surgical operations, as well as in the early postpartum period, it is advisable to carry out prophylactic transfusion of low plasma doses (200 ml every 48 hours) and subcutaneous injection of 5000 units of Heparin 2 times a day.
Isolated reception of Heparin without the introduction of plasma is not only ineffective, but also can aggravate the lack of antithrombin III.
The complex of therapeutic agents for the treatment of thrombophilia also includes drugs that strengthen the vessel wall (Trental 10 ml twice a day intravenously, Papaverin 40 mg 3 times a day orally).
As a preventive treatment and in addition to the main drug therapy all patients are recommended to take traditional medicine. The main products that reduce the activity of platelets are freshly squeezed grape juice and cranberry tea, which should be taken every day for half a cup twice a day.
A good blood-thinning remedy is tincture from the seeds of the Japanese Sophora. To prepare it, you must insist 100 g of seeds in 0.5 liter of alcohol for 2 weeks, then strain and take 20 drops 3 times a day.