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Thrombophilia: causes, symptoms, diagnosis, treatment
Last reviewed: 07.07.2025

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Thrombophilia is a chronic condition of the body, in which over a long period (months, years, throughout life) there is a tendency either to spontaneous thrombus formation or to uncontrolled spread of the thrombus beyond the damage. Usually, the term "thrombophilia" is understood as a genetically determined condition, however, there are acquired conditions of increased tendency to thrombus formation. Therefore, we believe that it is rational to divide thrombophilia into congenital and acquired.
The main role of hemostasis is to maintain the liquid state of blood in the vessels and create a hemostatic "plug" that closes the vessel defect during trauma or pathological process, preventing blood loss. The hemostatic plug should not interfere with the blood supply to the organs.
Thrombus formation is a dynamic process involving three main factors: hemostatic components of the blood, the state of the vascular wall, and the dynamics of blood flow (Virchow's triad). Normally, the components are in dynamic equilibrium, which helps maintain hemostatic balance. Violation of any of the components of Virchow's triad can lead to a change in the hemostatic balance towards insufficient or excessive thrombus formation. In the case of thrombophilia, as a rule, several components of the hemostasis system are disrupted, and it is often impossible to isolate the leading disorder.
It is impossible to equate thrombophilia, thrombosis and thromboembolism, since thrombophilia only defines a potential possibility, which is not necessarily realized in the form of thrombosis.
Thrombosis is a pathological condition associated with impaired blood flow and organ ischemia due to the closure of the vessel lumen by a thrombus. Thromboembolism is the obstruction of an arterial vessel by a thrombus that has formed in the overlying sections of the circulatory system and entered the vessel with the blood flow.
The development of thrombosis is a consequence of the interaction of factors of thrombus formation pathogenesis. Thrombosis can be arterial and venous.
Arterial and intracardiac thrombi consist mainly of platelets connected by fibrin bridges - white thrombi. Arterial thrombi are mainly parietal. The most important factors in the formation of an arterial thrombus are a congenital or acquired anomaly of the vascular wall and pathological activation of platelets. The most common anomaly is atherosclerosis. In addition, congenital vascular developmental disorders, angiomatous formations, infectious endothelial damage, and iatrogenic disorders are possible.
Venous thrombi include a significant amount of red blood cells and fibrin; they often completely obstruct the lumen of the vessel. The main mechanism of venous thrombus formation is associated with increased blood coagulability and stasis. In childhood, venous catheterization for infusions is of primary importance.
Thrombosis in children is much less common than in adults. In the first six months of life, the frequency of thrombotic episodes is 5.1 per 100,000 children per year, and after 6 months it ranges from 0.7 to 1.9 per 100,000 children per year. Venous thrombosis in children is approximately 2 times more common than arterial thrombosis.
The factors of pathogenesis of pathological thrombus formation can be congenital and acquired. Among congenital factors, hereditary ones are distinguished, as a rule, associated with a genetically determined change in the activity of various hemostasis proteins or with an increase in the concentration of substances in the blood that have prothrombotic activity.
Thrombophilia factors associated with changes in the activity of hemostasis proteins, in turn, can also be divided into several groups:
- pathological decrease in anticoagulant activity;
- pathological increase in the activity of procoagulants;
- polymorphism of procoagulants, protecting them from the effects of inhibitors.
The significance of each group of factors is not the same: if the role of factors of the first and second categories is proven, then factors of the second category are obviously less significant.
This group of factors can also include various anomalies in the development of blood vessels, which significantly increase the risk of pathological thrombus formation, but which cannot be classified as hereditary.
Acquired factors are varied. In children, they rarely become the only cause of pathological thrombus formation, but often serve as the "last straw" leading to thrombosis or embolism. Among the acquired factors in children, intravenous catheters occupy a leading place.
Hereditary risk factors for thrombosis in children:
- antithrombin III deficiency;
- protein C deficiency;
- Protenin S deficiency;
- factor V gene polymorphism (factor V Leiden);
- prothrombin gene polymorphism (single nucleotide substitution G20210A);
- polymorphism of platelet receptor glycoprotein IIIa;
- dysfibrinogenemia;
- hyperlipoproteinemia;
- hyperhomocysteinemia (in children, usually hereditary);
- thalassemia (postsplenectomy hepatic vein thrombosis);
- sickle cell anemia.
Acquired risk factors for thrombosis in children:
- venous catheterization, especially prolonged presence of a catheter in a vein;
- increased blood viscosity (polycythemia, fluid loss with a decrease in circulating blood volume);
- surgery or injury;
- infection (HIV, chickenpox, purulent thrombophlebitis);
- autoimmune diseases (lupus anticoagulant, antiphospholipid syndrome, diabetes mellitus, Behcet's disease, etc.);
- nephrotic syndrome;
- congenital malformations of the heart and blood vessels;
- oncological diseases;
- chemotherapy: asparaginase (L-asparaginase), prednisolone;
- liver disease;
- Purpose of protein C concentrates.
Factors whose role in the development of thrombosis is unclear:
- high level of activity of blood coagulation factors VIII, XI, XII, von Willebrand factor, plasminogen activator inhibitor;
- deficiency of factors XII, heparin cofactor II, plasminogen, plasminogen activators, thrombomodulin.
An important factor taken into account in the risk of pathological thrombus formation is the patient's age. In children, the risk of thrombus formation is greatest in the neonatal period. It is believed that newborns have an increased risk of thrombus formation due to the low fibrinolytic activity of natural anticoagulants (antithrombin III, proteins S and C (III, IIC) and the relatively high activity of factors VIII and von Willebrand factor. Perhaps it is more correct to speak of a lower stability of the hemostatic balance, which is associated with a relatively low concentration of many hemostatic proteins, leading to an easier occurrence of thrombotic or hemorrhagic disorders.
The risk of developing thrombotic complications increases in premature babies or babies with intrauterine growth retardation.
The development of thrombosis in childhood requires the interaction of a number of factors. With an isolated risk factor, thrombosis usually manifests in adulthood. However, in patients with severe ATIII, IIC, and ns deficiency, spontaneous or minimally induced thrombosis may develop at an early age.
Among the acquired risk factors for thrombosis, central venous catheterization ranks first in children of all ages. This factor is present in 90% of children with thrombosis under one year of age and in 66% of children with thrombosis over one year of age. Moreover, children with extensive thrombosis due to central venous catheterization have a serious risk of long-term complications, including post-thrombotic syndrome. In most cases, thrombosis associated with the installation of catheters occurs in the superior vena cava system and in the heart. The inferior vena cava system may be affected when a catheter is installed in the umbilical vein.
Laboratory diagnostics of thrombophilia
Laboratory analysis to identify pathogenetic factors of thrombosis should be performed immediately after diagnosis, before treatment. The recommended set of tests includes: APTT, prothrombin time, fibrinogen, blood coagulation factors V, VII, VIII, IX, XI, XII, VWF, a study of resistance to activated IIC, the activity of ATIII, IIC, ns, plasminogen, D-dimers, euglobulin clot lysis time, tests for the detection of lupus anticoagulant - a test with Russell's viper venom, neutralization tests on phospholipids or platelets, a study of the activity of factors in serial dilutions of plasma, mixed tests to determine the nature of the inhibitor. The activity and presence of plasminogen activator antigen and plasminogen activator inhibitor-1 are determined. It is necessary to determine the level of homocysteine in the blood, as well as the genetic polymorphism of factor V Leiden, methyltetrahydrofolate reductase, prothrombin (single nucleotide substitution G20210A).
Treatment of thrombophilia and thrombosis in children
At present, the problem of treating children has not been sufficiently studied. It is possible that the approaches to treating thrombosis adopted in adults are acceptable for older children. However, there are data suggesting differences in the reactions of adults and children (especially under 6 months of age) to anticoagulant and thrombolytic treatment. Age-related features of the hemostasis system should be taken into account when prescribing treatment.
The main tactics for managing children with thrombosis is to prescribe heparin therapy at the first stage, followed by a transition to long-term use of indirect anticoagulants. It is recommended to carry out maintenance treatment with anticoagulants for at least 3 months after the cessation of the action of thrombosis pathogenesis factors. In the presence of mild hereditary thrombophilia factors, the effect of anticoagulants should be extended to 6 months, and if there is a persistent serious risk of recurrent thrombosis, indirect anticoagulants can be used for years.
Replacement use of C3II or protein C concentrates (IIC), AT III can be carried out for the treatment of thrombotic episodes associated with severe deficiency of IIC, ns, AT III, for the prevention of thrombosis when invasive treatment is required or when additional risk factors for thrombosis are added (e.g., infections), especially in young children. In newborns and children of the first months of life, anticoagulant and thrombolytic treatment may be ineffective due to the low age-related level of AT III and plasminogen. In this case, infusion of C3II is indicated.
Recombinant tissue plasminogen activator (alteplase) is successfully used in thrombolytic treatment of arterial and venous thromboses. The combination of prourokinase and sodium heparin (heparin) is effective and relatively safe in children.
Other anticoagulants include synthetic analogues of hirudin, which block active sites of thrombin, including that associated with fibrinogen. They do not affect APTT and do not bind to platelets, and rarely cause hemorrhagic complications. There is evidence of their effective use in children.
Ankrod - prevents the formation of fibrin cross-links and facilitates its cleavage by plasmin. It has proven itself well in heparin-induced thrombocytopenia with thrombosis. The effectiveness of the drug in children in the treatment of thrombophilia has not yet been studied.
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