The main method of pathogenetic therapy and prevention of thromboembolism in thrombophilia is AT III replacement.
If the patient has already received intensive heparin therapy, which is ineffective due to a deficiency of AT III, then its administration with plasma can immediately cause deep hypocoagulation and even hemorrhagic complications. To avoid such an “overdose”, hematological preparations containing AT III are administered no earlier than 2-3 hours after the last injection of heparin.
In the future, combined therapy with lyophilized plasma and heparin remains under the control of general coagulation tests – activated partial thromboplastin time or reduced autocoagulogram. The therapeutic effect is usually achieved when the coagulation time is lengthened in these tests by 2-3 times and is maintained at this level throughout the treatment.
Plasma doses depend on the clinical situation and the AT III deficiency. In case of massive thrombosis of the great vessels and life-threatening embolic complications, 800-1200 ml of plasma is administered in 2-3 doses on the first day, and then 400 ml daily. With less pronounced thrombosis in the first days, 400 ml of fresh frozen plasma is injected daily, and then maintenance transfusions are made once every 2–4 days.
In case of milder thrombophilia, a pronounced therapeutic effect is achieved even with small doses of lyophilized plasma (200 ml every 1-2 days) in combination with the subcutaneous injection of small doses of heparin into the anterior abdominal wall (5000 IU 3-4 times a day). It is important to start such therapy as early as possible – at the first, even the most insignificant, exacerbations of the thrombotic process, which interrupts its further progression.
In the absence of lyophilized plasma, replacement therapy with dry donor plasma is possible, although it is less reliable and requires large doses of drugs.
There are also dry concentrated preparations of AT III or complex AT III. They are dosed in units of activity or concentration units (K / U is the amount of AT III, which is contained in 1 liter of standard donor plasma).
Such drugs are dissolved before use in isotonic sodium chloride solution and administered intravenously.
In severe thromboembolism, in particular of the pulmonary artery, fibrinolytic drugs, streptokinase or urokinase, are added to the basic substitution and anticoagulant therapy intravenously in doses depending on the severity of the process.
It is especially effective to conduct these drugs with the help of a vascular catheter to the site of vessel blockage and the simultaneous mechanical destruction of the embolus in the pulmonary trunk by the catheter, which contributes to the fastest restoration of the vessel.
For prophylactic purposes in thrombophilia, plasma transfusions are performed (200-300 ml every other day) in combination with the subcutaneous administration of low doses of heparin (5000 IU twice a day) before and after surgical interventions, in the postpartum period, after injuries and in other thrombogenic situations …
The use of heparin without plasma is ineffective and can aggravate AT III deficiency.
In complex therapy and prevention, some antiplatelet agents and vascular drugs are also used, more often dipyridamole, papaverine and trental.
They are indicated when a patient detects increased spontaneous platelet aggregation. Acetylsalicylic acid with a primary deficiency of AT III should not be used, because even in small doses and with intermittent administration, it suppresses the synthesis of not only thromboxane, but also prostacyclin, thereby reducing the stability of the vascular endothelium.
Secondary (symptomatic) deficiency of antithrombin III
Deep depression of the AT III level in plasma, creating or aggravating the thrombogenic hazard, is more often associated with the intensive consumption (consumption) of this anticoagulant to inactivate blood coagulation factors. This decrease usually develops in individuals with disseminated intravascular coagulation syndrome.
Such a violation contributes to the progression of intravascular blood coagulation and the development of pronounced resistance to heparin, which has the most unfavorable consequences and should be taken into account in the complex therapy of DIC.
The level of AT III in the plasma decreases in the same manner in case of massive thrombosis and thromboembolism, which in the acute period makes it difficult to differentiate between primary (genetically determined) thrombophilia and secondary depression of AT III.
A significant decrease in the plasma AT III, accompanied by a predisposition to thrombosis, is observed in nephrotic syndrome, severe liver disease and some malignant neoplasms. In these diseases, a decrease in AT III may also be secondary, associated with already existing thrombosis and (or) disseminated intravascular coagulation. A parallel study of other parameters of the coagulogram (the level of fibrinogen degradation products, the phenomenon of paracoagulation, the dynamics of platelets and fibrinogen in the blood) makes it possible to distinguish between these disorders.
A significant decrease in the plasma AT III, accompanied by a predisposition to thrombosis, is observed in nephrotic syndrome, severe liver disease and some malignant neoplasms. In these diseases, a decrease in AT III may also be secondary, associated with already existing thrombosis and (or) disseminated intravascular coagulation. A parallel study of other parameters of the coagulogram (the level of fibrinogen degradation products, the phenomenon of paracoagulation, the dynamics of platelets and fibrinogen in the blood) makes it possible to distinguish between these disorders.
Physiological decrease in the level of AT III in the blood is observed in newborns, but it is balanced by the low content of procoagulants in the plasma.
A small but regular decrease in AT III activity occurs at the end of pregnancy and after childbirth, in the postoperative period. These shifts are more pronounced in patients with A (II) blood group, with toxicosis and various complications, as well as in the elderly.
Of the drug-induced depression of AT III, the most important forms associated with the intake of synthetic progestins (hormones) for therapeutic purposes, as contraceptives or to disrupt the menstrual cycle, which athletes sometimes use. These drugs form a pre-thrombotic state, since they also activate platelet hemostasis. The simultaneous use of synthetic hormonal progestins and aminocaproic acid is especially dangerous. This combination, sometimes used to stop uterine bleeding in thrombocytopathies, von Willebrand disease and other forms of hemostatic pathology, can lead to disseminated intravascular coagulation or thrombosis. Thrombohemorrhagic syndrome in such cases is often not recognized in time, and increased bleeding is interpreted as a manifestation of the underlying disease and insufficient effectiveness of its treatment. In such cases, it is necessary to cancel the treatment and include plasma and heparin in therapy. Monitoring the hemostatic system during treatment allows the doctor to recognize this complication in a timely manner.
Intravenous and subcutaneous administration of heparin causes an accelerated metabolism of the “heparin – AT III” complex and a decrease in the level of AT III in plasma. The severity of this decrease and the timing of its development after the start of treatment are very different. It is significantly accelerated and intensified with previous thrombosis or disseminated intravascular coagulation, mitigated by plasma transfusions.
Treatment and prevention of secondary depression AT III consists of the treatment of the underlying disease and the use of the same methods of replacement and corrective therapy that are used in hereditary thrombophilia.