Tactics of pregnancy management with antiphospholipid syndrome

In the process of the first trimester, the most important period for autoimmune pathology, we control haemostasis every 2 weeks. From the 2nd day after ovulation in the cycle of conception, the patient receives 1 t (5 mg) of prednisolone or metipreal. Vitamins for pregnant women or metabolic complexes, folic acid and, if necessary, we connect antiplatelet agents and / or anticoagulants. From antiplatelet agents in the first trimester, it is preferable to use curantyl N in a dose of 25 mg 3 times a day. If there are signs of hypercoagulability or RCMF to treatment, we add heparin 5 000 units 3 times subcutaneously or LMWH (fractiparin) 0.3 ml subcutaneously once a day or 0.2 ml fragrance (2.500 ME) 2 times subcutaneously until the hemostasis parameters normalize.

An alternative option of anticoagulant and antiplatelet therapy is the use of rheopolyglucose 400.0 and 10 000 units of heparin intravenously every other day - 2-3 droppers. This treatment option can be used almost throughout the entire pregnancy to avoid long-term administration of a combination of glucocorticoids and heparin.

Based on their own extensive experience and good clinical results in the treatment of this category of patients, it is worthwhile to dwell on some of the debatable issues of therapy of antiphospholipid syndrome in pregnancy.

Monotherapy with unfractionated heparin or even in combination with aspirin does not give such therapeutic success as one would like. Monotherapy LMWH (Fraxiparin, Fragmin) is preferable to heparin. According to Shehota H. Et al. (2001), where the main type of therapy for antiphospholipid syndrome is aspirin and LMWH, the prevalence of preeclampsia is 18%, intrauterine growth retardation is 31% and preterm delivery is 43%, and perinatal mortality is 7%.

According to research, the frequency of complications for the fetus under different regimens of anticoagulant therapy is different. Thus, with the use of warfarin with or without heparin, the loss of pregnancy was 33.6%, fetal malformations 6.4%; heparin during the entire pregnancy from 6 weeks - developmental abnormalities, the incidence of pregnancy loss was 26.5%.

Another debatable question about the use of immunoglobulin in the treatment of pregnant women with antiphospholipid syndrome. All patients with antiphospholipid syndrome have a chronic viral infection. In connection with the peculiarities of the course of pregnancy, the use of glucocorticoids even in minimal doses, the reactivation of a viral infection is possible. Therefore, during pregnancy, it is recommended to take 3 courses of preventive therapy, which consists of intravenous immunoglobulin in a dose of 25 ml (1.25 g) every other day through 3 doses, while prescribing a suppository with viferon. Small doses of immunoglobulin do not suppress the production of immunoglobulins, but stimulate the body's defenses.

Reinjection of immunoglobulin is performed at 24 weeks gestation and before childbirth. This is one side of the issue - the introduction of immunoglobulin to prevent the activation of a viral infection.

There is a second side, the use of large doses of immunoglobulin to suppress the production of autoantibodies.

There is evidence that large doses of immunoglobulin inhibit the production of autoantibodies and this method can be used instead of glucocorticoid therapy. There is a whole series of works on the effectiveness of the use of immunoglobulin. So, according to research, the combination of small doses of aspirin, heparin and intravenous immunoglobulin at a dose of 1 g / 1 kg of weight for 2 days of each month of pregnancy to 36 weeks, produced very good results - all patients successfully completed the pregnancy. Immunoglobulin administration started before the 12th week of pregnancy, and in these groups patients were included who had the same therapy without immunoglobulin in previous pregnancies that ended unfavorably for the fetus. However, there are many opponents of immunoglobulin therapy and their main points are that:

• immunoglobulin is a very expensive drug, it is necessary to use large doses, and the cost of treatment is from 7000 to 14000 US dollars;
• there is a possibility of transmission of any viruses, if immunoglobulin is not prepared qualitatively;
• there are complications from the introduction of immunoglobulin in the form of headache, nausea, hypotension;
• The use of immunoglobulin does not significantly improve the result of treatment with heparin and aspirin.

Despite objections, interest in therapy with immunoglobulin is extremely high. Only the excessive cost of this drug for our patients and the inability to use domestic production of immunoglobulin in large doses because of possible anaphylactic complications limits the use of this extremely effective method of therapy. With the introduction of immunoglobulin, there may be complications in the form of allergic reactions, headache, often minor effects of acute respiratory disease. To prevent these complications, it is necessary to make an analysis of the total levels of immunoglobulins in the blood of the class IgG, IgM and IgA. With a low level of IgA, administering immunoglobulin is dangerous because of possible anaphylactic reactions. You can recommend the administration of antihistamines before and after the introduction of immunoglobulins, appoint abundant drink, tea, coffee, juices, with the phenomena of ARI - antipyretic agents. As a rule, all complications take place in a day or two. An integral part of the management of pregnancy in patients with antiphospholipid syndrome is the prevention of placental insufficiency.

The state of the fetoplacental system with antiphospholipid syndrome

The pathogenetic effect of antiphospholipid antibodies is associated with thrombosis in the vessels of the placenta with the formation of infarcts in the placenta and a violation of blood microcirculation. The consequence of these disorders is the development of placental insufficiency. According to ultrasound, placental insufficiency is diagnosed when there are signs of fetal hypotrophy. However, a careful study of the placenta reveals the presence of infarcts, cysts, thinning, placenta reduction, placental phenomena and other changes that indicate a violation of the normal functioning of the placenta. Cardiotocography data are also informative in assessing fetal status in patients with antiphospholipid syndrome. In 70% of pregnant women, despite the ongoing therapy, this or that degree of chronic fetal hypoxia is revealed. However, CTG data are informative only after 34 weeks of pregnancy. The ultrasound dopplerometry of the fetus-placental blood flow has great prognostic significance in the evaluation of the fetal condition. Ultrasound dopplerometry in various basins of the fetoplacental system is a valuable diagnostic method for assessing the fetal condition, can serve as a criterion for the effectiveness of the therapy and is one of the indicators that determine the timing and methods of delivery. The study is conducted from 16-20 weeks with intervals of 3-4 weeks before delivery. With a deterioration in the parameters of hemostasiograms, dopplerometry is performed weekly to assess the effectiveness of the therapy.

Studies of blood flow dopplerometry in the umbilical artery in dynamics during miscarriage have shown that "zero" and "negative" blood flow in any gestational age are extremely unfavorable signs in the evaluation of the fetal condition, the therapy does not give an effect, which corresponds to literary data. In such cases, if pregnancy allows, urgent delivery is necessary. The discrepancy between the blood flow indicators for gestational age (both "anticipation" and "lag") is also unfavorable signs requiring more intensive therapy for normalizing blood flow, improving placental function and fighting chronic fetal hypoxia. An "advance" is considered significant with a difference of 8 or more weeks.

Thus, dopplerometry of the fetoplacental blood flow, conducted in the dynamics of pregnancy, allows you to evaluate the effectiveness of the therapy and more accurately determine the timing of delivery.

Prevention and treatment of placental insufficiency in patients with antiphospholipid syndrome should be conducted from the first trimester of pregnancy. The complex of preventive measures, in addition to anti-blocking and, if necessary, anticoagulant therapy, includes courses of metabolic therapy, conducted regularly throughout the pregnancy with two-week breaks.

For the treatment of placental insufficiency in patients with antiphospholipid syndrome, it is advisable to use such agents as intravenous injection of actovegin in a dose of 5 ml in 250.0 ml of physiological sodium chloride solution (course - 5 droppers every other day), alternating with instenon in a dose of 2.0 ml in 200 , 0 ml of physiological sodium chloride solution, as well as 5 droppers. It is advisable to use the essense-forte intravenously drip or jet slowly, or in capsules, troxevasin intravenously or in capsules.

Treatment of placental insufficiency is advisable to be carried out under the control of dopplerometry of the placenta blood flow, hemostasiograms in order to evaluate the effectiveness of the therapy, the optimal timing of delivery and in order to avoid iatrogenic complications.

With placental insufficiency and the absence of the effect of drug therapy, plasmapheresis is advisable.

Such tactics of management and therapy before and during pregnancy allows us without serious complications to complete the pregnancy in 95-96.7% of women with a habitual loss of pregnancy due to antiphospholipid syndrome.

Thus, the combination of several differently directed drugs in a minimal but effective dose makes it possible to obtain a better effect with less iatrogenic complications.

In recent years, there have been reports of the use of fish oil in capsules at a dosage equivalent to 5.1 g of eicosapentaic acid (EPA) and decohexoenoic acid (DHA) for the treatment of patients with antiphospholipid syndrome in a ratio of 1: 1.5. EPA and DHA are unsaturated fatty acids derived from marine plankton. They are able to competitively suppress the saturation and lengthening of the alpha chain of the precursor of arachidonic acid-minolate. Due to its ability to inhibit the formation of thromboxane A, and the aggregation of platelets, these acids have antithrombotic activity.

A small experience of use does not allow us to assess the preventive value of this method of therapy.

It is extremely important for patients with antiphospholipid syndrome to get not only a live, but also a healthy child, since almost 90% or more of pregnancies die without therapy, and only 10% are born alive. Therefore, an important aspect is the evaluation of the course of the neonatal period in children with mothers with antiphospholipid syndrome. In mothers with antiphospholipid syndrome, using modern medical and diagnostic technologies 90.8% of children are born full-term and do not have gross violations in the functioning of vital organs and systems. The revealed deviations during the early neonatal period are regarded as the tension of the adaptation mechanisms due to the peculiarities of the intrauterine development period, which makes it possible to classify these children as an increased risk for disruption of adaptation. Features of the endocrine status in the form of hypocortisolemia at birth (46%) and thyroid insufficiency (24%) are transient in nature, as a rule, do not require hormone replacement therapy and disappear within the first month of life. Changes in the immune status, such as an increase in the content of T-lymphocytes (CD3 +), T-helper cells (CD4 +), B-lymphocytes (CD19 +), the percentage of cells expressing adhesion molecules (CD11 p +), serum interferon reduced interferon-producing activity of cells, are compensatory-adaptive in nature and indicate a strained state of the immune system in the period of early neonatal adaptation, which is consistent with the propensity to develop an infectious inflammatory pathology.

In newborns born to mothers with antiphospholipid syndrome, it is advisable to conduct control studies evaluating the pituitary-thyroid gland-adrenal system in a complicated period of early neonatal adaptation for timely corrective therapy. The changes in the immune status revealed during the newborn period make it possible to recommend dispensary observation of these children for the timely prevention of infectious and inflammatory diseases.

Prevention of thromboembolic complications after childbirth

The postpartum period is the most dangerous for the state of health of a woman with an antiphospholipid syndrome, as more often than in pregnancy, thromboembolic complications are observed. In our practice, we had all cases of thrombophilic complications in the postpartum period.

In order to prevent thromboembolic complications, it is necessary to continue taking prednisolone for two weeks at a dose of 5-10 mg. Evaluation of the hemostasis system is performed 3-5 days after delivery. With severe hypercoagulation, it is expedient to conduct a short course of heparin therapy at a dose of 10 thousand or 20 thousand units per day subcutaneously for 10-12 days (fractiparin, fragmine is preferable) and prescribe aspirin for 100 mg during the month.

It is necessary to recommend a paternity-restricted diet with a restriction of products that increase the blood coagulation potential, and a haemostasis study once every six months.

When joint pain, fever, proteinuria and other symptoms of autoimmune diseases appear, examination should be recommended in specialists-rheumatologists, as often subclinical autoimmune disorders precede manifest forms of autoimmune diseases.

"Catastrophic" antiphospholipid syndrome

Currently, along with the usual and secondary antiphospholipid syndrome, clinical and serological variants of the antiphospholipid syndrome are distinguished (Asherman RA, 1997).

• "Catastrophic" antiphospholipid syndrome.
• Other microangiopathic syndromes:
  • thrombotic thrombocytopenic purpura;
  • hemolyticcouremic syndrome;
  • HELLP-syndrome (hemolysis, increased hepatic enzymes, thrombocytopenia)
• Syndrome of hypothrombinemia;
• Disseminated intravascular coagulation;
• Antiphospholipid syndrome in combination with vasculitis.

The "catastrophic" antiphospholipid syndrome, the term proposed by Asherman RA in 1992, formerly known as "devastating noninflammatory vasculopathy" (Ingram S. Et al., 1987), is characterized by the development of multiple organ dysfunction due to recurrent thrombosis in various organs for a short period of time .

The combination of this syndrome with the development of ICE worsens the prognosis. The genesis of the "catastrophic" antiphospholipid syndrome is more complex than that which occurs in the antiphospholipid syndrome. It is believed that various cellular mediators (cytokines) are responsible for its development, responsible for the "explosion" of a clinically manifested inflammatory response with the development of multiple organ failure.