The Antiphospholipid Syndrome (APS) is a serious autoimmune disease that has a significant impact on the course of pregnancy. According to statistics, the phospholipid syndrome and pregnancy coexist in about 5% of women, but this association increases the risk of miscarriage by 30%. When monitoring the pregnancy in these patients, particular attention should be paid to the surveillance of the lupus anticoagulant, which is an important diagnostic marker and an indicator of disease activity. It is important to note that the presence of APS may manifest differently depending on the mode of conception. Studies show that APS is diagnosed more frequently in women undergoing an IVF protocol than in women who conceived naturally, as they are subject to closer medical monitoring. This does not necessarily mean that the disease is more frequent, but indicates the need for more thorough screening before assisted reproductive technology programs. Thus, the correlation between APS and IVF is due more to a higher detection frequency than to differences in pathogenesis.

What is Antiphospholipid Syndrome?

Antiphospholipid syndrome (APS) is an autoimmune disease in which the immune system produces antibodies against phospholipids, which are components of cell membranes. These antibodies disrupt the normal functioning of cells, particularly platelets and endothelial cells of blood vessels, leading to an increased risk of thrombosis and other complications. The lupus anticoagulant is one of the types of antiphospholipid antibodies detected in this syndrome.

In the context of pregnancy, APS can lead to serious complications such as:

• Recurrent miscarriages
• Intrauterine fetal death
• Premature birth
• Preeclampsia
• Intrauterine growth restriction

Causes of APS

Immunological and genetic factors

The etiology of Antiphospholipid Syndrome is complex and multifactorial. The main causes of APS are as follows:

• Genetic predisposition: hereditary factors play an important role in the development of APS, especially in cases of family history of autoimmune diseases.
• Associated autoimmune diseases: systemic lupus erythematosus (SLE) is the most common associated disease, diagnosed in about 30 to 40% of patients with APS.
• Infectious agents: such as Epstein-Barr virus, cytomegalovirus, human immunodeficiency virus, and hepatitis C virus can trigger the development of the syndrome.
• Malignant tumors: certain types of tumors may be associated with an increased risk of developing APS.
• Medications: some medications may induce the formation of antiphospholipid antibodies.

Influence of pregnancy on the development of the syndrome

Pregnancy itself is a state of physiological hypercoagulation that can potentially exacerbate the course of APS. During pregnancy, significant changes occur in the hemostatic system, including:

• Increased levels of blood coagulation factors
• Decreased activity of natural anticoagulants
• Inhibition of fibrinolysis

These changes, combined with APS, create a high risk of thrombotic complications. Furthermore, pregnancy may be a triggering factor for the initial diagnosis of APS in women with a genetic predisposition to this disease. Some patients only discover the presence of APS after several miscarriages.

Symptoms of APS during pregnancy

The clinical manifestations of Antiphospholipid Syndrome during pregnancy can vary from asymptomatic progression to severe complications. The most common symptoms are:

• Frequent and severe headaches
• Visual, coordination, and memory disturbances
• Sensation of lack of oxygen, shortness of breath, chest pain
• Increased blood pressure
• Redness and swelling of the legs, skin ulcers
• Numbness, pain in the limbs
• Pain behind the sternum after exertion
• Mottled complexion

Additionally, APS during pregnancy can manifest through the following pathologies:

• Miscarriages before 12 weeks
• Premature birth
• Intrauterine developmental delay of the fetus
• Intrauterine fetal death
• Feto-placental insufficiency
• Fetal hypoxia
• Hemolytic disease
• Preeclampsia
• Thromboses in various locations
• Venous thrombosis - embolism
• Stroke or infarction

In one-third of women who have experienced three or more miscarriages, autoimmune disorders, particularly APS, are detected.

Diagnosis of Antiphospholipid Syndrome

The diagnosis of APS is based on a combination of clinical and biological criteria. To establish the diagnosis, it is necessary to identify at least one clinical criterion and one biological criterion.

Clinical criteria:

• Venous or arterial thrombosis
• Obstetric pathology (recurrent miscarriages, premature births, intrauterine growth restriction)

Laboratory criteria:

• Lupus circulating anticoagulant (LAC)
• Anticardiolipin antibodies (IgG or IgM)
• Anti-β2-glycoprotein I antibodies (IgG or IgM)

To confirm the diagnosis of APS, it is necessary for positive laboratory tests to be detected at least twice after an interval of at least 12 weeks.

The normal lupus anticoagulant is the absence of activity in the blood plasma. Its detection is an important diagnostic criterion for APS.

Treatment of APS during pregnancy

The treatment of APS in pregnant women aims to prevent thrombosis and ensure normal fetal development. The approach is determined individually based on the situation and history. It is important to consider whether the pregnancy occurred naturally or as a result of an assisted reproductive technology technique, such as IVF (in vitro fertilization).

In cases of natural conception, the basic treatment relies on taking low doses of aspirin and low molecular weight heparins to prevent clot formation and improve placental blood circulation. These measures are generally sufficient in the absence of significant obstetric history.

In cases of IVF with egg donation and IVF with double donation, the burden on the body is greater, and the risk of complications increases. In such cases, treatment is more intensive: anticoagulant treatment begins before embryo transfer and is strictly monitored. Immunomodulatory medications, such as intravenous immunoglobulins or corticosteroids, are often added. Patients with APS undergoing IVF require more frequent laboratory and ultrasound monitoring, as the risk of thromboembolic and placental complications is significantly higher.

Thus, the therapeutic approach to APS varies depending on the mode of conception: in the case of IVF, stricter control and multi-component treatment are observed.

Standard treatment regimens include:

• Low doses of aspirin (75 to 100 mg/day)
• Low molecular weight heparin or unfractionated heparin
• Intravenous immunoglobulins (if indicated)
• Hydroxychloroquine (especially in cases of SLE)

Use of lupus anticoagulant during pregnancy

The term "lupus anticoagulant" refers to a diagnostic marker and not a therapeutic drug. In the treatment of APS, real anticoagulants are used:

Treatment peculiarities:

• Heparin does not cross the placenta and is safe during pregnancy
• Low molecular weight heparins are preferred due to their lesser side effects

Dosing:

• Prophylactic doses in the absence of thrombosis
• Therapeutic doses in case of a history of thrombosis

Aspirin:

• Prescribed in low doses, improves placental blood flow

Warfarin:

• Contraindicated during pregnancy, used only after delivery

Duration of treatment:

• From planning or the onset of pregnancy
• Throughout the entire duration of pregnancy
• At least 6 weeks after delivery (longer in case of risks)

At the Natuvitro clinic, pregnancy is monitored by experienced obstetricians-gynecologists who use modern diagnostic and treatment methods to ensure a complication-free pregnancy and the birth of a healthy child.