Antiphospholipid syndrome (APS) is an autoimmune disease. It is based on the formation of antibodies to phospholipids, which are the main components of cell membranes. Such a disease is manifested by problems with blood vessels, the heart, other organs, as well as with pregnancy.
In the article, we will consider the causes, symptoms, methods for diagnosing antiphospholipid syndrome. Clinical guidelines for the treatment of APS underwent public review and were approved in December 2013. The guidelines also provide a detailed description of what constitutes antiphospholipid syndrome. The information provided in this document is a practical guide for he althcare professionals working with patients diagnosed with APS.
General information
APS can be called a symptom complex, including recurrent arterial and venous thrombosis, as well as obstetric pathology. There are two types of disease:
- Primary antiphospholipid syndrome.
- Secondary API.
Primary is diagnosed when the patient has not shown other diseases except APS for 5 years.
Secondary is a pathology that has developed against the background of another pathology (lupus erythematosus, scleroderma, rheumatoid arthritis and others).
In the first variant, the patient has no erythema on the face, skin rashes, stomatitis, inflammation of the peritoneum, Raynaud's syndrome, and there is no antinuclear factor, antibodies to native DNA and antibodies to Sm-antigen in the blood test.
Diagnosis of disease
Antiphospholipid syndrome is diagnosed when people have at least one clinical and laboratory criterion for its manifestation. If there are only clinical criteria, and there are no laboratory parameters, then the diagnosis of this disease is not made. Also, the diagnosis of APS is not made in the presence of only laboratory criteria. The diagnosis of APS is ruled out if a person has antiphospholipid antibodies in their blood for more than five years in a row, but there are no clinical symptoms.
Diagnosis of antiphospholipid syndrome has its own nuances.
Given that to determine the laboratory parameters of APS, it is required to examine the concentration of antiphospholipid antibodies in the blood at least twice, it is impossible to make an accurate diagnosis within a single examination. Only when the appropriate tests have been passed twice can laboratory criteria be evaluated.
A positive test result will be considered only if the amount of antibodies to phospholipids in a blood test for antiphospholipid syndrome is increased twice in a row. In the event that only once antiphospholipid antibodies were observed in an increased amount, and upon re-examination they were normal, this is considered a negative criterion and does not serve as a sign of this disease. The diagnosis of antiphospholipid syndrome should be carried out by a highly qualified specialist.
The fact is that a temporary increase in antiphospholipid antibodies in the blood can occur very often. In fact, it is fixed after each infectious disease, even against the background of banal otolaryngological ailments. This temporary increase in antibody levels does not require treatment and resolves on its own within just a few weeks.
When the diagnosis of this syndrome is confirmed or refuted, it should not be immediately considered final, as their level can fluctuate depending on a variety of reasons, such as a recent cold or stress.
Differentiation from other diseases
Antiphospholipid syndrome according to ICD 10 has code D 68.6. The tenth revision was held in 1989 in Geneva. His innovation was the use of both numbers and letters in disease codes. Prior to this, the antiphospholipid syndrome according to ICD 9 had code 289.81 in the class “Diseases of the blood and hematopoietic organs”. APS can often be confused with other pathologies. Thus, the disease must be able to distinguish fromthe following diseases with similar clinical symptoms:
- The patient has acquired or genetic thrombophilia.
- Presence of fibrinolysis defects.
- Development of malignant tumors of absolutely any localization.
- Presence of atherosclerosis or embolism.
- Development of myocardial infarction with thrombosis of the heart ventricles.
- Development of decompression sickness.
- The patient has thrombotic thrombocytopenic purpura or hemolytic uremic syndrome.
What tests should be done to diagnose APS
As part of the diagnosis of a disease such as antiphospholipid syndrome, it is necessary to donate blood from a vein. This is done on an empty stomach in the morning. At the same time, a person should not have a cold.
In the event that the patient feels unwell, it is impossible to take an analysis for antiphospholipid syndrome. It is required to wait until the state is completely normal, and only after that do the necessary tests.
Immediately before taking these tests, there is no need to follow any special diet, but it is very important to limit alcohol, smoking and eating junk food. Tests can be taken absolutely on any day of menstruation, if it concerns a woman. So, as part of the diagnosis of antiphospholipid syndrome, it is necessary to perform the following studies:
- Antibodies to phospholipids like "IgG" and "IgM".
- Anti-antibodies to cardiolipin type "IgG" and "IgM".
- Antibodies to glycoprotein type "IgG" and"IgM".
- Research on lupus anticoagulant. It is considered optimal to determine this parameter in the laboratory using the Russell test using viper venom.
- Complete blood count with platelet count.
- Performing a coagulogram.
The indicated analyzes are quite sufficient for making or refuting the corresponding diagnosis. On the recommendation of a doctor, you can take other additional tests for indicators that characterize the state of the blood coagulation system. For example, you can additionally take a D-dimer, thromboelastogram, and so on. However, such additional tests will not allow to clarify the diagnosis, but on their basis it will be possible to most accurately assess the risk of thrombosis and the coagulation system as a whole.
Antiphospholipid syndrome and pregnancy
In women, APS can trigger miscarriage (if the period is short) or premature birth.
The disease can lead to developmental delay or fetal death. Termination of pregnancy occurs most often in the 2nd and 3rd trimesters. If there is no therapy, then such a sad outcome will be in 90-95% of patients. With timely proper treatment, adverse development of pregnancy is likely in 30% of cases.
Options for the pathology of pregnancy:
- Death of a he althy fetus for no apparent reason.
- Pre-eclampsia, eclampsia or placental insufficiency before 34 weeks.
- Spontaneous abortions up to 10 weeks, with no chromosomal abnormalities in the parents, as well as hormonal or anatomicalmaternal genital disorders.
Antiphospholipid syndrome can lead to normal pregnancy.
Clinical manifestations may be absent. In such cases, the disease is detected only when performing laboratory tests. Acetylsalicylic acid up to 100 mg per day is prescribed as a treatment, but the benefit of such therapy has not been definitively established.
Asymptomatic antiphospholipid syndrome is treated with Hydroxychloroquine. Especially often it is prescribed for concomitant connective tissue diseases, such as systemic lupus erythematosus. If there is a risk of thrombosis, "Heparin" is prescribed in a prophylactic dose.
Next, we will find out how this pathology is currently being treated.
Treatment
At present, unfortunately, the treatment of antiphospholipid syndrome is a very difficult task, since today there are still no accurate and reliable data on the mechanism and cause of this pathology.
Therapy is currently directed towards the elimination and prevention of thrombosis. Thus, the treatment is essentially symptomatic and does not allow to achieve an absolute cure for this disease. This means that such therapy is carried out for life, as it makes it possible to minimize the risks of thrombosis, but at the same time does not eliminate the disease. That is, it turns out that, according to the state of medicine and the knowledge of science today, patients must eliminate the symptoms of APS for life. In therapy for thisdiseases, two main directions are distinguished, which are the relief of already frolicking thrombosis, as well as the prevention of repeated episodes of thrombosis.
Providing emergency treatment
Against the background of catastrophic antiphospholipid syndrome, urgent treatment is carried out for patients, which is carried out in intensive care. To do this, use all available methods of anti-inflammatory and intensive care, for example:
- Antibacterial therapy that eliminates foci of infection.
- The use of "Heparin". In addition, such low-molecular drugs as Fraxiparin are used along with Fragmin and Clexane. These medications help reduce blood clots.
- Treatment with glucocorticoids in the form of "Prednisolone", "Dexamethasone" and so on. These medicines allow you to stop systemic inflammatory processes.
- Simultaneous use of glucocorticoids with "Cyclophosphamide" for the relief of severe systemic inflammatory processes.
- Intravenous injection of immunoglobulin on the background of thrombocytopenia. Such a measure is appropriate in the presence of a low number of platelets in the blood.
- In case of no effect from the use of glucocorticoids, immunoglobulin and Heparin, experimental genetically engineered drugs like Rituximab and Eculizumab are introduced.
- Plasmapheresis is performed only with an extremely high titer of antiphospholipid antibodies.
Some studies have proven the effectiveness of Fibrinolysin along with Urokinase, Alteplase and"Antisreplaza" as part of the relief of the catastrophic form of the syndrome. But I must say that these drugs are not prescribed constantly, since their use is associated with high risks of bleeding.
Drug treatment of thrombosis
As part of the prevention of thrombosis, people suffering from this syndrome must take lifelong medications that reduce blood clotting. Directly the choice of drugs determines the features of the clinical course of this disease. To date, doctors are recommended to adhere to the following tactics during the prevention of thrombosis in patients suffering from antiphospholipid syndrome:
- When APS with antibodies to phospholipids, against which there are no clinical episodes of thrombosis, you can limit yourself to acetylsalicylic acid in low doses of 75 milligrams per day. "Aspirin" in this case is taken for life or until a change in treatment tactics. In the event that this syndrome is secondary (for example, it occurs against the background of lupus erythematosus), patients are recommended to use Hydroxychloroquine simultaneously with Aspirin.
- Warfarin is recommended for APS with episodes of venous thrombosis. In addition to Warfarin, they may prescribe Hydroxychloroquine.
- In the syndrome of antiphospholipid antibodies with the presence of episodes of arterial thrombosis, it is also recommended to use Warfarin and Hydroxychloroquine. And in addition to "Warfarin" and "Hydroxychloroquine", in case of a high risk of thrombosis, they also prescribeAspirin at low dosage.
Additional medicines for treatment
In addition to any of the above regimens, certain drugs may be prescribed in order to correct existing disorders. For example, against the background of moderate thrombocytopenia, low dosages of glucocorticoids are used - Metipred, Dexamethasone, Prednisolone, and so on. In the presence of clinically significant thrombocytopenia, glucocorticoids are used, as well as Rituximab. "Immunoglobulin" can also be used.
In the event that the treatment does not allow to increase platelets in the blood, then surgical removal of the spleen is performed. In the presence of kidney pathologies against the background of this syndrome, drugs from the category of inhibitors are used, for example, Captopril or Lisinopril.
New drugs
Recently, the development of new drugs that prevent thrombosis, which include heparinoids, and in addition, receptor inhibitors, such as "Ticlopidine" along with "Tagren", "Clopidogrel" and "Plavix", has been actively carried out.
According to preliminary information, it is reported that these drugs are very effective in antiphospholipid syndrome. It is likely that they will soon be included in the treatment standards recommended by international communities. To date, these drugs are used as part of the treatment of antiphospholipid syndrome, but each doctor tries to prescribe them according to his own scheme.
If there is a need for surgical intervention in this syndrome, one shouldas long as possible to take anticoagulants in the form of "Warfarin" and "Heparin". They need to be canceled for the minimum possible period of time before the operation. It is necessary to resume taking Warfarin after surgery.
In addition, people who suffer from antiphospholipid syndrome should get out of bed and start moving as soon as possible after surgery. It will not be superfluous to wear stockings made of special compression stockings, which will allow for additional prevention of the risk of thrombosis. Instead of special compression underwear, a simple wrapping of the legs with elastic bandages will do.
Clinical guidelines for antiphospholipid syndrome should be strictly followed.
What other drugs are used
In the treatment of this disease, drugs from the following groups are used:
- Treatment with antiplatelet agents and indirect anticoagulants. In this case (in addition to Aspirin and Warfarin), Pentoxifylline is often used.
- The use of glucocorticoids. In this case, the drug "Prednisolone" can be used. In this case, it is also possible to combine it with immunosuppressants in the form of "Cyclophosphamide" and "Azathioprine".
- The use of aminoquinoline drugs, for example, Delagil or Plaquenil.
- Use of selective non-steroidal anti-inflammatory drugs in the form of Nimesulide, Meloxicam or Celecoxib.
- As part of obstetric pathologies, "Immunoglobulin" is used intravenously.
- Treatment with B vitamins.
- The use of polyunsaturated fatty acid preparations, for example, Omacora.
- Using antioxidants like Mexicora.
The following categories of drugs have not yet been widely used, but they are very promising in the treatment of antiphospholipid syndrome:
- Use of monoclonal antibodies to platelets.
- Treatment with anticoagulant peptides.
- Use of apoptosis inhibitors.
- The use of systemic enzyme therapy drugs, for example, Wobenzym or Phlogenzym.
- Treatment with cytokines (mostly used today is Interleukin-3).
As part of the prevention of recurrent thrombosis, predominantly indirect anticoagulants are used. In cases of the secondary nature of the antiphospholipid syndrome, treatment is carried out against the background of adequate therapy of the underlying disease.
Prognosis against the background of pathology
The prognosis for this diagnosis is ambiguous and primarily depends on the timeliness of treatment, as well as on the adequacy of therapeutic methods. Equally important is the discipline of the patient, compliance with all the necessary prescriptions of the attending physician.
What other recommendations are there for antiphospholipid syndrome? Doctors advise not to carry out treatment at their own discretion or on the advice of "experienced", but only under the supervision of a doctor. Remember, the selection of medicines for each patient is individual. Drugs that helped one patient can significantly aggravate the situation of another. Also doctorsadvise people with APS to regularly monitor their laboratory parameters. This is especially true for pregnant women and for those women who plan to become mothers.
Which doctor should I go to?
Treatment of such a disease is carried out by a rheumatologist. Considering that most cases of this disease are associated with pathologies during pregnancy, an obstetrician-gynecologist often also takes part in the treatment. Since this disease affects various organs, it may be necessary to consult the relevant specialists, for example, the participation of such doctors as a neurologist, nephrologist, ophthalmologist, dermatologist, vascular surgeon, phlebologist, cardiologist.
