Brief overview
- What is APS? APS is an autoimmune disease in which the immune system produces defensive substances (antibodies) against the body’s own cells. Blood clots occur, which can result in severe complications.
- Causes: The causes of APS are not clearly understood.
- Risk factors: Other autoimmune diseases, pregnancy, smoking, infections, estrogen-containing drugs, obesity, genetic predisposition.
- Symptoms: Vascular occlusions (thromboses), miscarriages.
- Diagnosis: Proven thrombosis or miscarriage(s), blood test (detection of antiphospholipid antibodies)
- Treatment: Blood thinning medication
- Prevention: No causal prevention possible
What is APS (Antiphospholipid Syndrome)?
Frequency of APS
Physicians estimate that about 0.5 percent of the general population has antiphospholipid syndrome. APS can occur at any age, but usually begins in young to middle adulthood: 85 percent of patients are between 15 and 50 years old. Women are generally more commonly affected than men.
Forms of APS
GSP is not a congenital condition, but develops over the course of a person’s lifetime. Depending on whether it occurs as an independent disease or together with another underlying disease, doctors distinguish between two forms of antiphospholipid syndrome:
Primary APS
APS occurs as an independent disease in 50 percent of all affected individuals.
Secondary APS
In 50 percent of all affected persons, APS develops as a result of another disease.
Most often, secondary antiphospholipid syndrome occurs together with other autoimmune diseases. These include:
- Lupus erythematosus
- Chronic polyarthritis
- Scleroderma
- Psoriasis
- Behçet’s syndrome
- Autoimmune thrombocytopenia
APS is also observed in certain infectious diseases. These include, for example, hepatitis C, HIV, syphilis and mumps, as well as infections with the Epstein-Barr virus (EBV). EBV infections lead to glandular fever, for example.
Rarely, drugs also trigger the formation of antibodies against the body’s own phospholipid-protein complexes. The most common drugs here are antiepileptic drugs, quinine and interferon.
In a few cases, APS occurs together with a tumor disease such as multiple myeloma (plasmocytoma).
Causes and risk factors
Causes
The causes of antiphospholipid syndrome have not been fully elucidated to date. However, it is certain that it is an autoimmune disease.
In APS, the antibodies are directed against certain phospholipid-protein complexes found in the body. They are found, for example, on the surface of body cells.
In healthy people, blood clotting starts as soon as a blood vessel is injured. Certain blood cells (called platelets) form a clot that reseals the wound and stops the bleeding.
In APS, normal blood clotting is disturbed: the blood clots faster, even without previous injury. A blood clot forms. When this reaches a certain size, vascular occlusion (thrombosis) occurs.
Since phospholipid-protein complexes are found in all body cells, blood clots and thrombosis can also occur anywhere in the body. If the blood vessel is blocked, the tissue is no longer (sufficiently) supplied with blood (ischemia). The most common sites of vascular occlusion in APS are the brain, the heart and, in pregnant women, the placenta.
Risk factors
Doctors assume that genetic predisposition plays a role: The literature describes that in APS patients, other family members are often affected as well. For example, around one third of the blood relatives of an APS patient also have elevated levels of the corresponding autoantibodies. However, the predisposition has not yet been clearly proven.
In addition, most people with APS who experience thrombosis have other risk factors. These include:
- Pregnancy
- Smoking
- Use of oral contraceptives (birth control pills)
- Obesity
- Infectious diseases such as hepatitis C
- Damage to the inner wall of blood vessels
Symptoms
Patients who have antiphospholipid antibodies in their blood but have not yet had thrombosis or pregnancy complications usually do not notice. The following signs indicate APS – but also many other diseases:
- Headache
- Dizziness @
- Memory problems
Antiphospholipid syndrome is usually not noticed until thrombosis occurs. This is the case in about half of all people with antiphospholipid antibodies. The symptoms depend on which vessel is occluded. The most common are:
- Swelling of the leg with pulling pain (deep leg thrombosis).
- Sudden shortness of breath with stabbing pain in the chest (pulmonary embolism)
- Sudden paralysis of one side of the body or speech problems (stroke)
- Seizure
- Migraine
- Bleeding under the fingernails or toenails
- Pregnancy complications
Vascular occlusion in the arteries (arterial thrombosis)
Arteries, with the exception of the pulmonary artery, carry blood rich in nutrients and oxygen to the organs. If an artery becomes blocked, the tissue behind it is no longer supplied with sufficient blood. An arterial thrombosis in the brain, for example, causes a stroke, in the heart a heart attack.
Vascular occlusion in the veins (venous thrombosis)
Blood clotting disorder in pregnancy
Many women who have antiphospholipid syndrome carry their pregnancy to term without complications and give birth to a healthy baby. In some cases, however, blood clots cause problems during pregnancy.
Blood clotting disorders in the uterine lining may prevent the embryo from implanting in the uterus. If this is the case, a miscarriage occurs.
If a blood clot develops in the placenta or in the umbilical cord, the baby will not be supplied with sufficient blood. The undersupply causes the unborn child to lag behind in its growth or even be rejected. Pregnancy diseases such as eclampsia and preeclampsia (high blood pressure with protein excretion in the urine) also indicate APS.
Diagnosis
The first contact person when antiphospholipid syndrome is suspected is the internist or rheumatologist.
Physical examination
The physician first inquires about the patient’s medical history (anamnesis) and performs a physical examination. If thromboses or miscarriages have already occurred in the past, the suspicion of APS is strengthened.
Blood test for antibodies
This is followed by a blood test. Here, the doctor examines the blood for antibodies that are indicative of APS:
- Antibodies against proteins of clotting factors: lupus anticoagulant (LA)
- Antibodies against cardiolipin: anti-cardiolipin antibodies (aCL)
- Antibodies against beta2-glycoprotein 1: anti-beta-2-glycoprotein I antibody (ab2gp1)
APS antibodies are found in one to five percent of the population, for example in association with bacterial or viral infections or cancer.
Sidney criteria
Physical signs of APS:
- Confirmed thrombosis in major or minor veins/arteries.
- Three (or more) miscarriages before the tenth week of pregnancy or one (or more) miscarriage(s) after the tenth week of pregnancy that cannot be explained by other causes.
Detection of APS antibodies:
- The diagnosis is considered confirmed if the elevated antiphospholipid antibodies can be detected twice at least twelve weeks apart.
Treatment
Since there are no drugs that inhibit the formation of the antiphospholipid antibodies or block their action, a cure is not possible. However, the risk of (further) blood clots is significantly reduced with anticoagulant medications.
The therapy used for antiphospholipid syndrome depends on the type of thrombosis (arterial, venous or during pregnancy) and the risk of the individual patient.
Treatment depending on personal thrombosis risk
According to one study, 37.1 percent of these patients suffer one or more further thromboses within ten years. If only the antibody against beta2-glycoprotein 1 is elevated, the risk is lower.
The risk of thrombosis also increases if patients have high cholesterol or high blood pressure or smoke. The same applies to women who take estrogen-containing drugs such as the pill or preparations for menopausal symptoms.
Medications
The doctor treats antiphospholipid syndrome with anticoagulant medications. They cause clotting to start later and more slowly than usual, thereby inhibiting the formation of blood clots. If an injury occurs, however, it takes longer for the wound to close and the bleeding to stop. So people who take anticoagulant medications have a potentially increased risk of bleeding.
Different anticoagulants are available for the treatment of APS:
In order to clot, the blood needs vitamin K. Vitamin K antagonists are antagonists of vitamin K and inhibit blood clotting. They are taken as tablets or capsules and usually take effect after a delay of two to four days. During treatment, the doctor regularly checks the INR value: this indicates how quickly the blood clots.
Vitamin K antagonists for the treatment of APS are:
- Phenprocoumon
- Warfarin
Vitamin K antagonists should not be taken by pregnant women because the unborn baby could be harmed.
Antiplatelet drugs
Antiplatelet drugs prevent platelets from easily attaching to blood vessel walls and forming a blood clot. They are also taken as tablets or capsules. The best-known example of a platelet inhibitor is acetylsalicylic acid (ASA).
Direct/New Oral Anticoagulants (DOAK, NOAK)
Heparin
Heparin is an anticoagulant that is injected under the skin or into the vein. Since it takes effect very quickly, heparin is used for the acute treatment of thrombosis.
Fondaparinux
Fondaparinux is an anticoagulant that, like heparin, is injected under the skin. It is suitable for acute treatment and prevention of thrombosis.
Treatment for existing thrombosis
If thrombosis occurs as a result of antiphospholipid syndrome, acute treatment is usually with heparin. It causes the thrombus to dissolve. The patient is then given the active ingredient phenprocoumon. It prevents further blood clots from forming.
Treatment if antibodies are detected without previous thrombosis
Treatment during pregnancy
For women diagnosed with antiphospholipid syndrome, it is advisable to consult with their physician before planning a pregnancy. Oral anticoagulants such as phenprocoumon may harm the unborn child. For this reason, the doctor will change any APS therapy already started before pregnancy accordingly.
APS patients who wish to have a child, as well as those who are found to be pregnant, will then receive (low-molecular-weight) heparin once daily. Heparin does not pass through the placenta to the child and is therefore safe for mother and child. Pregnant women often also receive acetylsalicylic acid in low doses until the 36th week of pregnancy.
Recent studies
Recent studies on antiphospholipid syndrome show that direct oral anticoagulants (DOAK/NOAK) should not be used in high-risk groups.
A meta-analysis (summary of several studies) also showed a higher risk for DOAK compared to vitamin K antagonists (e.g. warfarin).
Therefore, according to the current 2019 recommendations of the European Rheumatism League, rivaroxaban should not be used in triple-positive APS patients, but should be replaced by vitamin K antagonists.
Prevent
Because the trigger for antiphospholipid syndrome is unknown, there are no specific preventive measures. People who have already had a thrombosis should have regular checkups with their doctor and take prescribed medications carefully.
Women with APS are advised to avoid drugs containing estrogen, such as those used for contraception or to treat menopausal symptoms. This is because estrogen can significantly increase the risk of thrombosis.
Prognosis
APS is not curable. However, with individually tailored treatment and regular check-ups with a doctor, the risk of thrombosis can be significantly reduced.
