Antiphospholipid syndrome, or antiphospholipid antibody syndrome (APS or APLS), is an autoimmune, hypercoagulable state caused by antiphospholipid antibodies. APS can lead to blood clots (thrombosis) in both arteries and veins, pregnancy-related complications, and other symptoms like low platelets, kidney disease, heart disease, and rash. Although the exact etiology of APS is still not clear, genetics is believed to play a key role in the development of the disease.

Diagnosis is made based on symptoms and testing, but sometimes research criteria are used to aid in diagnosis. The research criteria for definite APS requires one clinical event (i.e. thrombosis or pregnancy complication) and two positive blood test results spaced at least three months apart that detect lupus anticoagulant, anti-apolipoprotein antibodies, and/or anti-cardiolipin antibodies.

Antiphospholipid syndrome often requires treatment with anticoagulant medication to reduce the risk of further episodes of thrombosis and improve the prognosis of pregnancy. The anticoagulant medication used for treatment may differ depending on the circumstance, such as pregnancy.

Signs and symptoms

Antiphospholipid syndrome is known for causing arterial or venous blood clots, in any organ system, and pregnancy-related complications. While blood clots and pregnancy complications are the most common and diagnostic symptoms associated with APS, other organs and body parts may be affected like platelet levels, heart, kidneys, brain, and skin. Also, people with APS may have symptoms associated with other autoimmune diseases like lupus erythematosus that are not caused by APS because APS can occur at the same time as other autoimmune diseases.

Blood clots

In APS patients, the most common venous event is deep vein thrombosis of the lower extremities, and the most common arterial event is stroke. People with a blood clot in their extremities may experience swelling, pain, or redness in the affected area. People experiencing a stroke can experience a variety of symptoms depending on what blood vessel in the brain is affected. Symptoms include but are not limited to trouble speaking, loss of sensation, or weakness in one side of the face or body. Blood clots can also occur in the lungs, which may cause trouble breathing or chest pain, and they can occur in the heart, which could lead to a heart attack.

In pregnant women affected by APS, there is an increased risk of recurrent miscarriage, preterm birth, intrauterine growth restriction, pre-eclampsia, eclampsia. Recurrent miscarriages associated with APS typically occur prior to 10th week of gestation, but miscarriage associated with APS can also occur after the 10th week of gestation.

Other symptoms

Other common findings that suggest APS are low platelet count, heart valve disease, high blood pressure in the lungs, kidney disease, and a rash called livedo reticularis. including headache, migraine, epilepsy, and dementia although more research is needed to prove that these symptoms are indicative of APS. Cancer is also observed to occur at the same time in some patients with APS.

Mechanisms

Antiphospholipid syndrome is an autoimmune disease, in which "antiphospholipid antibodies" react against proteins that bind to anionic phospholipids on plasma membranes. Anticardiolipin antibodies, β2glycoprotein 1, and lupus anticoagulant are antiphospholipid antibodies that are thought to clinically cause disease. These antibodies lead to blood clots and vascular disease in the presence (secondary APS) or absence (primary APS) of other diseases. While the exact functions of the antibodies are not known, the activation of the coagulation system is evident.

Anti-ApoH and a subset of anti-cardiolipin antibodies bind to ApoH. ApoH inhibits protein C, a glycoprotein with important regulatory function of coagulation (inactivates Factor Va and Factor VIIIa). Lupus anticoagulant antibodies bind to prothrombin, thus increasing its cleavage to thrombin, its active form.

Other antibodies associated with APS include antibodies against protein S and annexin A5. Protein S is a co-factor of protein C, which is one of the body's own anti-clotting factors. Annexin A5 forms a shield around negatively charged phospholipid molecules, which reduces the membrane's ability to participate in clotting. Thus, antibodies against protein S and anti-annexin A5 decrease protein C efficiency and increase phospholipid-dependent coagulation steps respectively, which leads to increased clotting potential.

The lupus anticoagulant antibodies are those that show the closest association with thrombosis; those that target β<sub>2</sub>glycoprotein 1 have a greater association with thrombosis than those that target prothrombin.

Anticardiolipin antibodies are associated with thrombosis at moderate to high titres (over 40 GPLU or MPLU).

Patients with both lupus anticoagulant antibodies and moderate or high titre anticardiolipin antibodies show a greater risk of thrombosis than with one alone.

The increased risks of recurrent miscarriage, intrauterine growth restriction and preterm birth by antiphospholipid antibodies, as supported by in vitro studies, include decreased trophoblast viability, syncytialization and invasion, deranged production of hormones and signalling molecules by trophoblasts, as well as activation of coagulation and complement pathways.

While APS was previously categorized into primary and secondary APS based on the absence or presence of concurrent autoimmune disease respectively, the 16th International Congress on Antiphospholipid Antibodies Task Force categorizes APS into 6 categories: were replaced by the Sydney criteria in 2006.

  • Blood clot in three or more organs or tissues and
  • Development of manifestations simultaneously or in less than a week and
  • Evidence of small vessel blood clot in at least one organ or tissue and
  • Laboratory confirmation of the presence of aPL.

Lab testing

Antiphospholipid antibody tests are either liquid-phase coagulation assays to detect lupus anticoagulant or solid phase ELISA (enzyme-linked immunosorbent assay) to detect anti-cardiolipin antibodies and β<sub>2</sub> glycoprotein 1. Typically a medication that decreases the body's ability to form blood clots is given to prevent future clots. Low dose aspirin can be given to people who have APS antibodies but no symptoms, high risk individuals with lupus erythematosus and APS antibodies but no symptoms of APS, and non-pregnant people who had APS during pregnancy. For those people with APS who have had a blood clot (venous or arterial), anticoagulants such as warfarin are used to prevent future clots. or are "triple positive" with all types of antiphospholipid antibody (lupus anticoagulant, anticardiolipin antibody and anti-β2 glycoprotein I antibody). In people with arterial blood clot related APS, using direct-acting oral anticoagulants has shown to increase the risk of future arterial blood clots and should not be used. Outside of people with APS having an increased risk of blood clots and pregnancy complications, people with APS generally have increased risk of atherosclerotic disease.

Other risk stratification criteria for predicting blood clots and pregnancy complications have been proposed, such as the aPL Score and the Global APS score, but further data is needed to validate these tools.

  • Race: Blacks, Hispanics, Asians, and Native Americans
  • Sex: female
  • Age: 30-40s

History

Antiphospholipid syndrome was described in full in the 1980s, by E. Nigel Harris and Aziz Gharavi. They published the first papers in 1983. The syndrome was referred to as "Hughes syndrome" among colleagues after the rheumatologist Graham R.V. Hughes (St. Thomas' Hospital, London, UK), who brought together the team.

Research

According to a 2006 Sydney consensus statement,