Antiphospholipid antibody syndrome (APS) is an autoimmune disease. It is caused by the immune system mounting an unwanted response against phospholipid-binding proteins present in the blood. This can lead to a wide range of serious events including thrombosis and miscarriage.
What is Antiphospholipid Antibody Syndrome (APS)?
One of the main targets of the immune response in APS is a protein called b(2)-glycoprotein. Antiphospholipid (aPL) antibodies can cause a wide range of medical problems. The first documented cases of APS in medical literature were around a hundred years ago. However it was not until the 1990’s that the immunology behind the disorder was properly defined.
Antiphospholipid antibody syndrome is commonly associated with vascular and cardiac conditions, pregnancy and Systemic Lupus Erythematosus (SLE). APS can occur in patients that have no other autoimmunity, or can occur alongside other autoimmune disorders, particularly SLE.
What Causes APS?
It is generally believed that the cause of APS is exposure to an environmental substance, usually an infectious organism, which contains peptides similar to those present in blood plasma proteins. Infectious agents associated with APS development include Hepatitis C, VZV and CMV.
Cases of APS have also been attributed to trauma and certain drug treatments. It is believed that genetic factors such as tissue type determine whether a person is susceptible to APS. It is likely that a single infection is not enough to induce APS in susceptible individuals, and that several infections are required.
How is APS Diagnosed?
Laboratory diagnosis of APS can be complex. However the generally accepted diagnostic criteria is persistently raised antiphospholipid antibodies in the blood. This can be assessed by basic measurements of antibody levels such as IgM or IgG or more specific measurements for aPL antibodies, such as antibodies to b(2)-glycoprotein.
Since aPL antibodies can be temporarily raised during infections, diagnosis must be based on at least two measurements of antibody levels taken 12 weeks apart.
APS and Vascular Disease
Theoretically any blood vessels can be affected by high aPL antibodies, but the most common vascular diseases associated with APS are stroke, transient ischemic attack and DVT (deep vein thrombosis). It is believed that this is caused by aPL antibodies sticking the blood vessel walls. This causes a range of complex events which make the formation of blood clots more likely.
Treatment usually involves the administration of anticoagulants such as heparin or warfarin. In addition, elimination of other factors that can increase the risk of thrombosis (oral contraceptive, smoking) should be eliminated.
APS and Cardiac Disease
The most common cardiac pathology associated with APS is heart valve disease (valve thickening) which is often asymptomatic. More seriously, there is accumulating evidence that APS leads to an increased risk of myocardial infarction (heart attack). APS patients have a reported higher risk of complications after surgical procedures such as angioplasty or coronary artery bypass.
Treatments that can be used in APS patients with cardiac disease include warfarin, aspirin, corticosteroids, anti-inflammatory drugs. However, use of all these treatments is controversial as there is little data to show they are effective.
APS and Pregnancy
APS is one of the known causes of recurrent miscarriage. Other serious problems include foetal growth retardation, premature delivery, eclampsia and preeclampsia. This is probably because the aPL antibodies hinder the function of the placenta and so impair the blood supply to the foetus. In addition, the mother herself can suffer thrombotic disease.
Low dose aspirin and heparin for pregnant women with APS is believed to reduce the incidence of miscarriage.
The Future for APS Patients
There are still many gaps in our understanding of the causes and mechanisms involved in antiphospholipid antibody syndrome. Although the majority of cases of APS are treatable with anti-coagulants, new drugs are being actively pursued. Researchers hope to develop treatments that target the aPL antibodies, so preventing them from causing thrombotic events.
Antiphospholipid Syndrome, D.George & D.Erkan, Progress in Cardiovascular Diseases, 52 (2009) P115-125
Genetics of Antiphospholipid Syndrome, T. Horita & T.J Merrill, Current Rheumatology Reports, 2004 (6), P458-62.
Antiphospholipid Syndrome (APS): Where does it come from? Y.Sherer, M. Blank & Y Shoenfeld, Best Practice and Research Clinical Rheumatology, 2007, 21(6) P1071-8.