Antiphospholipid Syndrome (APS)
Increased Blood Clotting and Recurrent Miscarriages
Antiphospholipid antibodies and antiprothrombin antibodies are one of the most common causes of miscarriages, strokes and other thrombotic (caused by blood clots) events.
Antiphospholipid syndrome (APS) refers to a number of different phenomenon including arterial and venous thrombosis (blood clotting), thrombocytopenia (decreased platelet counts), and obstetric complications such as recurrent spontaneous abortion (miscarriage). Antiphospholipid syndrome is caused by autoantibodies directed against specific proteins involved in blood coagulation, the process in which blood forms a clot. Clots are essential to staunch bleeding from wounds. However, within the body, clots can cause a number of clinical conditions, including strokes (cerebral thrombosis) and pulmonary embolisms (clots within the lungs).
There are two types of antiphospholipid syndrome: a primary syndrome, which occurs in the absence of any other underlying disease in which patients have antiphospholipid antibodies; a secondary syndrome, which is related to systemic lupus erythematosus (SLE), other autoimmune or neoplastic diseases, or other pathological conditions. In addition to antiphospholipid antibodies, antibodies to prothrombin (antiprothrombin antibodies) may also be present in patients with symptoms characteristic of APS. Recent studies show that high concentrations of antiprothrombin antibodies are also associated with recurrent miscarriages, especially at 8-12 weeks gestation. Antiprothrombin antibodies appear to have two subtypes, one which interferes with blood clotting and one which does not.
Because antiphospholipid and antiprothrombin antibodies often occur in patients with SLE, these antibodies are often referred to as lupus anticoagulant whether the patient with these antibodies has SLE or not. Lupus anticoagulant was originally used as a term to describe the abnormal blood clotting often seen in approximately 30 percent of patients with systemic lupus.
Antiphospholipid Antibodies
Antiphospholipid antibody is a term used to describe several different antiphospholipid and anticardiolipin antibodies directed against specific proteins necessary for blood clotting. Although the term antiphospholipid antibodies includes antibodies to beta2-glycoprotein, prothrombin, kininogens, annexin V, protein C and protein S. These antibodies do not target phospholipids. Rather they are directed at proteins with an affinity for anionic phospholipids surfaces. Most tests for antiphospholipid antibodies do not detect prothrombin antibodies.
Approximately 30 percent of patients with antiphospholipid antibodies are reported to have thrombotic (involving abnormal blood clotting) events. These events primarily include deep vein thrombosis of the legs and pulmonary embolism, which represent two-thirds of all events. The other thrombotic events include cerebral arterial thrombosis, spontaneous miscarriages, fetal deaths, or fetal growth retardations.
Obstetrical complications
Women with antiphospholipid antibodies are especially prone to second or early third trimester fetal deaths. Lack of oxygen secondary to spiral arterial blood clots is considered to be the primary cause. Low platelet counts resulting from antiphospholipid antibodies can also result in bleeding complications during delivery. When evaluating women with recurrent miscarriage, it’s important to test for both antiphospholipid and antiprothrombin antibodies.
Other symptoms
Other symptoms that often accompany APS include autoimmune hemolytic anemia, livedo reticularis, skin necrosis, dementia or neuropsychiatric events, a severe bleeding condition referred to as catastrophic antiphospholipid syndrome.
Diagnosis
Diagnosing antiphospholipid syndrome involves a series of different tests that detect abnormalities in blood clotting.
Tests for APS include:
- Anticardiolipin antibodies
- Antiphospholipid antibodies
- IgG and IgM Antiprothrombin antibodies
- Protein C functional activity
- Protein S functional activity
Other tests that test for other hypercoagulation syndromes include:
- DVVT test
- Factor V Leiden Mutation
- MTHR mutation
- APC test
Treatment
Treatment for APS, when indicated, includes anticoagulant therapies such as aspirin, warfarin or heparin and corticosteroids if antiprothrombin or platelet antibodies are present.
Resources
Monica Galli and Tiziano Barbui, Antiprothrombin antibodies: Detection and Clinical Significance in the Antiphospholipid Syndrome, Blood, 93(7), April, 1999, 2149-2157, bloodjournal.org/cgi/content/full/93/7/2149
Sabatini L, Torricelli M, Scaccia V, et al, Increased plasma concentrations of antiprothrombin antibodies in women with recurrent spontaneous abortions, Clinical Chemistry, 2007, Feb; 53(2): 228-232.
