Aetna considers antiprothrombin antibody testing experimental and investigational because its clinical value has not been established.

Antiphospholipid syndrome is an autoimmune condition characterized by moderate-to-high levels of circulating antiphospholipid antibodies and the presence of venous and arterial thromboses, autoimmune thrombocytopenia, fetal loss, and other clinical features, including transient ischemic attacks, amaurosis fugax, Coombs-positive hemolytic anemia, and livedo reticularis.

Most patients with antiphospholipid syndrome have lupus anticoagulant and anticardiolipin antibodies. However, some patients with antiphospholipid syndrome have either lupus anticoagulant or anticardiolipin antibodies, but not both. Thus, tests for both antibodies should be performed to confirm the diagnosis of antiphospholipid syndrome (ACOG, 1998).  Anticardiolipin antibodies are detected by conventional immunoassays.  There is no direct test for the lupus anticoagulant (LA); detection is based upon its inhibitory actions on coagulation.

Other autoantibodies have been associated with antiphospholipid syndrome, including those reactive with prothrombin.  However, current guidelines state that the clinical significance of antiprothrombin antibodies has not been defined (British Committee for Standards in Haematology, 2000; ACOG, 1998).  The Haemostasis and Thrombosis Task Force of the British Committee for Standards in Haematology reached the following conclusion: “Antiprothrombin antibodies generally exhibit poor specificity for venous thrombosis and recurrent fetal loss and may be found in patients with infection. Their precise clinical significance is not yet clear. One report has claimed an association with myocardial infarction, but more work is required to clarify the clinical importance of this observation.”

In a review of the literature, Galli and Barbui (1999) state that "[t]he question whether antiprothrombin antibodies increase the risk of thromboembolic events remains unanswered .…The retrospective nature of these studies [of antiprothrombin antibody and antiphospholipid syndrome] prevents from drawing definite conclusions. Only one prospective study has been performed that confirmed the association between high titers of antiprothrombin antibodies and an increased risk of developing myocardial infarction, which is not one of the typical features of the antiphospholipid syndrome. Therefore, more 'cross-sectional' or prospective clinical studies are warranted to establish the clinical relevance of antiprothrombin antibodies."

Donohoe (2001) has concluded that “[l]ongitudinal studies are required to asses the predictive value of these antibodies.  Pending those results, testing for antiprothrombin antibodies should remain a research procedure, as the detecting of those antibodies adds little to the clinical diagnosis and management of individual patients.”

Identification of antiphospholipid syndrome means that many patients who were in the past diagnosed as suffering from a 'vasculitis' and treated with anti-inflammatory regimes and high-dose corticosteroids, will, if found to be suffering from antiphospholipid syndrome, respond better to anticoagulation therapy (GP Notebook, 2001).  First-line treatment for antiphospholipid syndrome is low dose aspirin.  Patients with antiphospholipid syndrome who have had a documented major thrombotic event require long-term treatment with warfarin or coumarin anticoagulation.

Women with antiphospholipid syndrome should be treated during pregnancy with thromboprophylactic doses of heparin and low-dose aspirin. Close obstetric care is indicated in all cases because of an increased risk of pregnancy-induced hypertension, fetal growth restriction, and a non-reassuring fetal heart rate pattern (ACOG, 1998).

von Landenberg et al (2003) documented the association of IgG antiprothrombin antibodies with pregnancy loss and in particular early pregnancy loss in a large group of young female patients with antiphospholipid syndrome (APS).  These researchers recommended routine testing for antiprothrombin antibodies in young female patients with APS.  However, they also stated that there is a need for further prospective studies to confirm the association between antiprothrombin antibodies and pregnancy loss.  Furthermore, Lopez et al (2004) reported weak predictive value and association with pregnancy morbidity of 4 antiphospholipid antibodies (e.g., antiprothrombin antibodies) in patients with systemic lupus erythematosus and patients with APS.

Guidelines on antiphospholipid syndrome from the American College of Obstetricians and Gynecologists (ACOG, 2005) state that testing for antiprothrombin antibodies "cannot be recommended for clinical use at this time."

Tincani et al (2007) stated that prothrombin (PT) is a target for antibodies with LA activity, suggesting the possible application of anti-prothrombin antibody (aPT) assays in patients with APS.  Different methods - both homemade and commercial - for the detection of aPT are available, but they seem to produce conflicting results.  These researchers compared the performance of different assays on a set of well-characterized serum samples.  Sera were gathered from 4 FIRMA institutions, and distributed to 15 participating centers.  A total of 45 samples were from patients positive for LA and/or anti-cardiolipin antibodies (aCL) with or without APS, and 15 were from rheumatoid arthritis (RA) patients negative for antiphospholipid antibodies.  The samples were evaluated for IgG and IgM antibodies using a homemade direct aPT assay (method 1), a homemade phosphatidylserine-dependent aPT assay (aPS/PT, method 2), and two different commercial kits (methods 3 and 4).  In addition, a commercial kit for the detection of IgG-A-M aPT (method 5) was used.  Inter-laboratory results for the 5 methods were not always comparable when different methods were used.  Good inter-assay concordance was found for IgG antibodies evaluated using methods 1, 3, and 4 (Cohen k > 0.4), while the IgM results were discordant between assays.  In patients with thrombosis and pregnancy losses, method 5 performed better than the others.  The authors concluded that while aPT and aPS/PT assays could be of interest from a clinical perspective, their routine performance cannot yet be recommended because of problems connected with the reproducibility and interpretation of the results.