Should we be testing for antiphospholipid antibodies in unexplained pulmonary thromboembolism and atherosclerosis at autopsy?

Abstract

Antiphospholipid antibodies are antibodies against plasma proteins bound to anionic surfaces such as on endothelial cells and activated platelets. In addition to being present in antiphospholipid syndrome they may be found in a range of conditions, including systemic lupus erythematosus, infection, and following the use of some medications [1]. There are multiple antiphospholipid antibodies including anticardiolipin, lupus anticoagulant, and antiB2GP1. Evidence is building that these antibodies can have an effect on the vascular system resulting in the development of pulmonary emboli and atherosclerotic disease. A diagnosis of antiphospholipid syndrome requires vascular thrombosis or pregnancy-related complications in conjunction with elevated antiphospholipid antibodies persisting for at least 12 weeks [2]; thus, cases presenting to autopsy may not fulfill the diagnostic criteria for antiphospholipid syndrome. However, multiple studies have indicated that antiphospholipid antibodies are independent risk factors for venous thromboembolism—consisting of both deep vein thrombosis and pulmonary thromboembolism; this has been reported in patients with underlying disease [3] as well as in healthy men [4]. Therefore, the first presentation of raised antiphospholipid antibodies may be that of pulmonary thromboembolism [5], which could present as a case of sudden death. There is also evidence to suggest that antiphospholipid antibodies contribute to the progression of atherosclerosis. It was shown that patients with peripheral arterial disease were more likely to have anticardiolipin than the control group, and the presence of anticardiolipin antibodies (of IgG class) had a significant adverse effect on cardiovascular deaths and overall mortality [6]. In addition, in a group of patients under the age of 50 who were being operated on for peripheral arterial disease, there were significantly more patients with anticardiolipin compared to controls [7]. On an individual basis the presence of antiphospholipid antibodies may represent a risk factor for death due to deep vein thrombosis/pulmonary thromboembolism or atherosclerosis. Furthermore, the finding of antiphospholipid antibodies may also have implications for family members as antiphospholipid antibodies show a genetic predisposition (although specific genes have not been identified) [8]. It has been suggested that asymptomatic carriers of antiphospholipid antibodies should inform their healthcare provider, consider short-term blood-thinners during times of immobilisation, know the symptoms of deep vein thrombosis and pulmonary thromboembolism, and seek medical help immediately if these occur, in addition to reducing modifiable risk factors for blood clots [9]. Therefore, when a post-mortem examination reveals the presence of otherwise unexplained deep vein thrombosis/ pulmonary thromboembolism or unusually advanced atherosclerosis, testing for antiphospholipid antibodies may be warranted. C. Bierton School of Medicine, University of Adelaide, Frome Road, Adelaide, SA 5005, Australia