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Genetic factors related to aPL and APS have been widely investigated. Many candidate genes, including HLA class II haplotype, have been presented to predispose aPL or APS. However, it is difficult to determine genetic risk factors related to aPL development and clinical manifestations of APS in these patients as there is a high heterogeneity in antigen specificity and in the pathophysiology of thrombosis.

Our observations, and those from others, give further support to our hypothesis that “autoimmune aPL” may be generated by immunization with products from bacteria or viruses after incidental exposure or infection. We also were able to generate APS-like syndrome in a strain of mice susceptible to autoimmunity, indicating that other factors are likely to be involved, such as genetic predisposition. Furthermore, not all aPL generated were pathogenic. Based on the clinical experience and on the numerous reports indicating presence of aPL in large number of infectious diseases, it may be expected that not all aPL produced during infection will be pathogenic. A limited number aPL induced by certain viral/bacterial products would be pathogenic in certain genetically predisposed individuals. Further studies to identify the agents responsible for induction the pathogenic aPL are needed. Identification of those bacterial and/or viral agents may help finding strategies for the prevention of production of aPL “pathogenic” antibodies. Alternatively, free peptides may be used to induce tolerance against aPL production or to abrogate their pathogenic effects.

Drugs such as procainamide and phenothiazines can also induce aPL. The prevalence and pathogenicity of drug-induced aPL is generally low and has been discussed in this chapter.

In conclusion, annexin A5 is a potent anticoagulant protein that forms an antithrombotic shield over anionic phospholipids containing bilayers. Autoantibodies may interfere with this shielding function via high affinity antibodies that recognize phospholipid binding proteins that are capable of interfering with the assembly of the annexin A5 shield on phospholipid surfaces or via direct recognition of annexin A5 functional epitopes by autoantibodies. Antibody mediated interference with the integrity of the two-dimensional annexin A5 crystal shield may be a mechanism for thrombosis and for pregnancy complications, including recurrent spontaneous pregnancy losses, in APS.

Pregnant women with APS are at risk of complications at all stages of pregnancy. They require specialist care and a team approach involving obstetricians, obstetric physicians, rheumatologists, hematologists, neonatologists, and specialist midwives. Close monitoring of the various aspects of the condition may reduce maternal morbidity and improve fetal outcome. Therapeutic options include aspirin, LMWH, and, less commonly, warfarin and steroids.

The pathogenesis of the adverse pregnancy outcome in APS has not yet been fully elucidated although there is active research in this field. Until this is ascertained, we must accept that many aspects of management are purely empirical and it is our duty to counsel women thoroughly such that they understand the risks and benefits of the treatment options they are offered.

Moderate thrombocytopenia is frequent in Hughes syndrome and, as a rule, does not modify the policy for treatment of thrombosis. Severe thrombocytopenia is relatively uncommon and it is seldom associated with bleeding events. When required, its treatment is similar to that of idiopathic thrombocytopenic purpura. Finally, much clinical and laboratory work is still required to elucidate the role of aPL antibodies and platelets in the pathogenesis of the thrombotic complications typical of Hughes syndrome.

Multi-slice CT is a new and evolving non-invasive technology to visualize the coronary arteries. It was found to be safe and reliable to detect or exclude the presence of quality-of-life-limiting CAD. Multislice CT appears to be useful as a first-line imaging technique in carefully selected patients to evaluate the need for ICA. While clinical reliability of 4-slice CT scanners is questionable in patients with higher heart rates, severe calcification, shortness of breath, and high body mass index, 16-slice CT and, even more so, 64-slice CT provide sufficient robustness to justify introducing multi-slice coronary CTA for patients with chest pain into clinical practice. Further studies with larger patient numbers and the use of later-generation scanner technology are required to underline the place of multi-slice CT in the diagnostic algorithm of CAD in patients with chest pain.