Clin Exp Rheumatol. 2005 Mar-Apr;23(2):199-204. CONCLUSION: We found that the prevalence of antiphospholipid antibodies in SSc patients was low. However, aCL antibodies were associated with PAH and endothelial injury.

Arthritis Rheum 2006;54:3918-3925.

Lupus. 2002;11(4):253-6. The antiphospholipid or Hughes syndrome is the association between antiphospholipid antibodies (aPL), venous and arterial thromboses and pregnancy morbidity. Antiphospholipid syndrome (APS) commonly coexists with autoimmune diseases usually systemic lupus erythematosus (SLE), when it is known as secondary APS. When present in isolation it is known as primary APS (PAPS). Although the kidney may be affected in APS, its involvement is perhaps not as well described as that of other organs. Thrombotic microangiopathy (TMA) affecting the kidney has been reported as a manifestation in both primary and secondary APS. This report describes hypertension related to underlying renal TMA as a presenting symptom of APS.

Z Kardiol. 2004 Jul;93(7):546-54. CONCLUSION: Secondary cardiac valve operations on patients with primary antiphospholipid syndrome may be successfully performed within a multidisciplinary approach. Oral anticoagulation remains the treatment of choice to prevent further thromboembolic events.

Eur J Echocardiogr. 2008 Jan;9(1):192-3. In antiphospholipid syndrome (APS), there is a high prevalence of valvular heart disease which leads to increased risk of thrombo-embolic events, in particular, cerebrovascular events. We present a patient with cerebral infarction, previous deep-vein thrombosis, and miscarriages with positive lupus anticoagulant and anticardiolipin antibodies. Echocardiographic examination revealed mitral valve leaflet thickening and verrucous vegetations consistent with Libman-Sacks endocarditis, which is commonly associated with APS. In patients with combined Libman-Sacks endocarditis and antiphospholipid antibodies, anticoagulation therapy with warfarin is indicated due to high risk of valvular thrombus formation and subsequent embolization.

Am Heart J. 1992 Nov;124(5):1331-8. The antiphospholipid syndrome has been associated with multiple cardiac abnormalities. The earliest reports were of valvular disease, including verrucous endocarditis, as well as valvular thickening and insufficiency. Subsequently, antiphospholipid antibodies were implicated in coronary artery disease manifested by premature myocardial infarction and coronary artery bypass graft occlusion. In addition, there have been rare reports of intracardiac thrombi and diffuse cardiomyopathy in association with antiphospholipid antibodies. In this review, we discuss the nature and prevalence of the cardiac manifestations of the antiphospholipid antibody syndrome as well as some of the proposed pathophysiologic mechanisms. We also provide examples from our own experience. The expanding spectrum of cardiac disease associated with antiphospholipid antibodies suggests an important role for these antibodies in certain types of cardiac pathology.

Lupus. 2005;14(9):691-6. Antiphospholipid syndrome (APS) is a systemic autoimmune disease, associated with a hypercoagulable state and fetal loss and with other clinical manifestations including cardiac involvement. Cardiac manifestations of APS are valve abnormalities (valve thickening and vegetations), occlusive arterial disease (atherosclerosis and myocardial infarction), intracardiac emboli, ventricular dysfunction, and pulmonary hypertension. Antiphospholipid antibodies (aPLs) may have a role in the accelerated atherosclerotic arterial disease observed in APS, related to their ability to induce endothelial activation. aPLs have been incriminated in the pathogenesis of heart valve lesions in APS patients. Markers of endothelial cell activation are up-regulated with prominent deposition of aPL in heart valves, suggesting aPL deposition initiates an inflammatory process that recruits complement leading to the valve lesion. Autoantibody-mediated endothelial cell activation probably plays a role in sustaining a proadhesive, proinflammatory, and procoagulant phenotype. The heterogeneity of APS clinical manifestations is likely linked to the varied effects that aPL can induce on endothelial cells and to the different functions that endothelial cells display depending on the anatomic localization.

DALLAS, TX -- April 20, 1998

Mayo Clin Proc. 2000;75:971-976 © 2000 Mayo Foundation for Medical Education and Research. Hemostatic aspects of antiphospholipid syndrome (APS) present unique challenges to clinicians and laboratory personnel alike, particularly in the perioperative period. These challenges are especially evident in patients requiring cardiac valve replacement surgery. However, the literature outlining the optimal approach in such patients is limited. We present the case of a 25-year-old woman with severe aortic regurgitation as a result of APS with particular reference to the precautions necessary during perioperative care. Particularly important are the prevention of thrombotic or hemorrhagic complications, management of associated thrombocytopenia, and laboratory methods of perioperative anticoagulation monitoring in the setting of prolonged clotting times.

Obstetrics & Gynecology 1999;93:819-821 © 1999 by The American College of Obstetricians and Gynecologists. Conclusion: With rapid decompensation of acute respiratory distress syndrome in pregnancy, despite aggressive medical therapy, complicating processes must be considered, especially with antiphospholipid antibodies, which can be associated with sterile heart vegetations and subsequent fatal thromboembolism.

Source: Clinical Reviews in Allergy and Immunology, Volume 23, Number 3, December 2002, pp. 341-348(8) Abstract: The Libman and Sacks non bacterial endocarditis was reported in 1924 in patients with SLE. Its relation to the anti cardiolpin syndrome has only been described as recently as the last decade. In this paper we review the deposition of theses antibodies on the valve with complement components initiating the deformation of the valve. The valvulopathy in APS is quite common and may lead to valve replacement. In addition, a diversity of manifestations are detailed. More awareness should be drawn to this new complication of APS.

A 51-year-old woman with overt congestive heart failure with pleural and pericardial effusion was treated with furosemide and nifedipine, leading to improvement in her condition and a decrease in effusions. An echocardiography demonstrated mitral and aortic regurgitation with mitral valve prolapse, which caused the congestive heart failure. Since leukocytopenia and lymphocytopenia with arthralgia could be observed, serological investigations were performed. She was diagnosed as having systemic lupus erythematosus (SLE) with antiphospholipid syndrome, and started on a treatment of prednisolone and aspirin. Based on the treatment, the pleural and pericardial effusion went into complete remission, indicating that the serositis related to SLE had overlapped the heart failure. Since there was no evidence of any other diseases that could be responsible for the valvular lesions, we concluded that they were due to antiphospholipid syndrome. The administration of prednisolone had no significant effect on valvular morphology or function as demonstrated by echocardiography. When patients with valvular disease are seen, a valvulopathy related to antiphospholipid syndrome should be considered as part of the differential diagnosis.

Yonsei Med J 48(6):901 - 926, 2007. DOI 10.3349/ymj.2007.48.6.901. CONCLUSION The nature of APS, as well as the evolving symptomatology of SLE, contributed to the recognition that anticoagulating approaches, rather than steroids or immunosuppressive drugs, significantly improved the outcome in a substantial number of patients with APS. We may also conclude that CNS disease in SLE is significantly associated with aPLs. Cerebral ischaemia due to vessel occlusion is considered the most important cause of CNS diseases in SLE, and aPLs play an important role in their pathogenesis. There is a strong association between aPLs and CVD, headache, cognitive dysfunction, and seizures, thus supporting the importance of occlusive vasculopathies in neuro-psychiatric lupus. Hence, testing for aPLs should be recommended not only for patients with autoimmune diseases and neuropsychiatric syndromes but also for younger patients (age 3.0 and cerebral ischaemia should undergo anticoagulation therapy to prevent recurrences. All patients with thrombosis associated with aPLs should undergo long-term (life-long) warfarin therapy. Unfortunately, low-dose aspirin alone does not prevent recurrent thrombosis. Additionally, oral anticoagulation carries an increased risk of serious haemorrhage; however, this risk, if well controlled, might be lowered to acceptable levels. Steroids and immunosuppressive drugs in aPLpositive patients and thrombosis may be justified only in life-threatening situations when episodes of thrombosis occur despite adequate anticoagulation treatment. In aPL-positive patients without previous thrombosis, low-dose aspirin (75 mg/day) indefinitely as a thromboprophylactic measure is recommended. In neuropsychiatric appearances different from CVD (e.g., headache, seizures), anticoagulation therapy should be considered for patients with more severe disease and unsatisfactory responses to traditional treatments for headache or conventional anti-epileptic drugs.

Ann Intern Med. 1992 Jun 15;116(12 Pt 1):974-6. Antiphospholipid antibodies occur in various clinical states, including the primary antiphospholipid syndrome. Clinical features in these conditions appear to be caused by vasculopathy associated with the presence of these antibodies. We report the case of a patient with primary antiphospholipid syndrome who experienced cardiac necrosis secondary to myocardial microvasculopathy in the absence of vasculitis. This case demonstrates unequivocally that noninflammatory myocardial microvasculopathy occurs in the primary antiphospholipid syndrome per se without any clinical or immunologic signs of systemic lupus erythematosus or other disease process. The histopathologic findings in the skin and myocardial biopsies showed a noninflammatory vasculopathy characterized by bland thrombi and lack of infiltration of the vessel wall by inflammatory cells. Ultrastructural examination of the myocardial biopsy confirmed the vascular thrombosis and endothelial activation and showed no deposits in basement membranes. The patient survived after appropriate treatment. Evidence presented here supports the concept that the vasculopathy in the antiphospholipid syndrome is distinct from other types of vascular occlusions seen in systemic lupus erythematosus. We suggest that myocardial biopsy can be crucial in showing an underlying myocardial ischemic process despite "normal" findings on coronary angiography. Results of the biopsy hastened the decision to use potentially lifesaving plasmapheresis and anticoagulation therapy in this patient.

Arthritis Rheum. 2005 Jun 2;53(3):460-467 CONCLUSION: In SLE patients, the presence of high levels of IgG anticardiolipin antibodies is associated with the development of severe valvular regurgitation and with a high incidence of thromboembolic events and the need for valvular surgery.

Nihon Kyobu Shikkan Gakkai Zasshi. 1994 Jan;32(1):3-8.

Here are flat, pale tan, spreading vegetations over the mitral valve surface and even on the chordae tendineae. This patient has systemic lupus erythematosus. Thus, these vegetations that can be on any valve or even on endocardial surfaces are consistent with Libman-Sacks endocarditis. These vegetations appear in about 4% of SLE patients and rarely cause problems because they are not large and rarely embolize. Note also the thickened, shortened, and fused chordae tendineae that represent remote rheumatic heart disease.

Circulation. 1996;93:1579-1587. © 1996 American Heart Association, Inc. The antiphospholipid syndrome (APS) is defined by the presence of anti-phospholipid antibodies (aPLs) and venous or arterial thrombosis, recurrent pregnancy loss, or thrombocytopenia. The syndrome can be either primary or secondary to an underlying condition, most commonly systemic lupus erythematosus (SLE). Echocardiographic studies have disclosed heart valve abnormalities in about a third of patients with primary APS. SLE patients with aPLs have a higher prevalence of valvular involvement than those without these antibodies. Valvular lesions associated with aPLs occur as valve masses (nonbacterial vegetations) or thickening. These two morphological alterations can be combined and are thought to reflect the same pathological process. Both can be associated with valve dysfunction, although such association is much more common with the latter alteration. The predominant functional abnormality is regurgitation; stenosis is rare. The mitral valve is mainly affected, followed by the aortic valve. Valvular involvement usually does not cause clinical valvular heart disease. The presence of aPLs seems to further increase the risk for thromboembolic complications, mainly cerebrovascular, posed by valve lesions. Superadded bacterial endocarditis is rare but may be difficult to distinguish from pseudoinfective endocarditis. The current therapeutic guidelines are those for APS in general. Secondary antithrombotic prevention with long-term, high-intensity oral anticoagulation is advised. The efficacy of aspirin, either alone or in combination, is yet to be assessed. Corticosteroids are not beneficial and may even facilitate valve damage. Immunosuppressive agents should only be used for the treatment of an underlying condition. Current data suggest a role for aPLs in the pathogenesis of valvular lesions. aPLs may promote the formation of valve thrombi. These antibodies may also act by another mechanism, as indicated by the finding of subendothelial deposits of immunoglobulins, including anti-cardiolipin antibodies, and of colocalized complement components in deformed valves from patients with APS.

J Am Soc Nephrol 10:507-518, 1999 © 1999 American Society of Nephrology

Ann Rheum Dis. Published Online First: 1 November 2006. doi:10.1136/ard.2005.044073 © 2006 by BMJ Publishing Group Ltd & European League Against Rheumatism. Conclusion: Abnormal echocardiographic findings were detected frequently in asymptomatic patients with SLE or PAPS. Although SLE patients were younger, LV systolic function was more impaired in SLE compared to PAPS patients while LV and RV diastolic function, as reflected by LVIVRT and E/A ratios, were significantly more impaired in APS patients.

CHEST, April, 1994.

Thromb Res. 2004;114(5-6):509-19. Atherosclerosis has been considered an inflammatory disease based on the finding that atherosclerotic lesion contains activated T lymphocytes reacting with oxidized low-density lipoproteins (oxLDL) and heat shock proteins (HSP); it also contains autoantigens like beta2GPI, a target of antibodies occurring in an immune-mediated thrombophilia called antiphospholipid syndrome (APS). Further support to this hypothesis comes from the cross-reactivity, which occurs between antiphospholipid antibodies (aPL) and antibodies to oxLDL. Animal experiments have shown that aPL are associated with atheroma. In addition, accelerated atherosclerosis has been detected in patients with a prototype systemic autoimmune disease, such as systemic lupus erythematosus (SLE). However, the association of APS or aPL with atherosclerosis is a matter of debate due to the small numbers of patients studied, and the fact that traditional risk factors for atherosclerosis coexist. The prevalence of APS ranges from 1.7% to 6%, and that of aPL reaches to 14% among patients with peripheral vascular disease defined on the basis of clinical outcomes. On the other hand, the prevalence of asymptomatic atherosclerosis, defined in terms of plaques in ultrasonography, reaches to 15% of patients with APS compared to 9% of SLE patients and 3% of normal controls. Among SLE patients with aPL, the prevalence of plaques ranges from 6% in premenopausal women to 31% in unselected patients. Less than 10% of APS patients express premature atherosclerosis in the absence of other risk factors. Which APS patient will develop atherosclerosis is unpredictable.

(Circulation. 1996;93:1579-1587.) © 1996 American Heart Association, Inc. Conclusion: Data provided by clinical and immunopathological studies support an association between aPLs and heart valve lesions. They also imply that aPLs play a pathogenetic role in endocardial damage. Basic and randomized, prospective, controlled clinical studies are needed to further define the role of aPLs in cardiac valve disease, elucidate its natural history, and establish optimal treatment and prevention of the disease and its potential clinical sequelae.

© 2004. The Journal of Rheumatology Publishing Company Limited.

J Heart Lung Transplant. 2005 Aug;24(8):1133-6. Autoantibodies to prothrombin, first described almost 50 years ago, are paradoxically associated with thrombosis. Described is an unusual case of fatal hypercoagulability in a patient with multiple arterial and venous thromboembolic complications despite intense anticoagulation while being bridged to transplantation with a left ventricular assist device. Serum analysis revealed the presence of prothrombin autoantibodies and high titers of anti-nuclear antibodies, and autopsy revealed pulmonary arteriolar vasculitis. These findings suggest an autoimmune basis for the presence of anti-prothrombin antibodies and the hypercoagulable state observed in the present case.