Ozan Unlu

Catastrophic Antiphospholipid Syndrome: Candidate Therapies for a Potentially Lethal Disease

Catastrophic antiphospholipid syndrome (CAPS) is a potentially lethal disease that presents with rapidly progressive multiple organ thromboses. Anticoagulation, corticosteroids, intravenous immunoglobulin, and plasma exchange are the most commonly used treatments for CAPS patients. However, the high mortality despite these medications necessitates new treatment strategies. Following a brief review of current diagnostic and management strategies, we discuss the candidate therapies, i.e., hydroxychloroquine, rituximab, eculizumab, sirolimus, and defibrotide, that can be considered in CAPS patients refractory to traditional treatment.

Recurrent thrombosis in patients with antiphospholipid antibodies and arterial thrombosis on antithrombotic therapy

Management for patients with antiphospholipid syndrome (APS) and arterial thrombosis is controversial. There are no prospective data demonstrating the superiority of high- or moderate-intensity anticoagulation with vitamin K antagonists over antiplatelet agents. Using 2 antiphospholipid antibody databases (single center [New York Presbyterian Hospital] and multicenter [Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking]), we retrospectively collected demographic and clinical data of patients with APS and arterial thrombosis. The primary outcome was recurrent thrombosis rate after initial arterial thrombosis in patients with APS treated with antiplatelet and/or anticoagulant therapy. We identified 139 patients with a median follow-up time of 4.24 years after initial thrombosis. Thirty-seven patients (27.3%) received anticoagulants, 43 (30.9%) antiplatelets, and 58 (41.7%) combined therapy. Sixteen patients (37.2%) in the antiplatelet group, 9 (23.7%) in the anticoagulant group, and 4 (6.9%) in the combined therapy group experienced recurrent thrombosis. We estimate that 20% of patients will experience a recurrence by 3.4, 7.3, and 16.3 years, respectively, depending on assignment to antiplatelet, anticoagulant, or combined therapy. These results suggest that combined therapy decreases the rate of and increases the time to thrombosis recurrence in patients with APS presenting with arterial thrombosis.

Comment on: “The use of direct oral anticoagulants in 56 patients with antiphospholipid syndrome”

We read the study byMalec et al. titled “the use of direct oral anticoagulants (DOACs) in 56 patients with antiphospholipid syndrome (APS)” with a great interest [1]. Based on a recurrence rate of 5.8 per 100 patient-years (6/56 patients [11%] during a mean follow-up of 22 months), authors conclude that “DOACs can be used in patients with APS”. Although we appreciate the prospective nature and relatively large sample size of this study, we want to emphasize the following points. Firstly, as the authors point out, by the timeof their publication there had been four case reports and seven case series of DOAC use in APS patients. In fact, based on our recent systematic reviewof DOACuse in APS, including aforementioned four case reports and seven case series, we found the recurrent thrombosis risk as 20% in DOAC-receiving APS patients during a mean follow-up of 12months (Table 1) [2], which is significantly higher than the annual thrombosis risk of 6% reported by the authors. Secondly, the authors compare the thrombosis risk of their DOACreceiving APS patients to the results of a European cohort of 1000 patients [3], and suggest that the efficacy of DOACs is similar to vitamin K antagonists (VKA) in patients with APS (6% annual thrombosis risk in DOACvs 1.5% in VKA-receiving patients). Based on this comparison,

Antiphospholipid Syndrome: What Should Patients Know?

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the production of antiphospholipid antibodies (aPL) resulting in clinical complications such as blood clots and pregnancy complications. The purpose of this chapter is to provide a general review of APS for patients and those who are interested in learning more about aPL/APS. Detailed information about aPL-related pregnancy problems can be found in Chapter 20.

Definition and Epidemiology of Antiphospholipid Syndrome

Accurate definition and epidemiology of a disease are the first steps to understand clinical and global burden of a disease. Although antiphospholipid syndrome (APS) has a clear definition for classification of patients with a limited spectrum of clinical and laboratory criteria, a broader spectrum of clinical manifestations exists, and thrombosis may be multifactorial. A standard definition of APS is challenging. Although data on epidemiology of APS are limited, being based on small scale studies or studies with methodological limitations, this chapter gives the best synthesis possible today.

Immunoglobulin G4-related Aortitis

A 62-year-old woman presented with progressive exertional substernal chest pain for 1 year. A cardiac computerized tomography angiography (CTA) was performed, demonstrating focal high-grade stenosis and possible occlusion of the middle portion of the left anterior descending (LAD) artery, as well as a stenosis with multifocal calcification/plaque in the proximal and middle right coronary artery (RCA). An ascending aortic aneurysm with intramural hematoma measuring 4.1 × 3.7 cm was also detected. The patient had a coronary artery calcium score (CAC) of 429. The CAC score predicts cardiovascular outcomes independent of traditional cardiovascular risk profile [3, 20] and the patient’s calcium score corresponded to 97th percentile showing a high risk of coronary atherosclerotic plaque presence [3]. She subsequently underwent a cardiac catheterization, which confirmed threevessel coronary disease (LAD, RCA, and diagonal 2). One week later, she underwent a three-vessel coronary bypass graft with repair of the ascending aortic aneurysm. After the operation, the rheumatology service was consulted about the appearance of the patient’s aorta, which was thickened and covered with a whitish, fibrinous, and friable material. No hematoma was demonstrated on gross pathology, and the overall scenario raised a concern for aortitis (Fig. 1, arrow). The patient’s past medical history included diet-controlled hyperlipidemia, hypothyroidism, and Lyme disease, which had been treated 24 years earlier without any visceral or articular complications. She was married, had two healthy grown children, and was physically active. She did not have a history of tobacco use, illicit drug use, or sexually transmitted diseases. Her family history was significant for coronary artery disease in her father—diagnosed in his 70s—but no other autoimmune or connective tissue diseases. She had a penicillin allergy. Her medications at presentation included levothyroxine 75 mcg once daily and a multivitamin. HSSJ (2017) 13:307–312 DOI 10.1007/s11420-017-9565-5 HSS Journal ® The Musculoskeletal Journal of Hospital for Special Surgery

Mitral Valve Vegetation in Antiphospholipid Syndrome

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