Objective
An international multidisciplinary initiative, jointly supported by the American College of Rheumatology and European Alliance of Associations for Rheumatology, is underway to develop new ...rigorous classification criteria to identify patients with high likelihood of antiphospholipid syndrome (APS) for research purposes. The present study was undertaken to apply an evidence‐ and consensus‐based approach to identify candidate criteria and develop a hierarchical organization of criteria within domains.
Methods
During phase I, the APS classification criteria steering committee used systematic literature reviews and surveys of international APS physician scientists to generate a comprehensive list of items related to APS. In phase II, we reviewed the literature, administered surveys, formed domain subcommittees, and used Delphi exercises and nominal group technique to reduce potential APS candidate criteria. Candidate criteria were hierarchically organized into clinical and laboratory domains.
Results
Phase I generated 152 candidate criteria, expanded to 261 items with the addition of subgroups and candidate criteria with potential negative weights. Using iterative item reduction techniques in phase II, we initially reduced these items to 64 potential candidate criteria organized into 10 clinical and laboratory domains. Subsequent item reduction methods resulted in 27 candidate criteria, hierarchically organized into 6 additive domains (laboratory, macrovascular, microvascular, obstetric, cardiac, and hematologic) for APS classification.
Conclusion
Using data‐ and consensus‐driven methodology, we identified 27 APS candidate criteria in 6 clinical or laboratory domains. In the next phase, the proposed candidate criteria will be used for real‐world case collection and further refined, organized, and weighted to determine an aggregate score and threshold for APS classification.
A thrombotic microangiopathy that is identified in patients with the antiphospholipid syndrome (APS) represents only a part of the vascular pathology that can be associated with antiphospholipid ...antibodies (aPL). Tissues from two autopsies, four renal biopsies, two skin biopsies, and one amputated leg were obtained from six patients who met criteria for the diagnosis of APS. Three patients had systemic lupus erythematosus (SLE), one had lupus-like disease, and two had a primary APS. Five of the patients were hypertensive. Arteries of three patients disclosed fibrin thrombi along with widespread obstruction by recanalized intimal connective tissue. Small renal, leptomeningeal, and pulmonary arteries showed concentric cellular and fibrous intimal hyperplasia indistinguishable from hypertensive vascular disease. Glomerular capillary and afferent arteriolar thrombi were found in renal biopsies from two SLE patients. One of these SLE patients required a leg amputation in which the popliteal artery demonstrated thrombosis, intimal hyperplasia, and acute inflammation. The findings support clinical and experimental data that indicate aPLs cause thrombosis but suggest diversity in the pathogenetic mechanisms aPLs are capable of promoting. Inflammation seems to be rare and to accompany thrombosis. Intimal hyperplasia is particularly common. Its involvement of renal arteries may contribute to hypertension that develops in some APS patients.
Antiphospholipid Syndrome (APS) has been widely recognized as a risk factor for the recurrence of both thrombosis and pregnancy losses; however the optimal treatment of patients is debatable. The aim ...of this paper was to establish a consensus among experts on the treatment of APS in pregnancy. A questionnaire that described possible different clinical situations was sent to the International Advisory Board of the 10th International Congress on AntiphospholipidAntibodies. Sixteen experts from different medical branches and different geographic areas sent their replies. The consensus was that treatment for APS pregnant patients should be low molecular weight heparin (LMWH) and low dose aspirin (LDA). The dosage, and frequency of LMWH depends on different situations, including the body weight and past history. Patients with previous thromboses usually receive two injections per day. Warfarin can also be used from 14 to 34 weeks, for patients with previousstroke or severe arterial thromboses. The use of intravenous immunoglobulin (IVIG) seems to be restricted to patients with pregnancy losses despite conventional treatment. The experts usually advised barrier methods of contraception, intrauterine device (if the patient is not taking corticosteroids) or progestins. Oral contraception with oestrogens was usually avoided.
We present the case of a 26-year-old man with an exacerbation of apparent chronic asthma with chronic peripheral vascular disease due to recurrent venous thrombosis. Localized livedo reticularis, new ...cutaneous infarctions, severe venous insufficiency, thrombocytopenia, renal failure, and cerebral supratentorial dysfunction were noted. During hospital admission, antibodies to phospholipids in high titer were present by three different testing methods. Renal biopsy demonstrated significant renal vasculature abnormalities characteristic of hemolytic endovasculopathy, and magnetic resonance imaging showed multiple cerebral infarctions. This case exemplifies the spectrum of presentations and management of the primary antiphospholipid antibody syndrome. The clue to its presence in this patient was the livedo reticularis rash, a cutaneous marker for this syndrome that was evident in the emergency department.
Current management of primary or secondary antiphospholipid antibody (aPL) syndromes with known embolic phenomena requiring anticoagulation is empiric in the setting of elective orthopedic ...procedures. Short-term withdrawal of warfarin with continuance of aspirin and glucocorticoid therapy was undertaken for sequential bilateral knee replacements in a lupus patient with aPL. Her course was successfully managed without thrombo-embolic complications.
A new method for the cytological analysis of antinuclear antibody binding offers several advantages over conventional techniques. Nuclei in meiosis, prepared by surface-spreading spermatocytes, ...provide a detailed examination of the constituents of the nucleus--euchromatin, heterochromatin, sex chromatin, nucleoli, centromeres, and dense patches that seem related to RNA metabolism--and each of these structures can be seen to change in morphology and antibody labeling during the course of meiotic prophase. Results using sera from humans and mice with autoimmune disease, and using several mouse monoclonal antibodies, demonstrate the potential of this method for clinical and research applications, both for more common antibody types and for those that bind epitopes which are unique to germ cells.
Antiphospholipid antibodies (aPL) are associated with a clear but variable risk for thromboses at multiple vascular sites and with a wide spectrum of clinical features comprising both the primary and ...secondary antiphospholipid antibody syndromes (APS). The recent literature reviewed here includes refined and more quantitative descriptions of aPL-associated clinical phenomena and APS features in studies of increasingly larger patient cohorts, and better understanding of the heterogeneity of aPL relative to binding dependency on beta 2 glycoprotein I and other phospholipids. There is expanded knowledge of pathogenesis of aPL from in vitro and in vivo studies in murine and human models and intriguing data on therapeutic modalities, old and new.
The spectrum of clinical descriptions and clinicopathologic studies on patients with primary and secondary forms of antiphospholipid antibody syndrome continues to widen. Some differences exist for ...patients with lupus compared with those with Sjogren's syndrome. Some new thoughts regarding pathogenetic mechanisms and the cofactor beta 2 glycoprotein I have been generated. Last year marked the first time the International Symposium on Anti-Phospholipid Antibodies was held in the United States; new data regarding the heterogeneity of antiphospholipid antibodies and lupus anticoagulant were highlighted, as well as the growing concept that assay modifications should not only include attention to the cofactor but also to prothrombin and other phospholipids such as phosphatidylserine and phosphatidylethanolamine. Prognostic and predictive factors of both a clinical and serologic nature of antiphospholipid antibodies are the focus of much recent work, as is the controversial role of steroid therapy for specific patients. Murine models of antiphospholipid antibody syndrome have opened new avenues to explore pathogenesis and therapeutic efficacy.
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