June 01, 2011

By: Diana Mahoney

Catastrophic antiphospholipid syndrome is a potentially fatal thrombotic disease that develops in a subset of patients with antiphospholipid syndrome. Survival of patients with the rare condition, which is characterized by the development of multiple organ thromboses over a short period of time, depends on the vigilance of the treating clinicians, early diagnosis, and aggressive therapy, all of which can be compromised by multiple factors including the overlap of clinical and laboratory features with other autoimmune and infectious conditions, according to rheumatologist Dr. Doruk Erkan.

Dr. Erkan (along with Dr. Gerard Espinosa and Dr. Ricard Cervera of the Hospital Clinic Barcelona) recently published a summary of the diagnostic challenges associated with catastrophic antiphospholipid syndrome (APS) and proposed updated diagnostic algorithms to streamline its management (Autoimmun. Rev. 2010;10:74-9). In this issue's column, Dr. Erkan discusses the critical diagnostic and management considerations necessary to improve the outcomes of catastrophic APS patients.

RN: What risk factors, if any, have been identified for catastrophic APS?

RN: What are the key elements for establishing a timely, accurate diagnosis of catastrophic APS?

▸ A positive aPL test can be associated with infections (usually low-titer aPL ELISA) or anticoagulation (positive LA test); thus, at times it can be difficult to exclude the possibility that positive aPL tests are occurring as bystanders, not necessarily as contributors for thrombosis.

▸ False-negative aPL results may occur during acute catastrophic APS events.

▸ A continuum of thrombotic microangiopathic conditions exists, accounting for patients with thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome, and catastrophic APS.

▸ Both sepsis and heparin-induced thrombocytopenia share similarities with catastrophic APS, and these three conditions may overlap.

For these reasons, the timely diagnosis of catastrophic APS can be challenging. At times, the differential diagnosis cannot be narrowed to a single disease during the acute period, and thus continuous assessment of patients is warranted. The most recent updated algorithms provide a “step-by-step” approach for clinicians in the assessment of patients with multiorgan thrombosis. Important steps of the diagnostic algorithms include the assessment of a history of APS or persistent aPL positivity; three or more new organ new thromboses developing in less than a week; biopsy diagnosis of microthrombosis; and other explanations for multiple organ thromboses and/or microthrombosis.

RN: Once a diagnosis has been established, what are the most important management considerations?

The most pressing treatment challenges in catastrophic APS include delay in diagnosis for the reasons discussed above, ongoing thrombosis despite anticoagulation, high risk of simultaneous thrombosis and bleeding, and high prevalence of accompanying comorbidities (such as sepsis) that directly affect the mortality.

RN: How has the availability of the International CAPS Registry changed the understanding and management of catastrophic APS?

www.med.ub.es/MIMMUN/FORUM/CAPS.HTM

Because of the rarity of catastrophic APS, it is very difficult to study this life-threatening disease. The CAPS Registry is currently the only source that allows researchers to systematically analyze the demographic and clinical characteristics of these patients. Furthermore, there are no randomized, controlled trials evaluating the efficacy of various therapies, and the treatment outcome data are also based on the analysis of the registry. Thus, the registry has been crucial in our understanding as well as the management of catastrophic APS.

DR. ERKAN is an associate physician-scientist at the Barbara Volcker Center for Women and Rheumatic Diseases; assistant attending rheumatologist and clinical researcher at Hospital for Special Surgery; and assistant professor of medicine at Weill Cornell Medical College in New York. Dr. Erkan disclosed having a research grant from Genentech.