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 column, Dr. Erkan discusses the critical diagnostic and management considerations necessary to improve the outcomes of catastrophic APS patients.

SKIN & ALLERGY NEWS: What are the characteristic signs and symptoms of catastrophic APS?

DR. ERKAN: Multiple organ dysfunction, driven mainly by thrombotic microangiopathy, is responsible for the majority of the clinical events in catastrophic APS, although large venous or arterial thrombosis can also occur. The three most commonly involved organs are kidneys (renal thrombotic microangiopathy, and renal artery/vein thrombosis), lungs (pulmonary infarction and/or hemorrhage, and acute respiratory distress syndrome), and brain (stroke, seizure, and encephalopathy). However, thromboses in atypical locations are common in catastrophic APS patients. Any organ system can be involved, including the myocardial, skin, hepatic, and adrenal systems. Intestinal infarctions and peripheral gangrene can also develop, and hematologic manifestations such as thrombocytopenia and schistocytic hemolytic anemia commonly occur, creating a diagnostic challenge for physicians.

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

DR. ERKAN: The presence of multiple thrombosis risk factors is associated with a higher risk of thrombosis in individuals with antiphospholipid antibodies (aPL) and even in aPL-negative populations. A "trigger event" such as surgery, pregnancy, infection, or oral contraceptive use is commonly identified in aPL-positive patients when they develop thrombosis. Similarly, about 50%-60% of patients with catastrophic APS have an identifiable "trigger event." However, it is not well understood why some aPL-positive patients develop only single-vessel thrombosis and others go on to develop the rapidly progressive microthrombosis and organ failure that are seen in catastrophic APS. Potential genetic risk factors that may predispose aPL-positive patients to catastrophic APS are under investigation (Am. J. Med. 2011;124:290-6).

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

DR. ERKAN: The first step in diagnosis is to obtain an accurate history. Previous APS diagnosis and/or persistent clinically significant aPL positivity (as determined by a positive lupus anticoagulant [LA] test and/or moderate- to high-titer aPL on ELISA) is of great importance for diagnosis. However, almost half of the patients who develop catastrophic APS do not have any previous history of a thrombosis or aPL positivity. In this group of patients, the diagnosis is a particular challenge as multiple factors can impede the timely diagnosis, as in the following examples: