Catastrophic antiphospholipid syndrome: international consensus statement on classification criteria and treatment guidelines

Abstract

The term 'catastrophic' antiphospholipid syndrome (APS) is used to define an accelerated form of APS resulting in multiorgan failure. Although catastrophic APS patients represent less than 1% of all patients with APS, they are usually in a life-threatening medical situation that requires high clinical awareness. The careful and open discussion of several proposals by all participants in the presymposium workshop on APS consensus, held in Taormina on occasion of the 10th International Congress on aPL and chaired by Munther A Khamashta and Yehuda Shoenfeld (29 September 2002), has allowed the acceptation of a preliminary set of classification criteria. On the other hand, the optimal management of catastrophic APS must have three clear aims: to treat any precipitating factors (prompt use of antibiotics if infection is suspected, amputation for any necrotic organ, high awareness in patients with APS who undergo an operation or an invasive procedure), to prevent and to treat the ongoing thrombotic events and to suppress the excessive cytokine 'storm'. Anticoagulation (usually intravenous heparin followed by oral anticoagulants), corticosteroids, plasma exchange, intravenous gammaglobulins and, if associated with lupus flare, cyclophosphamide, are the most commonly used treatments for catastrophic APS patients.

Catastrophic Antiphospholipid Syndrome Triggered by Sepsis

“…The characteristic features of CAPS are: (a) rapid onset thrombosis (usually within 1 week) resulting in multiple-organ dysfunction syndrome (MODS), (b) pathological evidence of small-vessel thrombosis, (c) evidence of systemic inflammatory response syndrome (SIRS), and (d) high risk of unusual organ involvement [1]. Based on the international consensus of the classification criteria for CAPS, this case can be classified as "probable CAPS" with thrombocytopenia (Table 2) [1]. Although the thrombotic events occurred within 3 weeks (the ischemia and necrosis of the hand was noted between days 4 and 7 of hospital stay, and change in mental status reflecting frontal lobe infarct occurred on day 28), it was clear that these events (including the deep-vein thrombosis and bilateral adrenal infarcts that had occurred 2 months prior) were all part of a continuous thrombotic process.…”

“…The classification Table 2 International classification criteria for catastrophic antiphospholipid syndrome [1] 1) Evidence of involvement of three or more organs, systems, and/or tissues a 2) Development of manifestations simultaneously or in less than 1 week 3) Confirmation by histopathology of small-vessel occlusion in at least one organ or tissue b 4) Laboratory confirmation of the presence of aPL (LA and/or aCL and /or anti-B2 GPI antibodies) c Definite CAPS →All 4 criteria Probable CAPS → All 4 criteria, except for involvement of only 2 organs, systems, and/or tissues → All 4 criteria, except for the absence of laboratory confirmation at least 6 weeks apart attributable to the early death of a patient never tested for aPL before CAPS → 1, 2, and 4 → 1, 3, and 4 and the development of a third event in more than 1 week but less than 1 month, despite anticoagulation treatment a Usually, clinical evidence of vessel occlusions, confirmed by imaging techniques. Renal involvement is defined by 50% increase in serum creatinine, severe systemic hypertension (>180/ 100 mmHg), and/or proteinuria (>500 mg/24 h) b For histopathological confirmation, significant evidence of thrombosis must be present, although vasculitis may coexist occasionally c If the patient had not been previously diagnosed as having APS, the laboratory confirmation requires that presence of aPL must be detected on two or more occasions at least 6 weeks apart (not necessarily at the time of the event)…”

The Infectious Origin of the Antiphospholipid Syndrome

“…14 Since then, we have analysed the pathogenesis of catastrophic APS in more than 300 patients. [15][16][17][18][19] We observed that ''triggering'' factors become increasingly apparent and were present in 51% of cases in the latest analysis. 17 These factors included trauma (including surgical, both major and minor), anticoagulation withdrawal, a variety of carcinomas and, most importantly and commonly, infections, which were identified in 24% of these patients.…”

Eculizumab Prevents Recurrent Antiphospholipid Antibody Syndrome and Enables Successful Renal Transplantation

“…A diagnosis of CAPS requires that three specific criteria are fulfilled: vascular occlusions involving three or more organ systems either simultaneously or within less than 1 week, histopathological confirmation of small vessel occlusion in at least one organ or tissue and serologic demonstration of circulating antiphospholipid antibodies (APLA) (3)(4)(5). CAPS frequently culminates in multiorgan system failure and is fatal in 50% of patients in whom it develops (6).…”