ReviewMultiorgan failure and antiphospholipid antibodies: the catastrophic antiphospholipid (Asherson's) syndrome
Introduction
This is a new disease and represents a major challenge to attending physicians in intensive care units where most of these patients are seen.
The antiphospholipid syndrome (APS) consisting of recurrent venous/arterial occlusions, recurrent fetal losses accompanied by a moderate thrombocytopenia and positive tests of the lupus anticoagulant, antibodies to cardiolipin (aCL) or β2-glycoprotein I (β2GPI), mainly was first defined by Harris et al. (1987) working at the Royal Postgraduate Medical School, the syndrome now referred to as the Hughes’ syndrome (Khamashta and Asherson, 1996) and latterly the systemic APS (Shoenfeld, 2003) replaces the earlier descriptions of these associations. Several years later, a “primary” syndrome, distinct from other connective tissue diseases was first recognized in 1985 (Asherson, unpublished data). It was first defined however some 3 years later in 1988 (Asherson, 1988) and three series of patients were then published in the following year (Asherson et al.,1989; Alarcon-Segovia and Sanchez-Guerrero, 1989; Mackworth-Young et al., 1989). The “primary” syndrome has now overtaken those patients with systemic lupus erythematosus (SLE) in frequency (Cervera et al., 2002).
Multiorgan failure is distinctly uncommon during the course of most connective tissue diseases.
In 1987, a single unusual case of a young female who had developed multiorgan failure associated with gangrene of all her extremities, elevated antiphospholipid antibodies (aPL) and features of disseminated intravascular coagulation was published (Bird et al., 1987), followed by several similar cases (Ingram et al., 1987; Greisman et al., 1991). The condition was defined as the catastrophic antiphospholipid syndrome (CAPS) in 1992 (Asherson, 1992). Since then, 250 cases have been analyzed and almost 300 have now been encountered and documented (Asherson et al., 1998; Asherson, 1992). It seems clear that many more cases remain unidentified and unpublished. The eponym “Asherson's syndrome” was attached in 2003 (Piette et al., 2003).
Section snippets
Pathogenesis
It is still unclear as to why some patients will develop recurrent thromboses, mainly affecting large vessels, while others develop rapidly recurrent vascular occlusions, predominantly affecting small vessels. Indeed, the preceding precipitating or “trigger” factors may be identical in either simple or classic APS patients and in those with CAPS. Clearly, other factors, as yet unidentified, must play important roles.
General factors implicated in the causation of thromboses including prolonged
Clinical features
The demographic characteristics of the patients were 175 females (70%) and 75 males (30%). The mean age was 38 years (range 7–76 years).
A diagnosis of primary antiphospholipid syndrome (PAPS) was made in the majority (49.6%), with SLE in 40%, lupus-like disease in 5%, systemic sclerosis in 1.6%, rheumatoid arthritis in 1.2%, ulcerative colitis in 1.2%, Crohn's disease in 0.4%, two patients with vasculitis (polychondritis, Behcet's) (0.4% each), and single patients suffering from
Treatment
Management of CAPS is challenging for all attending physicians. Early diagnosis and aggressive therapies are essential in order to “rescue” such patients from succumbing to this potentially fatal condition. Unfortunately, at this time, despite all therapies advised, the mortality is extremely high (>50%). Treatment guidelines were recently published (Asherson et al., 2003).
The treatment may be divided into three major categories: (a) prophylactic therapy, (b) primary specific therapies, and (c)
Outcome and prognosis
The mortality of the condition is high despite present-day therapy. Mortality is of the order of 50%. In the present series of patients, there was a 54% recovery (135 patients) and 45% demise (115 patients). Once they have recovered, patients usually have a stable course with continued anticoagulation. It has recently been shown (Erkan et al., 2003) that 66% of CAPS patients who have survived the initial catastrophic event had remained symptom-free for an average follow-up of 62.7 months.
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