Mortality in the catastrophic antiphospholipid syndrome: Causes of death and prognostic factors
Introduction
The ‘catastrophic’ variant of the antiphospholipid syndrome (APS) was described by Asherson in 1992 [1] as a condition characterized by multiple vascular occlusive events, usually affecting small vessels, presenting over a short period of time, and laboratory confirmation of the presence of antiphosphoplipid antibodies (aPL). Several large series have been reported demonstrating an increase in the number of patients with this condition over the past few years [2], [3].
Although patients with catastrophic APS represent less than 1% of all patients with APS [4], they are usually in a life-threatening situation. In this respect, the mortality rate is around 50% in the largest published series [2], [3]. Classically, it has been described as a syndrome resulting in multiorgan failure [5] but the cause of this high mortality is still unknown.
In order to know the causes of death and the prognostic factors, our group analyzed the case reports included in the web-site based international registry of patients with catastrophic APS (“CAPS Registry”) [6]. This registry has been recently created by the European Forum on Antiphospholipid Antibodies, a study group devoted to the development of multicenter projects with large populations of APS patients. It contains clinical, laboratory, and therapeutic data on all reported cases of catastrophic APS, and it can be freely consulted through the Internet (http://www.med.ub.es/MIMMUN/FORUM/CAPS.HTM). Currently, it contains information on 250 patients. Among them, 112 (44.8%) died at the time of the catastrophic APS event.
Section snippets
Major cause of death
We selected those patients who died and analyzed their clinical diagnosis considered by their physician-in-charge as cause of the death and the necropsy characteristics when they were described (Table 1).
With regard to clinical diagnosis of death, cerebral involvement was considered the main cause of death, mainly consisting of stroke, followed by cardiac involvement and infection.
The main finding at necropsy studies was microthrombosis, present in 89% of patients. This is one of the features
Prognostic factors
In order to identify prognostic factors in patients with catastrophic APS, we compared the main clinical and immunologic features, and the types of treatment that were used in the patients who died with those in the patients who survived.
The presence of systemic lupus erythematosus and positive antinuclear antibody titre were related with a higher mortality in patients with catastrophic APS. However, the association of positive antinuclear antibody with an increased mortality can be explained
Treatment and outcome
We confirmed the lower mortality (36.9% versus 77.8%; p < 0.0001) that is associated with the use of anticoagulation (AC) as it was demonstrated in a previous study from our group [3].
When we analyzed the diverse combinations of treatments, AC + corticoids (CS) was the most common combination of treatment, followed by AC + CS + plasma exchange (PE) and/or intravenous immunoglobulins (IVIG), used in almost 40% of the patients. The higher recovery rate was achieved by the combination of AC +CS + PE (77.8%),
Time of diagnosis
To assess the influence of the time of diagnosis on their evolution, we divided the 250 patients into two groups according to their year of diagnosis: 149 patients were diagnosed before 2000, and 78 patients from 2001 to February 2005. In 23 patients, this information was not obtained. The year 2001 was selected as cut-off because the largest series of 80 patients with catastrophic APS was published this year [3].
We demonstrated that the episodes of catastrophic APS diagnosed and, therefore,
Conclusion
The only identified prognostic factor for higher mortality rate in patients with catastrophic APS was the presence of systemic lupus erythematosus. According to the results of the present study, we advocate the use of a combined treatment of AC + CS + PE as a first line of therapy in catastrophic APS. The higher use rate of combined treatments with AC+ CS + PE and/or IVIG seems to be the main reason to explain the significant reduction of mortality that we found in catastrophic APS episodes diagnosed
Take-home messages
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Cerebral involvement followed by cardiac involvement and infections were the most common causes of death.
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Systemic lupus erythematosus was associated with a higher mortality rate.
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The higher recovery rate was achieved by the combination of anticoagulation (AC) plus corticoids (CS) plus plasma exchange (PE) followed by AC + CS +PE and/or intravenous immunoglobulins (IVIG).
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The addition of cyclophosphamide did not demonstrate any additional benefit.
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The mortality rate decreased 20% after the year 2001.
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