Abstract Body

Patients with COVID-19 with lung or systemic involvement present coagulation abnormalities, such as prolongation of prothrombin time and activated partial thromboplastin time, increased D-dimer levels, and, in some cases, severe thrombocytopenia. These patients are at high risk for thromboembolic events (arterial or venous) and thrombotic microangiopathy. The incidence of thromboembolic events in patients with COVID-19 is probably underestimated because of the asymptomatic presentation and the failure to perform systematic imaging studies. Thrombotic microangiopathy has been found in most of the few autopsies that have been performed to date, and the presence of pulmonary thromboembolism and deep vein thrombosis is striking in many of them. This hypercoagulability situation resembles antiphospholipid syndrome (APS), especially in its most severe form, catastrophic APS.

Although it has been described that up to 87.7% of patients with severe forms of COVID-19 were positive for lupus anticoagulant (LA) during their stay in the Intensive Care Units, the prevalence and clinical association of the presence of antiphospholipid antibodies (aPL) and other molecules related to APS is not sufficiently known.

Recently, we have been able to demonstrate that blood levels of β2-glycoprotein I (GPI) are much lower in patients with COVID-19 than in the general population. Moreover, none of the patients who had normal β2GPI levels had respiratory failure or died. We have also found that the aPL prevalence in patients with COVID-19 is similar to that in controls of the same age (except for IgA-aβ2GPI, whose prevalence is significantly higher) without being associated with the incidence of thrombotic events or other complications of the disease.

Lack of β2GPI would impede regulatory function of coagulation and platelet aggregation, leaving patients without weapons to control a thrombotic storm. This situation would be clinically and functionally equivalent to APS, although autoantibodies would not be involved.

Background and Aims

To describe the real-world experience of eculizumab use in patients with catastrophic antiphospholipid syndrome (CAPS) according to the information provided by the “CAPS Registry”.

Methods

We analyzed the demographic, clinical and immunological data from all the patients included in the “CAPS Registry” treated with eculizumab and described the indications for eculizumab administration, dose, outcome, use of prophylactic vaccines and adverse effects.

Results

The “CAPS Registry” currently includes 584 patients from whom 39 (6.7%) were treated with eculizumab (it was used as a rescue therapy in 30 cases while in 6 cases it was used as first line therapy). Mean age of eculizumab treated patients was 39 years (SD=14.6), 72% were female, 77% had a primary APS and 79% had a precipitating factor before the CAPS event. Thrombocytopenia was present in 28 (72%) cases and features of microangiopathic hemolytic anemia were present in 15 (38.5%). Twenty-nine (74.4%) patients recovered from the episode of CAPS (four showed only partial remission). Symptoms worsened in 9 patients, from whom 5 finally died despite the treatment. There was only one relapse after a median follow up of 10.7 months. The most common treatment regimen was 900 mg weekly for four weeks and 1200mg fortnightly.

Conclusions

According to the real-world experience provided by the “CAPS Registry”, eculizumab can be considered in some patients with CAPS refractory to previous therapies, especially if they present with features of complement-mediated thrombotic microangiopathy.