Antiphospholipid syndrome (APS) may be complicated by a ‘thrombotic storm’ called catastrophic antiphospholipid syndrome (CAPS), which can lead to multiple organ failure and admission of patients to the intensive care unit. An international consensus statement defined CAPS as the occurrence of: at least three organ/tissue/vessel involvement, occurring in less than a week, with biopsy-proven small vessel occlusion, in patients with defined APS.¹ The prognosis of CAPS is severe but has drastically improved in the last two decades from a 58% mortality in 1996 to a 23% in-hospital death in 2020.² The CAPS classification criteria do not encompass the full spectrum of severe thrombotic APS and patients with pre-CAPS or near-CAPS share the same prognosis as CAPS patients and should probably be treated identically.³ Several treatments have been tested, reported and recommended in the management of CAPS, but all these recommendations rely on a very low level of evidence and are mainly based on the publications from the a single group, the CAPS Registry.⁴ Anticoagulation is the cornerstone treatment of CAPS as it is the only one associated with better outcome in several cohorts.⁵ Heparin (unfractionated or low-molecular-weight) is the treatment of choice and its efficacy must be monitored with heparinemia. The combination of anticoagulation and corticosteroids (i.e. double-therapy) should be provided for every CAPS patient and triple-therapy (double-therapy plus plasma exchange or intravenous immunoglobulins) in patients with life-threatening involvement. In patients with CAPS associated with systemic lupus erythematosus, cyclophosphamide should probably be associated to triple-therapy. When triple-therapy has failed, antiplatelet agents can be added to the standard regimen. Successful use of rituximab and eculizumab have been reported in some refractory patients, however the level of evidence supporting their use is extremely low.

Learning Objectives

• Describe CAPS as a rare and severe complication of antiphospholipid syndrome

• Explain the importance of early treatment, even in pre-CAPS/near-CAPS patients

• Describe why combination of anticoagulation and corticosteroids is the cornerstone treatment of CAPS and that life-threatening CAPS episodes should be treated with a triple-therapy including anticoagulation, corticosteroids and intravenous immunoglobulins or plasma exchange

• Discuss the importance of continued anticoagulation in CAPS-related severe thrombocytopenia

• Explain why rituximab and eculizumab may be useful in refractory CAPS patients

References

1. Asherson RA, Cervera R, de Groot PG, et al. Catastrophic antiphospholipid syndrome: international consensus statement on classification criteria and treatment guidelines. Lupus. 2003;12(7):530–4.

2. Pineton de Chambrun M, Larcher R, Pène F, et al. In-Hospital Mortality-Associated Factors in Patients With Thrombotic Antiphospholipid Syndrome Requiring ICU Admission. Chest. 2020;157(5):1158–66.

3. Pineton de Chambrun M, Larcher R, Pène F, et al. CAPS criteria fail to identify most severely-ill thrombotic antiphospholipid syndrome patients requiring intensive care unit admission. J Autoimmun. 2019;103:102292.

4. Cervera R, Rodríguez-Pintó I, Espinosa G. The diagnosis and clinical management of the catastrophic antiphospholipid syndrome: A comprehensive review. J Autoimmun. 2018;92:1–11.

5. Legault K, Schunemann H, Hillis C, et al. McMaster RARE-Bestpractices clinical practice guideline on diagnosis and management of the catastrophic antiphospholipid syndrome. J Thromb Haemost. 2018.