Antiphospholipid syndrome (APS) is an acquired autoimmune disease characterised by laboratory criteria (persistent antiphospholipid antibodies) and clinical criteria (venous/arterial/micro-thromboses and/or pregnancy morbidity).
Catastrophic antiphospholipid syndrome (CAPS) is a rare manifestation of APS, which is characterised by rapid onset of multi-organ thromboses in the context of antiphospholipid antibodies or known APS. Prompt identification of this disease and intervention significantly improves prognosis (recovery rates range from 50 to 80% if treated effectively).
This summary focuses on CAPS.
- Extremely rare disease
- Female > male
- Occurs in both paediatric and adult patients
- Occurs as first presentation of APS (50% of cases) or in the context of known APS
- Primary or secondary
- Secondary APS/CAPS usually due to underlying SLE
- Precipitating factor often identified, e.g. infection, malignancy, surgery
- Rapid onset (within a week) of multiple organ thromboses
- Microvascular thromboses predominates: renal failure, ARDS, ischaemic encephalopathy, cutaneous mainfestiations (livedo reticularis, necrosis, ulceration)
- Large-vessel arterial thromboses: stroke, myocardial infarction
- Large vessel venous thromboses: DVT, PE, thrombosis at unusual sites (e.g. CVST)
- Systemic inflammatory response syndrome
- Persistent antiphospholipid antibodies
- Lupus anticoagulant (LA): detected using functional assay, e.g. dRVVT
- Anti-cardiolipin antibodies
- Anti-beta2-glycoprotein I antibodies
- Prolonged aPTT (if lupus-sensitive reagent used)
- Mild thrombocytopenia is common
- Minimal/absent MAHA – should only see a few fragments (if any!)
- Anti-nuclear antibodies (especially with underlying SLE)
Diagnostic criteria for CAPS
- Evidence of involvement of three or more organs/tissues
- Rapid onset of multi-organ thromboses simultaneously or within one week
- Histological evidence of microvascular thrombosis affecting at least one organ
- Laboratory evidence of antiphospholipid antibodies
All four required for definite CAPS diagnosis; however, criterion 3 not readily available in acute phase, so probable diagnosis can be made from criteria 1, 2 and 4.
- Given rarity of disease entity, treatment is not standardised
- Essential elements of treatment
- Unfractionated heparin or LMWH in acute phase
- After recovery from CAPS, long term warfarin is the preferred anticoagulant of choice
- High dose corticosteroids
- e.g. IV methylprednisolone followed by oral prednisolone
- Optional additional front-line treatment options
- Plasma exchange
- Intravenous immunoglobulin
- Started after final day of PEX to avoid removal
- Cyclophosphamide in patients with underlying SLE
Treatment of refractory CAPS
- Treatment of refractory CAPS heavily relies on case reports and small case series
- Treatment options include
- Rituximab (anti-CD20)
- Eculizumab (terminal complement inhibitor)
Kazzaz NM, McCune WJ, Knight JS. Treatment of catastrophic antiphospholipid syndrome. Curr Opin Rheumatol. 2016;28(3):218-227.
Nayer A, Ortega LM. Catastrophic antiphospholipid syndrome: a clinical review. J Nephropathol. 2014;3(1):9-17.
Ortel TL, Erkan D, Kitchens CS. How I treat catastrophic thrombotic syndromes. Blood 2015;126(11):1285–1293.