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.

Epidemiology

• Extremely rare disease
• Female > male
• Occurs in both paediatric and adult patients

Clinical manifestations

• 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

Laboratory features

• 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

1. Evidence of involvement of three or more organs/tissues
2. Rapid onset of multi-organ thromboses simultaneously or within one week
3. Histological evidence of microvascular thrombosis affecting at least one organ
4. 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.

First-line Treatment

• Given rarity of disease entity, treatment is not standardised
• Essential elements of treatment
  • Anticoagulation
    • 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)

References

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.