Dr Rachel Frederick1,2, Dr Luigi Zolio3, Associate Professor Evange Romas3,4, Professor Francesco Ierino2,4
1Department of General Medicine, St Vincent’s Hospital Melbourne, Fitzroy, Australia, 2Department of Nephrology, St Vincent’s Hospital Melbourne, Fitzroy, Australia, 3Department of Rheumatology, St Vincent’s Hospital Melbourne, Fitzroy, Australia, 4University of Melbourne, Department of Medicine, Melbourne, Australia
Background: Catastrophic Antiphospholipid Syndrome (CAPS) is a rare, life-threatening form of antiphospholipid syndrome characterised by diffuse arterial and venous thrombosis, in the presence of positive antiphospholipid antibodies. The mechanism of CAPS involves antiphospholipid antibodies activating complement leading to a cascade of thrombosis and cytokine storm. Patients with CAPS have an increased rate of complement regulator gene mutation leading to the proposal that complement dysregulation is instrumental to the pathophysiology of CAPS.
Case Report: We report a case of an 18-year-old female with a history of miscarriages presenting with clinical and laboratory findings consistent with life-threatening CAPS, resistant to initial treatment, and finally responding to Eculizumab (C5-inhibitor monoclonal antibody). The clinical features included oligoanuric renal failure, profound thrombocytopenia, a large pulmonary embolus, upper limb deep venous thrombosis, and splenic/renal infarcts. The presumed trigger was an upper respiratory tract infection. The patient was supported with haemofiltration, heparin infusion, immunosuppressive therapy with methylprednisolone and cyclophosphamide, IVIg and plasma exchange. The patient developed gastrointestinal bleeding, and despite aggressive standard therapy as described, failed to improve. Eculizumab was commenced on the basis that complement dysregulation was a major contributor to the resistant CAPS, supported by laboratory evidence of profound hypocomplementaemia. Following the addition of Eculizumab, the patient clinically improved, transitioned off haemofiltration, and the heparin infusion changed to warfarin without further bleeding. Follow up care demonstrated impaired renal function (eGFR = 27) and genetic analysis for complement regulator mutations are in progress.
Conclusions: (1) Supports a central role for complement dysregulation in the pathophysiology of CAPS; (2) Eculizumab therapy and targeted complement regulation may be a life-saving therapy for resistant CAPS.
Biography:
Bio to come