36-Year-Old Female with Catastrophic Antiphospholipid Syndrome Treated with Eculizumab: A Case Report and Review of Literature

Abstract

Catastrophic antiphospholipid syndrome (CAPS) is a rare but potentially life-threatening condition characterized by diffuse vascular thrombosis, leading to multiple organ failure developing over a short period of time in the presence of positive antiphospholipid antibodies (aPL). CAPS is a severe form of antiphospholipid syndrome, developing in about 1% of cases of classic antiphospholipid syndrome, manifesting as microangiopathy, affecting small vessels of multiple organs. It is acute in onset, with majority of cases developing thrombocytopenia and less frequently hemolytic anemia and disseminated intravascular coagulation. Lupus anticoagulant and anticardiolipin antibodies have been reported as predominant antibodies associated with CAPS. Treatment options often utilized in CAPS include anticoagulation, steroids, plasma exchange, cyclophosphamide therapy, and intravenous immunoglobulin therapy. Even though the reported incidence of this condition is considered to be low, the mortality rate is approaching 50%. The high rate of mortality should warrant greater awareness among clinicians for timely diagnosis and treatment of this life-threatening condition. Studies have shown that complement activation plays a key role in the pathogenesis of aPL mediated thrombosis in CAPS. We report a case of a 36-year-old female admitted with clinical and laboratory findings consistent with CAPS successfully treated with eculizumab, a terminal complement inhibitor.

Complement activation, inflammation and relative ADAMTS13 deficiency in secondary thrombotic microangiopathies

“…Therefore, the targeted inhibition of the complement terminal pathway appears reasonable in those secondary TMA cases associated with cancer, malignancy, open-heart surgery, solid organ transplantation, or systemic autoimmune disease, -none of which responds clinically to plasma therapy. Several recent observations (Kronbichler et al, 2014;Strakhan et al, 2014;Morales et al, 2015;Kransdorf et al, 2014) support this hypothesis as clinical improvement of secondary TMA has been reported in response to eculizumab treatment. Therefore, randomized clinical studies are necessary in the future to determine the efficacy of targeted complement inhibition in secondary TMA.…”

Síndrome antifosfolípidos catastrófico. Reporte de caso y revisión bibliográfica

“…Se ha comunicado dos casos en los cuales se realizó prevención de la trombosis de injertos renales en pacientes con SAF catastrófico, con buen resultado; sin embargo, se recomienda realizar ensayos con mayor cantidad de pacientes. Un reporte de caso empleó eculizumab en una paciente a la que se habían dado esteroides y ciclofosfamida, y persistía el daño renal ameritando hemodiálisis, pero tras el uso del anticuerpo se logró prescindir de dicha terapia por mejoría importante de la función renal 13 . De igual forma, otro reporte de caso de un varón demostró mejoría que no se había logrado con anticoagulación, inmunosupresión y recambio plasmático.…”

“…En conclusión, el eculizumab podría implementarse como preventivo en los pacientes con SAF catastrófico que serán sometidos a trasplante renal y en aquellos en que las terapias convencionales han fallado para controlar la enfermedad, así como en cuadros recurrentes. Acorde a las conclusiones tomadas del International CAPS registry, el rituximab se recomienda para pacientes con SAF catastrófico refractario al tratamiento convencional [11][12][13][14][15] . Como resumen del tratamiento, todos los pacientes con SAF catastrófico deben ser tratados con anticoagulantes, esteroides y recambio plasmático/inmunoglobulina intravenosa.…”

How I treat catastrophic thrombotic syndromes

“…Less frequently, these patients have been treated with cyclophosphamide, 79 azathioprine, 79 rituximab, 80 and eculizumab. 15 Immunomodulatory therapies, particularly prednisone and rituximab, are also frequently used for TTP, but typically not for the other catastrophic thrombotic disorders.…”

“…7 Other therapies that have been used include IV immunoglobulin, cyclophosphamide, rituximab, and eculizumab. [13][14][15] Atypical thrombotic thrombocytopenic purpura/thrombotic microangiopathies Patients with thrombotic thrombocytopenic purpura (TTP) and other thrombotic microangiopathies typically exhibit schistocytes, thrombocytopenia, and organ injury secondary to arteriole and capillary thrombosis. 16 Atypical presentations of TTP have been reported, however, which include patients with macrovascular occlusions, such as acute thromboembolic stroke [17][18][19] and acute coronary syndromes.…”