Critical ischemia of multiple organ systems in a patient with systemic lupus erythematosus complicated by catastrophic antiphospholipid syndrome: potential pathogenetic role of non-inhibitory anti-ADAMTS13 autoantibodies

Abstract

We report a 33-year-old woman with systemic lupus erythematosus (SLE) who developed fulminant multiorgan ischemic manifestations and hematologic abnormalities. She presented with persistent fever, newly developed painful fingertip cyanosis, and acute kidney injury. Laboratory tests showed severe thrombocytopenia, hemolytic anemia with fragmented red blood cells, positive direct and indirect Coombs tests, hypocomplementemia, and positivity for multiple autoantibodies, including a triple-positive antiphospholipid antibody profile. Within the first week of hospitalization, in addition to digital ischemia, she developed multiple cerebral infarctions and acalculous cholecystitis, findings consistent with catastrophic antiphospholipid syndrome (APS). Unexpectedly, the activity of a disintegrin and metalloproteinase with thrombospondin type 1 motifs member 13 (ADAMTS13) was severely reduced to 5%, whereas ADAMTS13 inhibitor was not detected by the Bethesda assay. There was no past medical or family history suggestive of congenital thrombotic thrombocytopenic purpura. After treatment with high-dose glucocorticoids and nine sessions of plasma exchange (PE), abdominal pain resolved and digital ischemia improved, accompanied by improvement in hematologic and renal abnormalities and disappearance of fragmented red blood cells. Subsequently, ADAMTS13 activity normalized to 63% and remained stable after completion of PE. Later, non-inhibitory anti-ADAMTS13 autoantibodies were detected by enzyme-linked immunosorbent assay in a stored serum sample obtained on admission. ADAMTS13 deficiency due to non-inhibitory anti-ADAMTS13 autoantibodies may modify the complications of SLE and APS by promoting thrombotic microangiopathy.