Monocyte activation and acquired autoimmune protein S deficiency promote disseminated intravascular coagulation in a patient with primary antiphospholipid syndrome

Abstract

Autoimmune protein S (PS) deficiency is a highly thrombotic, potentially life‐threatening disorder. Its pathophysiological relevance in the context of primary antiphospholipid syndrome (APS) is unclear. Here, we report the case of a 76‐year‐old woman, who presented with a painful reticular skin erythema caused by microvascular thromboses. Disseminated intravascular coagulation (DIC) with consumptive coagulopathy was controlled only by continuous anticoagulation. While significantly elevated IgM antibodies to cardiolipin and β 2 ‐glycoprotein‐I were consistent with primary APS, a function‐blocking PS autoantibody of the IgG isotype was detected. Robust microvesicle (MV)‐associated tissue factor (TF) procoagulant activity (PCA) was isolated from patient plasma. Moreover, patient IgG, but not IgM, induced expression of TF PCA and release of TF‐bearing MVs by peripheral blood mononuclear cells from healthy donors. In primary APS, induction of monocyte TF in combination with an acquired PS inhibitor may provoke a deleterious imbalance of procoagulant and anticoagulant pathways with evolution of thrombotic DIC.

Purpura Fulminans Triggered by the Formation of Anti-Endothelial Autoantibodies in a Patient with Chronic Lymphocytic Leukemia

“…It is thus tempting to speculate that the pathophysiology of PF in CLL patients might be distinct from other common conditions. Of note, we have recently demonstrated the serious consequences of the formation of a function-blocking anti-PS antibody in a woman with primary APS [18]. The patient suffered from overt DIC, recurrent arterial and venous thrombosis, and a highly painful livid skin erythema triggered by antiphospholipid antibody-mediated coagulation activation.…”