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

TY - JOUR

T1 - Monocyte activation and acquired autoimmune protein S deficiency promote disseminated intravascular coagulation in a patient with primary antiphospholipid syndrome

AU - Beckmann, Lennart

AU - Voigtländer, Minna

AU - Holstein, Katharina

AU - Lennartz, Maximilian

AU - Schneider, Stefan W

AU - Haddad, Munif

AU - Renné, Thomas

AU - Bokemeyer, Carsten

AU - Rolling, Christina C

AU - Langer, Florian

N1 - © 2021 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).

PY - 2021/7

Y1 - 2021/7

N2 - 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 β2-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.

AB - 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 β2-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.

U2 - 10.1002/rth2.12559

DO - 10.1002/rth2.12559

M3 - SCORING: Journal article

C2 - 34263105

VL - 5

JO - RES PRACT THROMB HAE

JF - RES PRACT THROMB HAE

SN - 2475-0379

IS - 5

M1 - e12559

ER -