Journal Article

POS1146 LOW MOLECULAR WEIGHT HEPARINS INTERFERE WITH NEUTROPHIL ACTIVATION AND NET GENERATION IN HIGH-RISK PREGNANT PATIENTS WITH ANTIPHOSPHOLIPID SYNDROME

Manfredi, A., Manfredi, E., Rosa, S., Rovere-Querini, P., Canti, V., Frascella, B., Castiglioni, M.T., D'alberti, V., Maugeri, N., D'angelo, A.

2023

Overview

Neutrophil activation and the generation of neutrophils extracellular traps (NETs) contribute to vascular damage and thrombosis in antiphospholipid syndrome (aPS). We reported that Low molecular weight heparin (LMWH) prevent neutrophil activation induced by P-selectin expressed by activated platelets [1, 2] and jeopardize in healthy subjects the ability of neutrophils to generate NETs and to mobilize granule contents [3]. To investigate whether LMWH, used on empirical bases to in high-risk patients, regulate neutrophil/platelet interaction in pregnant women. Here we report preliminary data from a prospective monocentric study in which the activation of platelets and neutrophils was assessed in sixteen pregnant women treated with LMWHs, with or without aPS at 12, 24 and 32 weeks of gestation. Patients were studied again when feasible after pregnancy completion. Sixteen healthy pregnant women, ten healthy women outside pregnancy and ten women with Systemic Lupus Erythematosus outside pregnancy served as controls. Platelets of pregnant healthy women were activated, as assessed by the increased expression of P-selectin and tissue factor. All patients successfully completed the pregnancy. Abnormalities were evident at the pathological assessment of the placentae despite the treatment with LMWHs. The treatment was associated with significantly reduced: i) platelet/neutrophil interaction, as assessed by heterotypic aggregates; ii) neutrophil expression of tissue factor; iii) platelet expression of the prototypic DAMP, HMGB1; iv) accumulation in the blood of byproducts of NET formation/catabolism, such as myeloperoxidase-DNA complexes. P-selectin expression was, in contrast, unaffected. The results indicate that neutrophil and platelet activation/interaction, which may reflect detrimental intravascular immune events leading to pregnancy complications, abate in patients treated with LMWHs. [1]Maugeri N et al. Prevention of platelet-polymorphonuclear leukocyte interactions: new clues to the antithrombotic properties of parnaparin, a low molecular weight heparin. Haematologica. 2005; 90(6):833-9. [2]Maugeri N et al. Parnaparin, a low-molecular-weight heparin, prevents P-selectin-dependent formation of platelet-leukocyte aggregates in human whole blood. Thromb Haemost. 2007 Jun;97(6):965-73. doi: 10.1160/th06-12-0680. [3]Manfredi AA et al. Low molecular weight heparins prevent the induction of autophagy of activated neutrophils and the formation of neutrophil extracellular traps. Pharmacol Res. 2017 Sep;123:146-156. doi: 10.1016/j.phrs.2016.08.008 NIL. None Declared.

• Publisher: Elsevier B.V,Elsevier Limited
• Subject: Antiphospholipid syndrome / Autoimmune diseases / Autophagy / Blood platelets / Cell activation / Cell biology / Heparin / HMGB1 protein / Innate immunity / Leukocytes / Leukocytes (neutrophilic) / Molecular weight / Neutrophils / P-selectin / Peroxidase / Platelets / Pregnancy / Pregnancy and reproduction / Pregnancy complications / Risk groups / Systemic lupus erythematosus / Thrombosis / Tissue factor