57. Jahrestagung der Deutschen Gesellschaft für Transfusionsmedizin und Immunhämatologie

Prof. Dr. med. Dipl.-Kfm.

Vorsitz

Prof. Dr. med.

Antithrombotische Therapie bei Gerinnungsstörungen

Referent

Lecture

Molekulargenetische Diagnostik von Thrombozytopathien

PD Dr. rer. nat.

Prof. Dr.

Comparative analysis of hereditary and acquired thrombosis risk factors in a cohort of patients with thrombosis in atypical sites

Hemostaseology

Vergleichende Untersuchung angeborener und erworbener Risikofaktoren für Thrombosen in einer Patientenkohorte mit Thrombosen in atypischer Lokalisation

Thrombosis in atypical sites include splanchnic vein thrombosis (SVT), cerebral venous sinus thrombosis (CVST), and deep venous thrombosis (DVT) of the upper extremity. Their underlying mechanisms share similarities with typical venous thromboembolism (VTE), i.e. DVT of the lower extremity and/or pulmonary embolism, in addition to specific pathogenic factors. Compared with VTE in typical sites, their pathomechanisms are less understood.Records of unselected patients with a history of VTE in typical sites (n=2,011), SVT (n=83), CVST (n=82), and DVT of the upper extremity (n=117), who were referred to the University Hospital Bonn for ambulatory thrombophilia testing, were retrospectively analyzed. In addition to demographic features, we comparatively assessed hereditary as well as site-specific and non-site-specific acquired thrombosis risk factors.Compared with VTE in typical sites, SVT was more frequently associated with systemic inflammation, infection, or malignancy (2.2% vs. 12.2%; OR 6.2, 95% CI 3.0-12.6) and the JAK2 V617F mutation was present in 16.9%. In CVST compared with typical VTE, demographics and higher rates of oral contraception (43.2% vs. 57.6%; OR 1.9, 95% CI 1.1-3.2), and pregnancy (4.2% vs. 10.9%; OR 2.8, 95% CI 1.2-6.5) suggest a significant hormonal influence on its pathomechanism. DVT of the upper extremity was characterized by a particularly high rate (50.4%) of site-specific acquired risk factors. The prevalence of the F2 20210G&gt;A mutation was higher in SVT and CVST (15.7% respectively 15.9%; OR 2.5, 95% CI 1.3-4.6 for both cohorts) than in VTE in typical sites (7.0%). The prevalence of the factor V Leiden mutation and of inhibitor deficiencies did not differ between cohorts.The cohorts with thrombosis in atypical sites showed distinctive patterns of acquired risk factors. Further studies are warranted to provide additional mechanistic insight into the contribution of F2 20210G&gt;A to the development of SVT and CVST, and the role of hormonal influence in CVST.Nothing to disclose.

Abstract lecture

Dr. med.

Antibody-induced procoagulant platelets are important mediators of neutrophil extracellular trap formation

Antikörper-induzierte prokoagulante Plättchen sind wichtige Vermittler von Neutrophil extracellular traps

Neutrophil activation and subsequent formation of neutrophil extracellular traps (NETs) are increasingly identified to play an important role in the context of thromboinflammation and immunothrombosis. Activated platelets (PLTs) are reported to amplify neutrophil-mediated effector mechanisms. However, the relevance of other PLT subpopulations remains elusive. In this study, we aimed to dissect the role of antibody (Ab)-induced procoagulant PLTs in neutrophil activation and NET formation in vitro.PLTs from healthy individuals were stimulated with monoclonal antibody (Ab) anti-CD9 to induce the formation of P-selectin (CD62p) and phosphatidylserine (PS) double positive procoagulant PLTs. Afterwards anti-CD9 or control Ab treated PLTs were co-incubated with purified neutrophils which was followed by the assessment of NET formation in an immunefluorescence microscopy-based NET detection assay.Coincubation of neutrophils with anti-CD9-induced procoagulant PLTs resulted in a dramatic increase of NET formation compared to control (mean percentage [%] of NETs±SEM: 60.2±6.8 vs. 6.5±2.7, p&lt;0.001). Interestingly, specific blockade of PLT Fc-gamma-RIIA (FcγRIIA) using IV.3 monoclonal blocking Ab resulted in a near complete abrogation of procoagulant PLT-mediated NET formation in vitro (mean% NETs±SEM: 65.4±4.3 vs. 6.4±2.8, p=0.02). Additionally, pretreatment of PLTs with a selective inhibitor of PLT spleen tyrosine kinase (SYK), a key regulatory enzyme in the PLT activating FcγRIIA-mediated signaling cascade, prior to incubation with anti-CD9, resulted in a significant reduction of Ab-induced procoagulant PLT-mediated NET formation in vitro (mean %±SEM: 65.5±3.1 vs. 9.5±2.3, p&lt;0.0001).Our findings indicate that Ab-induced procoagulant PLTs mediate increased NET formation in a PLT FcγRIIA-dependent manner. Selective inhibition of PLT SYK could be a potential therapeutic approach to prevent from procoagulant PLT-mediated NET formation and subsequent associated prothrombotic effects in different Ab-induced PLT FcγRIIA -mediated diseases.All authors have no potential conflicts to disclose.

Raum 28

Hämostaseologie

Sektionssitzungen

Hämostaseologie

Termin

Vorsitz

Sprache

Programm