Journalartikel

Jahr der Veröffentlichung: 2016

Seiten: 324-332

Zeitschrift: Thrombosis and Haemostasis

Bandnummer: 115

Heftnummer: 2

ISSN: 0340-6245

DOI Link: https://doi.org/10.1160/TH15-07-0539

Verlag: Thieme Publishing

Abstract: 
Protamine (PRT) is the standard drug to neutralise heparin. PRT/heparin complexes induce an immune response similar to that observed in heparin-induced thrombocytopenia (HIT). Partially desulfated heparin (ODSH) was shown to interfere with anti-platelet factor 4/heparin antibodies (Abs), which are responsible for HIT. In this study, we analyse the impact of ODSH on the interaction between anti-PRT/heparin Abs and platelets. The ability of ODSH to prevent anti-PRT/heparin Ab-induced platelet destruction in vivo was investigated using the NOD/SCID mouse model. ODSH improved platelet survival in the presence of PRT, heparin and anti-PRT/heparin Abs (median platelet survival after 300 minutes (min) with 20 mu g/ml ODSH: 75 %, range 70-81 % vs without ODSH: 49 %, range 44-59 %, p=0.006). Furthermore, when ODSH was applied 60 min after Ab injection platelet survival was improved (median platelet survival after 300 min with ODSH: 83 %, range 77-93 % vs without ODSH: 59 %, range 29-61 %, p=0.02). In in vitro experiments ODSH inhibited platelet activation at concentrations > 16 mu g/mL (p<0.001), as well as PRT/heparin complex binding to platelets (mean fluorescence intensity [MFI] without ODSH: 85 +/- 14 vs with ODSH: 15 +/- 0.6, p=0.013). ODSH also displaced pre-bound complexes from the platelet surface (MFI without ODSH: 324 +/- 43 vs with 32 mu g/ml ODSH: 53 +/- 9, p<0.001). While interfering with platelet activation by anti-PRT/heparin Abs, up to a concentration of 16 mu g/ml, ODSH had only minimal impact on neutralisation of heparin by PRT. In conclusion, our study shows that ODSH is able to inhibit platelet activation and destruction suggesting a potential clinical use to reduce anti-PRT/heparin Ab-mediated adverse effects.

Harvard-Zitierstil: Jouni, R., Zoellner, H., Khadour, A., Wesche, J., Grotevendt, A., Brandt, S., et al. (2016) Partially desulfated heparin modulates the interaction between anti-protamine/heparin antibodies and platelets, Thrombosis and Haemostasis, 115(2), pp. 324-332. https://doi.org/10.1160/TH15-07-0539

APA-Zitierstil: Jouni, R., Zoellner, H., Khadour, A., Wesche, J., Grotevendt, A., Brandt, S., Delcea, M., Krauel, K., Schwertz, H., Sachs, U., Greinacher, A., & Bakchoul, T. (2016). Partially desulfated heparin modulates the interaction between anti-protamine/heparin antibodies and platelets. Thrombosis and Haemostasis. 115(2), 324-332. https://doi.org/10.1160/TH15-07-0539