PB0327 - Antibody-induced procoagulant platelets cause increased thrombus formation in heparin-induced thrombocytopenia

Sunday, July 10, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

Jan Zlamal

Resident/PhD Student
Institute for clinical and experimental transfusion medicine Tübingen
Tübingen, Baden-Wurttemberg, Germany

Co-Author(s)

HJ

Hisham Jaffal

Student
Institute for clinical and experimental transfusion medicine Tübingen
Tuebingen, Baden-Wurttemberg, Germany
Anurag Singh, PhD

Institute for Clinical and Experimental Transfusion Medicine, University Hospital of Tuebingen, Tuebingen, Germany
LP

Lisann Pelzl

Post Doc
Institute for Clinical and Experimental Transfusion Medicine, Medical Faculty of Tuebingen, University Hospital of Tuebingen, Tuebingen, Germany
Tuebingen, Baden-Wurttemberg, Germany
KW

Karoline Weich

TA
Institute for clinical and experimental transfusion medicine Tübingen
Tuebingen, Baden-Wurttemberg, Germany
Karina Althaus, MD

Physician, Director of Platelet Immunology Lab.
Center for Clinical Transfusion Medicine, University Hospital of Tübingen
Tübingen, Baden-Wurttemberg, Germany
Tamam Bakchoul, MD

Medical Director
Center for Clinical Transfusion Medicine, University Hospital of Tübingen
Tübingen, Baden-Wurttemberg, Germany

Background: Thromboembolic events are life-threatening complication frequently observed in patients with heparin-induced thrombocytopenia (HIT). The interplay of platelets (PLTs) and different actors of the adaptive and innate immune system are increasingly identified to cause a procoagulant state in HIT. However, the impact of antibody (Ab)-induced Fc-gamma-RIIA (FcγRIIA) mediated procoagulant PLTs and their role regarding thrombus formation in HIT remains elusive.

Aims: In this study, the ability of HIT Abs to induce procoagulant PLTs and their potential to propagate thrombus formation was investigated.

Methods: PLTs from healthy individuals were incubated with IgG fractions from well characterized HIT patients or healthy controls (HCs) in the presence of low or high dose heparin. Changes in the expression of CD62P (P-selectin) and phosphatidylserine (PS) were assessed using a flow-cytometric procoagulant PLT-assay. To investigate whether HIT Ab-induced procoagulant PLTs affect thrombus formation, an ex-vivo model of thrombosis was used under flow conditions.

Results: HIT IgG fractions induced significant increase in the formation of CD62P/PS positive procoagulant PLTs compared to buffer and HC IgG (38.87%±1.99 vs. 4.43%±3.25, p=0.001; and vs. 1.43%±0.83, p=0.050, respectively, Figure 1A). Of note, HIT IgG incubated PLTs reconstituted into autologous whole blood induced marked increase in thrombus formation on collagen whereas these changes were nearly absent in HCs (Figure 1B). Interestingly, and of potential therapeutic interest, Ab-induced procoagulant PLT formation as well as increased thrombus formation were significantly reduced in the presence of the prostacyclin derivate Iloprost, an elevator of PLTs' intracellular cAMP (Figure 1A).

Conclusion(s): Findings of our study indicate that HIT Abs harbour the ability to induce procoagulant PLTs via PLT FcγRIIA mediated signalling pathways. The observation that Iloprost showed the potential to reduce the formation of procoagulant PLTs and most importantly inhibits thrombus formation indicates a potential therapeutic use.