PB1367 - Pilot study of microRNA (mir148a) identification as a biomarker for early diagnosis and treatment of Heparin Induced Thrombocytopenia (HIT)

Tuesday, June 27, 2023

18:30 – 19:30 ET

Room: Exhibition

Co-Author(s)

EK

Evangelia Kourepini

Onassis Cardiac Surgery Center
Athens, Attiki, Greece

Co-Author(s)

GS

Giannoula Soufla

Molecular Biologist, Chemist
Department of Haematology/Blood Transfusion, Onassis Cardiac Surgery Center
Athens, Attiki, Greece
EI

Eugenia Iliopoulou

Biologist
Department of Haematology/Blood Transfusion, Onassis Cardiac Surgery Center
Athens, Attiki, Greece
SG

Stavros Georgantis

Lab Technologist
Department of Haematology/Blood Transfusion, Onassis Cardiac Surgery Center
Athens, Attiki, Greece
TK

Theoni Kanellopoulou

Hematologist
Department of Haematology/Blood Transfusion, Onassis Cardiac Surgery Center
athens, Attiki, Greece
DB

Dimitrios T. Boumpas

Professor
Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens
Athens, Attiki, Greece

Presenting Author(s)

Theodora Kostelidou, MD, MSC (she/her/hers)

Hematologist, Director of Hematology/ Haemostasis /Blood Transfusion Department
Onassis Cardiac Surgery Center Athens,Greece
kallithea - Athens, Attiki, Greece

Background: Acute and life-threatening complications are common in 2-5% of heparin administered patients. HIT is well correlated with the danger of arterial or vein thrombosis (pulmonary embolism), ischemic stroke, deep vein thrombosis, skin necrosis etc. Cardiothoracic patients are of high danger for HIT development as they have been repeatedly treated with heparin due to previous procedures (angiography etc.). HIT syndrome is due to IgG antibody (Ab) formation against heparin-PF4 complexes causing strong activation and cross-linking of platelets through Fc receptors (FcγRIIa). Only a fragment of these patients develops “functional” Abs that can activate platelets and lead to thrombosis.

Aims: Platelet microRNAs have been shown to contribute to Ab-mediated activation, the mechanism of platelet recruitment, clot formation, and to control immune responses that lead to HIT. We aim to shed light on the above mechanism of platelet disfunction and immune cell contribution during HIT development.

Methods: We used Real Time PCR to measure plasma miR148a expression and TULA-2, FcγRIIa, CD40L gene expression on platelets. We also measured plasma cytokine levels by ELISA.

Results: Our findings demonstrate significantly enhanced expression of miR148a in the plasma of patients with functionally active HIT Abs (HIT-pos), when compared with patients with non-active Abs, or patients without HIT-specific Abs which serve as negative controls. Moreover, platelets of the same patients had increased TULA-2 mRNA expression with a concomitant decrease in FcγRIIa mRNA expression, demonstrating that these genes interrelate and regulate each other. Also, HIT-pos group had both increased platelet expression of CD40L and plasma levels of pro-inflammatory cytokines TNF-α and IL-6.

Conclusion(s): Changes in the above gene and cytokine expression may provide possible mechanistic explanation of HIT induction. Finally, upon analysis of a larger cohort of patients, miR148a could be utilized as a potential biomarker for HIT prevention and treatment.