PB0868 - Cerebral venous sinus thrombosis and thrombocytopenia after adenovirus infection due to heparin-independent anti-PF4 antibodies

Monday, June 24, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Co-Author(s)

Günalp Uzun

MD
Center for Clinical Transfusion Medicine Tuebingen, Tuebingen. Germany
Tuebingen, Baden-Wurttemberg, Germany
Jan Zlamal

MD
Institute for Clinical and Experimental Transfusion Medicine, University Hospital of Tuebingen, Germany
Tuebingen, Baden-Wurttemberg, Germany

Presenting Author(s)

Karina Althaus, MD

MD
Center for Clinical Transfusion Medicine, University Hospital Tuebingen
Tuebingen, Baden-Wurttemberg, Germany

Co-Author(s)

AB

Andrea Bevot

MD
Department of Neuropediatrics and Developmental Medicine, University Children's Hospital, University of Tuebingen, Tuebingen, Germany
Tuebingen, Baden-Wurttemberg, Germany
FH

Florian Hennersdorf

MD
Department of Diagnostic and Interventional Neuroradiology, University Hospital Tübingen, Germany.
Tuebingen, Baden-Wurttemberg, Germany
NW

Nina Wolska

PhD
Institute for Clinical and Experimental Transfusion Medicine, University Hospital of Tuebingen, Tuebingen, Germany.
Tuebingen, Baden-Wurttemberg, Germany
AJ

Anna Jock

MD
Department of Pediatric Cardiology, Pulmonology and Intensive Care Medicine, University Children's Hospital, University of Tuebingen, Tuebingen, Germany.
Tuebingen, Baden-Wurttemberg, Germany
JK

Jan Kern

MD
Department of Neuropediatrics and Developmental Neurology, University Children's Hospital, University of Tuebingen, Tuebingen, Germany.
Tuebingen, Baden-Wurttemberg, Germany
VI

Vanya Icheva

MD
Department of Pediatric Cardiology, Pulmonology and Intensive Care Medicine, University Children's Hospital, University of Tuebingen, Tuebingen, Germany.
Tuebingen, Baden-Wurttemberg, Germany
SP

Sven Poli

Prof.Dr.
Department of Neurology & Stroke, University Hospital of Tuebingen, Tuebingen, Germany.
Tuebingen, Baden-Wurttemberg, Germany
UE

Ulrike Ernemann

Prof.Dr.
Department of Diagnostic and Interventional Neuroradiology, University Hospital Tübingen, Germany.
Tuebingen, Baden-Wurttemberg, Germany
AN

Andreas Neu

Prof.Dr.
Department of Pediatric Endocrinology and Diabetes, University Children's Hospital, University of Tuebingen, Tuebingen, Germany.
Tuebingen, Baden-Wurttemberg, Germany
Tamam Bakchoul, Professor MD

Medical Director
Center for Clinical and Experimental Transfusion Medicine, University Hospital of Tuebingen
Tuebingen, Baden-Wurttemberg, Germany

Background: Cerebral venous sinus thrombosis (CVST) is a rare cerebrovascular disease that primarily affects adults. We present a paediatric case of severe CVST and thrombocytopenia following adenovirus infection, resembling vaccine-induced immune thrombotic thrombocytopenia (VITT).

Aims: To serologically characterize antibodies against platelet factor 4 (PF4)/heparin detected in patient's serum and to investigate their ability to induce thrombosis ex vivo.

Methods: Serum sample was investigated for anti-PF4/heparin antibodies using a commercially available enzyme immunoassay (EIA). The functionality of anti-PF4 antibodies were investigated using modified heparin induced platelet agregation (HIPA) assay as well as procoagulant platelet assay in flow cytometry. The ability of patient’s serum to induce thrombosis was investigated using an ex vivo thrombosis model.

Results: A 7-year-old girl presented with sudden onset of severe headache and vomiting after adenovirus infection. Superior sagittal sinus thrombosis and thrombocytopenia were noted. Thrombectomy was performed, but recurrent thrombosis occurred. Therapeutic anticoagulation with unfractionated heparin was started and a second mechanical thrombectomy was performed. Due to thrombocytopenia and bleeding complications, the patient received high-dose intravenous immunoglobulin (IVIG), which rapidly normalised the platelet count. Examination of the sample taken before heparin therapy showed a strong IgG PF4/heparin EIA reaction (OD 2.8; normal range: 0-0.5). However, the HIPA assay was negative with a low concentration of heparin, making heparin-induced thrombocytopenia (HIT) very unlikely. In contrast, HIPA was positive with buffer and exogenous PF4, a serological pattern that mimics VITT. Patient's serum induced procoagulant platelet formation, which was inhibited by IV.3 and IVIG, indicating FcγRIIA dependence. Patient serum induced significant thrombus formation ex vivo, which was prevented by IV.3 and IVIG.

Conclusion(s): This case suggests that anti-PF4 antibodies can develop after adenovirus infection without prior heparin or COVID-19 vaccine exposure, leading to severe CVST and thrombocytopenia. The mechanisms behind this phenomenon warrant further investigation, potentially impacting the management of unexplained thrombosis and thrombocytopenia.