Fatal Cerebral Venous Sinus Thrombosis and Thrombocytopenia due to Anti-PF4 Disorder Following Adenovirus Infection in a 3-year-old Boy

Introduction

Vaccination against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been crucial in managing the COVID-19 pandemic. In 2021, a rare syndrome characterized by thrombotic events and thrombocytopenia was identified in individuals who received the ChAdOx1 nCoV-19 or the Ad26.COV2.S vaccine, both of which use adenoviral vectors.[1] [2] [3] [4] [5] This syndrome, known as vaccine-induced immune thrombocytopenia and thrombosis (VITT), is linked to high levels of immunoglobulin G (IgG) antibodies targeting platelet factor 4 (PF4), a chemokine released from platelet α-granules.[6] Similar conditions associated with anti-PF4 antibodies include classic heparin-induced thrombocytopenia (HIT), autoimmune HIT (aHIT), and spontaneous HIT.[7] Additionally, prothrombotic, platelet-activating anti-PF4 antibodies not associated with heparin have been identified in a patient with monoclonal gammopathy.[8] These anti-PF4 disorders present with thrombosis and thrombocytopenia following exposure of PF4 to polyanions like DNA, heparin, or polyphosphate.[9] [10] Recently, anti-PF4 antibodies were detected in two individuals who developed a VITT-like syndrome after adenovirus infection, despite not receiving COVID-19 vaccination or heparin treatment.[11] In the meantime, further such cases, some of them with a preceding respiratory infection and positive testing for adenovirus, have been reported (see [Table 1]).[12] [13] [14] Here, we report the case of a 3-year-old boy who developed fatal cerebral venous sinus thrombosis (CVST) and thrombocytopenia several days after an adenovirus infection. Postmortem studies revealed the presence of anti-PF4 antibodies in his serum. This case further confirms the existence of adenovirus-triggered anti-PF4 antibodies, emphasizing the need to study anti-PF4 antibodies in patients with unexplained thrombosis and thrombocytopenia.

Table 1 Summary of published cases of VITT-like syndrome without prior vaccination or heparin treatment

Patient number	Sex	Age (years)	Preceding infection/pathogen	Underlying disease	Clinical diagnosis	Outcome	Source
#1	M	5	Yes/Adenovirus	None	CVST	Fatal	Warkentin et al[11]
#2	F	58	Yes/Adenovirus	None	Multiple arterial strokes, MI, multiple DVT	Survived	Warkentin et al[11]
#3	F	40	Yes/Adenovirus	None	PE, DVT, ICB	Survived	Campello et al[12]
#4	F	70–80[1]	None	Monoclonal gammopathy	Multiple DVT, PE, stroke	Survived	Schönborn et al[13]
#5	F	30–40	Yes/Unknown	None	CVST	Fatal	Schönborn et al[13]
#6	F	70–80	None	None	PE	Survived	Schönborn et al[13]
#7	M	60–70	None	None	Stroke with secondary ICB	Survived	Schönborn et al[13]
#8	F	20–30	Yes/RSV	None	CVST, PE, DVT	Survived	Schönborn et al[13]
#9	F	30–40	None	None	Multiple TE	Survived	Schönborn et al[13]
#10	M	60–70	Yes (UTI)/Unknown	Crohn‘s disease	DVT, PE	Fatal	Schönborn et al[13]
#11	M	20–30	Yes/Unknown	None	CVST	Survived	Schönborn et al[13]
#12	M	5–10	Yes/Adenovirus	None	CVST	Survived	Schönborn et al[13]
#13	F	7	Yes/Adenovirus	None	CVST	Survived	Uzun et al.[14]
#14	M	3	Yes/Adenovirus, bocavirus	None	CVST	Fatal	This case

Abbreviations: CVST, cerebral venous sinus thrombosis; DVT, deep venous thrombosis; ICB, intracerebral bleeding; MI, myocardial infarction; PE, pulmonary embolism; RSV, respiratory syncytial virus; TE, thrombotic events; UTI, urinary tract infection; VITT, vaccine-induced immune thrombocytopenia and thrombosis.

Note: Schönborn et al reported patients’ ages as ranges to respect confidentiality.

Publication History

Received: 18 December 2024

Accepted: 06 January 2025

Article published online:
31 January 2025

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