Case report

Cerebral venous sinus thrombosis after 
ChAdOx1 nCov- 19 vaccination with a 
misleading first cerebral MRI scan

Benno Ikenberg      ,1 Antonia Franziska Demleitner      ,1 Thomas Thiele,2 
Benedikt Wiestler,3 Katharina Götze,4 Georg Mößmer,5 Paul Lingor      1

To cite: Ikenberg B, 
Demleitner AF, Thiele T, 
et al. Cerebral venous sinus 
thrombosis after ChAdOx1 
nCov- 19 vaccination with 
a misleading first cerebral 
MRI scan. Stroke & Vascular 
Neurology 2021;6: e001095. 
doi:10.1136/svn-2021-001095

BI and AFD contributed equally.

Received 3 May 2021
Accepted 9 June 2021
Published Online First 
8 July 2021

SUMMARY
Vaccine- induced immune thrombotic thrombocytopenia 
(VITT) and cerebral venous sinus thrombosis (CVST) have 
been recently described as rare complications following 
vaccination against SARS- CoV- 2 with vector vaccines. 
We report a case of a young woman who presented with 
VITT and cerebral CVST 7 days following vaccination with 
ChAdOx1 nCov- 19 (AstraZeneca). While the initial MRI was 
considered void of pathological findings, MRI 3 days later 
revealed extensive CVST of the transversal and sigmoidal 
sinus with intracerebral haemorrhage. Diagnostic tests 
including a platelet- factor- 4- induced platelet activation 
assay confirmed the diagnosis of VITT. Treatment with 
intravenous immunoglobulins and argatroban resulted in a 
normalisation of platelet counts and remission of CVST.

and  reported  mild  myalgia,  holocephalic 
headache  and  chills,  which  subsided  within 
24 hours. The neurological examination was 
normal.  Particularly,  no  meningism  and  no 
petechia  were  observed.  Laboratory  results 
showed  an  otherwise  unexplained  throm-
bocytopenia  of  97  000/µL  and  a  C  reactive 
protein of 8.1 mg/dL (figure 1A). A cerebral 
MRI  scan  was  without  pathological  finding, 
in particular without any clear sign for CVST 
(figure  1B- 1).  The  patient  was  discharged 
from our hospital on the same day.

BACKGROUND
Active  vaccination  against  SARS- CoV- 2 
is 
currently one of the most important measures 
to  contain  the  COVID- 19  pandemic.  With 
increasing  numbers  of  ChAdOx1  nCov- 19 
(AstraZeneca)  vaccinations,  adverse  events 
such  as  thrombotic  thrombocytopenia  and 
cerebral  venous  sinus  thrombosis  (CVST) 
were  observed  as  very  rare  complications.1 
Vaccine- induced 
thrombocyto-
penia (VITT) mediated by platelet- activating 
antibodies against platelet factor 4 (PF4) was 
observed  and  considered  causative  for  such 
vascular  events.2  Here,  we  report  a  case  of 
VITT causing a CVST in an otherwise healthy 
young  woman  following  ChAdOx1  nCov- 19 
vaccination  and  highlight  particular  labora-
tory  and  imaging  features  which  may  advise 
clinical decision making in the next weeks.

thrombotic 

CASE PRESENTATION
A young woman in the early 30s presented to 
our  emergency  department  with  an  isolated 
headache  (Numerical  Rating  Scale  (NRS) 
score=5).  The  patient  denied  any  premedi-
cation (including oral contraception or prior 
heparin treatment), vascular risk factors, and 
pre- existing  disease  or  family  history  of  any 
thrombotic  event.  She  had  the  first  dose  of 
ChAdOx1  nCov- 19  vaccination  7 days  before 

INVESTIGATIONS
Three  days  later,  the  patient  was  referred  to 
our  department  with  persisting  headaches 
(NRS  score=8),  progressive  thrombocyto-
penia of 37 000/µL and an increased D- dimer 
fibrinogen 
concentration  of  12 859 µg/L 
equivalent  unit  (FEU)  (reference  range: 
<500 µg/L  FEU).  The  screening  test  for 
heparin- induced  thrombocytopenia  (HIT) 
was positive (particle gel agglutination immu-
noassay  for  antibodies  against  PF4/heparin, 
polyvalent, ie, not specific for IgG antibodies; 
ID- PaGIA  Heparin/PF4  Antibody  Test, 
DiaMed). The PCR test for SARS- CoV- 2 from 
a nasopharyngeal swab was negative. On clin-
ical  examination,  the  patient  presented  with 
a  discrete  gait  ataxia  and  reported  progres-
sive  amnestic  difficulties  as  well  as  discrete 
amnesic  aphasia.  A  new  MRI  scan  revealed 
CVST  of  the  left  transverse  and  sigmoidal 
sinus  with  a  left- temporal  and  left- cerebellar 
intracerebral  haemorrhage  (figure  1B- 2). 
The  results  of  the  heparin- induced  platelet 
activation  assay  (HIPA)  and  the  platelet- 
factor- 4- induced  platelet  activation  assay 
(PIPA,  a  modified  HIPA  test)  showed  strong 
IgG- receptor- mediated  platelet  activation  in 
both  the  presence  and  absence  of  heparin 
confirming  the  diagnosis  of  VITT.  In  addi-
tion, a hypercoagulable state work- up showed 
no relevant findings.

© Author(s) (or their 
employer(s)) 2021. Re- use 
permitted under CC BY- NC. No 
commercial re- use. See rights 
and permissions. Published by 
BMJ.
1Department of Neurology, 
Klinikum rechts der Isar der 
Technischen Universität 
München, Munchen, Germany
2Institut für Immunologie 
und Transfusionsmedizin, 
Universitätsmedizin Greifswald, 
Greifswald, Germany
3Department of Diagnostic und 
Interventional Neuroradiology, 
Klinikum rechts der Isar der 
Technischen Universität 
München, Munchen, Germany
4Department of Medicine 
III, Klinikum rechts der Isar 
der Technischen Universität 
München, Munchen, Germany
5Institute for Clinical Chemistry 
and Pathobiochemistry, Klinikum 
rechts der Isar der Technischen 
Universität München, Munchen, 
Germany

Correspondence to
Dr Benno Ikenberg;  
 benno. ikenberg@ tum. de

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Ikenberg B, et al. Stroke & Vascular Neurology 2021;6:e001095. doi:10.1136/svn-2021-001095

Open access 

OUTCOME AND FOLLOW-UP
Under  continuous  anticoagulation  with  argatroban,  the 
patient  improved  with  regressive  headache  but  persistent 
minimal  gait  ataxia,  amnestic  deficits  as  well  as  discrete 
amnesic  aphasia.  A  follow- up  MRI  scan  showed  persisting 
CVST but regressive cerebellar haemorrhage with a slightly 
progressive temporal perifocal oedema (figure 1B- 3). Subse-
quently,  the  platelet  count  increased  in  the  following  days 
(figure 1A).

DISCUSSION
Consistent with the initial description of VITT following 
ChAdOx1  nCov- 19  vaccination,1  2  we  report  on  a  young 
woman with unremarkable medical history suffering from 
CVST. The delay between vaccination and symptom onset 
was 7 days, which is in the range of 5–16 days reported for 
VITT. A positive PIPA confirmed the diagnosis.

Following  positive  HIT  screening  test,  treatment  of 
CVST  was  started  with  argatroban.  Because  of  contin-
uous clinical improvement, this treatment was continued 
before switching the patient to anticoagulation with dabig-
atran (Pradaxa) on day 8 after hospitalisation. According 
to current recommendations,3 we treated the patient with 
intravenous  immunoglobulins  for  2 days.  Subsequently, 
the platelet count increased continuously.

Although  our  patient  suffered  from  headache  and  mild 
thrombocytopenia at first presentation, the initial MRI scan 
was  without  any  clear  pathological  finding.  The  follow- up 
MRI scan, however, revealed an extensive CVST. There is an 
ongoing debate about the appropriate imaging modality for 
detecting CVST. In a recent meta- analysis,4 CT and MRI had 
similar  diagnostic  performance.  Retrospectively,  we  noted 
small irregularities at the bottom of the left transverse sinus 
in the contrast- enhanced T1w image (figure 1B- 1). In view 
of the clinical course, this warrants a high sensitivity also for 
(small) abnormalities in cerebral veins and sinuses in these 
patients. The clinical challenge of managing such patients 
and the importance of high vigilance are also supported by a 
similar patient who also deteriorated at second presentation 
to the hospital in a recent case series.1

Given the high number of patients presenting to emer-
gency  departments  with  headache  or  other  unspecific 
symptoms following vaccination with ChAdOx1 nCov- 19 
or  other  vector  vaccines  for  SARS- CoV- 2,  our  case  advo-
cates to give high priority to patients with signs of throm-
bocytopenia  and/or  elevated  D- dimer.  Importantly,  our 
case demonstrates that an initial MRI scan can be normal 
and  a  re- examination  should  be  performed  if  clinical 
suspicion  persists.  Progression  of  thrombocytopenia 
should be monitored, while a platelet substitution is not 
recommended  as  it  could  further  aggravate  thrombosis 
and thrombocytopenia.3 Although our HIT test was posi-
tive,  it  is  important  to  note  that  commercially  available 
tests  are  not  sufficient  to  exclude/confirm  VITT  so  far 
and  literature  should  be  screened  regularly  for  avail-
ability  of  new  tests/recommendations3  in  this  rapidly 
evolving  field.  Given  the  high  number  of  vaccinations 

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Figure 1  A time course of clinical characteristics and 
laboratory results following vaccination. Platelet count 
is depicted in red. The value of day 9 prior to second 
presentation in our hospital was provided by the generalist. 
Headache intensity is shown in black according to the 
Numerical Rating Scale. (B) Serial cerebral MRI scans. Upper 
row: axial T2* sequence of the infratentorial brain; lower row: 
coronal T1w sequence of the cerebellum, temporal lobe 
and sinus transversus. (B- 1) MRI scan at first presentation 
in our emergency department with thrombocytopenia and 
headache. At first look, the MRI scan was without a clear sign 
for CVST. Retrospectively (red arrows), a slight irregularity 
as indicator of beginning thrombosis may be discussed. 
(B- 2) First follow- up MRI 3 days later revealed a CVST of 
the left transverse and sigmoidal sinus (red arrows) with a 
left- temporal and left cerebellar intracerebral haemorrhage 
(asterisks). (B- 3) Most recent follow- up MRI showing a 
persisting CVST and intracerebral haemorrhage with a 
slightly progressive perifocal oedema. Volume of cerebellar 
haemorrhage slightly decreased. CVST, cerebral venous 
sinus thrombosis; ER, emergency room; HIPA, heparin- 
induced platelet activation assay; HIT, heparin- induced 
thrombocytopenia; IVIG, intravenous immunoglobulin; PIPA, 
platelet- factor- 4- induced platelet activation assay.

TREATMENT
The  patient  was  admitted  to  our  stroke  unit;  anticoagu-
lation  with  argatroban  (Argatra)  was  initiated  immedi-
ately;  and  intravenous  immunoglobulin  therapy  (1 g/kg 
body weight/day for 2 days) was applied for treatment of 
suspected VITT.

 

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Open access

Ikenberg B, et al. Stroke & Vascular Neurology 2021;6:e001095. doi:10.1136/svn-2021-001095

with  ChAdOx1  nCov- 19,  the  occurrence  of  VITT  and 
subsequent CVST has to be considered a very rare compli-
cation: according to a recent European Medicines Agency 
report  as  of  4  April  2021,  34 million  people  have  been 
vaccinated  with  ChAdOx1  nCov- 19  (Vaxzevria,  formerly 
COVID- 19 Vaccine, AstraZeneca), and 169 cases of CVST 
and 53 cases of splanchnic vein thrombosis were recorded 
by EudraVigilance.5 Our case report intends to raise alert-
ness  in  emergency  departments  and  to  provide  a  diag-
nostic and therapeutic work- up for this rare complication 
of vector vaccines against SARS- CoV- 2.

Learning points

 ► High priority should be given to patients presenting with headaches 

following ChAdOx1 nCov- 19 vaccination.

 ► Screening for thrombocytopenia and/or elevated D- dimer is manda-

tory in such patients.

 ► Initial cerebral MRI scans can be normal—if clinical suspicion for 
sinus vein thrombosis persists, a repeated MRI scan should be per-
formed in patients following ChAdOx1 nCov- 19 vaccination.

 ► Current  commercially  available  heparin- induced  thrombocytope-
nia screening tests are not sufficient to diagnose vaccine- induced 
thrombotic thrombocytopenia.

Acknowledgements  We are indebted to the patient who gave informed consent 
for publication of this case report.

Contributors  Treating neurologists: BI, AFD and PL; MRI analysis and 
interpretation: BW; laboratory tests and interpretation: TT, KG and GM; first draft: 
BI; supervision: PL. All authors revised and approved the final version of the 
manuscript.

Funding  The authors have not declared a specific grant for this research from any 
funding agency in the public, commercial or not- for- profit sectors.

Competing interests  None declared.
Patient consent for publication  Not required.
Provenance and peer review  Not commissioned; internally peer reviewed.

Open access  This is an open access article distributed in accordance with the 
Creative Commons Attribution Non Commercial (CC BY- NC 4.0) license, which 
permits others to distribute, remix, adapt, build upon this work non- commercially, 
and license their derivative works on different terms, provided the original work is 
properly cited, appropriate credit is given, any changes made indicated, and the use 
is non- commercial. See: http:// creativecommons. org/ licenses/ by- nc/ 4. 0/.

ORCID iDs
Benno Ikenberg http:// orcid. org/ 0000- 0002- 0798- 7149
Antonia Franziska Demleitner http:// orcid. org/ 0000- 0001- 9557- 9243
Paul Lingor http:// orcid. org/ 0000- 0001- 9362- 7096

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670

Open access 

Ikenberg B, et al. Stroke & Vascular Neurology 2021;6:e001095. doi:10.1136/svn-2021-001095