PostScript

Letter

Ischaemic stroke as a 
presenting feature of ChAdOx1 
nCoV- 19 vaccine- induced 
immune 
thrombotic thrombocytopenia

thrombocytopenia 

A  syndrome  of  vaccine- induced  immune 
(VITT) 
thrombotic 
has  recently  been  reported  following 
the  ChAdOx1  nCoV- 19  (Oxford–Astra-
Zeneca)  recombinant  adenoviral  vector 
vaccine  encoding  the  spike  glycoprotein 
of  SARS- CoV- 2.1–4  Previously  described 
patients  developed  thrombosis,  mainly 
affecting  cerebral  venous  sinuses,  with 
thrombocytopenia  and  antibodies 
to 
platelet  factor  4  (PF4),  but  the  charac-
teristics of VITT with arterial thrombosis 
have not previously been described. Here, 

we  report  three  patients  with  VITT  who 
presented with ischaemic stroke.

Patient  1,  a  35- year- old  Asian  woman, 
developed  episodic  right  temporal  and 
periorbital headache 6 days after receiving 
the  ChAdOx1  nCoV- 19  vaccine.  Five 
days  later,  she  awoke  with  left  face,  arm 
and  leg  weakness,  right  gaze  preference 
and  drowsiness.  Non- contrast  CT  and 
CT  angiography  (CTA)  revealed  occlu-
sion  of  the  right  middle  cerebral  artery 
(MCA) distal M1 segment with extensive 
ischaemia  and  haemorrhagic  transforma-
tion  (figure  1A- C)).  Subsequent  imaging 
revealed  right  portal  vein  thrombosis. 
The  platelet  count  was  64 x  109/L  (refer-
ence  range  150 –400 x  109/L);  D- dimer 
was raised at 11 220 µg/L (reference range 
0–550);  and  the  Asserachrom  HPIA  IgG 
assay  for  anti- PF4  antibodies  was  posi-
tive  (76.1%).  The  patient  underwent 
urgent  decompressive  hemicraniectomy 
(figure  1D).  The  platelet  count  increased 

after  intravenous  immune  globulin  and 
plasmapheresis. She received anticoagula-
tion with intermediate dose fondaparinux. 
Fourteen  days  after  presentation,  her 
conscious  level  suddenly  dropped;  CT 
head  showed  extensive  haemorrhagic 
transformation  of  the  left  MCA  infarct 
with  mass  effect  and  herniation  of  the 
brain  through  the  decompressive  hemi-
craniectomy.  Brainstem  death  was  subse-
quently confirmed.

Patient  2,  a  37- year- old  White  female, 
presented  12  days  after  receiving  the 
ChAdOx1  nCoV- 19  vaccine  with  diffuse 
headache,  left  visual  field  loss,  confu-
sion and left arm weakness. CTA showed 
occlusion of both internal carotid arteries 
(figure 1E) and left transverse sinus throm-
bosis 
(figure  1F);  diffusion- weighted 
MRI  showed  bilateral  acute  infarcts  in  a 
borderzone  distribution  (figure  1G,H). 
Subsequent  imaging  confirmed  pulmo-
nary  embolism  and  thromboses  of  the 

Figure 1  Patient 1: (A–D) non- enhanced CT (A) shows hyperdense clot in the distal right M1 segment (arrow), which corresponds to site of the occlusion 
demonstrated on the CT angiogram (B, arrow). The non- enhanced CT at the level of the basal ganglia (C) shows a large acute right middle cerebral 
artery infarct with loss of grey–white matter differentiation (arrows) and early haemorrhagic transformation (short arrow). A non- enhanced CT following 
emergency craniectomy (D) demonstrates swelling of the right hemisphere and extension of the haemorrhagic transformation (short arrows). Patient 2: (E–H) 
the extracranial CT angiogram (E) shows occlusion of both internal carotid arteries (arrows), the right being occluded from its postbulbous portion and the 
left at its origin. The intracranial CT angiography (F) demonstrates patent middle cerebral arteries bilaterally (arrows), which fill via collaterals predominantly 
from the posterior communicating arteries. There is also a lack of filling of the mid- portions and distal portions of the left transverse sinus (short arrow), 
suspicious of a thrombosis, later confirmed with a dedicated CT venogram. Magnetic resonance diffusion- weighted images (G,H) reveal several acute infarcts 
in the right occipital lobe (arrow in G) and centrum semiovale bilaterally (arrows in H), corresponding to cortical as well as deep and superficial arterial 
borderzone territories.

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J Neurol Neurosurg Psychiatry November 2021 Vol 92 No 11

PostScript

left  transverse  and  sigmoid  sinuses,  left 
jugular, right hepatic and both iliac veins. 
The platelet count was 9 x 109/L; D- dimer 
was raised at 34 000 µg/L; and the anti- PF4 
antibody assay was positive (99.7%). The 
platelet  count  increased  following  treat-
ment  with  intravenous  immune  globulin, 
two  intravenous  pulses  of  methylpred-
nisolone  and  plasmapheresis;  the  patient 
then received fondaparinux and improved 
clinically.

Patient  3,  a  43- year- old  Asian  male, 
presented  21  days  after  the  ChAdOx1 
nCoV- 19  vaccine  with  dysphasia.  CT 
and magnetic resonance (MR) showed an 
acute left frontal and insular infarct corre-
sponding to the anterior cortical territory 
of  the  left  MCA,  with  a  small  volume  of 
haemorrhagic  transformation  within  the 
infarct.  MR  and  CT  venography  showed 
no  evidence  of  cerebral  venous  sinus 
thrombosis.  The  platelet  count  was  48 x 
109/L; D- dimer was raised at 24 000 µg/L; 
and the anti- PF4 antibody assay was posi-
tive.  He  was  treated  with  platelet  trans-
immune  globulin 
fusion, 
and  fondaparinux  and  remains  clinically 
stable.

intravenous 

Our observations suggest that, in addi-
tion to venous thrombosis, the neurolog-
ical spectrum of VITT can include arterial 
occlusion.  Young  patients  presenting 
with 
ischaemic  stroke  after  receiving 
the  ChAdOx1  nCoV- 19  vaccine  should 
urgently be evaluated for VITT with labo-
ratory tests (including platelet count, D- di-
mers, fibrinogen and anti- PF4 antibodies) 
and  assessment  for  co- existing  venous 
thromboses;  they  should  be  managed  by 
a  multidisciplinary  team  (haematology, 
stroke,  neurosurgery  and 
neurology, 

including 

intravenous 

neuroradiology) for rapid access to treat-
ments 
immune 
globulin,  methylprednisolone,  plasma-
pheresis  and  non- heparin  anticoagulants, 
for example fondaparinux, argatroban, or 
direct  oral  anticoagulants.  Endovascular 
therapy  or  decompressive  hemicraniec-
tomy  may  also  be  indicated  in  carefully 
selected patients.1 3 5

Talal Al- Mayhani,1 Sadia Saber,1 
Matthew J Stubbs,2 Nicholas A Losseff,1 
Richard J Perry     ,1,3 Robert J Simister,1,3 
David Gull,4 Hans Rolf Jäger,3,5 Marie A Scully,2 
David J Werring     1,3

1Comprehensive Stroke Service, National Hospital 
for Neurology and Neurosurgery, University College 
London Hospitals NHS Foundation Trust, London, UK
2Department of Haematology, University College 
London Hospitals NHS Foundation Trust, London, UK
3Stroke Research Centre, UCL Queen Square Institute of 
Neurology, London, UK
4Stroke Service, Sandwell and West Birmingham 
Hospitals NHS Trust, Birmingham, UK
5Academic Neuroradiological Unit, UCL Queen Square 
Institute of Neurology, London, UK

Correspondence to Professor David J Werring, 
Stroke Research Centre, UCL Queen Square Institute of 
Neurology, London, UK;  d. werring@ ucl. ac. uk

Contributors  DJW and MAS had the idea for the 
paper. TA- M prepared the first draft with DJW and SS. 
HRJ prepared the draft figures. MJS, NAL, RJP, RS and 
DG were involved in the clinical care of the patients. 
All authors critically reviewed the manuscript for 
intellectual content.

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.

© Author(s) (or their employer(s)) 2021. No commercial 
re- use. See rights and permissions. Published by BMJ.

 jnnp. bmj. com

To cite Al- Mayhani T, Saber S, Stubbs MJ, et al. J 
Neurol Neurosurg Psychiatry 2021;92:1247–1248.

Received 27 April 2021
Accepted 28 April 2021
Published Online First 25 May 2021

 ► http:// dx. doi. org/ 10. 1136/ jnnp- 2021- 327057

J Neurol Neurosurg Psychiatry 2021;92:1247–1248.
doi:10.1136/jnnp-2021-326984

ORCID iDs
Richard J Perry http:// orcid. org/ 0000- 0002- 4536- 9018
David J Werring http:// orcid. org/ 0000- 0003- 2074- 1861

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