Case report

Rare case of COVID-19 vaccine- associated 
intracranial haemorrhage with venous 
sinus thrombosis
Pujon Purkayastha      ,1 Charlie Mckechnie,1 Pallavi Kalkur,1 Marie Scully2 

SUMMARY
Vaccine- induced immune thrombotic thrombocytopenia 
(VITT) is a relatively novel term which describes 
patients who have developed a low platelet count 
and prothrombotic tendencies secondary to receiving 
a vaccine. The concept has been derived from the 
well- established phenomenon of heparin- induced 
thrombocytopenia, and several cases of VITT have 
now been reported in patients who have received the 
AstraZeneca (ChAdOx1 nCov-19) vaccine. Unfortunately, 
some of these patients have gone on to develop 
intracranial venous sinus thrombosis. We present a case 
of VITT- associated sinus thrombosis secondary to the 
AstraZeneca (ChAdOx1 nCov-19) vaccine, which was 
complicated by a large intracerebral haemorrhage.

BACKGROUND
With  a  total  mortality  figure  now  approaching 
5 million  people,  the  current  coronavirus  pandemic 
caused  by  the  SARS- CoV-2  virus  (termed  COVID-
19), has grippled countries worldwide. A global race 
to develop an effective vaccine has led to the successful 
development of some messenger RNA- based vaccines 
by pharmaceutical companies including Pfizer–BioN-
Tech  (BNT162b2)  and  Moderna  (mRNA-1273). 
Another  group  of  vaccines  has  focused  on  deliv-
ering a small quantity of a vector encoding the spike 
glycoprotein of SARS- CoV-2. One such vaccine was 
produced  by  AstraZeneca  (ChAdOx1  nCov-19) 
which uses a recombinant adenovirus vector derived 
from chimpanzees.1

Concerns  have  been  raised  surrounding  the 
prothrombotic nature of the AstraZeneca (ChAdOx1 
nCov-19) vaccine, with cases of venous sinus throm-
bosis being reported in previously fit and well recip-
ients. In this case study, we report on a 55- year- old 
man  who  received  the  ChAdOx1  nCov-19  vaccine 
and  subsequently  developed  a  venous  sinus  throm-
bosis  complicated  by  a  large  volume  intracerebral 
haemorrhage.  We  will  discuss  the  complexity  of 
management  in  such  prothrombotic  patients  where 
there is a concurrent bleed.

CASE PRESENTATION
A previously fit and well 55- year- old man presented 
to the emergency department 18 days after receiving 
his  first  dose  of  the  ChAdOx1  nCov-19  vaccine 
(AstraZeneca), reporting a 2- day history of a frontal 
headache.  This  was  combined  with  a  7- day  history 
of  abdominal  pain  associated  with  several  episodes 
of  diarrhoea.  The  patient  reported  no  significant 

medical history and was not taking any regular medi-
cation.  In  the  emergency  department,  the  patient 
appeared  to  be  alert  and  oriented  with  a  Glasgow 
Coma Score (GCS) of 15 and the absence of any focal 
neurological signs. A diagnosis of a tension headache 
was made and the patient was discharged on the same 
day with simple analgesia.

The following day, he had developed severe confu-
sion, dysphasia and began to have episodes of emesis. 
On  arrival  to  the  emergency  department,  he  was 
found to have a reduced GCS of 13, with a National 
Institutes of Health Stroke Score score of 3 and visual 
inattention  on  his  right  side.  An  urgent  CT  of  the 
head was requested and showed a large 7.0×4.4×5.0 
cm  intracranial  haemorrhage  in  the  left  temporo- 
parietal region with surrounding oedema and efface-
ment  of  the  left  lateral  ventricle  causing  an  8 mm 
midline shift (figure 1A,B). A CT venogram showed 
a left- sided venous sinus thrombosis (figures 2 and 3) 
with  associated  large  volume  haemorrhage,  as  well 
as  thromboses  in  the  left  internal  jugular  vein  and 
transverse sinus. A CT of the abdomen and pelvis was 
also  performed  in  view  of  the  abdominal  pain  and 
demonstrated multiple disseminated thrombi within 
the portal vein and the left kidney.

OUTCOME AND FOLLOW-UP
Blood  tests  revealed  a  thrombocytopenia  with  a 
platelet count of 70×109/L and a raised D- dimer at 
6177 ng/mL. Interestingly, his fibrinogen level was 
within normal range at 2.85 g/L.

Other  laboratory  investigations  included:  haemo-
globin  132  g/L;  international  normalised  ratio  1.6; 
prothrombin time 16.5 s; activated partial thrombo-
plastin time 28.0 s; alanine aminotransferase 537 U/L; 
alkaline phosphatase 149 U/L; albumin 34 g/L. Serum 
creatinine was 59 µmol/L with an estimated glomer-
ular filtration rate of 108 mL/min/1.73 m2. An ELISA 
detected  antibodies  to  platelet  factor  4  (PF4).  Von 
Willebrand  factor–cleaving  protease  (ADAMTS13) 
levels, reticulocytes and lactate dehydrogenase levels 
were within normal range. Advice was sought from 
the haematology team at UCLH (University College 
London Hospital), and the patient was treated with 
intravenous  immunoglobulin  (IVIG)  and  started  on 
non- heparin- based  anticoagulation  (fondaparinux). 
He  was  subsequently  transferred  from  Southend 
Hospital 
the  neurointensive  care  depart-
ment  at  UCLH  for  ongoing  care  which  included 
plasmapheresis.

to 

In total, the patient received five sessions of plasma-
pheresis. Approximately 1 week after treatment, the 

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1Acute Medicine, Southend 
Hospital, Westcliff- on- Sea, UK
2Haematology, University 
College London Hospitals NHS 
Foundation Trust, London, UK

Correspondence to
Dr Pujon Purkayastha;  
 dr. purkayastha@ doctors. org. uk

Accepted 31 July 2021

© BMJ Publishing Group 
Limited 2021. No commercial 
re- use. See rights and 
permissions. Published by BMJ.

To cite: Purkayastha P, 
Mckechnie C, Kalkur P, 
et al. BMJ Case Rep 
2021;14:e245092. 
doi:10.1136/bcr-2021-
245092

Purkayastha P, et al. BMJ Case Rep 2021;14:e245092. doi:10.1136/bcr-2021-245092

Case report

Figure 1  Non- contrast CT of the head in axial (A) and coronal 
(B) plane, showing left temporo- parietal haemorrhage measuring 
7.0×4.4×5.0 cm.

patient’s anti- PF4 antibody titre was negative and his platelet count 
began to recover. He was therefore switched from fondaparinux to 
apixaban, and was subsequently stepped down from intensive care 
and  transferred  to  the  Centre  for  Neurology  in  Queen’s  Square 
for  neurorehabilitation.  The  patient  had  an  episode  of  a  seizure 
while undergoing rehabilitation and was therefore started on the 
anti- epileptic levetiracetam. He made a prompt recovery and was 
successfully discharged home on apixaban and levetiracetam.

DISCUSSION
ChAdOx1 nCov-19 vaccine (AstraZeneca) and venous sinus 
thrombosis
In July 2020, Nature journal published a study suggesting the use 
of the ChAdOx1 nCov-19 vaccine can prevent the development 
of  SARS- CoV-2  in  rhesus  macaques.2  This  was  closely  followed 
in  August  2020  by  The  Lancet,  which  published  a  preliminary 
report  of  a  phase  1/2  randomised  controlled  trial  (RCT),  where 
they  assessed  the  safety  and  immunogenicity  of  the  ChAdOx1 
nCov-19 vaccine (AstraZeneca).3 The authors reported favourably 
on the vaccine, with boosted antibody responses and an acceptable 
safety profile, and recommended a larger scale evaluation as part 
of  a  phase  3  trial.  In  December  2020,  results  from  a  phase  2/3 
RCT reported a positive immunogenic response to the ChAdOx1 

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Figure 3  Axial view of CT venogram showing a filling defect in the 
left transverse sinus.

nCov-19  vaccine  across  all  age  groups  with  no  serious  adverse 
events  being  directly  related  to  the  vaccine.4  Since  then,  further 
international  RCTs  have  all  demonstrated  an  acceptable  safety 
profile  of  the  ChAdOx1  nCov-19  vaccine,5  and  it  has  formed  a 
key component of many national vaccination programmes across 
Europe.

Some clinicians have stipulated that patients developing venous 
sinus  thrombosis  post- ChAdOx1  nCov-19  vaccine  are  at  the 
same risk as the general population for developing such events. 
However,  given  the  relatively  young  and  healthy  population 
groups  inflicted  with  such  thrombotic  events,  it  is  understand-
ably  not  easy  to  accept  such  a  pure  coincidental  explanation. 
This is especially the case when these patients have a consistent 
abnormal serological profile. In March 2021, the European Medi-
cine Agency (EMA) stated that the incidence of thromboembolic 
events in people receiving the ChAdOx1 nCov-19 vaccine was no 
higher than the incidence in the general population.6 However in 
April 2021, the EMA later conceded that there was a probable 
association between the two with an event rate of approximately 
1 per 200 000 doses.7 Some authors have even used the Bradford- 
Hill  criteria  to  demonstrate  a  causal  relationship  between  the 
ChAdOx1  nCov-19  vaccine  and  immune  thrombotic  thrombo-
cytopenia.7 It is worth noting that a few cases of vaccine- induced 
immune  thrombotic  thrombocytopenia  (VITT)  have  also  been 
reported following mRNA- based vaccines, namely Pfizer–BioN-
Tech (BNT162b2) and Moderna (mRNA-1273).8 However, this 
being  said,  no  convincing  causal  relationship  has  been  demon-
strated to date.

Serological markers
In the majority of cases where patients have developed thrombotic 
complications as a result of the ChAdOx1 nCov-19 vaccine, blood 
tests usually reveal a low platelet count (thrombocytopenia) which 
may be associated with raised D- dimer levels alongside low fibrin-
ogen  levels.9  This  biochemical  picture  mirrors  that  of  heparin- 
induced  thrombocytopenia  (HIT),  which  is  a  well- documented 
phenomenon  caused  by  platelet- activating  antibodies,  namely 
PF4, which arise shortly following the administration of heparin- 
containing  medication.  Despite  causing  a  dramatic  fall  in  the 

Figure 2  Coronal view of CT venogram depicting a filling defect 
within the left sigmoid sinus in keeping with a venous sinus thrombosis.

2

Purkayastha P, et al. BMJ Case Rep 2021;14:e245092. doi:10.1136/bcr-2021-245092

platelet  count,  patients  with  HIT  tend  to  be  in  a  prothrombotic 
state  where  they  are  likely  to  develop  complications  including 
disseminated emboli. It is worth mentioning that this HIT phenom-
enon has previously been witnessed in patients even in the absence 
of heparin administration. For instance, the serological picture has 
been found in cases of bacterial and viral infections,10 and even in 
postoperative surgical patients.11 Such spontaneous cases of HIT 
have been grouped together and termed autoimmune HIT.12

VITT  is  one  such  example  of  autoimmune  HIT,  and  is 
being reported with increasing frequency in patients who have 
received the AstraZeneca (ChAdOx1 nCov-19) vaccine. Serum 
analysis of these patients often displays an exaggerated response 
on the PF4- heparin ELISA, with anti- PF4 antibodies being asso-
ciated  with  greater  levels  of  platelet  activation.1  Greinacher  et 
al  suggest  one  potential  mechanism  for  this  platelet  activation 
may  relate  to  the  presence  of  free  DNA  within  the  ChAdOx1 
nCov-19 vaccine. The authors did not test this phenomenon in 
other available COVID-19 vaccines, but do report that to date 
only  patients  receiving  the  AstraZeneca  (ChAdOx1  nCov-19) 
vaccine have been found to display VITT.1

Management
Immunomodulation  in  the  form  of  high- potency  glucocorticoids 
and IVIG forms key aspects of the acute management of patients 
who develop VITT. Prompt treatments with such measures have 

Patient’s perspective

I had the Astrazeneca vaccine back in March, and initially 
thought I was okay. It’s hard to remember what happened 
next. My whole life has changed. Before this, I can’t remember 
the last time I saw my GP. I was completely independent and 
working, now my life has been turned completely upside down. 
With my rehab, I can feel my body and my mind getting stronger 
and stronger. I am having ongoing sessions with speech and 
language therapists as well as physiotherapists. There were 
definitely moments where I felt down; I feel for the other people 
who have had similar reactions to vaccines. I hope that if they 
are finding things hard they can hear my story and find some 
motivation. In terms of the vaccine, I know there are many 
different types. We are still learning more and more about them 
and I wish I could have been told the risks. Now, I feel like I am 
getting stronger and stronger. I am looking forward to what the 
rest of the year holds for me, and waiting for someone to make a 
film about the whole thing.

Learning points

 ► We have presented a case of vaccine- induced immune 
thrombotic thrombocytopenia (VITT) secondary to the 
AstraZeneca (ChAdOx1 nCov-19) vaccine.

 ► The patient in this case developed a venous sinus thrombosis, 
which was complicated by a large intracerebral haemorrhage. 
The combination of these devastating conditions occurring 
simultaneously makes management of such patients 
particularly challenging.

 ► This case study highlights key features and management 

strategies for patients who are likely to suffer from VITT and 
subsequently develop major complications.

Case report

been shown to effectively raise the platelet count, and thus reduce 
the chances of haemorrhagic complications. One of the mechanisms 
IVIG  may  act  is  by  blocking  FcRγIIA  receptors  found  on  plate-
lets.13 This can directly downregulate platelet activation; much like 
in classic HIT. In treatment- resistant cases, plasma exchange may 
be used in a critical care setting as a means of temporarily reducing 
the titre of anti- PF4 antibodies.14 Plasmapheresis was given to our 
patient as he displayed disseminated thrombotic events in addition 
to an intracranial haemorrhage.

With regard to prophylaxis against the development of venous 
thromboembolic  events,  most  clinicians  agree  that  non- heparin- 
based  anticoagulants  ought  to  be  used  in  preference  to  heparin- 
based  medication.9  14  It  is  also  recommended  to  avoid  platelet 
transfusions  in  patients  with  VITT,  as  there  is  a  significantly 
increased risk of developing thrombotic events.

Contributors  PP is the primary author of this case study. CM contributed 
significantly to the case study and was responsible for obtaining patient consent. PK 
was the haematology consultant in charge of the patient’s care at Southend Hospital. 
MS provided valuable contributions to the overall management of the patient.

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  Obtained.

Provenance and peer review  Not commissioned; externally peer reviewed.

This article is made freely available for use in accordance with BMJ’s website 
terms and conditions for the duration of the covid-19 pandemic or until otherwise 
determined by BMJ. You may use, download and print the article for any lawful, 
non- commercial purpose (including text and data mining) provided that all copyright 
notices and trade marks are retained.

ORCID iD
Pujon Purkayastha http:// orcid. org/ 0000- 0001- 6711- 2507

REFERENCES
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vaccine prevents SARS- CoV-2 pneumonia in rhesus macaques. Nature 2021;590:E24.

  3  Folegatti PM, Ewer KJ, Aley PK, et al. Safety and immunogenicity of the ChAdOx1 
nCoV-19 vaccine against SARS- CoV-2: a preliminary report of a phase 1/2, single- 
blind, randomised controlled trial. Lancet 2020;396:467–78.

  4  Ramasamy MN, Minassian AM, Ewer KJ, et al. Safety and immunogenicity of 

ChAdOx1 nCoV-19 vaccine administered in a prime- boost regimen in young and 
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  5  Voysey M, Clemens SAC, Madhi SA, et al. Safety and efficacy of the ChAdOx1 nCoV-
19 vaccine (AZD1222) against SARS- CoV-2: an interim analysis of four randomised 
controlled trials in Brazil, South Africa, and the UK. Lancet 2021;397:99–111.

  6  Østergaard SD, Schmidt M, Horváth- Puhó E, et al. Thromboembolism and the Oxford- 
AstraZeneca COVID-19 vaccine: side- effect or coincidence? Lancet 2021;397:1441–3.

  7  MacIntyre CR. Using the Bradford- Hill criteria to assess causality in the association 
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  8  Lee E- J, Cines DB, Gernsheimer T, et al. Thrombocytopenia following pfizer and 

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Purkayastha P, et al. BMJ Case Rep 2021;14:e245092. doi:10.1136/bcr-2021-245092

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