National Center for Immunization & Respiratory Diseases

Reports of cerebral venous sinus thrombosis with 

thrombocytopenia after Janssen COVID-19 vaccine

Advisory Committee on Immunization Practices (ACIP)

April 14, 2021

Tom Shimabukuro, MD, MPH, MBA

CDC COVID-19 Vaccine Task Force 

Vaccine Safety Team
2

Disclaimer

 The findings and conclusions in this report are those of the authors 

and do not necessarily represent the official position of the Centers for 

Disease Control and Prevention (CDC) or the U.S. Food and Drug 

Administration (FDA).

 Mention of a product or company name is for identification purposes 

only and does not constitute endorsement by CDC or FDA.
3

Topics

 Background

 Reports of cerebral venous sinus thrombosis (CVST) 

with thrombocytopenia (low platelets) following 

Janssen COVID-19 vaccine

 Summary
Background
5

Platelets and thrombocytopenia (low platelets)*

 Platelets (thrombocytes) are colorless blood cells that help blood clot; 

normal platelet count is 150,000–450,000 per microliter

 Platelets stop bleeding by clumping and forming plugs in blood vessel 

injuries

 Thrombocytopenia is a condition in which you have a low blood 

platelet count (<150,000 per microliter)

 Dangerous internal bleeding can occur when your platelet count falls 

below 10,000 platelets per microliter

 Though rare, severe thrombocytopenia can cause bleeding into the 

brain, which can be fatal

* Source: https://www.mayoclinic.org/diseases-conditions/thrombocytopenia/symptoms-causes/syc-20378293
https://www.ema.europa.eu/en/news/astrazenecas 6 -covid-19-vaccine-ema-finds-possible-link-very-rare-cases-unusual-blood-clots-low-blood
7

Janssen COVID-19 vaccine timeline* (2021)

6 CVST† with thrombocytopenia cases reported to VAERS; 

records collection and investigation by CDC and FDA

Feb 

27

Feb 

28

Mar 

2 Apr 

13

Mar 19 thru Apr 12

* For illustrative purposes, not drawn to scale, † cerebral venous sinus thrombosis 
https://emergency.cdc.gov/han/2021/han00442.asp 8
9

Cerebral venous sinus anatomy

Silvis SM et al, Nature Reviews Neurology 13, 555-565(2017)
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Cerebral venous sinus thrombosis (CVST)

Background epidemiology1-3

 Rare, 0.22–1.57 per 100,000, 

~0.5-1% of all strokes

 Median age 37 years

 8% of patients >65 years

 Female:male ratio of 3:1

Risk factors

4

 Prothrombotic conditions (genetic or acquired)

 Oral contraceptives

 Pregnancy and the post-partum period

 Malignancy

 Infection

 Mechanical precipitants (lumbar puncture)

1 Cerebral vein and dural sinus thrombosis in Portugal: 1980-1998. Ferro JM, Correia M, Pontes C, Baptista MV, Pita F, Cerebral Venous Thrombosis Portuguese Collaborative Study Group (Venoport) Cerebrovasc Dis. 2001;11(3):177. 

2 The incidence of cerebral venous thrombosis: a cross-sectional study. Coutinho JM, Zuurbier SM, Aramideh M, Stam J. Stroke. 2012 Dec;43(12):3375-7.. 

3 Cerebral Venous Sinus Thrombosis Incidence Is Higher Than Previously Thought: A Retrospective Population-Based Study. Devasagayam S, Wyatt B, Leyden J, Kleinig T. Stroke. 2016 Sep;47(9):2180-2. 

4 Diagnosis and management of cerebral venous thrombosis: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Saposnik G, et al. 2011;42(4):1158. 
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CVST signs and symptoms

 More common presentations

–

–

–

–

–

–

Isolated intracranial hypertension syndrome (headache with or without 

vomiting, papilledema, and visual problems)

Focal syndrome (focal deficits, seizures, or both)

Encephalopathy (multifocal signs, mental status changes, stupor, or coma)

 Rare presentations

Cavernous sinus syndrome

Subarachnoid hemorrhage

Cranial nerve palsies
Data source and case reports
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+ co-managed by

CDC and FDA

Vaccine Adverse Event 

Reporting System

http://vaers.hhs.gov

VAERS is the nation’s early warning system for vaccine safety
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Reports of CVST to VAERS after COVID-19 vaccines 

as of April 12, 2021

 Janssen COVID-19 vaccine

‒

‒

‒

‒

6 reports of CVST with thrombocytopenia (platelet counts <150K/mm3) 

following 6.86 million doses administered

• Reporting rate of 0.87 cases per million doses administered

 Pfizer-BioNTech COVID-19 vaccine

0 reports following 97.9 million doses administered

 Moderna COVID-19 vaccine

3 reports following 84.7 million doses administered

All 3 with normal platelet counts; onset 2, 6, and 12 days after vaccination

Source of doses administered: https://covid.cdc.gov/covid-data-tracker/#vaccinations
15

Reports of CVST to VAERS after COVID-19 vaccines 

as of April 12, 2021

 Janssen COVID-19 vaccine

‒

‒

‒

‒

6 reports of CVST with thrombocytopenia (platelet counts <150K/mm3) 

following 6.86 million doses administered

• Reporting rate of 0.87 cases per million doses administered

 Pfizer-BioNTech COVID-19 vaccine

0 reports following 97.9 million doses administered

 Moderna COVID-19 vaccine

3 reports following 84.7 million doses administered

All 3 with normal platelet counts (150–450K/mm3)

Source of doses administered: https://covid.cdc.gov/covid-data-tracker/#vaccinations
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Characteristics of patients with CVST and thrombocytopenia* 

after Janssen COVID-19 vaccine, N=6

 Median age 33 years (range 18–48)

 Median time to symptom onset 8 days (range 6–13 days)

 All cases occurred in white females

 Current estrogen/progesterone use (n=1)

 Pregnant or post-partum (n=0)

 Pre-existing conditions

–

–

–

–

–

Obesity (n=3)

Hypothyroidism (n=1)

Hypertension (n=1)

Asthma (n=1) 

Coagulation disorders (none known)

* Note: Thrombosis usually does not occur in the 

presence of low platelets; these case presentations 

are atypical and consistent with cases observed 

after AstraZeneca COVID-19 vaccine
17

Initial and late signs and symptoms among 

CVST patients*, N=6 (patients listed in no particular order)

*All were hospitalized and admitted to the intensive care unit

Initial features Late features

Patient 1 Headaches, lethargy

Severe headache, left-sided weakness, 

vomiting

Patient 2 Headaches Severe headache, aphasia

Patient 3 Headaches, vomiting, fever

Left arm weakness, right gaze deviation, 

left neglect

Patient 4 Headaches, chills, myalgias Severe abdominal pain and fever

Patient 5 Headache, chills, dyspnea, fever

Bruising, unilateral leg swelling, loss of 

consciousness

Patient 6 Back pain, bruising Headache, abdominal pain
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Locations of CVST, intracerebral hemorrhage, and 

other thromboses, N=6

Characteristic Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6

Location of CVST Right transverse 

sinus and right 

sigmoid sinus

Left transverse 

sinus, left 

sigmoid sinus, 

confluence of 

sinuses, and 

straight sinus

Superior sagittal 

sinus, inferior 

sagittal sinus, 

and straight 

sinus

Right transverse 

sinus and right 

sigmoid sinus

Right 

transverse sinus 

and right 

sigmoid sinus

Right 

transverse 

sinus

Location of 

intracerebral 

hemorrhage

Right temporoparietal lobeLeft temporal 

lobe

Bilateral frontal 

lobes, 

intraventricular

None None Occipital lobe

Locations of other 

thromboses

None None None Portal vein and 

right 

pulmonary 

artery

Bilateral lower 

extremity VTE, 

right internal 

jugular vein

Portal vein
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SARS-CoV-2 test results among CVST patients, N=6

SARS-CoV-2 viral test SARS-CoV-2 serology

Patient 1 Negative Not documented

Patient 2 Negative Nucleocapsid Ab negative

Patient 3 Negative Not documented

Patient 4 Negative Not documented

Patient 5 Negative Unspecified COVID Ab negative

Patient 6 Negative Unspecified COVID Ab negative
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Hematology test results among CVST patients, N=6

*Platelet factor 4 heparin induced thrombocytopenia

Lowest platelet value

(per mm3)

PF4 HIT* antibody 

test result(s)

Patient 1 12,000 Not done

Patient 2 69,000 Positive

Patient 3 18,000 Positive

Patient 4 127,000 Positive

Patient 5 10,000 Positive

Patient 6 14,000 Positive
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Treatment and outcomes among CVST patients, N=6

 Treatment

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‒

‒

‒

‒

‒

‒

Heparin (n=4)

Nonheparin anticoagulants (n=5)

Platelets (n=3)

Intravenous immunoglobulin (n=3)

 Outcomes

Death (n=1)

Remain hospitalized (n=3)

• Intensive care unit (n=2)

Discharged home (n=2)

* All 5 of these patients received Argatraban
22

Observed vs. expected CVST cases following Janssen 

COVID-19 vaccine

 Estimated annual incidence of CVST ~0.5–2 cases per 100,000 population*

 Assumed risk period of 5.6% of a calendar year: (41 days/2) ÷ 365 days

 Doses administered among women aged 20–50 years = 1,402,712 doses 

(as of Apr 12)

Est. annual 

background incidence 

Expected cases in 

women aged 20–50 yrs

Reporting ratio, 

women aged 20–50 yrs

0.5 per 100K 0.39 15.2

1.0 per 100K 0.79 7.6

1.5 per 100k 1.18 5.1

2.0 per 100k 1.58 3.8

* https://www.hopkinsmedicine.org/health/conditions-and-diseases/cerebral-venous-sinus-thrombosis, http://www.med.umich.edu/1libr/Stroke/SinusVeinThrombosis.pdf, https://www.nejm.org/doi/10.1056/NEJMra042354?url_ver=Z39.88-

2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub, https://www.ahajournals.org/doi/pdf/10.1161/STROKEAHA.116.013617, https://www.nature.com/articles/nrneurol.2017.104
Summary
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Summary

 CVST is rare, but clinically serious, and can result in substantial morbidity and mortality; 

not usually associated with thrombocytopenia

 Observed cases following Janssen COVID-19 vaccines appear to exceed expected based 

on background rates of CVST among women aged 20–50 years (3-fold or greater)

‒

‒

‒

All 6 reports were in women age range 18–48 years, all with thrombocytopenia

No obvious patterns of risk factors detected

 CVST with thrombocytopenia has not been observed after the two authorized mRNA 

vaccines

182 million mRNA COVID-19 doses administered with no reported cases to date

 Clinical features of Janssen cases are similar to those observed following the 

AstraZeneca COVID-19 vaccine in Europe

 Both Janssen and AstraZeneca vaccines contain replication-incompetent adenoviral 

vectors (human [Ad26.COV2.S] for Janssen and chimpanzee [ChAdOx1] for AstraZeneca)
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Summary (cont.)

 For clinicians

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Maintain a high index of suspicion for symptoms that might represent serious thrombotic events 

or thrombocytopenia in patients who have recently received the Jansen COVID-19 vaccine, 

including severe headache, backache, new neurologic symptoms, severe abdominal pain, 

shortness of breath, leg swelling, petechiae (tiny red spots on the skin), or new or easy bruising. 

Obtain platelet counts and screen for evidence of immune thrombotic thrombocytopenia.

In patients with a thrombotic event and thrombocytopenia after the Jansen COVID-19 vaccine, 

evaluate initially with a screening PF4 enzyme-linked immunosorbent (ELISA) assay as would be 

performed for autoimmune HIT. Consultation with a hematologist is strongly recommended.

Do not treat patients with thrombotic events and thrombocytopenia following receipt of Janssen 

COVID-19 vaccine with heparin, unless HIT testing is negative.

If HIT testing is positive or unable to be performed in patient with thrombotic events and 

thrombocytopenia following receipt of Jansen COVID-19 vaccine, non-heparin anticoagulants and 

high-dose intravenous immune globulin should be strongly considered.

Report adverse events to VAERS, including serious and life-threatening adverse events and deaths 

in patients following receipt of COVID-19 vaccines as required under the Emergency Use 

Authorizations for COVID-19 vaccines.
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Summary (cont.)

 For public health

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Encourage healthcare providers and the public to report all serious and life-threatening adverse 

events and deaths following receipt of COVID-19 vaccines to VAERS as required under the EUAs 

for COVID-19 vaccines.

Disseminate information to healthcare providers in your jurisdictions.

 For the public

If you have received the Janssen COVID-19 vaccine and develop severe headache, abdominal 

pain, leg pain, or shortness of breath within three weeks after vaccination, contact your 

healthcare provider, or seek medical care.

Report adverse events following receipt of any COVID-19 vaccine to VAERS.

If you are scheduled to receive the Janssen vaccine, please contact your healthcare provider, 

vaccination location, or clinic to learn about additional vaccine availability.
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How to report an adverse event to VAERS

 Go to vaers.hhs.gov

 Submit a report online

 For help:

Call 1-800-822-7967

Email info@VAERS.org

video instructions 

https://youtu.be/sbCWhcQADFE

 Please send records to VAERS 

ASAP if contacted and asked

‒ HIPAA permits reporting of 

protected health information 

to public health authorities 

including CDC and FDA
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Next steps

 Continue enhanced monitoring in VAERS and other vaccine safety 

systems (e.g., Vaccine Safety Datalink [VSD])

‒ VSD: ~113K Janssen doses administered, 0 cases in risk interval(s)

 Investigate potential cases through detailed clinical reviews/chart reviews

 Refine analyses to better quantify risk
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Acknowledgments

Centers for Disease Control and Prevention

COVID-19 Vaccine Task Force

COVID-19 Vaccine Task Force, Vaccine Safety Team

Immunization Safety Office

Division of Healthcare Quality Promotion

Clinical Immunization Safety Assessment Project

Vaccine Adverse Event Safety Network

We wish to acknowledge the contributions of investigators from the following organizations:
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