Frequency of Thrombocytopenia and Platelet Factor 4/Heparin Antibodies in Patients With Cerebral Venous Sinus Thrombosis Prior to the COVID-19 Pandemic.

Sánchez van Kammen, Mayte; Heldner, Mirjam R.; Brodard, Justine; Scutelnic, Adrian; Silvis, Suzanne; Schroeder, Verena; Kremer Hovinga, Johanna A.; Middeldorp, Saskia; Levi, Marcel; Hiltunen, Sini; Lindgren, Erik; Mansour, Maryam; Arauz, Antonio; Barboza, Miguel A.; Zuurbier, Susanna M.; Aguiar de Sousa, Diana; Ferro, Jose M.; Fischer, Urs; Field, Thalia S.; Jood, Katarina; ... (2021). Frequency of Thrombocytopenia and Platelet Factor 4/Heparin Antibodies in Patients With Cerebral Venous Sinus Thrombosis Prior to the COVID-19 Pandemic. JAMA : the journal of the American Medical Association, 326(4), pp. 332-338. American Medical Association 10.1001/jama.2021.9889

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Importance

Cases of cerebral venous sinus thrombosis in combination with thrombocytopenia have recently been reported within 4 to 28 days of vaccination with the ChAdOx1 nCov-19 (AstraZeneca/Oxford) and Ad.26.COV2.S (Janssen/Johnson & Johnson) COVID-19 vaccines. An immune-mediated response associated with platelet factor 4/heparin antibodies has been proposed as the underlying pathomechanism.

Objective

To determine the frequencies of admission thrombocytopenia, heparin-induced thrombocytopenia, and presence of platelet factor 4/heparin antibodies in patients diagnosed with cerebral venous sinus thrombosis prior to the COVID-19 pandemic.

Design, Setting, and Participants

This was a descriptive analysis of a retrospective sample of consecutive patients diagnosed with cerebral venous sinus thrombosis between January 1987 and March 2018 from 7 hospitals participating in the International Cerebral Venous Sinus Thrombosis Consortium from Finland, the Netherlands, Switzerland, Sweden, Mexico, Iran, and Costa Rica. Of 952 patients, 865 with available baseline platelet count were included. In a subset of 93 patients, frozen plasma samples collected during a previous study between September 2009 and February 2016 were analyzed for the presence of platelet factor 4/heparin antibodies.

Exposures

Diagnosis of cerebral venous sinus thrombosis.

Main Outcomes and Measures

Frequencies of admission thrombocytopenia (platelet count <150 ×103/μL), heparin-induced thrombocytopenia (as diagnosed by the treating physician), and platelet factor 4/heparin IgG antibodies (optical density >0.4, in a subset of patients with previously collected plasma samples).

Results

Of 865 patients (median age, 40 years [interquartile range, 29-53 years], 70% women), 73 (8.4%; 95% CI, 6.8%-10.5%) had thrombocytopenia, which was mild (100-149 ×103/μL) in 52 (6.0%), moderate (50-99 ×103/μL) in 17 (2.0%), and severe (<50 ×103/μL) in 4 (0.5%). Heparin-induced thrombocytopenia with platelet factor 4/heparin antibodies was diagnosed in a single patient (0.1%; 95% CI, <0.1%-0.7%). Of the convenience sample of 93 patients with cerebral venous sinus thrombosis included in the laboratory analysis, 8 (9%) had thrombocytopenia, and none (95% CI, 0%-4%) had platelet factor 4/heparin antibodies.

Conclusions and Relevance

In patients with cerebral venous sinus thrombosis prior to the COVID-19 pandemic, baseline thrombocytopenia was uncommon, and heparin-induced thrombocytopenia and platelet factor 4/heparin antibodies were rare. These findings may inform investigations of the possible association between the ChAdOx1 nCoV-19 and Ad26.COV2.S COVID-19 vaccines and cerebral venous sinus thrombosis with thrombocytopenia.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Haematology and Central Haematological Laboratory
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Pavillon 52 > Forschungsgruppe Experimentelle Hämostase

UniBE Contributor:

Heldner, Mirjam Rachel; Brodard, Justine; Scutelnic, Adrian; Schröder, Verena; Kremer Hovinga, Johanna Anna; Fischer, Urs and Arnold, Marcel

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1538-3598

Publisher:

American Medical Association

Language:

English

Submitter:

Pierrette Durand Lüthi

Date Deposited:

12 Jul 2021 13:33

Last Modified:

15 Sep 2021 15:37

Publisher DOI:

10.1001/jama.2021.9889

PubMed ID:

34213527

Additional Information:

Drs Sánchez van Kammen and Heldner shared first authorship.
Drs Arnold and Coutinho shared last authorship.

BORIS DOI:

10.48350/157466

URI:

https://boris.unibe.ch/id/eprint/157466

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