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Frequency of Thrombocytopenia and Platelet Factor 4/Heparin Antibodies in Patients With Cerebral Venous Sinus Thrombosis Prior to the COVID-19 Pandemic.
JAMA. 2021 07 27; 326(4):332-338.JAMA

Abstract

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.

Authors+Show Affiliations

Department of Neurology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.Department of Hematology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.Department of Neurology, Albert Schweitzer Hospital, Dordrecht, the Netherlands.Experimental Haemostasis Group, Department for BioMedical Research DBMR, University of Bern, Bern, Switzerland.Department of Hematology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.Department of Internal Medicine & Radboud Institute of Health Sciences (RIHS), Radboud University Medical Center, Nijmegen, the Netherlands.National Institute for Health Research University College London Hospitals (UCLH) Biomedical Research Centre, London, United Kingdom. Department of Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.Department of Neurology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden. Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.Sina Hospital, Hamadan University of Medical Science, Hamadan, Iran.National Institute of Neurology and Neurosurgery Manuel Velasco Suarez, Mexico-City, Mexico.Neurosciences Department, Hospital Dr R.A. Calderón Guardia, CCSS, San José, Costa Rica.Department of Neurology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.Department of Neurosciences and Mental Health, Neurology Service, Hospital de Santa Maria/CHULN, University of Lisbon, Lisbon, Portugal.Department of Neurosciences and Mental Health, Neurology Service, Hospital de Santa Maria/CHULN, University of Lisbon, Lisbon, Portugal.Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.Division of Neurology, University of British Columbia, Vancouver Stroke Program, Vancouver, British Columbia, Canada.Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden. Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden. Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.Department of Neurology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.Department of Neurology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

34213527

Citation

Sánchez van Kammen, Mayte, et al. "Frequency of Thrombocytopenia and Platelet Factor 4/Heparin Antibodies in Patients With Cerebral Venous Sinus Thrombosis Prior to the COVID-19 Pandemic." JAMA, vol. 326, no. 4, 2021, pp. 332-338.
Sánchez van Kammen M, Heldner MR, Brodard J, et al. Frequency of Thrombocytopenia and Platelet Factor 4/Heparin Antibodies in Patients With Cerebral Venous Sinus Thrombosis Prior to the COVID-19 Pandemic. JAMA. 2021;326(4):332-338.
Sánchez van Kammen, M., Heldner, M. R., Brodard, J., Scutelnic, A., Silvis, S., Schroeder, V., Kremer Hovinga, J. A., Middeldorp, S., Levi, M., Hiltunen, S., Lindgren, E., Mansour, M., Arauz, A., Barboza, M. A., Zuurbier, S. M., Aguiar de Sousa, D., Ferro, J. M., Fischer, U., Field, T. S., ... Coutinho, J. M. (2021). Frequency of Thrombocytopenia and Platelet Factor 4/Heparin Antibodies in Patients With Cerebral Venous Sinus Thrombosis Prior to the COVID-19 Pandemic. JAMA, 326(4), 332-338. https://doi.org/10.1001/jama.2021.9889
Sánchez van Kammen M, et al. Frequency of Thrombocytopenia and Platelet Factor 4/Heparin Antibodies in Patients With Cerebral Venous Sinus Thrombosis Prior to the COVID-19 Pandemic. JAMA. 2021 07 27;326(4):332-338. PubMed PMID: 34213527.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Frequency of Thrombocytopenia and Platelet Factor 4/Heparin Antibodies in Patients With Cerebral Venous Sinus Thrombosis Prior to the COVID-19 Pandemic. AU - Sánchez van Kammen,Mayte, AU - Heldner,Mirjam R, AU - Brodard,Justine, AU - Scutelnic,Adrian, AU - Silvis,Suzanne, AU - Schroeder,Verena, AU - Kremer Hovinga,Johanna A, AU - Middeldorp,Saskia, AU - Levi,Marcel, AU - Hiltunen,Sini, AU - Lindgren,Erik, AU - Mansour,Maryam, AU - Arauz,Antonio, AU - Barboza,Miguel A, AU - Zuurbier,Susanna M, AU - Aguiar de Sousa,Diana, AU - Ferro,Jose M, AU - Fischer,Urs, AU - Field,Thalia S, AU - Jood,Katarina, AU - Tatlisumak,Turgut, AU - Putaala,Jukka, AU - Arnold,Marcel, AU - Coutinho,Jonathan M, PY - 2022/01/02/pmc-release PY - 2021/7/3/pubmed PY - 2021/8/10/medline PY - 2021/7/2/entrez SP - 332 EP - 338 JF - JAMA JO - JAMA VL - 326 IS - 4 N2 - 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. SN - 1538-3598 UR - https://www.unboundmedicine.com/medline/citation/34213527/Frequency_of_Thrombocytopenia_and_Platelet_Factor_4/Heparin_Antibodies_in_Patients_With_Cerebral_Venous_Sinus_Thrombosis_Prior_to_the_COVID-19_Pandemic. L2 - https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2021.9889 DB - PRIME DP - Unbound Medicine ER -