Vaccine-induced thrombocytopenia with severe headache

For the publisher:

Vaccine-induced immune thrombocytopenia (VITT), a serious adverse event after vaccination with ChAdOx1 nCoV-19 (AstraZeneca) or Ad26.COV2.S (Johnson & Johnson – Janssen), is caused by platelet factor 4 (PF4 ) –Dependent, platelet activating antibodies.^1-3 High-dose immunoglobulins and anticoagulation are the main treatments.^4.5 In this report, we present evidence showing that vaccine-induced thrombocytopenia (VIT) without associated cerebral venous sinus thrombosis (CVST) or other thrombosis and with severe headache as a heraldic symptom may precede VITT (“pre-VITT syndrome”). .

Figure 1. Figure 1. Clinical and laboratory data for patients with VIT and severe headache (pre-VITT syndrome).

Temporal periods of manifestation of pre-VITT syndrome (defined by the onset of headache), hospital admission (including admission and discharge to the emergency department in patients 1 and 2) are shown, platelet count and cerebrovascular complications (in patients 1, 2, and 3), as well as medical and neurosurgical treatment (decompressive craniectomy). Each graph shows the number of days since the onset of the headache on the x-axis and the number of platelets on the y-axis. Results were evaluated with the modified Rankin scale (mRS); scores on the scale of 0 to 6, with higher scores indicating greater disability (0 indicates no symptoms and 6 indicates death). CVST denotes cerebral venous sinus thrombosis, VIT vaccine-induced thrombocytopenia, and VITT vaccine-induced immune thrombotic thrombocytopenia.

Eleven patients presented with severe headache in the absence of CVST between 5 and 18 days after vaccination with ChAdOx1 nCoV-19. All patients had high thrombocytopenia dlower levels and higher levels of anti-PF4-heparin IgG antibodies. During follow-up, intracranial hemorrhage occurred in three patients (patients 1, 2, and 3), with radiological evidence of new CVST in patients 2 and 3 (figure 1, and Table S1 in the supplementary appendix, available with the full text of this letter at NEJM.org). Only two patients (patients 2 and 4) were initially admitted with conditions that met the VITT criteria; both patients had pulmonary embolism and additional splanchnic venous thrombosis was present in patient 2. In patient 2, anticoagulant treatment had been initiated several days earlier for pulmonary embolism (no diagnosis of VITT), but was subsequently stopped. of the onset of headache, shortly before CVST. developed. In two patients (patients 1 and 3), peripheral thrombosis was finally identified during follow-up. Thrombotic complications did not develop in seven of the patients (patients 5 to 11); all but one received high-dose immunoglobulin, glucocorticoids, or anticoagulation with therapeutic doses within 5 days of the onset of the headache. In contrast, in all four patients with posterior thrombosis (patients 1 to 4), anticoagulation of therapeutic doses did not begin until 6 to 9 days after the onset of the headache or stopped prematurely before of CVST development.

Although the combination of thrombocytopenia and severe headache due to CVST has been recognized as the typical presentation of VITT,^1.2 experience with these 11 patients suggests that VIT with severe headache was elevated dLower levels and strongly positive results in the immunosorbent assay bound by anti-PF4-heparin IgG enzymes may precede VITT.

Our findings have immediate implications for clinical practice: in this pre-VITT syndrome, severe headache may not develop as a secondary symptom to CVST, but may precede it several days, potentially in association with microthrombosis in the smaller cortical veins. Accordingly, patients with severe headache between 5 and 20 days after vaccination against vector adenovirus against coronavirus disease 2019 should undergo immediate thrombocytopenia and d-dimers and, if available, anti-PF4-heparin IgG antibody tests. When these antibodies are present at elevated levels, patients present with an imminent risk of CVST and it is likely that this disease can be prevented with immediate treatment, such as with intravenous immunoglobulin. The decision to initiate anticoagulation of therapeutic doses is difficult; the risk of emerging thrombosis, including CVST, must be balanced against the risk of intracranial hemorrhage individually (e.g., taking into account platelet count and fibrinogen levels).

Farid Salih, MD
Charité University Medicine Berlin, Berlin, Germany
[email protected]

Linda Schönborn, MD
Greifswald University Medicine, Greifswald, Germany

Siegfried Kohler, MD
Christiana Franke, MD
Martin Möckel, MD
Thomas Dörner, MD
Hans C. Bauknecht, MD
Christian Pille, MD
Jan A. Graw, MD
Charité University Medicine Berlin, Berlin, Germany

Angelika Alonso, MD
Mannheim University Hospital, Mannheim, Germany

Johann Pelz, MD
Leipzig University Hospital, Leipzig, Germany

Hauke ​​Schneider, MD
Antonios Bayas, MD
Monika Christ, MD
Augsburg University Hospital, Augsburg, Germany

Joji B. Kuramatsu, MD
Erlangen University Hospital, Erlangen, Germany

Thomas Thiele, MD
Andreas Greinacher, MD
Greifswald University Medicine, Greifswald, Germany
[email protected]

Matthias Endres, MD
Charité University Medicine Berlin, Berlin, Germany
[email protected]

This letter was published on September 15, 2021 on NEJM.org.