COVID-19 vaccination and cerebral venous thrombosis: a very rare occurrence

Although extremely rare, adverse effects related to vaccination against COVID-19 are feared and have a strong emotional impact. One of those that have emerged in recent months, since the vaccination campaign began, is cerebral venous thrombosis, which can however occur in different haemocoagulative contexts.

Some cases of severe venous thrombosis with thrombocytopenia have been reported several days after administration of the vector vaccines AstraZeneca and Johnson & Johnson, sometimes involving the cerebral venous sinus. Due to its clinical and haematological characteristics, this condition has been defined as vaccine-induced immune thrombotic thrombocytopenia (VITT), a form of vaccine-induced thrombocytopenic thrombosis of immune origin. In fact, in a high percentage of these patients the presence of antibodies against platelet factor 4 (PF4) was detected.

From a technical point of view, this syndrome was then better framed, defining it as suspicious in the presence of a D-dimer> 4,000 μg/L and unlikely for D-dimer values ​​<2,000 μg/L.

On the other hand, cases of thrombocytopenia have also been reported after the administration of mRNA vaccines, such as Moderna and Pfizer.

Thrombosis of the cerebral venous sinus

Thrombosis of the cerebral venous sinus is a rare event that usually affects young women of childbearing age, with an incidence of 3-4 cases per million per year. It appears to be associated with the most common risk factors for venous thrombosis, such as pregnancy, oral contraceptives and changes in blood clotting factors.

Recent data show how this form of cerebral thrombosis can occur after a COVID-19 infection with a frequency ranging from 39 patients per million to 20 patients per 100,000 cases.

Recent European data estimate that cases of cerebral venous sinus thrombosis occur with a frequency of one in 100,000 after the administration of the AstraZeneca vaccine and one in 1,000,000 cases after the administration of the Johnson & Johnson vaccine.

Clinical features, laboratory results and radiological features

A recent study, published in the journal The Lancet, evaluated clinical and laboratory features of patients with cerebral venous thrombosis in which the presence of a VITT was detected and compared them with those of subjects in which a cerebral venous thrombosis occurred without the typical characteristics of VITT.

To do this, data from 95 patients collected in 43 different UK hospitals were analyzed, in which cerebral venous thrombosis had occurred following a COVID-19 vaccination, regardless of the type of vaccine.

Clinical characteristics, laboratory results, radiological characteristics were evaluated and the quantity of anti-PF4 antibodies measured.

The presence of a VITT among the patients analyzed was defined by the presence of a platelet count less than 150 × 109/L and a D-dimer greater than 2,000 μg/L.

In addition to patients with post-vaccination complications, a large group of subjects with cerebral venous thrombosis included in the International Study on Cerebral Vein and Dural Sinus Thrombosis were also included in the analysis.

Patients with VITT were younger

Among the 95 patients included in the analysis, 70 had parameters compatible with a VITT and 25 did not. All 70 cases of VITT-associated cerebral venous thrombosis occurred after a first dose of the AstraZeneca vaccine. Four patients with non-VITT cerebral venous thrombosis received the first or second dose of the Pfizer vaccine.

The median time interval between vaccination and onset of symptoms of cerebral venous thrombosis was 9 days in patients with VITT and 11 days in those without VITT. The formers were younger (mean age 47 versus 57), had a greater number of intracranial vein thrombosis and more frequently had extracranial thrombosis (44% versus 4%).

Of the 75 patients found thrombocytopenic on platelet counts, seven were negative for anti-PF4 antibodies on the ELISA test.

The outcome of death or dependency following the event occurred more frequently in patients with cerebral venous thrombosis associated with VITT (47% versus 16%). These events were attenuated with the administration of non-heparin anticoagulants or intravenous immunoglobulins.

VITT-associated cerebral venous thrombosis has a worse clinical picture

The merit of this study is that of provide precise and complete information on the clinical and laboratory characteristics of patients with cerebral venous thrombosis following a vaccination for COVID-19.

As noted by the same authors, the United Kingdom’s policy of vaccinating older patients first may have distorted the results of the study somewhat, which thus refer to a population made up mostly of subjects in this age group. On the other hand, the youngest subjects were those who most frequently manifested a VITT.

Perhaps the most important element emerging from this research is that patients with cerebral venous thrombosis associated with VITT had a worse clinical picture, with more extensive venous thrombosis, higher rates of multiple heart attacks, multiple intracerebral hemorrhages and extracranial thrombosis. VITT was eventually associated with significantly more deaths or dependency at the end of hospitalization.

This study also provided some useful guidance regarding the treatment of patients with cerebral venous thrombosis. In fact, it emerged that the most effective drugs were non-heparin anticoagulants and immunoglobulins administered intravenously.

Finally, the observations collected in the study prompt the authors to propose new diagnostic criteria for cerebral venous thrombosis associated with VITT. According to these criteria, a diagnosis of probable VITT can be made in patients with a normal platelet count (≥150 × 109/L), a normal D-dimer or a negative anti-PF4 antibody test, provided that other evidence strongly supports the diagnosis. (See below).

All valuable information, useful for adequately managing the rare cases of cerebral venous thrombosis that occur after the administration of some COVID-19 vaccines.

This post is also available in: Chinese (Simplified)

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