A new study of patients who suffered blood clots in the brain following Covid-19 vaccination provides data to help clinicians diagnose and treat this rare but dangerous condition.

The study, initiated by Keele’s Professor Christine Roffe, describes the symptoms and outcomes of the first UK cases of cerebral venous thrombosis with vaccine-induced immune thrombotic thrombocytopenia (VITT).

VITT is characterised by platelets, key elements of the body’s clotting system, clumping together. This leads to blockage of blood flow in the veins and bleeding risk due to a lack of platelets available for normal clotting processes. The most common and severe manifestation of VITT is cerebral venous thrombosis, in which veins draining blood from the brain become blocked leading to severe congestion and very high pressure in the brain.

The new study, published in The Lancet, provides the most detailed observational study of such cases so far, in which 70 patients with VITT-associated cerebral venous thrombosis following vaccination were compared to 25 with cerebral venous thrombosis without evidence of VITT.

The authors found that anticoagulation with non-heparin anticoagulants and intravenous immunoglobulin were associated with better outcomes, but, as the study was not randomized other variables cannot be excluded.

The NHS’s success with the vaccination programme makes the UK a very good place to study rare side-effects of Covid-19 vaccination. The authors started collecting their cases within a few weeks of the discovery of this new condition and submitted their report within two months of it being reported in the medical literature.

VITT-associated cerebral venous thrombosis has a very high mortality rate. Even without VITT, cerebral venous thrombosis is a serious medical condition, with around 4% of patients dying during their hospital admission. In the patients with VITT-associated cerebral venous thrombosis in this study mortality was around seven times higher than that at 29%.

This poorer outcome is explained at least in part because the abnormal blockage of veins is much more extensive in this condition, with more veins blocked both in the head and elsewhere in the body.

Although VITT-associated cerebral venous thrombosis is a severe condition, it appears to be extremely rare and the authors stress that, for most individuals, the risk to their health of not getting vaccinated against Covid-19 is much higher.

The study also supports the three principles of treating cerebral venous thrombosis established so far by the Expert Haematology Panel, based on early work at UCLH and two other European sites:

• The use of non-heparin-based anticoagulation
• Giving treatments such as immunoglobulin to try to reduce the level of the abnormal antibody that is implicated in this condition, and
• Avoiding giving platelet transfusions.

Senior author Christine Roffe, Professor of Stroke Medicine at Keele University, said: “Although there are sound theoretical reasons supporting the adoption of these treatment strategies, until now there has been no clinical evidence for their use. In our study, non-heparin blood thinners and intravenous immunoglobulin were both associated with better patient outcomes, providing the first clinical evidence from a large case series in support of these treatments.”

Lead author Dr Richard Perry, a consultant neurologist at the National Hospital for Neurology and Neurosurgery said: “With an illness of such severity, often in young patients who were previously fit and well, doctors have been desperate for evidence regarding treatments that might prevent some of the death and disability that arises from this condition.

“While an observational study is not the ideal platform to provide evidence for which medications work, it may be a long time before we have evidence from randomised clinical trials, the gold standard for testing new treatments. For the moment we are dependent on observational studies like CAIAC for our evidence.”