Stimulus Podcast 45 - The Story Behind COVID Vaccines and Brain Blood Clots

The news this week has been replete with stories about increased clot risk in those who have received the AstraZeneca and Johnson & Johnson COVID-19 vaccines. In this episode, we break down: what we know so far about vaccine induced thrombotic thrombocytopenia (VITT), the research that has revealed an underlying mechanism, CDC and NHS recommendations, and a primer on cerebral venous thrombosis -- the primary clot site associated with VITT. We Discuss:   Vaccine induced thrombotic thrombocytopenia (VITT)   The similar mechanism of AstraZeneca's and Johnson & Johnson's COVID-19 vaccines [01:00];   Proposed mechanism of VITT [03:20]; Greinacher, Andreas, et al. "Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination." New England Journal of Medicine (2021). PDF Brief Report: Thrombosis and Thrombocytopenia after ChAdOx1 nCoV-19 Vaccination PDF   Types of clots associated with VITT [04:00];   Below is a breakdown of the first 6 US patients with reported VITT. Note that they all ended up having cerebral venous thrombosis, but half of them had additional clot locations. Image source CDC.   Incidence of VITT in the US and UK [05:00];   A frequent question in the conversation of this newly recognized phenomenon is, "How is this different than the regular background rate of disease? Isn't this consistent with the number of people who would get it anyway?" This CDC graphic suggests not.       In the UK, there have been 79 reported cases of VITT, over half with CVT. Like the US, there is female predominance.   The CDC rallying cry to treat this differently that other causes of cerebral venous thrombosis (CVT) [06:30];   Image source CDC CDC and FDA Statement Here   The Guy and St. Thomas UK algorithm for evaluating and managing patients with suspected VITT [08:00];     Thank you to St. Emlyn’s for posting this doc!   A primer on CVT   Why CVT can cause problems [10:30] Spadaro, Anthony, et al. "Cerebral venous thrombosis: Diagnosis and management in the emergency department setting." The American Journal of Emergency Medicine (2021).   Presenting symptoms of CVT [11:00] Headache is present in 90%, meaning it's common, but also means that 10% won't have headache (at least initially). 25% present with headache alone, but the majority also have another sign or symptom. Image source Spadaro, Anthony, et al. "Cerebral venous thrombosis: Diagnosis and management in the emergency department setting." The American Journal of Emergency Medicine (2021).   Physical exam findings and the sensitivity of papilledema [15:00]   Using D-dimer in the evaluation of CVT [16:50]; Ferro, José M., et al. "European Stroke Organization guideline for the diagnosis and treatment of cerebral venous thrombosis–endorsed by the European Academy of Neurology." European stroke journal 2.3 (2017): 195-221. Tanislav, Christian, et al. "Cerebral vein thrombosis: clinical manifestation and diagnosis." BMC neurology 11.1 (2011): 1-5. A new clinical score for CVT [19:00]; Heldner, Mirjam R., et al. "Prediction of cerebral venous thrombosis with a new clinical score and D-dimer levels." Neurology 95.7 (2020): e898-e909. Full Text Image source Spadaro, Anthony, et al. "Cerebral venous thrombosis: Diagnosis and management in the emergency department setting." The American Journal of Emergency Medicine (2021). Utility of spinal tap as a rule out test [21:00];     Imaging options (CT venogram vs MR venogram) [22:00];     CDC treatment recommendations for VITT associated CVT and how it’s different than most other CVT’s [25:00]; CDC full slide deck Here   Testing patients with VITT for heparin-PF4 antibodies and how that may guide whether or not to use IVIG [26:35].   PF4 HIT antibodies are a common finding in VITT, consistent with the current thinking that VITT is a variant of HIT. Image source CDC CDC recs for testing and IV IG treatment   Refs Padmanabhan, Anand, et al. "IVIg for treatment of severe refractory heparin-induced thrombocytopenia." Chest 152.3 (2017): 478-48