Thrombocytopenia with acute ischemic stroke and bleeding in a patient newly vaccinated with an adenoviral vector‐based COVID‐19 vaccine

Abstract

We describe the first Danish case of presumed inflammatory and thrombotic response to vaccination with an adenoviral (ChAdOx1) vector‐based COVID‐19 vaccine (AZD1222). The case describes a 60‐year‐old woman who was admitted with intractable abdominal pain 7 days after receiving the vaccine. Computed tomography of the abdomen revealed bilateral adrenal hemorrhages. On the following day, she developed a massive right‐sided ischemic stroke and magnetic resonance imaging angiography showed occlusion of the right internal carotid artery. The ischemic area was deemed too large to offer reperfusion therapy. During admission, blood tests showed a remarkable drop in platelet counts from 118,000 to 5000 per μl and a substantial increase in D‐dimer. The patient died on the sixth day of hospitalization. Blood tests revealed platelet factor 4 reactive antibodies, imitating what is seen in heparin‐induced thrombocytopenia. This may be a novel immune‐mediated response to the vaccine.

Arterial events, venous thromboembolism, thrombocytopenia, and bleeding after vaccination with Oxford-AstraZeneca ChAdOx1-S in Denmark and Norway: population based cohort study

“…This is now collectively referred to as vaccine induced thrombotic thrombocytopenia (VITT) or thrombosis with thrombocytopenia syndrome (TTS), with a suggested potential mechanism involving platelet activating antibodies directed against platelet factor 4, which are known to be triggered by heparin and sometimes other environmental factors 33. As of yet, no individual level risk factors for vaccine induced thrombotic thrombocytopenia or thrombosis with thrombocytopenia syndrome have been confirmed,14 with previously reported cases among both, for example, men and women and among users and non-users of hormone therapy 10111213. To the extent that the excess rate of venous thrombosis events reported in this manuscript is associated with vaccine induced thrombotic thrombocytopenia or thrombosis with thrombocytopenia syndrome, our study has insufficient data, and it is not designed to identify subgroups at particular risk, which constitutes an important area for further research 14.…”

“…This is currently under investigation. Reports in the New England Journal of Medicine by now have described three detailed case series of 39 patients (5 in Norway,10 11 in Germany and Austria,11 and 23 in the UK 12) who presented with thrombocytopenia and thrombosis beginning five to 24 days after vaccination with ChAdOx1-S. Another case was reviewed in Denmark 13. Among these 40 patients, 35 (88%) experienced any venous thrombosis, including a high proportion (26 patients, 65%) who experienced cerebral venous thrombosis, whereas 6 (15%) had splanchnic thrombosis and 7 (18%) pulmonary embolism, with multiple embolisms being common.…”

“…The EMA subsequently stated that “The number of thromboembolic events in vaccinated people is no higher than the number seen in the general population.”9 Adverse events might, however, be substantially underestimated if based only on spontaneous adverse event reporting. Moreover, since early March 2021, an increasing number of case reports from Austria, Norway, Denmark, Germany, the United Kingdom, and other countries has suggested a potentially distinct thrombotic syndrome associated with ChAdOx1-S 10111213. These reports have described severe thrombocytopenia, bleeding, arterial thrombosis, and venous thrombosis in unusual anatomical locations (cerebral venous sinus thrombosis, or thrombosis in the portal, splanchnic, or hepatic veins) but also lower limb venous thrombosis or pulmonary embolism in some patients, occurring within five to 24 days after vaccination 14.…”

Untangling the Intricacies of Infection, Thrombosis, Vaccination, and Antiphospholipid Antibodies for COVID-19

“…Nevertheless, the latter authors have rightfully acknowledged the potential for other causes of thrombosis and thrombocytopenia and have urged caution in the nature of investigations required including the search for antiphospholipid syndrome. Many case reports of a similar event among those receiving adenovirus-vectored vaccine have emerged both in media and scientific journals [117][118][119][120][121][122][123][124][125][126][127][128][129][130][131][132]. Typical features include thrombocytopenia, increases in circulating D-dimer, and low fibrinogen levels.…”

Vaccine‐induced immune thrombotic thrombocytopenia: Consider IVIG batch in the treatment

“…beneficial effects of vaccines outweigh the risks associated with vaccination, unusual but life threatening thrombosis and thrombocytopenia, termed as vaccine-induced immune thrombotic thrombocytopenia (VITT) or vaccine-induced prothrombotic immune thrombocytopenia (VIPIT) have been observed in certain individuals who received recombinant adenoviral vector encoding spike protein of SARS-CoV-2 ChAdOx1 nCov-19 (AstraZeneca). [1][2][3][4] Exploration of underlying mechanisms have identified that ChAdOx1 nCov-19 vaccine-induced platelet-activating antibodies against platelet factor 4 (PF4) are responsible for these adverse events. [1][2][3] Based on the in vitro experimental evidence that showed therapeutic potential of intravenous immunoglobulin (IVIG), a pooled normal IgG, in preventing the platelet activation by anti-PF4 antibodies, and also founded on the initial experience with IVIG-treatment in these patients, 1,2 a recent report by Thaler et al 5 Intravenous immunoglobulin is obtained from pooled plasma of several thousand healthy donors.…”