Embolic and thrombotic events after COVID-19 vaccination
Post-vaccination embolic and thrombotic events, termed vaccine-induced immune thrombotic thrombocytopenia (VITT),[1][2][3][4][5] vaccine-induced prothrombotic immune thrombocytopenia (VIPIT),[6] thrombosis with thrombocytopenia syndrome (TTS),[7][4][5] vaccine-induced immune thrombocytopenia and thrombosis (VITT),[5] or vaccine-associated thrombotic thrombocytopenia (VATT),[5] are rare types of blood clotting syndromes that were initially observed in a number of people who had previously received the Oxford–AstraZeneca COVID‑19 vaccine (AZD1222)[a] during the COVID‑19 pandemic.[6][12] It was subsequently also described in the Janssen COVID‑19 vaccine (Johnson & Johnson), leading to the suspension of its use until its safety had been reassessed.[13] On 5 May 2022 the FDA posted a bulletin limiting the use of the Janssen Vaccine to very specific cases due to further reassessment of the risks of TTS, although the FDA also stated in the same bulletin that the benefits of the vaccine outweigh the risks.[14]
"VITT" redirects here. For other uses, see VITT (disambiguation).In April 2021, AstraZeneca and the European Medicines Agency (EMA) updated their information for healthcare professionals about AZD1222, saying it is "considered plausible" that there is a causal relationship between the vaccination and the occurrence of thrombosis in combination with thrombocytopenia and that, "although such adverse reactions are very rare, they exceeded what would be expected in the general population".[12][15][16][17]
Signs and symptoms[edit]
The thrombosis events associated with the COVID‑19 vaccine may occur 4–28 days after its administration and mainly affects women under 55.[6][2][18] Several relatively unusual types of thrombosis were specifically reported to be occurring in those with the reaction: cerebral venous sinus thrombosis and thrombosis of the splanchnic veins.[19][20] Cerebral venous sinus thrombosis may cause severe headache, stroke-like symptoms (weakness of a limb and/or facial muscles), seizures and coma.[21] Splanchnic vein thrombosis may cause abdominal pain, accumulation of fluid in the abdominal cavity, and gastrointestinal bleeding.[22][23]
Other forms of thrombosis, such as the more common pulmonary embolism, may also occur. Arterial thrombosis has also been reported.[24] The low platelet count may manifest as petechia (tiny blood spots under the skin) beyond the site of the injection.[19]
Disseminated intravascular coagulation (DIC), diffuse formation of blood clots throughout the blood vessels of the body, has been reported as part of the syndrome.[25] DIC may cause a range of symptoms, including abnormal bleeding, breathlessness, chest pain, neurological symptoms, low blood pressure, or swelling.[26]
COVID‑19 vaccines have some adverse effects that are listed as common in the two or three days following vaccination which are usually mild and temporary.[19]
Causes[edit]
The rare simultaneous occurrence of thrombocytopenia (low blood platelets) with blood clots after vaccination raised the original concern about this condition. In many cases where acute thrombosis and thrombocytopenia have been found together after COVID‑19 vaccination, an antibody against platelet factor 4 has been identified.[1] This phenomenon is mostly encountered in some people who have been administered heparin, but none of the reported cases had received heparin.[1] More rarely, this phenomenon had previously been described as an autoimmune phenomenon in people who had not been exposed to heparin.[27] One striking feature of thrombocytopenia in the presence of anti-PF4 antibodies is the propensity of some to develop thrombosis, a phenomenon called heparin-induced thrombocytopenia if heparin is involved.[28]
Thrombocytopenia is generally a common symptom after or during many viral infections,[29] and it "has been consistently reported" after intravenous administration of adenoviral gene transfer vectors,[30] although its mechanisms are not yet clear.
There is no confirmed causal link to the syndrome and any COVID‑19 vaccination, however EMA is conducting investigations into AZD1222 and the Janssen COVID‑19 vaccine (Johnson & Johnson) for possible causal links.[31]
On 7 April 2021, the EMA noted one "plausible explanation" for the combination of blood clots and low blood platelets is "an immune response, leading to a condition similar to one seen sometimes in people treated with heparin", that is heparin induced thrombocytopenia (HIT).[19]
Diagnosis[edit]
In the United Kingdom, professional societies led by the Royal College of Emergency Medicine have issued a guideline for suspected cases. Someone presenting with concerning symptoms between five and 28 days after administration of the vaccine is assessed for a possible thrombotic complication, with a full blood count (which includes a platelet count) as the initial investigation. If the platelet count is decreased, determination of the D-dimer and fibrinogen levels may be performed, with hematology expert advice recommended if these are elevated above specific cut offs.[24]
Management[edit]
Guidelines from professional societies recommend treatment with alternative anticoagulants instead of heparin, as there is a possibility that it may aggravate the phenomenon.[32][33] Alternative options as the directly acting oral anticoagulants (DOACs), argatroban, fondaparinux or danaparoid depending on the circumstances.[32] Platelet transfusion is discouraged, as this too may aggravate thrombosis.[32] UK guidelines by the British Society for Haematology recommend the administration of intravenous immunoglobulin (IVIG) to reduce levels of the pathogenic antibody.[32] Low fibrinogen levels may require correction with fibrinogen concentrate or cryoprecipitate.[32]
History[edit]
Organizations[edit]
Global vaccine safety comes under the remit of the World Health Organization (WHO), and in particular its Global Advisory Committee on Vaccine Safety (GAVCS). Other drug regulatory agencies significantly involved include:
Studies[edit]
A study convened by a group of British hematologists on 19 March 2021, just two days after the acknowledgement of the condition, published its finding in The New England Journal of Medicine, establishing case definition criteria. The study included 294 participants who presented with symptoms of thrombocytopenia and thrombosis after receipt of the first dose of the Oxford–AstraZeneca COVID‑19 vaccine, showing an independent association between baseline platelet count and the presence of intracranial hemorrhage. The study established that 85% of the participants effected by the condition were aged younger than 60 years, and that those participants with a history of thrombosis or prothrombotic disorders did not appear to be at increased risk. The study showed an overall mortality rate of 22% and set out plans for additional research to determine the genetic factors that may increase risk of the condition and identify potential therapeutic agents.[58]