key: cord-0740974-5xynxxpm authors: Serrao, Alessandra; Agrippino, Roberta; Brescini, Mattia; Mormile, Rosaria; Chistolini, Antonio title: Thromboembolic events following mRNA vaccines for COVID 19: a case series date: 2022-02-03 journal: J Thromb Thrombolysis DOI: 10.1007/s11239-021-02627-9 sha: 38f0fe98ba582dbf0c238e3561b2f4df61f9b146 doc_id: 740974 cord_uid: 5xynxxpm nan and 22 days respectively from the administration of Spikevax 1273. The VTE onset was documented either after the first (n = 9) or the second dose (n = 6) of vaccine. Among the BNT162b2 vaccinated population, 7 patients (63.6%) experimented thrombosis after the first dose and 4 (36.4%) after receiving the second dose. Among the Spikevax 1273 vaccinated population, 2 experimented thrombosis after the first dose and 2 after the second one. Overall, we observed 10/15 deep-vein thrombosis (DVT), in two cases complicated by pulmonary embolism and in a single case involving the cerebral circle (transverse and sigmoid sinus). In the other 5/15 cases a superficial-vein thrombosis (SVT) was documented, affecting the lower limbs (n = 2) or the upper limbs (n = 2); one case among these latter was associated to pulmonary embolism (PE). The different sites affected by thrombosis are specified in Table 1 . All patients denied familiar history of VTE, trauma, recent surgery. They were investigated to exclude solid or hematologic malignancy and for the presence of congenital and acquired thrombophilia. Overall, 3/15 patients (20%) had no pro-thrombotic risk factors. Conversely, 3 patients were on treatment with estroprogestinic therapy, respectively from 5, 6 and 8 years; one of them also exhibited the presence of prothrombin G20210A heterozygous. Two other patients reported a previous history of superficial venous thrombosis (SVT). In 2 patients elevated homocysteine levels were detected (41 and 50 µmol/L). In a single case there was a mild congenital thrombophilia (factor V Leiden heterozygous). In another single case there was a previous diagnosis of essential thrombocythemia (ET), not requiring treatment, and thoracic outlet syndrome (TOS). Two patients presented a chronic venous disease one associated to obesity; one patient had smoking habit. Regarding the treatment administered for VTE, 10/15 patients who presented DVT/EP received low molecular weight heparin (LMWH) or fondaparinux and subsequently oral anticoagulation: 8 were treated with apixaban, 1 patient with rivaroxaban, 1 with dabigatran. The patient affected by cerebral venous thrombosis was treated with the vitamin K antagonist, warfarin. The others 4/15 patients, who presented SVT, were treated with fondaparinux or EBPM for 45 days. The patient who presented EP and SVT of the arm was treated with LMWH and subsequently apixaban. Moreover, among patients who experienced thrombosis after the first dose of the vaccine, 5/9 did not complete the scheduled vaccination with the second dose because of patient's decision. Conversely, 4/9 patients (44.4%) received the second dose with the same type of vaccine during anticoagulant therapy and after a median time of 61 days (range 14-111 days) from the onset of thrombosis. Importantly, none of them experienced recurrence of thrombosis nor worsening of the clinical status. None of the patients required hospitalization. It is known that thromboembolic events are part of the clinical manifestations of COVID-19 [12] and even if rare, VTE could complicate the administration of vaccines. This is particularly true for the ChAdOx1 n COV-19 vaccine [3] . Regarding the mRna vaccines, there are few reported cases of venous thrombosis including those of the cerebral district [9, 10] . Their incidence is lower than expected and the current evidences do not suggest a causal relationship. We described our single centre experience of 15 patients presenting VTE after the administration of BNT162b2 vaccine or Spikevax 1273 vaccine. Although temporal relationship suggests that the vaccine may have caused thrombotic events, it could be coincidental as some patients presented additional risk factors for thrombosis. For instance, 1 patient had a history of ET and congenital TOS. In 2 patients we found a mild congenital thrombophilia; in 2 cases we found high levels of homocysteinemia. Three patients were on estroprogestinic treatment for many years. It is not possible to document a clear association between these thromboembolic events and the mRNA vaccines. There is the probability that these events may correspond to a normal incidence of VTE among general population. Even though the temporal linkage between the thromboembolic complications and anti-COVID vaccination is strongly suggestive for a correlation, [13] . Interestingly, no recurrence of thrombosis occurred after the second dose administration in patient who experimented VTE after the first vaccination. The thromboembolic complications do not represent a contraindication to complete the vaccination cycle; indeed, many our patients completed the vaccination scheduled. The vaccination for SARS-Cov-2 is essential to overcome the pandemic, therefore it is important to continue to be vigilant for possible complications emerging during the campaign. Sistematic safety monitoring of COVID-19 vaccines is essential to ensure that benefits are superior to risks. A longer follow up is needed to clarify and to document this relationship between VTE and mRNA vaccines. The limitations of this study include the monocentric and retrospective nature that can't permit to calculate the real incidence of thromboembolic complications in the vaccinated population compared to the general population. Author contributions A.S. analyzed the data and parteciped in the writing the manuscript; M.B. collected and analyzed the data; R.M. performed laboratory tests; A.C. analyzed, supervised and interpreted the data and wrote the manuscript. Funding Funding is not applicable. The data are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. 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