key: cord-1046524-3byij9a5 authors: Yousaf, Zohaib; Ata, Fateen; Mohammed Hammamy, Riyadh Ali title: Thrombosis post-mRNA-based SARS-CoV-2 vaccination (BNT162b2) – Time to think beyond thrombosis with thrombocytopenia syndrome (TTS) date: 2022-04-18 journal: Thrombosis Update DOI: 10.1016/j.tru.2022.100104 sha: b56b28941da2fd6ea4219738bbbc0a90283e83b0 doc_id: 1046524 cord_uid: 3byij9a5 COVID-19 pandemic has affected the global socioeconomic and healthcare infrastructure. Vaccines have been the cornerstone in limiting the global spread of the pandemic. However, the mass scale vaccination has resulted in some unanticipated adverse events. Arguably the most serious of these has been the development of widespread thrombosis with viral-vectored vaccines. We present a case of extensive thrombosis associated with the messenger RNA (m-RNA) vaccine. Vaccination against SARS-CoV-2 is arguably the single most effective preventive strategy 35 against COVID-19 [1] . With the short time to development and unprecedented scale of vaccination, one 36 of the reasons behind vaccine hesitancy is the lack of knowledge regarding the safety and side effects of 37 the vaccine [2] . Arguably, the single adverse effect that has produced widespread hysteria and led to a 38 temporary halt of vaccinations in certain countries is thrombosis associated with the viral vectored 39 `vaccines AZD1222/ ChAdOx1 nCoV-19 and Ad26.COV2.S [3] [4] [5] . This phenomenon was initially 40 labeled as "vaccine-induced pro-thrombotic immune thrombocytopenia (VIPIT)" or "vaccine-induced 41 immune thrombotic thrombocytopenia (VITT)" [6] . The CDC and FDA recently renamed it as 42 "thrombosis with thrombocytopenia syndrome (TTS)" [7] . 43 Even though thrombosis is commonly reported in association with the viral vectored vaccines, the 44 phenomenon is rare with mRNA vaccines. Thromboembolism has been observed with all mainstream 45 mRNA vaccines including mRNA-1273, BNT162b2, and AZD1222 COVID-19 Vaccines [8] . We report 46 a middle-aged lady with no risk factors or history of thrombosis, who presented with extensive lower limb 47 superficial and deep thrombosis. 48 49 A 57-year-old non-smoker Filipino lady with a history of dyslipidemia presented with the first 51 episode of progressive severe left leg pain, erythema, and swelling for two weeks. She received 52 amoxicillin/clavulanate from primary care 11 days before presentation for suspected cellulitis, but the 53 symptoms progressed. Relevant history of recent travel, trauma, surgery, prolonged immobilization, use 54 of hormonal medications, or oral contraceptives was negative. Family or personal history of thrombosis, 55 malignancy, a pro-thrombotic state, or bleeding diathesis was negative. Age-appropriate malignancy 56 screen including PAP-smear, mammogram, and fecal immunochemical test was negative. She received 57 the second dose of BNT162b2 three weeks before this presentation. 58 Upon presentation, her blood pressure was 145/88, not tachycardiac (70 beats/min), not 59 tachypneic (19/min), afebrile (37.3C), and maintaining saturation on room air. The examination was 60 normal except for an erythematous, tender, hot, and swollen left lower limb with the left calf 3cm larger 61 than the right. Complete blood count, peripheral smear, electrolyte panel, renal function test, liver 62 function tests, and coagulation profile, were normal except a D-dimer above the detection range of assay 63 i.e., >35. The patient did well during her hospital stay and received subcutaneous therapeutic enoxaparin for 2 days 79 followed by Rivaroxaban. Three months later the patient was followed up in medicine clinic. He was 80 asymptomatic and his thrombophilia workup (normal protein C and S, negative for antithrombin and 81 factor V Leiden mutation) did not reveal any coagulation disorder. As the patient was low risk for 82 bleeding, the plan was made to continue anticoagulation for 6 months and to decide on lifelong 83 anticoagulation versus discontinuation at 6-month follow-up visit (which is still due). 84 85 86 Thrombosis associated with COVID-19 vaccination is a major concern with the recent mass 88 allergic or anaphylactoid reaction [11] . Another case of Kounis syndrome associated with inactivated 103 SARS-CoV-2 vaccine (CoronaVac, Sinovac Life Sciences, Beijing, China) is reported [49] . The lower 104 limb DVT postsecond dose of vaccination reported by Carli G et al. was not as extensive as reported in 105 our case, and superficial veins were not involved. The authors report successful management of the DVT 106 using direct oral anticoagulants (DOAC), albeit a different one from the case we present; apixaban vs. 107 Rivaroxaban, respectively [12] . 108 Of interest is that most of the adverse reactions to AZD1222 were reported after the first dose 109 vaccination in vaccine-associated-myocarditis [50] . This is in keeping with the trend of side effects 120 associated with BNT162b2 being common post-second dose [51] . A similar mechanism may be 121 implicated for thrombosis associated with BNT162b2. As the mechanism seems to be different from TTS 122 as reported with AZD 1222, these patients may still be able to take heparin formulations safely, as we did 123 in our case, without any bleeding complications. 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publication of this article was funded by Qatar National Library.Financial support and sponsorship: No funding was acquired for this paper.