Case Presentation: A previously healthy 57-year-old man with a history of chronic sinusitis who received the Ad26.COV2.S vaccination 13 days ago without incident presented to the ED with left lower extremity swelling and pain, left medial thigh ecchymosis, transient episodes of right hand paresthesia and weakness, severe headache with transient blurry vision, and progressively worsening dyspnea with minimal exertion. Symptoms began the day after endoscopic sinus surgery with septoplasty, turbinate reduction was completed 5 days ago. The initial evaluation at another hospital showed normal hemoglobin, platelets at 6 x 10^3/µL, and D-dimer at 114,166 ng/mL FEU. SARS-CoV-2 RNA was not detected on RT-PCR assay. Imaging studies showed left lower extremity deep venous thrombosis, bilateral pulmonary embolism, left frontoparietal subarachnoid hemorrhage and bilateral lacunar cerebellar infarcts. Dexamethasone 40 mg IV and 10 mg orally and 3 units of platelets were administered prior to transfer to our Neuroscience Intensive Care Unit.The timing of the Ad26.COV2.S vaccine, thrombocytopenia, and further workup including extensive occlusive thrombus throughout the superior sagittal sinus and positive PF4 ELISA were consistent with a diagnosis of thrombosis and thrombocytopenia syndrome (TTS). Starting on hospital day (HD) two, treatment included a non-heparin anticoagulation bivalirudin (HD2-5), methylprednisolone 1g (HD2-4), plasma exchange once to remove circulating antibodies (HD2), and intravenous immune immunoglobin 1 g/kg (HD2-3). By HD5, the platelet count normalized to 176 x 10^3/µL, and anti-PF4 ELISA was downtrending. A prednisone taper starting at 40mg was initiated, and bivalirudin was switched to rivaroxaban. By HD8, the patient was stable without further bleeding events, with resolution of headaches and focal deficits, and ultimately discharged. At 3-month follow-up in hematology clinic, patient remained symptom free, platelets were stable at 186 x 10^3/µL, and anti-PF4 ELISA was negative at 0.19 OD. Patient remains on therapeutic rivaroxaban to be reassessed at his six-month follow-up.

Discussion: As of May 7, 2021 in the United States, 28 cases of TTS following Ad26.COV2.S vaccination (22 female, 6 male) have been reported out of 8,739,657 total shots given, 19 of which had CVST. Our case is the first case report of a male with TTS and CVST following Ad26.COV2.S vaccination and the only case of TSS after surgery. Early recognition and prompt management is the key to improved patient outcomes. Severe, recurrent, or persistent symptoms including intense headache, abdominal and back pain, nausea and vomiting, vision and mental status changes, shortness of breath, leg pain and swelling, and/or bleeding and petechiae within 4 to 42 days following COVID-19 vaccination should prompt urgent evaluation by a medical provider.

Conclusions: While TTS is a clinically serious and potentially life-threatening condition, the risk is very low, and the benefits outweigh the risks. Continuing to work towards gaining public trust in the safety and efficacy of vaccination in protecting against COVID-19 is still of great importance especially with recent CDC approvals of COVID-19 booster vaccines and Pfizer vaccines for children 5 – 11 years old, continued hospitalizations and deaths, and the persistent burden of the COVID-19 pandemic on our society.

IMAGE 1: Hospitalization Platelet and anti-PF4 ELISA Trends and Treatments