VACCINE INDUCED IMMUNE THROMBOTIC THROMBOCYTOPENIA; THROMBOCYTOPENIA; NON-OCCLUSIVE THROMBI IN THE LEFT DISTAL POPLITEAL VEIN AND PERONEAL VEIN; This spontaneous report was received from literature: Ad26.COV2.S vaccination presenting without radiographically demonstrable thrombosis. BLOOD ADVANCES. This report concerned a 32 year old male of unspecified race and ethnic origin. The objective of this study was to describe VITT following Ad26.COV2.S vaccination presenting without radiographically demonstrable thrombosis. The patient's height, and weight were not reported. No past medical history or concurrent conditions were reported. The patient received covid-19 vaccine ad26.cov2.s (suspension for injection, route of administration not reported, batch number: unknown) 1 total, start therapy date were not reported for prophylactic vaccination. The batch number was not reported and has been requested. No concomitant medications were reported. Eight days after receiving the covid-19 vaccine ad26.cov2.s, the patient developed left leg pain, erythema, and gravity-dependent venous distention. Three days later, he was presented to an urgent care center. A lower extremity ultrasound was negative for deep venous thrombosis and a complete blood count (CBC) showed thrombocytopenia with a platelet count of 61 x 10*9 /L. Due to the unexplained thrombocytopenia, he returned the following day. A repeat CBC showed a platelet count of 52 x 10*9 /L that remained unexplained. The next day, he was presented to an emergency department with worsening leg pain. He was otherwise asymptomatic post-vaccination. He reported left leg pain regardless of position, and physical examination revealed left leg venous distention and erythema upon standing. When asked about COVID vaccine status, he reported that he had not previously been asked. Laboratory evaluation demonstrated worsening thrombocytopenia with a platelet count of 43 x 10*9 /L, elevated prothrombin time of 16.3 seconds (INR 1.4), elevated activated partial thromboplastin time of 35 seconds, decreased fibrinogen of 110 mg/dL, and markedly elevated D-dimer of greater than 14,000 ng/mL. A lower extremity ultrasound was again negative for thrombosis from the proximal femoral vein to the ankle. Chest/abdomen/pelvis computed tomography with contrast demonstrated no thrombosis. Brain magnetic resonance imaging revealed patent sinuses without thrombosis. VITT (Vaccine-induced Immune Thrombotic Thrombocytopenia) was suspected given his vaccination history, symptoms, and laboratory findings. He was admitted and started on 1 g/kg of Intravenous immune globulin (IVIG) daily for two days to increase his platelet count and given 1 mg/kg of prednisone. The following day his pain worsened. Despite lack of radiographically-demonstrable thrombosis, anticoagulation with argatroban was started. Later that day, the enzyme-linked immunosorbent assay (ELISA) for anti-PF4 antibodies were drawn the day prior which returned strongly positive at 2.79 optical-density (OD) units (normal, less than or equal to 0.40) in the absence of added heparin; The assay was negative in the presence of high-dose heparin (100 U/mL). The confirmatory washed-platelet heparin-induced platelet activation assay was positive. His platelets rose quickly in response to the IVIG allowing the doctors to start anticoagulation. Within 24 hours of starting argatroban, his pain began to improve. Given persistent venous distention, a repeat lower extremity ultrasound was performed that demonstrated reflux throughout the deep veins and the greater saphenous vein from the saphenofemoral junction to the mid-calf. The exam also identified non-occlusive thrombi in the left distal popliteal vein and peroneal vein, which were not present on admission. Over the next few days the platelets rose steadily, D-dimers fell precipitously, and he was transitioned from argatroban to apixaban. On the 6th hospital day, repeat anti-PF4 ELISA remained positive (OD 2.68) in the absence of added heparin; negative in the presence of high dose heparin (100U/mL). The confirmatory washed-platelet heparin induced platelet activation assay was negative at the time of reporting. On the 7th hospital day, he was discharged home. Seven days after discharge, the anti-PF4 ELISA remained positive (OD 2.32), the washed platelet heparin induced platelet activation assay remained negative, and his INR, Activated partial thromboplastin time, fibrinogen, platelet count and D-dimer had normalized. The action taken with covid-19 vaccine ad26.cov2.s was not applicable. The outcome of the vaccine induced immune thrombotic thrombocytopenia, thrombocytopenia and non-occlusive thrombi in the left distal popliteal vein and peroneal vein was not reported. The author suggested that early VITT recognition and immediate treatment initiation provides a window of opportunity wherein non-heparin-based anticoagulation may prevent serious thrombotic complications. Study also highlighted the critical importance of knowing COVID-19 vaccine history. The author emphasized on timely recognition that would be essential to prevent catastrophic complications and will require knowing the patient's vaccine history. This report was serious (Hospitalization Caused / Prolonged, and Other Medically Important Condition).; Sender's Comments: V0: 20211004121-covid-19 vaccine ad26.cov2.s-Vaccine induced immune thrombotic thrombocytopenia, thrombocytopenia and non-occlusive thrombi in the left distal popliteal vein and peroneal vein. This event(s) is labeled per RA and is therefore considered potentially related.