THROMBOTIC THROMBOCYTOPENIC PURPURA; This spontaneous report was received from literature: This report concerned a 50 year old female. The objective of this study to discuss a case of thrombotic thrombocytopenic purpura (TTP) that developed after vaccination with Ad26.COV2.S COVID vaccine. The patient's height, and weight were not reported. The patient's concurrent conditions included: type 2 diabetes mellitus, hypertension, chronic obstructive pulmonary disease, and bipolar disorder, and other pre-existing medical conditions included: The patient had poly-substance use disorder including cocaine use. The patient received covid-19 vaccine ad26.cov2.s (suspension for injection, unknown, batch number: unknown, expiry: unknown) dose was not reported, 1 total, start therapy date were not reported for covid-19 prophylaxis. The batch number was not reported. Per procedure, no follow-up will be requested for this case. No concomitant medications were reported.  On an unspecified date, after a week of vaccination the patient presented to the emergency department with a two-day history of shortness of breath/dyspnea. Patient denied fevers, chills, nausea, cough, sputum production, chest pain, palpitations, leg swelling or pain, bleeding, bruising, hematuria, rash, headaches, and focal weakness. She did not have any other medical conditions. Physical examination showed normal vital signs, mild-respiratory distress, and normal breath sounds, and abdominal examination was unremarkable. Clinical suspicion for infections was low as she was hemodynamically stable and a focus of infection was identified. Peripheral Blood smear test showed schistocytes. The patient's presentation and laboratory findings were consistent with hemolytic anemia. The ultrasound of bilateral lower extremities and CT chest did not show any evidence of thrombosis. The patient was suspected to have thrombotic thrombocytopenic purpura (TTP). The patient's plasmic score (prediction tool for diagnosis and treatment of TTP) was 7 (high), this put the patient at considerable risk for severe ADAMTS13 (a disintegrin-like metalloprotease domain with thrombospondin type 1 motifs) deficiency (less than 15 percent activity level), prompting urgent plasmapheresis. The patient underwent treatment with corticosteroids. The patient received three cycles of plasma exchange along with a dose of rituximab. She also got high-dose steroids in the form of methyl prednisone 125 mg twice a day for five days. The patient's platelet counts slowly started to recover during that time. The patient's ADAMTS 13 level came out to be less than 10 percent with an elevated ADAMTS13 inhibitor level which suggested an acquired cause for the TTP. The patient was discharged after three days of plasma exchange; she was maintained on a steroid taper and followed up with outpatient hematology to complete a total of five rituximab infusions. The number of days of hospitalization was reported as 4 days. Laboratory data (dates unspecified) included: Plasma bilirubin total 1.8 mg/dl (normal range less than 1.2 mg/dl), Blood urea nitrogen (NR: 10 - 25) 17 mg/dL, C-reactive protein 4.9 mg/dl (normal range less than 0.5 mg/dl), Creatinine 0.8 mg/dl (normal range less than 1.03 mg/dl), Bilirubin direct (NR: 0 - 0.3) 0.4 mg/dL, Erythrocyte sedimentation rate (NR: 0 - 20) 78 mm/h, Ferritin (NR: 11 - 307) 603 ng/mL, Fibrin D dimer 9.18 ug/ml (normal range less than 0.5 ug/ml), Haptoglobin (NR: 30 - 300) 30 mg/dL, Hematocrit 20.4 (normal range 36 to 46), Hemoglobin (NR: 12 - 15) 6.5 mg/dL, Lactate dehydrogenase (NR: 100 - 220) 1126 IU/L, Platelet count 11000/ul (normal range 150000 to 450000/ul), Reticular cell count (NR: 0.5 - 1.5) 5.1 percent, and WBC count 9.4 K/ul (normal range 3.8 to 10.6 K/ul). On Day 0 of hospitalization, the platelet count was 10 K/ul, LDH 1129 IU/l, Bilirubin 1.8 mg/dl and fibrinogen was 446 mg/dl. On day 1, the platelet count was 39 K/ul, LDH 741 IU/l, Bilirubin 0.7 mg/dl and fibrinogen was 250 mg/dl. On day 2, the platelet count was 73 K/ul, LDH 401 IU/l, Bilirubin 0.4 mg/dl. On day 3, the platelet count was 126 K/ul, LDH 358 IU/l and Bilirubin 0.4 mg/dl. On day 4, the platelet count was 188 K/ul, LDH 296 IU/l and Bilirubin 0.2 mg/dl.  The action taken with covid-19 vaccine ad26.cov2.s was not applicable. The patient was recovering from thrombotic thrombocytopenic purpura. The authors emphasized that TTP and VITT (vaccine-induced immune thrombocytopenia and thrombosis) are the possible differential diagnosis for a patient presenting with anemia, thrombocytopenia, and markers of hemolysis after vaccination with Ad26.COV2.S. This case provides an understanding of the possibility of having TTP after vaccinations, which may not necessarily be VITT. It is necessary to differentiate these two entities as the management differs significantly. This report was serious (Hospitalization Caused / Prolonged).; Sender's Comments: V0: 20221018533 -covid-19 vaccine ad26.cov2.s-Thrombotic thrombocytopenic purpura. The event(s) has a compatible/suggestive temporal relationship, is unlabeled, and has unknown scientific plausibility. There is no information on any other factors potentially associated with the event(s). Therefore, this event(s) is considered unassessable.