Atypical hemolytic uremic syndrome; generalized abdominal; night sweats; Chills; cola-colored urine; Acute distress; hyperbilirubinemia; esophageal dysmotility; hiatal hernia; stenosis at the gastroesophageal junction; acute kidney injury; thrombotic thrombocytopenic purpura; mild antral gastritis; Thrombocytopenia; hemolytic anemia; This case was reported in a literature article and described the occurrence of atypical hemolytic uremic syndrome in a 30-year-old male patient who received Flu unspecified (Influenza vaccine) for prophylaxis.   The patient's past medical history included cholecystectomy, biliary dyskinesia, grand mal seizure (Family History) (in a brother), leukemia (Family History) (in uncle) and loose stools (had intermittent loose stools after cholecystectomy three months ago before presentation). Concurrent medical conditions included anxiety, depression, alcohol use (drinking four to five beers a day), dysphagia (started suddenly, mainly with solids), abstains from recreational drugs (denied use of illicit drugs ) and nonsmoker (denied smoking). Concomitant products included LIVE ATTENUATED INFLUENZA VIRUS VACCINE (LIVE ATTENUATED INFLUENZA VACCINE) and escitalopram (Lexapro).   On an unknown date, the patient received Influenza vaccine (intramuscular). On an unknown date, less than a week after receiving Influenza vaccine, the patient experienced atypical hemolytic uremic syndrome (serious criteria hospitalization and GSK medically significant), abdominal discomfort (serious criteria hospitalization), night sweat (serious criteria hospitalization), chills (serious criteria hospitalization), urine discoloration (serious criteria hospitalization), emotional distress (serious criteria hospitalization), hyperbilirubinemia (serious criteria hospitalization and GSK medically significant), dyskinesia of esophagus (serious criteria hospitalization), hiatal hernia (serious criteria hospitalization), gi tract stenosis any site (serious criteria hospitalization and GSK medically significant), acute kidney injury (serious criteria hospitalization and GSK medically significant), thrombotic thrombocytopenic purpura (serious criteria hospitalization and GSK medically significant), antral gastritis (serious criteria hospitalization), thrombocytopenia (serious criteria hospitalization and GSK medically significant) and hemolytic anemia (serious criteria hospitalization and GSK medically significant). The patient was treated with intravenous fluid (nos) (Intravenous Fluids), prednisone, platelets, human blood (Platelet), red blood cells, concentrated (Packed Rbc), meningococcal vaccines (nos) (Meningococcal Vaccine), phenoxymethylpenicillin potassium (Penicillin Vk), eculizumab and operations and procedures (Plasmapheresis (Nos)). On an unknown date, the outcome of the atypical hemolytic uremic syndrome, abdominal discomfort, night sweat, chills, urine discoloration, emotional distress, hyperbilirubinemia, dyskinesia of esophagus, hiatal hernia, gi tract stenosis any site, acute kidney injury, thrombotic thrombocytopenic purpura and antral gastritis were unknown and the outcome of the thrombocytopenia and hemolytic anemia were recovering/resolving.   The reporter considered the atypical hemolytic uremic syndrome, abdominal discomfort, night sweat, chills, urine discoloration, emotional distress, hyperbilirubinemia, dyskinesia of esophagus, hiatal hernia, gi tract stenosis any site, acute kidney injury, thrombotic thrombocytopenic purpura, antral gastritis, thrombocytopenia and hemolytic anemia to be related to Influenza vaccine.     Additional Information: GSK receipt date: 04-MAY-2022 Author comment: The patient's past medical and surgical history include anxiety, depression, daily alcohol use and biliary dyskinesia with cholecystectomy in July 2020, respectively. The patient was drinking four to five beers a day and denied smoking and illicit drug use. Family history was positive for grand mal seizure in a brother and leukemia in an uncle. Of note, the patient had previously received an intranasal live attenuated influenza vaccine. Three days after receiving intramuscular influenza vaccination, the patent was directly admitted to the hospital from a walk-in clinic due to dysphagia which he experienced for last five days. The patient developed generalized abdominal discomfort, night sweats, chills, and cola-colored urine for two to three days before hospitalization. The patient denied nausea, vomiting, fever, dizziness, or any other symptoms. The patient was only taking Lexapro 10 mg daily before hospitalization. On physical examination, the patient's vitals were temperature 99.3 degrees Fahrenheit, blood pressure 143/90 mmHg, heart rate 90 beats per minute, respiratory rate 17 per minute, and oxygen saturation 96% on room air. The patient was awake, alert, oriented, and in acute distress. The patient's pupils were equal bilaterally and reactive, extraocular movements were normal. There was no jugular venous distention. Heart sounds were normal. Lungs were clear to auscultation. The abdomen was soft, non-tender, and non-distended. Bowel sounds were normal. The genitourinary exam was unremarkable. There was no peripheral edema and the neurologic exam was also unremarkable. There were no petechiae or ecchymoses. The patient's abnormal labs tests included Hb 13.1 gm/dl, platelets 26 K/ul, sodium 135 mmol/l, creatinine (Cr) 2 mg/dl, BUN 51 mg/dl, AST 103 U/l, total bilirubin 4.9 mg/dl, indirect bilirubin 2.4 mg/dl, phosphorus 4.7 mg/dl, and LDH 5797 U/l. Urinalysis and microscopy showed moderate blood with only five red blood cells (RBC) per high power field (HPF). Urine myoglobin was 1260 mcg/L. Urine protein was also elevated more than 500 mg/dl. Urine toxicology was negative. The patients' corrected reticulocyte count was not significantly elevated (1.1%) with an absolute reticulocyte count of 57.6 k/ul. The coronavirus disease 2019 (COVID-19) test came back negative. Peripheral smear demonstrated one to two schistocytes per HPF. Abdominal ultrasound was done due to hyperbilirubinemia and elevated AST, which showed no acute abnormalities. Esophagram done due to dysphagia showed esophageal dysmotility, hiatal hernia, and stenosis at the gastroesophageal junction. Endoscopy was not done initially due to the low platelet count. The patient was started on IV fluids for acute kidney injury. Workup for hemolytic anemia was ordered by a hematologist. The patient's haptoglobin came back low (28 mg/dL). As the coagulation panel and fibrinogen were normal, disseminated intravascular coagulation was ruled out. Vitamin B12 and folate were normal. Autoimmune panels including antinuclear antibody (ANA) and anti-citrullinated antibody (anti-CCP) were negative, as was Coombs' test. HUS was ruled out, as the stool culture was negative. Acute infection of Epstein Barr virus, Cytomegalovirus, human immunodeficiency virus, and hepatitis was negative. To rule out malignancy, computed tomography of the chest, abdomen, and pelvis was done; it was also negative for acute abnormality. Non-tunneled hemodialysis catheter was placed for plasmapheresis. Plasmapheresis and prednisone 1 mg/kg were started for suspected thrombotic thrombocytopenic purpura (TTP) while ADAMTS13 protein was pending. The patient's hemoglobin and platelets continued to downtrend even though the patient was started on plasmapheresis. One unit of platelets was transfused when platelets were 6 K/ul, leading to an increase in platelet count. The patient was transfused packed red blood cell (PRBC) when hemoglobin down trended to 6 g/dl. The patient's ADAMTS13 came back normal. Also, complement CH50, C3, and C4 were normal. Hence, aHUS seemed more likely at this point. The patient was given meningococcal vaccine and started on penicillin VK for prophylaxis along with eculizumab for the treatment of aHUS. The eculizumab dose recommended by the hematologist was 900 mg weekly for four weeks and from Week 5, a maintenance dose of 1200 mg every other week. Plasmapheresis and steroids were discontinued. Platelet count and hemoglobin started improving after eculizumab therapy. Once platelet counts improved, upper endoscopy was done for questionable stricture on esophagogram, which showed mild antral gastritis, no stricture or mass was seen. As Hb, platelets, Cr, AST, and bilirubin continued to improve, the patient was discharged home with outpatient follow-up with a hematologist. Genetic analysis was performed as an outpatient; the patient was found to have a heterozygous mutation in membrane complex protein (MCP)/CD46, putting him at high risk of developing aHUS, which was likely triggered by influenza vaccination as other causes were ruled out. Eculizumab was continued. The patient had normal Cr, BUN, AST, bilirubin, platelets, and LDH and improved hemoglobin on the most recent labs. "Influenza A H1N1, seasonal influenza A with or without streptococcal pneumonia co-infection, and influenza B are known to be associated with aHUS. Neuraminidases play a central role in secondary HUS caused by influenza A and streptococcal pneumonia by cleaving sialic acid from glycoproteins on cell surface leading to the unmasking of Thomsen-Friedenreich antigen. Influenza A and B may trigger aHUS in a similar manner. Neuraminidase in influenza vaccine can trigger aHUS in susceptible patients, as in ours with MCP/CD46 deficiency." The authors concluded, "Influenza A and B are known triggers of aHUS in patients with complement deficiency, but the influenza vaccine is rare. Further studies may be needed to stratify such patients to weigh the risks and benefits of influenza vaccination". Additional supportive information: This article corresponding to this case is not available for regulatory submission due to copyright restriction.