Age: 26.0
Sex: M
Vaccine: COVID19
Symptoms: ADAMTS13 activity assay, ADAMTS13 inhibitor screen assay, Blood bilirubin, Blood creatinine, Blood lactate dehydrogenase
Clinical narrative: Status epilepticus; thrombotic thrombocytopenic purpura; encephalopathy; COVID-19 infection; This literature-non-study case was reported in a literature article and describes the occurrence of STATUS EPILEPTICUS (Status epilepticus), THROMBOTIC THROMBOCYTOPENIC PURPURA (thrombotic thrombocytopenic purpura), ENCEPHALOPATHY (encephalopathy) and COVID-19 (COVID-19 infection) in a 26-year-old male patient who received mRNA-1273 (Spikevax) for COVID-19 prophylaxis.   LITERATURE REFERENCE:     No Medical History information was reported.    On an unknown date, the patient received first dose of mRNA-1273 (Spikevax) (unknown route) 1 dosage form. On an unknown date, the patient experienced STATUS EPILEPTICUS (Status epilepticus) (seriousness criteria hospitalization, medically significant and life threatening), THROMBOTIC THROMBOCYTOPENIC PURPURA (thrombotic thrombocytopenic purpura) (seriousness criteria hospitalization and medically significant), ENCEPHALOPATHY (encephalopathy) (seriousness criteria hospitalization and medically significant) and COVID-19 (COVID-19 infection) (seriousness criterion hospitalization). The patient was treated with RITUXIMAB at a dose of 1 dosage form, weekly; CAPLACIZUMAB at a dose of 1 dosage form; FOLIC ACID at a dose of 1 dosage form and PREDNISONE at a dose of 1 dosage form. At the time of the report, STATUS EPILEPTICUS (Status epilepticus), THROMBOTIC THROMBOCYTOPENIC PURPURA (thrombotic thrombocytopenic purpura) and ENCEPHALOPATHY (encephalopathy) was resolving and COVID-19 (COVID-19 infection) had resolved. Related    DIAGNOSTIC RESULTS (normal ranges are provided in parenthesis if available): On an unknown date, ADAMTS13 activity assay (0.65-1.78): It was reported on day 3, ADAMTS13 activity was less than 0.03 IU/mL and It was reported on day 24 Rituxan third dose was started and  ADAMTS13 activity was 0.9 IU/mL. On an unknown date, ADAMTS13 inhibitor screen assay: It was reported that ADAMTS13 inhibitor levels was 4 on Day-3. Reference value was provided: undetectable Bethesda units. and It was reported on day 24, Rituxan third dose was started and ADAMTS13 inhibitor levels were undetectable. On an unknown date, Blood bilirubin (0.1-1.2 mg/dl): 1.2 mg/dl It was reported on day-3, bilirubin level was 1.2 mg/dl, 2 mg/dl It was reported on day 9, Cablivi was initiated daily and bilirubin level was 2 mg/dL, 1.4 mg/dl It was reported on day 10, Rituxan was initiated weekly and bilirubin level was 1.4 mg/dL., 0.8 mg/dl It was reported on Day 17, Rituxan second dose was initiated and bilirubin level was 0.8 mg/dL, 1.0 mg/dl It  was reported on day 37, patient was  discharge and the bilirubin level was 1 mg/dL, 1.3 mg/dl First outpatient follow-up with hematology (1-week post-discharge) was done and the bilirubin level was 1.3 mg/dL, 0.9 mg/dl Second outpatient follow up with hematology (monthly visit) was done and the bilirubin level was 0.9 mg/dL and 0.9 mg/dl Third outpatient follow-up with hematology (monthly visit) was done and the bilirubin level was 0.9 mg/dL. On an unknown date, Blood creatinine (0.7-1.3 mg/dl): 1.7 mg/dl It was reported on day 0, plasmapheresis and glucocorticoids were initiated and creatinine level was 1.7 mg/dL., 4.68 mg/dl It was reported on Day-2, creatinine level  was 4.68 mg/dL, 5.58 mg/dl It was reported on day-3, creatinine level was 5.58 mg/dL, 6.71 mg/dl It was reported on day 9, Cablivi initiated daily and creatinine was  6.71 mg/dL, 7.41 mg/dl It was reported on day 10,Rituxan initiated weekly and creatinine was 7.41 mg/dL, 6.44 mg/dl It was reported on day 17, Rituxan 2nd dose was initiated and creatinine was 6.44 mg/dL., 4.08 mg/dl It was reported on day 24,Rituxan 3rd dose was initiated and creatinine was 4.08 mg/dL, 2.96 mg/dl It was reported on day 31, Rituxan 4th dose was initiated and creatinine was 2.96 mg/dL, 1.63 mg/dl It was reported on Day 37, patient was discharge and creatinine was 1.63  mg/dL, 2.0 mg/dl First outpatient follow-up with hematology (1-week post-discharge) was done  and creatinine was 2.0 mg/dL, 0.9 mg/dl Second outpatient follow up with hematology (monthly visit) was done and creatinine was 0.9 mg/dL and 1 mg/dl Third outpatient follow-up with hematology (monthly visit) was done and creatinine was 1 mg/dL. On an unknown date, Blood lactate dehydrogenase (105-333): It was reported on day 0, plasmapheresis and glucocorticoids were initiated and LDH was 2836 IU/L., It was reported on day-2, LDH was 875 IU/L, It was reported on day-3, LDH was  587 IU/L, It was reported on day 9,Cablivi initiated daily and LDH was 596 IU/L, It was reported on day 10,Rituxan Initiated weekly and LDH was 372 IU/L, It was reported on day 17,Rituxan 2nd dose initiated and LDH was  300 IU/L, It was reported on day 24,Rituxan 3rd dose initiated and LDH was 184 IU/L, It was reported on day 31,Rituxan 4th dose was initiated and LDH was 237 IU/L, It was reported on day 37, patient was discharge and LDH was 299 IU/L, First outpatient follow-up with hematology (1-week post-discharge)was done and LDH was 440 IU/L, Second outpatient follow up with hematology (monthly visit) was done and LDH was 303 IU/L and Third outpatient follow-up with hematology (monthly visit) was done and LDH was 326 IU/L. On an unknown date, Blood smear test: It was reported that Peripheral blood smear with Leishman stain showed anisopoikilocytosis, nucleated RBCs, severe thrombocytopenia, and schistocytes. Image captured  under 1000x magnification.. On an unknown date, Blood thromboplastin (11-13.5 Second): 14.4 Second It was reported on day 0, plasmapheresis and glucocorticoids were initiated and PT was 14.4 sec., 13.8 Second It was reported on day-2 and PT was 13.8 sec, 13.9 Second It was reported on day 3 and PT was  13.9 sec, 12.7 Second It was reported on day 31, Rituxan 4th dose was initiated and PT was  12.7 sec, 11.1 Second It was reported on day 37, patient was discharge and PT was  11.1 sec, 37.7 Second It was reported on day 0, plasmapheresis and glucocorticoids were initiated and PTT was 37.7 sec. and 30.4 Second It was reported on Day 31, Rituxan 4th dose was initiated and PTT was 30.4 sec. On an unknown date, Chest X-ray: Chest X-ray (anteroposterior view) demonstrated that right-side pulmonary infiltration which causes patchy airspace disease predominantly in the right lung.. On an unknown date, Computerised tomogram head: It was reported that CT of the head was performed at another hospital and found to be unremarkable.. On an unknown date, Coombs test: (Negative) It was reported on day 10, Rituxan initiated weekly and Coombs C3 was Negative. Reference value was Negative., (Negative) It was reported on Day 17, Rituxan 2nd dose was initiated and coombs C3 was negative. Reference value provided: Negative, (Negative) It was reported on Day 9, Cabliv  was initiated daily and coombs C3 was negative. Reference value provided: Negative, (Negative) It was reported on Day 10, Rituxan  was initiated  weekly  and coombs C3 was negative. Reference value provided: Negative  . and (Negative) It was reported on Day 17, Rituxan 2nd dose was initiated   and coombs C3 was negative. Reference value provided: Negative. On an unknown date, Haematocrit (41-50 %): 18.3 % It was reported on day 0, plasmapheresis and glucocorticoids were initiated and hematocrit was 18.3%., 25.9 % It was reported on day-2 and hematocrit was  25.9%, 26.8 % It was reported on day-3 and hematocrit was 26.8%., 29.9 % It was reported on day 9,Cablivi  initiated daily and hematocrit was 29.9%, 27.3 % It was reported on day 10, Rituxan Initiated weekly and hematocrit was  27.3%, 24.2 % It was reported on day 17,Rituxan 2nd dose was initiated and hematocrit was 24.2 %, 18.2 % It was reported on day 24,Rituxan 3rd dose was initiated and hematocrit was 18.2%, 20.4 % It was reported on day 31, Rituxan 4th dose was initiated and hematocrit was 20.4%, 26.7 % It was reported on day 37, patient was discharge and hematocrit was 6.7%, 41 % First outpatient follow-up with hematology (1-week post-discharge) and hematocrit was 41%., 34.4 % Second outpatient follow up with hematology (monthly visit) and hematocrit was 34.4% and 36.4 % Third outpatient follow-up with hematology (monthly visit) and hematocrit was 36.4 %. On an unknown date, Haemoglobin (13.2-16.6): It was reported on day 0, plasmapheresis and glucocorticoids were initiated and hemoglobin was 6.4 g/dL., It was reported on day-2 and hemoglobin was  8.8 g/dL, It was reported on day-3 and hemoglobin was 9.2 g/dL, It was reported on day 9, Cablivi initiated daily and hemoglobin was 10 g/dL, It was reported on day 10, Rituxan Initiated weekly and hemoglobin was 9 g/dL, It was reported on day 17, Rituxan 2nd dose was initiated and hemoglobin was 8.2 g/dL, It was reported on day 24, Rituxan 3rd dose was initiated and hemoglobin was 6.3 g/dL, It was reported on day 31, Rituxan 4th dose was initiated and hemoglobin was 7 g/dL, It was reported on day 37, Patient was  discharge and Hemoglobin was 9.3  g/dL, First outpatient follow-up with hematology (1-week post-discharge) and  hemoglobin was 13.4 g/dL., Second outpatient follow up with hematology (monthly visit) and hemoglobin was 11.5 g/dL and Third outpatient follow-up with hematology (monthly visit) and hemoglobin was 12.2 g/dL. On an unknown date, Haptoglobin: It was reported on day 37, patient was discharge and Hepatoglobin was less than 30 mg/dl and 37.7 mg/dl It was reported on day 0, plasmapheresis and glucocorticoids were initiated and haptoglobin was 37.7 mg/dl.. On an unknown date, International normalised ratio: It was reported on day 0, plasmapheresis and glucocorticoids were initiated and INR was 1.2., It was reported on day-2 and INR was 1.1, It was reported on day-3  and INR was  1.1, It was reported on day 31, Rituxan 4th dose was initiated and INR was 1 and It was reported on day 37, patient was discharge and INR was 0.9. On an unknown date, Magnetic resonance imaging head: MRI of the brain without contrast at T2-weighted sequence demonstrating "halos" pointed which were thought to be microbleeds with ongoing MAHA.. On an unknown date, Physical examination: Scleral icterus, multiple petechiae, and hematuria were evident upon physical exam. On an unknown date, Platelet count (150000-450000): It was reported on day 0, plasmapheresis and glucocorticoids were initiated and platelets was 15/uL, It was reported on day-2 and platelets was found  30/uL, It was reported on day-3 and platelets was 48/uL, It was reported on Day 9, Cablivi initiated daily and Platelets was 116/uL, It was reported on Day 10, Rituxan Initiated weekly and Platelet was 111/uL, It was reported on day 17, Rituxan 2nd dose  initiated and platelet was  90/uL, It was reported on day 24,Rituxan 3rd dose initiated and platelet was  70/uL, It was reported on day 31, Rituxan 4th dose initiated and platelets was  70/uL, It was reported on day 37, patient was discharge and platelet was 137/uL, First outpatient follow-up with hematology (1-week post-discharge)  and platelet was 199/uL, Second outpatient follow up with hematology (monthly visit) and platelet was 154/uL and Third outpatient follow-up with hematology (monthly visit) and platelet was 161/uL. On an unknown date, Reticulocyte count (0.5-2.5 %): 13.16 % It was reported on day 0, plasmapheresis and glucocorticoids were initiated and reticulocyte count was 13.6%., 8.76 % It was reported on day-2, reticulocyte count was  8.76 %, 9.21 % It was reported on day-3, Reticulocyte count was  9.21 %, 1.54 % It was reported on day 31, Rituxan 4th dose initiated and Reticulocyte count was 1.54 %, 1.46 % It was reported on day 37,patient was  discharge and Reticulocyte count was 1.46 % and 2.5 % Second outpatient follow up with hematology (monthly visit)  and reticulocyte count was 2.5 %.     The action taken with mRNA-1273 (Spikevax) (Unknown) was unknown.   For mRNA-1273 (Spikevax) (Unknown), the reporter considered STATUS EPILEPTICUS (Status epilepticus), THROMBOTIC THROMBOCYTOPENIC PURPURA (thrombotic thrombocytopenic purpura), ENCEPHALOPATHY (encephalopathy) and COVID-19 (COVID-19 infection) to be related.    Patient had no significant past medical history who presented with fever, AKI, severe thrombocytopenia, seizures, and acute hemolytic anemia. It was reported that higher dose IV steroids along with rituximab are used as an adjunct to plasma exchange. It was reported that patient was successfully treated by multiple cycles of plasmapheresis procedure. At the time of presentation to the hospital, the patient was intubated, unresponsive, and subsequently transferred to the critical care unit (CCU) due to concerns for status epilepticus.  Patient had completely recovered from a prior COVID-19 infection three weeks before the current hospital visit and was discharged home with a short course of antibiotics after one day's stay at another facility. The patient had improvement in encephalopathy by day five. However, lactate dehydrogenase was high and platelet counts were still low after five days of admission. It was stated, platelet counts started improving by day nine with the use of caplacizumab, as would be expected since caplacizumab works on decreasing the interaction between multimers and platelets glycoproteins.  The patient was discharged home with folic acid supplementation, tapering dose prednisone, and caplacizumab with close follow-up with hematology and oncology with regular monitoring of laboratory studies. It was reported, patient initially developed seizures after playing a video game approximately one day prior to admission in hospital.  Laboratory studies revealed severe thrombocytopenia and anemia with hemolysis. Hemodialysis was done as a treatment for thrombotic thrombocytopenic purpura.   No concomitant medications was reported.  This literature non-study case concerns a 26-year-old female patient with no reported medical history, who experienced the unexpected serious (caused hospitalization, medically significant) AESIs of Status epilepticus (also life threatening), Thrombotic thrombocytopenic purpura (TTP), unexpected serious (caused hospitalization) event of Encephalopathy (also medically significant) and COVID-19 (AESI) which occurred approximately 7 months after receiving a dose of mRNA-1273 vaccine in the covid 19 vaccination series. Patient was diagnosed with COVID 19 and stayed for a short course of antibiotics for 1 day at a health care facility and was completely recovered. 3 weeks later patient developed seizures (status epilepticus) that were unresponsive to antiepileptics, was intubated and was transferred to higher facility. Laboratory studies revealed severe thrombocytopenia and anemia with hemolysis and a probable diagnosis of TTP was made. Patient was started on plasma exchange and high dose steroids. Due to worsening renal function and oliguria, hemodialysis was initiated. ADAMTS13 activity was undetectable and ADAMTS13 inhibitor levels were elevated. Rituximab was then started and caplacizumab was added due to high-risk features. The patient had improvement in encephalopathy by day five. Hemodialysis was stopped as renal function normalized. Then plasma exchange was stopped as his platelet counts continued to improve. The patient was discharged home with folic acid supplementation, tapering dose prednisone, and caplacizumab with close follow-up. The benefit-risk relationship of mRNA-1273 is not affected by this report.; Sender's Comments: This literature non-study case concerns a 26-year-old female patient with no reported medical history, who experienced the unexpected serious (caused hospitalization, medically significant) AESIs of Status epilepticus (also life threatening), Thrombotic thrombocytopenic purpura (TTP), unexpected serious (caused hospitalization) event of Encephalopathy (also medically significant) and COVID-19 (AESI) which occurred approximately 7 months after receiving a dose of mRNA-1273 vaccine in the covid 19 vaccination series. Patient was diagnosed with COVID 19 and stayed for a short course of antibiotics for 1 day at a health care facility and was completely recovered. 3 weeks later patient developed seizures (status epilepticus) that were unresponsive to antiepileptics, was intubated and was transferred to higher facility. Laboratory studies revealed severe thrombocytopenia and anemia with hemolysis and a probable diagnosis of TTP was made. Patient was started on plasma exchange and high dose steroids. Due to worsening renal function and oliguria, hemodialysis was initiated. ADAMTS13 activity was undetectable and ADAMTS13 inhibitor levels were elevated. Rituximab was then started and caplacizumab was added due to high-risk features. The patient had improvement in encephalopathy by day five. Hemodialysis was stopped as renal function normalized. Then plasma exchange was stopped as his platelet counts continued to improve. The patient was discharged home with folic acid supplementation, tapering dose prednisone, and caplacizumab with close follow-up. The benefit-risk relationship of mRNA-1273 is not affected by this report.