Age: 58.0
Sex: M
Vaccine: COVID19
Symptoms: Hepatitis B antibody, Hepatitis C antibody, Inappropriate schedule of product administration, Influenza virus test, International normalised ratio
Clinical narrative: Ventricular fibrillation; Cardiac arrest; Acquired thrombotic thrombocytopenic purpura; Respiratory failure; Acute kidney injury; altered mental status; Patient was administered second dose of moderna vaccine 3 weeks after first dose; This literature-non-study case was reported in a literature article and describes the occurrence of VENTRICULAR FIBRILLATION (Ventricular fibrillation), CARDIAC ARREST (Cardiac arrest), THROMBOTIC THROMBOCYTOPENIC PURPURA (Acquired thrombotic thrombocytopenic purpura), RESPIRATORY FAILURE (Respiratory failure), ACUTE KIDNEY INJURY (Acute kidney injury) and ALTERED STATE OF CONSCIOUSNESS (altered mental status) in a 58-year-old male patient who received mRNA-1273 (Spikevax) for COVID-19 prophylaxis. The occurrence of additional non-serious events is detailed below.        The patient's past medical history included Antiretroviral therapy (to treat Human immunodeficiency virus (HIV) infection) since an unknown date. Concurrent medical conditions included Hypertension, Morbid obesity and HIV infection. Concomitant products included DOLUTEGRAVIR, LOPINAVIR and RITONAVIR for HIV infection.   On an unknown date, the patient received second dose of mRNA-1273 (Spikevax) (unknown route) 1 dosage form. On an unknown date, received first dose of mRNA-1273 (Spikevax) (unknown route) dosage was changed to 1 dosage form. On an unknown date, the patient experienced VENTRICULAR FIBRILLATION (Ventricular fibrillation) (seriousness criteria death, hospitalization and medically significant), CARDIAC ARREST (Cardiac arrest) (seriousness criteria death, hospitalization and medically significant), THROMBOTIC THROMBOCYTOPENIC PURPURA (Acquired thrombotic thrombocytopenic purpura) (seriousness criteria hospitalization and medically significant), RESPIRATORY FAILURE (Respiratory failure) (seriousness criteria hospitalization and medically significant), ACUTE KIDNEY INJURY (Acute kidney injury) (seriousness criteria hospitalization and medically significant), ALTERED STATE OF CONSCIOUSNESS (altered mental status) (seriousness criteria hospitalization and medically significant) and INAPPROPRIATE SCHEDULE OF PRODUCT ADMINISTRATION (Patient was administered second dose of moderna vaccine 3 weeks after first dose). The patient was treated with DEXAMETHASONE (intravenous) at a dose of 10 milligram twice a day. The patient died on an unknown date. The reported cause of death was Ventricular fibrillation and Cardiac arrest. An autopsy was not performed. At the time of death, THROMBOTIC THROMBOCYTOPENIC PURPURA (Acquired thrombotic thrombocytopenic purpura), RESPIRATORY FAILURE (Respiratory failure), ACUTE KIDNEY INJURY (Acute kidney injury), ALTERED STATE OF CONSCIOUSNESS (altered mental status) and INAPPROPRIATE SCHEDULE OF PRODUCT ADMINISTRATION (Patient was administered second dose of moderna vaccine 3 weeks after first dose) outcome was unknown.      DIAGNOSTIC RESULTS (normal ranges are provided in parenthesis if available): On an unknown date, ADAMTS13 activity assay (66.8-Unknown): less than 2.8% and (Positive) 48 unit/ml, elevated ADAMTS13 antibodies confirmed diagnosis of thrombotic thrombocytopenic purpura. On an unknown date, Activated partial thromboplastin time (21.3-35.1): 27.4 Second. On an unknown date, Alanine aminotransferase (0-44): 21 U/L. On an unknown date, Anti-cyclic citrullinated peptide antibody: Negative. On an unknown date, Antibody test: Negative. On an unknown date, Antinuclear antibody: Negative, Negative, Negative, Negative and Negative. On an unknown date, Antiribosomal P antibody: Negative. On an unknown date, Aspartate aminotransferase (0-44): 38 U/L. On an unknown date, Bacterial test: (Negative) rare. On an unknown date, Blood HIV RNA (Unknown-20): Less than 20. On an unknown date, Blood bilirubin (0.3-1.1): 4.7 g/dL. On an unknown date, Blood creatine phosphokinase (30-223): 110 U/L. On an unknown date, Blood creatinine (0.74-1.35): 1.62 mg/dl. On an unknown date, Blood culture: Negative. On an unknown date, Blood fibrinogen (183-510): 512 mg/dl. On an unknown date, Blood lactate dehydrogenase (140-271): 936 U/L. On an unknown date, Blood urea (6-24): 28 mg/dl. On an unknown date, Blood urine present: large. On an unknown date, CD4 lymphocytes (359-1519): 500 per microlitre on time of presentation and 506 per microlitre four months prior to presentation. On an unknown date, CD8 lymphocytes (109-897): 340 per microlitre. On an unknown date, Cold agglutinins: Negative. On an unknown date, Coombs direct test: Negative. On an unknown date, Cryptococcus test: Negative. On an unknown date, Culture urine: Negative. On an unknown date, Cytomegalovirus test: Negative. On an unknown date, Double stranded DNA antibody: Negative. On an unknown date, Drug screen: Negative. On an unknown date, Epstein-Barr virus antibody: Negative. On an unknown date, Fibrin D dimer (Unknown-0.5): 1.56 microgram per millilitre. On an unknown date, Haemoglobin (13.5-17.5): 13.4 g/dL. On an unknown date, Haptoglobin (30-200): Less than 10 mg/dl. On an unknown date, Hepatitis A antibody: Negative. On an unknown date, Hepatitis B antibody: Negative. On an unknown date, Hepatitis C antibody: Negative. On an unknown date, Influenza virus test: Negative and (Negative) Parainfluenza was negative. On an unknown date, International normalised ratio: 1.0. Normal reference- Critical greater than 4.0. On an unknown date, Legionella test: Negative. On an unknown date, Mean cell volume (80.0-100.0): 93 fL. On an unknown date, Mycoplasma test: (Negative) Mycoplasma Pneumoniae was negative. On an unknown date, Nitrite urine: Negative. On an unknown date, Parvovirus B19 test: Negative. On an unknown date, Physical examination: was unremarkable except for non-painful ecchymosis in the antecubital fossa of his right arm. On an unknown date, Platelet count (140-440): 5 thousand per cubic millimetre on presentation, 170 thousand per cubic millimetre 3 month before presentation and 12 thousand per cubic millimetre. On an unknown date, Prothrombin time (12.2-14.9): 13.2 Second. On an unknown date, Red blood cell count (4.33-5.83): 4.26 thousand per cubic millimetre. On an unknown date, Red blood cells urine (0-3): Greater than 100 cells per cubic millimetre. On an unknown date, Red cell distribution width (11.5-16.5): 13.2 %. On an unknown date, Respiratory syncytial virus test: Negative. On an unknown date, Reticulocyte count (0.5-2.0): 2.61 %. On an unknown date, SARS-CoV-2 test: Negative. On an unknown date, Smear test: on initial presentation peripheral smear is revealing thrombocytopenia, decreased lymphocytes, few schistocytes, target cells, few reticulocytes and Peripheral smear within hours later from presentation revealing markedly abnormal cells including thrombocytopenia, lymphopenia, target cells, and abundant schistocytes. On an unknown date, Staphylococcus test: Negative. On an unknown date, Troponin (3-23): 209 pg/ml and 7229 pg/ml. On an unknown date, Troponin I: Increased. On an unknown date, Urine analysis: Color/appearance: Amber/ cloudy. Normal reference- Clear yellow. On an unknown date, Urine leukocyte esterase: Negative. On an unknown date, White blood cell count (4.5-11): 5.2 thousand per cubic millimetre. On an unknown date, White blood cells urine (0-3): 6-10 cells/mm3.     For mRNA-1273 (Spikevax) (Unknown), the reporter did not provide any causality assessments.   The patient was sent to the emergency room by his primary care physician. The patient complained of significant fatigue, non-traumatic bruises on his right arm, and persistent dark colored urine. Patient denied any other active muco-cutaneous bleeding or lesions, headache, confusion, dizziness, recent nausea, vomiting, diarrhea, upper or lower respiratory symptoms, or neurological deficits. He denied any recent changes in medications, recent antibiotic, or herbal supplements use. Patient received the 1st dose of the Moderna vaccine 6 weeks prior to presentation, followed by the 2nd dose of the same vaccine 3 weeks later without any complications. Precise platelet count when he received the 1st and 2nd doses of the vaccine is unknown. In the ER, patient was afebrile, and hemodynamically stable.  Patient also had acute kidney injury and hematuria. Patient had a high PLASMIC score of 6, thrombotic thrombocytopenic purpura (TTP) was considered the working diagnosis. Laboratory results were suggestive for microangiopathic hemolyticanemia (MAHA).  The patient was started on temporary resuscitation measures while preparing for therapeutic plasma exchange (TPE). He received two units of plasma (approximately 10 to 15 mL/kg), in addition to Dexamethasone, and planned to transition to methylprednisolone 80 mg IV q8h in the following day. He was also initiated on mechanical venous thromboembolism prophylaxis given his severe thrombocytopenia and the active bleeding. CT scans of the head, chest, abdomen and pelvis were done to rule out any possibility of active internal bleeding and/or any source of infection.  Unfortunately, within the subsequent 12 hours before initiating TPE, the patient quickly decompensated with rapidly rising troponin-I, and developed altered mental status, and respiratory failure. Eventually, patient went into ventricular fibrillation and cardiac arrest. Full resuscitative measures were implemented with no return of spontaneous circulation.  Company Comment  This literature non-study case concerns a 58 year-old, male patient with  history of hypertension, morbid obesity, and human immunodeficiency virus (HIV) infection on HAART (highly active antiretroviral therapy), complaint with his medication and with stable CD4 count(506) reported, who experienced the serious (fatal/medically significant/hospitalization) unexpected events of Ventricular fibrillation(AESI) and Cardiac arrest, serious (medically significant/hospitalization) unexpected events of Thrombotic thrombocytopenic purpura(AESI), Acute kidney injury(AESI), Respiratory failure , Altered state of consciousness about 3 weeks after the second dose of mRNA-1273 vaccination. Patient was referred by his primary care physician for platelet count of 12×10^3/mm3, with complaints of significant fatigue, non-traumatic bruises on his right arm, and persistent dark colored urine. He denied any other active muco-cutaneous bleeding or lesions, headache, confusion, dizziness, recent nausea, vomiting, diarrhea, upper or lower respiratory symptoms, or neurological deficits, no prior history of TTP, no past covid-19 infection, no recent changes with medications. Patient had received first dose of mRNA-1273 vaccine 6 weeks prior to presentation, followed by the second dose of the same vaccine 3 weeks later, so Inappropriate schedule of product administration was noted. Patient's average platelet count (PLT) was stable three months before presentation. In the ER, he was afebrile with stable hemodynamics, unremarkable physical examination except for non-painful ecchymosis in the antecubital fossa of his right arm. Admission labs were significant for normocytic anemia with marked thrombocytopenia 5 (x10^3/mm3) and elevated absolute reticulocyte count 2.61% indicating adequate bone marrow response. He also had acute kidney injury 1.62 mg/dL and hematuria. His peripheral smear demonstrated schistocytes (>2-3/HPF). Further laboratory results were suggestive for microangiopathic hemolytic anemia (MAHA) with negative direct Coombs test and disseminated intravascular coagulopathy (DIC). No evidence of acute infection (including opportunistic infections in HIV) was noted clinically or on laboratory testing. Viral/bacterial studies were negative. He had undetectable HIV viral load with stable, high CD4 to CD8 ratio. Given his high PLASMC score of 6, thrombotic thrombocytopenic purpura (TTP) was considered the working diagnosis. Patient was started on temporary resuscitation measures while preparing for therapeutic plasma exchange (TPE). He received two units of plasma (approximately 10 to 15 mL/kg), in addition to Dexamethasone 10 mg intravenously twice daily, and planned to transition to methylprednisolone 80 mg IV q8h in the following day. He was also initiated on mechanical venous thromboembolism prophylaxis given his severe thrombocytopenia and the active bleeding. Further laboratories had definitely ruled out an active source of infection, underlying Systemic auto-immune diseases (SAID). Computed tomography scans of the head, chest, abdomen and pelvis were done to rule out any possibility of active internal bleeding or any source of infection.  Finally, ADAMTS13 activity was reported to be low less than 2.8%, with positive elevated ADAMTS13 antibodies 48 unit/mL which confirmed the diagnosis. Unfortunately, within the subsequent 12 hours before initiating TPE, patient quickly decompensated with rapidly rising troponin-I, and developed altered mental status, and respiratory failure. Eventually, he went into ventricular fibrillation and cardiac arrest. Full resuscitative measures were implemented with no return of spontaneous circulation. Cause of death was considered as ventricular fibrillation and cardiac arrest. Date of death was not available. No autopsy was performed on the patient. Author concludes that given the high mortality rates of TTP with delayed adequate treatment, the criteria for presumptive diagnosis only rely on thrombocytopenia with active hemolysis, in the absence of an obvious alternative cause, as in this case. Although the exact pathophysiology is still in question, one theory suggests it`s secondary to immune complex mediated or direct cytokine mediated endothelial injury. The benefit-risk relationship of mRNA-1273 vaccine is not affected by this report.   Most recent FOLLOW-UP information incorporated above includes: On 08-Dec-2022: Live follow up received by safety on 09-Dec-2022 has Email with full text article received contains significant information: Reporter information, literature information, patient details, medical history, laboratory tests, product details, concomitant, treatment medications, event, seriousness and narrative were updated.; Sender's Comments: This literature non-study case concerns a 58 year-old, male patient with  history of hypertension, morbid obesity, and human immunodeficiency virus (HIV) infection on HAART (highly active antiretroviral therapy), complaint with his medication and with stable CD4 count(506) reported, who experienced the serious (fatal/medically significant/hospitalization) unexpected events of Ventricular fibrillation(AESI) and Cardiac arrest, serious (medically significant/hospitalization) unexpected events of Thrombotic thrombocytopenic purpura(AESI), Acute kidney injury(AESI), Respiratory failure , Altered state of consciousness about 3 weeks after the second dose of mRNA-1273 vaccination. Patient was referred by his primary care physician for platelet count of 12×10^3/mm3, with complaints of significant fatigue, non-traumatic bruises on his right arm, and persistent dark colored urine. He denied any other active muco-cutaneous bleeding or lesions, headache, confusion, dizziness, recent nausea, vomiting, diarrhea, upper or lower respiratory symptoms, or neurological deficits, no prior history of TTP, no past covid-19 infection, no recent changes with medications. Patient had received first dose of mRNA-1273 vaccine 6 weeks prior to presentation, followed by the second dose of the same vaccine 3 weeks later, so Inappropriate schedule of product administration was noted. Patient's average platelet count (PLT) was stable three months before presentation. In the ER, he was afebrile with stable hemodynamics, unremarkable physical examination except for non-painful ecchymosis in the antecubital fossa of his right arm. Admission labs were significant for normocytic anemia with marked thrombocytopenia 5 (x10^3/mm3) and elevated absolute reticulocyte count 2.61% indicating adequate bone marrow response. He also had acute kidney injury 1.62 mg/dL and hematuria. His peripheral smear demonstrated schistocytes (>2-3/HPF). Further laboratory results were suggestive for microangiopathic hemolytic anemia (MAHA) with negative direct Coombs test and disseminated intravascular coagulopathy (DIC). No evidence of acute infection (including opportunistic infections in HIV) was noted clinically or on laboratory testing. Viral/bacterial studies were negative. He had undetectable HIV viral load with stable, high CD4 to CD8 ratio. Given his high PLASMC score of 6, thrombotic thrombocytopenic purpura (TTP) was considered the working diagnosis. Patient was started on temporary resuscitation measures while preparing for therapeutic plasma exchange (TPE). He received two units of plasma (approximately 10 to 15 mL/kg), in addition to Dexamethasone 10 mg intravenously twice daily, and planned to transition to methylprednisolone 80 mg IV q8h in the following day. He was also initiated on mechanical venous thromboembolism prophylaxis given his severe thrombocytopenia and the active bleeding. Further laboratories had definitely ruled out an active source of infection, underlying Systemic auto-immune diseases (SAID). Computed tomography scans of the head, chest, abdomen and pelvis were done to rule out any possibility of active internal bleeding or any source of infection.  Finally, ADAMTS13 activity was reported to be low less than 2.8%, with positive elevated ADAMTS13 antibodies 48 unit/mL which confirmed the diagnosis. Unfortunately, within the subsequent 12 hours before initiating TPE, patient quickly decompensated with rapidly rising troponin-I, and developed altered mental status, and respiratory failure. Eventually, he went into ventricular fibrillation and cardiac arrest. Full resuscitative measures were implemented with no return of spontaneous circulation. Cause of death was considered as ventricular fibrillation and cardiac arrest. Date of death was not available. No autopsy was performed on the patient. Author concludes that given the high mortality rates of TTP with delayed adequate treatment, the criteria for presumptive diagnosis only rely on thrombocytopenia with active hemolysis, in the absence of an obvious alternative cause, as in this case. Although the exact pathophysiology is still in question, one theory suggests it`s secondary to immune complex mediated or direct cytokine mediated endothelial injury. The benefit-risk relationship of mRNA-1273 vaccine is not affected by this report.; Reported Cause(s) of Death: Ventricular fibrillation; Cardiac arrest