Age: 67.0
Sex: F
Vaccine: COVID19, FLUX, PPV
Symptoms: Cytogenetic analysis, Cytomegalovirus test, Epstein-Barr virus test, Flow cytometry, HIV test
Clinical narrative: Severe aplastic anaemia; Pulsatile tinnitus; This literature-non-study case was reported in a literature article and describes the occurrence of APLASTIC ANAEMIA (Severe aplastic anaemia) in a 67-year-old female patient who received mRNA-1273 (Moderna COVID-19 Vaccine) for COVID-19 prophylaxis. The occurrence of additional non-serious events is detailed below.       Co-suspect products included non-company products PNEUMOCOCCAL VACCINE POLYV (PNEUMOCOCCAL VACCINE POLYVALENT) for an unknown indication and INFLUENZA VACCINE for an unknown indication.    Concurrent medical conditions included Hashimoto's thyroiditis.   On an unknown date, the patient received second dose of mRNA-1273 (Moderna COVID-19 Vaccine) (unknown route) 1 dosage form On an unknown date, received first dose of mRNA-1273 (Moderna COVID-19 Vaccine) (unknown route) dosage was changed to 1 dosage form., dose of PNEUMOCOCCAL VACCINE POLYV (PNEUMOCOCCAL VACCINE POLYVALENT) (unknown route) 1 dosage form and dose of INFLUENZA VACCINE (unknown route) 1 dosage form. On an unknown date, the patient experienced APLASTIC ANAEMIA (Severe aplastic anaemia) (seriousness criteria hospitalization and medically significant) and TINNITUS (Pulsatile tinnitus). The patient was treated with ANTITHYMOCYTE IMMUNOGLOBULIN (HORSE) for Immunosuppression, at an unspecified dose and frequency; CYCLOSPORINE ongoing since an unknown date for Immunosuppression, at an unspecified dose and frequency and ELTROMBOPAG ongoing since an unknown date for Immunosuppression, at an unspecified dose and frequency. At the time of the report, APLASTIC ANAEMIA (Severe aplastic anaemia) and TINNITUS (Pulsatile tinnitus) outcome was unknown.      DIAGNOSTIC RESULTS (normal ranges are provided in parenthesis if available): On an unknown date, Antinuclear antibody: weakly positive(1:80) and (Negative) Negative After 8 months(Approximately). On an unknown date, Biopsy bone marrow: revealed a hypocellular marrow(5%) with severe trilineage hypoplasia with a relative increase in lymphocytes, composed of CD3+ T-cells and CD20+ B-cells forming occasional clusters. CD34 immunostaining highlighted rare (<1%) blasts, with no morphologic or immunophenotypic evidence of myeloid or lymphoid neoplasms.. On an unknown date, Blood folate: Normal After 8 months(Approximately). On an unknown date, Blood iron: Normal After 8 months(Approximately). On an unknown date, Cytogenetic analysis: Normal. On an unknown date, Cytomegalovirus test: Negative After 8 months(Approximately). On an unknown date, Epstein-Barr virus test: Negative After 8 months(Approximately). On an unknown date, Flow cytometry: revealing minor clones in monocyte (0.08%), neutrophil (0.65%), and red blood cell populations (0.02%).. On an unknown date, HIV test: (Negative) Negative After 8 months(Approximately). On an unknown date, Haemoglobin: 11.9 g/dL, 11.9 g/dL Four weeks later (and 6 weeks total after her vaccination sequence), 4.5 g/dL After 8 months(Approximately) and 13 g/dL 2 years before her index presentation. On an unknown date, Hepatitis A virus test: (Negative) Negative. On an unknown date, Hepatitis B virus test: (Negative) Negative and (Negative) Negative After 8 months(Approximately). On an unknown date, Hepatitis C virus test: (Negative) Negative After 8 months(Approximately). On an unknown date, Neutrophil count: 1761 cells per microlitre, 1284 cells per microlitre Four weeks later (and 6 weeks total after her vaccination sequence) and 310 cells per microlitre After 8 months(Approximately). On an unknown date, Parvovirus B19 test: (Negative) Negative After 8 months(Approximately). On an unknown date, Platelet count: 171 thousand per microlitre, 146 thousand per microlitre Four weeks later (and 6 weeks total after her vaccination sequence), 3 thousand per microlitre After 8 months(Approximately) and 343 thousand per microlitre 2 years before her index presentation. On an unknown date, Reticulocyte count: 0.8 % After 8 months(Approximately). On an unknown date, Thyroid function test: Normal. On an unknown date, Vitamin B12: Normal After 8 months(Approximately). On an unknown date, White blood cell count: 3.5 thousand per microlitre, 3.3 thousand per microlitre Four weeks later (and 6 weeks total after her vaccination sequence), 1.8 thousand per microlitre After 8 months(Approximately) and 6.3 thousand per microlitre 2 years before her index presentation.     For mRNA-1273 (Moderna COVID-19 Vaccine) (Unknown), the reporter considered APLASTIC ANAEMIA (Severe aplastic anaemia) and TINNITUS (Pulsatile tinnitus) to be related.    No concomitant medication was reported. Patient developed progressive pancytopenia over 10 months, concomitant with administration of severe adult respiratory syndrome coronavirus-2 , pneumococcal and influenza vaccines.Two weeks after second vaccination, patient was first noted to have mild leukopenia and anaemia on routine laboratory studies. 6 weeks total after vaccination sequence, patient developed further mild reductions in WBC and platelet count, as well as mild neutropenia. Patient had no nutritional deficiencies (vitamin B12, folate). Patient was given a presumed diagnosis of autoimmune leukopenia and was recommended to undergo biannual blood count monitoring. Patient continued to be asymptomatic during this time. Approximately 6 months after SARS-CoV-2 vaccine series, patient received a routine pneumococcal polyvalent booster (Pneumovax 23, Merck), about 5 weeks later, a seasonal influenza vaccine (Fluzone High Dose Quadruvalent, Sanofi Pasteur) with no laboratory work obtained in the interim. 2 weeks after receiving influenza vaccination,  began experiencing pulsatile tinnitus, leading to a normal otologic work-up. CBC was performed (after 8 months approximately),revealing severe pancytopenia. Immature platelet fraction was 2.6%. Patient was admitted to the hospital for transfusions and further evaluation. Single nucleotide polymorphism array analysis showed no evidence of a clonal process. Patient was continuing with cyclosporine, eltrombopag, and supportive transfusions, achieving transfusion independence and a near complete response 4 months after immunosuppressive therapy, at the time of reporting. While the initial cytopenias were mild and subclinical, patient developed severe pancytopenia following further routine vaccinations.   Most recent FOLLOW-UP information incorporated above includes: On 18-Aug-2022: Live follow up received by safety on 18-Aug-2022 has Email with Agency and article propagated contains significant information: Reporter information, citation details were added, medical history was added, suspect dosage regimen updated, co-suspects were added, laboratory tests were added, treatment medications were added.  Company comment: This literature-non-study case concerns 67-year-old female patient, with medical history of Hashimoto's thyroiditis, who experienced the unexpected serious (due to hospitalization and medically significant) event of aplastic anaemia, approximately 9-10 months after the second dose of mRNA-1273 vaccine. As per source document, she was first noted to have mild subclinical persistent pancytopenia 4 weeks following the mRNA-1273 vaccination. She developed further mild reductions in white blood cell and platelet count, as well as mild neutropenia, with repeat cell blood count that showed persistent cytopenias. A haematology evaluation showed a weakly positive anti-nuclear antibody (ANA; 1:80), normal thyroid function, normal iron studies, vitamin B12, and folate levels; unremarkable inflammatory markers with negative infectious work-up for hepatitis A/B/C, human immunodeficiency virus, Epstein-Barr virus, cytomegalovirus and parvovirus B-19. Approximately 6 months after her mRNA-1273 vaccine series, she received a routine pneumococcal polyvalent booster, followed by a seasonal influenza vaccine about 5 weeks later. After two weeks she began experiencing pulsatile tinnitus, and a month later she had visual disturbances, easy bruising, progressive dyspnea on exertion, and palpitations. Her planned monitoring CBC was performed, revealing severe pancytopenia with WBC 1.8 × 103/µl, haemoglobin 4.5 g/dl, and platelet 3 × 103/µl, with 310 neutrophils/µl, reticulocyte count 0.8%, and immature platelet fraction 2.6%. She was admitted for transfusions and a bone marrow biopsy that revealed a hypocellular marrow (5%) with severe trilineage hypoplasia with a relative increase in lymphocytes, composed of CD3+ T-cells and CD20+ B-cells forming occasional clusters. CD34 immunostaining highlighted rare (<1%) blasts, with no evidence of neoplasms. She was treated with frontline immunosuppressive therapy with horse antithymocyte globulin, cyclosporine, eltrombopag and supportive transfusions, near to complete response 4 months after immunosuppressive therapy. Medical history of Hashimoto's thyroiditis remains as a latent autoimmunity risk factor for aplastic anaemia. The benefit-risk relationship of mRNA-1273 Vaccine is not affected by this report.; Sender's Comments: This literature-non-study case concerns 67-year-old female patient, with medical history of Hashimoto's thyroiditis, who experienced the unexpected serious (due to hospitalization and medically significant) event of aplastic anaemia, approximately 9-10 months after the second dose of mRNA-1273 vaccine. As per source document, she was first noted to have mild subclinical persistent pancytopenia 4 weeks following the mRNA-1273 vaccination. She developed further mild reductions in white blood cell and platelet count, as well as mild neutropenia, with repeat cell blood count that showed persistent cytopenias. A haematology evaluation showed a weakly positive anti-nuclear antibody (ANA; 1:80), normal thyroid function, normal iron studies, vitamin B12, and folate levels; unremarkable inflammatory markers with negative infectious work-up for hepatitis A/B/C, human immunodeficiency virus, Epstein-Barr virus, cytomegalovirus and parvovirus B-19. Approximately 6 months after her mRNA-1273 vaccine series, she received a routine pneumococcal polyvalent booster, followed by a seasonal influenza vaccine about 5 weeks later. After two weeks she began experiencing pulsatile tinnitus, and a month later she had visual disturbances, easy bruising, progressive dyspnea on exertion, and palpitations. Her planned monitoring CBC was performed, revealing severe pancytopenia with WBC 1.8 × 103/µl, haemoglobin 4.5 g/dl, and platelet 3 × 103/µl, with 310 neutrophils/µl, reticulocyte count 0.8%, and immature platelet fraction 2.6%. She was admitted for transfusions and a bone marrow biopsy that revealed a hypocellular marrow (5%) with severe trilineage hypoplasia with a relative increase in lymphocytes, composed of CD3+ T-cells and CD20+ B-cells forming occasional clusters. CD34 immunostaining highlighted rare (<1%) blasts, with no evidence of neoplasms. She was treated with frontline immunosuppressive therapy with horse antithymocyte globulin, cyclosporine, eltrombopag and supportive transfusions, near to complete response 4 months after immunosuppressive therapy. Medical history of Hashimoto's thyroiditis remains as a latent autoimmunity risk factor for aplastic anaemia. The benefit-risk relationship of mRNA-1273 Vaccine is not affected by this report.