Case Presentation: A 38 year old male with a history of anxiety and hypothyroidism who received the second dose of SARS-COV2 Pfizer-Biontech vaccination 17 days prior, presented with 4 days of severe gingival bleeding after dental cleaning, epistaxis and a petechial rash of his extremities and was found to have new onset severe thrombocytopenia of 2,000/μl. Complete blood count (CBC) was normal 1 month prior. Exam revealed petechiae and ecchymoses of extremities, crusted blood on oral mucosa and normal vitals. Lab studies revealed pancytopenia, Hgb 11.2 g/dl (normocytic), low reticulocyte count 10,000/μl, WBC 2.09 K/uL, Absolute Neutrophil Count (ANC) 800/μl, PLT 2,000/μl. Hemolytic screen was negative and B12 levels were normal. Hep B, Hep C, EBV, CMV, SARS COV-2 and HIV serology were negative. Parvovirus IgG antibodies (Abs) were elevated, however IgM Abs were negative. Paroxysmal Nocturnal Hemoglobinuria assay and ANA were negative. ADAMSTS13 activity was normal. Bone marrow biopsy revealed an aplastic marrow with a cellularity of < 5% (Figure 1,2). Flow cytometry was negative for malignancy. 2 units of PLT were transfused with only transient improvement. ANC fell to 0. Acyclovir and Posacomazole were given for HSV/VSV and antifungal prophylaxis. He later developed neutropenic fever, treated with broad spectrum antibiotics. Cultures were negative and fever was thought to be due to a viral pharyngitis. He had an allohematopoietic stem cell transplant and was found to be positive as a carrier of Fanconi Anemia (FA) Type C. Prior to transplant, he was conditioned with cyclophosphamide/hATG (horse anti-thymocyte globulin). ANC improved to > 500/μl 19 days post-transplant. Intermittent G-CSF/GM-CSF injections were also given.
Discussion: Aplastic anemia (AA) is characterized by pancytopenia, variable bone-marrow hypocellularity, and the absence of underlying malignant or myeloproliferative disease (1). It can be classified as non-severe, severe or very severe based on the Camitta criteria. Very severe AA as in our case, ANC counts are < 200/μl. Causes include drugs, toxins, viral infections, autoimmune disorders, inherited causes such as FA. Increasing numbers of case reports show a possible relationship of autoimmune cytopenias post COVID-19 vaccination (2,4,6). Reports of AA post COVID-19 vaccination are scarce given the recent development of mRNA vaccines. In April 2021 a 76 year old male developed severe AA one month after completion of second dose of SARS-CoV-2 Pfizer-Biontech vaccination (3). Treatment included steroids, cyclosporine and hATG with improvements in his counts initially. Our case differs given the younger age and history of being a carrier of FA Type C. It is unlikely that his bone marrow failure was primarily due to FA as he was only a carrier and bone marrow failure typically presents in the first decade of life in patients with FA (5). Though such hematological adverse effects have rarely been observed following vaccination, we have to be concerned about a causal relationship given the time course of his illness and recently normal CBC. Additionally, a thorough work up ruled out other possible causes for his AA. Regardless of this potential relationship observed, the risk-benefits of not vaccinating patients who are carriers for FA must be considered.
Conclusions: There is increasing evidence showing a causal relationship between COVID-19 vaccinations and hematological cytopenias, more rarely AA as seen in this case. More research is needed to further clarify this observed relationship.