Sex: F
Vaccine: COVID19
Symptoms: Antiphospholipid antibodies, Biopsy, Biopsy bone marrow, Biopsy lymph gland, Blood alkaline phosphatase
Clinical narrative: Acute Immune Thrombocytopenia; Acute Immune Thrombocytopenia; This is a literature report. Here we present the case of a patient with a known history of ITP and subsequent flare-up after the first dose of the Pfizer-BioNTech COVID mRNA vaccine. CASE REPORT: A 47-year-old female with a medical history of hypothyroidism (secondary to Hashimotos thyroiditis), iron deficiency anemia, lymphadenopathy, and ITP received her first dose of the Pfizer BioNTech mRNA vaccine and experienced mild arm soreness for 2 days postvaccination but did not experience any other adverse effects. The patient had ITP diagnosed in 2002, during pregnancy, when platelets were decreased to as low as 4000/mcL. After initial treatment with prednisone, she had a response of complete remission (CR) (platelets >100 000, as described) . She had another ITP flare-up 6 years later, with platelets decreasing to 3000/mcL, which responded to human immune globulin (IVIG) and dexamethasone in another CR response. Workup during this time frame yielded a direct platelet antibody level of 1962 and a mildly elevated rheumatoid factor of 20.7 IU/mL. Negative tests included antinuclear antigen (ANA), double-stranded DNA (dsDNA), anticardiolipin immunoglobulin M and immunoglobulin G, and lupus anticoagulant. A bone marrow biopsy yielded no morphologic or immunophenotypic evidence of a lymphoproliferative disorder, increased blasts, or presence of clonal blast cells. Karyotyping showed a normal karyotype of 46XX. Her platelet count was recorded on many occasions in the interval years and ranged from 164 000 to 36 000. She was not maintained on any therapy for ITP during this time. She was found to have an enlarged left axillary lymph node of routine mammogram in 2018 as well as left axillary and retroperitoneal adenopathy on chest computed tomography (CT) in 12/2018 and abdominal pelvis CT in 6/2019. Biopsy of the left axillary lymph node in 2018 showed no malignancy, and an excisional biopsy in 3/2019 of the area showed follicular hyperplasia without malignancy. Flow cytometry was negative for lymphocytic malignancy in 2018, and fine needle aspirate of adenopathy in the breast and 2 excisional biopsies were negative for malignancy in 2019. Eighteen days post administration, the patient presented to the emergency room with complaints of easy bruising, gum bleeding, and an episode of epistaxis. She denied any history of trauma, headache, visual changes, rectal bleeding, or gastrointestinal symptoms. Physical exam was remarkable for ecchymosis and petechiae on her bilateral upper and lower extremities and dried blood within her oropharynx. No splenomegaly or hepatomegaly was noted. A CT of the head was negative for hemorrhage, and a chest radiograph was clear. Her platelet count was noted to be 1000/mcL (her last platelet count 3 months prior was 62 000/mcL). Peripheral smear confirmed the thrombocytopenia and showed normal red blood cell (RBC) morphology (Figures 1 & 2). Her prothrombin time was 16.2 seconds and international normalized ratio 1.5 mg/dL, her reticulocyte count showed mildly elevated reticulocytes of 2.2%, lactate dehydrogenase (LDH) was mildly elevated at 310 U/L, and a manual white blood cell differential showed 13 atypical lymphocytes. She had a mildly elevated alkaline phosphatase of 109 U/L, and antinuclear antibody screen (ANA) was negative. Her other cell lines and labs were within normal limits. The labs within normal limits included white blood cell count and differential, hemoglobin, red cell distribution width (RDW), aPPT, haptoglobin, and basic metabolic panel; a point-of-care test was negative for SARS CoV-2 as well as flu A and B. She had fibrin ogen, which was normal at 280, and denied headaches, but no D-dimer or DVT study was done. She received dexamethasone and was admitted to the intensive care unit (ICU). In the ICU, 1 unit of platelets and 1 unit of IVIG (Privigen) were given, with improvement of platelets to 61 000/mcL. On day 2, the platelet level again fell to 19 000/mcL, and 1 unit of platelet transfusion and IVIG were again given, with platelets subsequently rising to 72 000/mcL. CT scans of the chest, abdomen, and pelvis were performed to evaluate lymphadenopathy and showed resolution of the previously noted adenopathy. Further workup was significant for Sjogrens SS-A antibody (RO) at 2.8 AI, a repeat ANA was positive at 1:80 with a speckled pattern, an Epstein-Barr virus (EBV) DNA by polymerase chain reaction (PCR) test was positive at 429 IU/mL, and hepatitis C, hepatitis B, HIV, and thyroid-stimulating hormone were negative. She was discharged with clinic follow-up. Up to the time of this report, she has received only the first dose of the vaccine.  DISCUSSION: Our patient with a history of ITP received the first dose of the Pfizer-BioNTech mRNA vaccine. Her last ITP flare was 13 years ago, and she has had a stable platelet count above 30 000/mcL since then. After 18 days of vaccine administration, she presented with acute on chronic ITP. Workup ruled out any other etiology of thrombocytopenia, including active COVID-19 infection. The patient did not complain of any headaches, and thus the likelihood of thrombosis was very low. Although the positive EBV DNA PCR may have been a factor contributing to the acute on chronic ITP, there is no way to tell if the vaccine may have caused a reactivation of EBV, which triggered the acute ITP. However, given her infrequency of ITP flares and the fact that the event occurred after receiving the vaccine, an association of thrombocytopenia with the COVID-19 vaccine should be considered. The underlying mechanism requires further research. CONCLUSIONS: The temporal relation of ITP exacerbation after receiving the Pfizer-BioNTech mRNA COVID-19 vaccine in this patient, especially considering the infrequency of her flare-ups and her stable platelet count for many years, is of considerable significance. The best available evidence from all clinical trials and reported side effects from vaccinated individuals suggest that ITP secondary to the COVID vaccine is an exceedingly rare reportable adverse effect, but the benefits of vaccination outweigh the risks of COVID infection in these patients. Considering the few similar cases recently reported, patients with chronic ITP should be monitored closely for any suspicious symptoms following vaccination. The underlying mechanism of this autoimmunity is still unclear and needs further research.; Sender's Comments: Based on the current available information and the plausible drug-event temporal association, a possible contributory role of the suspect product BNT162B2 to Immune thrombocytopenia and Condition aggravated cannot be excluded. The impact of this report on the benefit/risk profile of the Pfizer product is evaluated as part of Pfizer procedures for safety evaluation, including the review and analysis of aggregate data for adverse events. Any safety concern identified as part of this review, as well as any appropriate action in response, will be promptly notified to regulatory authorities, Ethics Committees, and Investigators, as appropriate.