Acute Immune Thrombocytopenia following administration of Shingrix recombinant zoster vaccine

To the Editor: A 63-year-old male with a history of basal cell carcinomas of multiple skin sites, open-angle glaucoma, and hypercholesterolemia received the initial recombinant zoster (Shingrix) Vaccine on September 1, 2020. On September 15, 2020 he presented to his primary care physician with observation of bleeding oral blisters. He did not report any other abnormal bleeding or bruising, or associated fevers, chills, anorexia or weight loss. Physical exam revealed several 5 mm purpuric blisters inside his mouth and on the inside upper lip, as well as small purpura at the site of an adhesive bandage on his left upper arm, and petechiae on his bilateral lower extremities. A complete blood count (CBC) revealed a platelet count of 1000/μL. White blood cell count and hemoglobin were within normal limits. He was admitted to the general medicine service at which point Hematology was consulted. Review of the peripheral blood smear showed severe thrombocytopenia with rare large and giant platelets. Erythrocyte morphology was normal and there were no schistocytes or evidence of dysplasia. Isolated severe thrombocytopenia with giant platelets on the peripheral blood smear was thought to be consistent with ITP and Hematology recommended starting dexamethasone 40 mg daily with a plan to complete 4 days. He received 5 days of dexamethasone 40 mg daily between September 15 and September 19, and an extra dose was administered due to an order duplication. During this time his platelet count remained in the 0–1000/μL range. Given the lack of improvement in his platelet count and concern for risk of bleeding, he received IVIG 1 g/kg (total dose 75 g) on September 21. On September 22 his platelet count had increased to 25 000/μL, and he was discharged home on September 23 with a platelet count of 30 000/μL. On follow up September 29 platelets had increased to 59 000 k/μL and subsequently normalized at 268 000 k/μL on December 4. While ITP following zoster vaccine has not been previously described, the temporal relation between administration of the shingles vaccine with development of ITP about 2 weeks later does suggest causality, particularly without other obvious triggers. Thrombocytopenia has been described following infection with varicella zoster in children both during acute infection and as a post-infectious sequelae occurring days to weeks after symptom resolution. The mechanism is thought to be development of IgG and IgM directed against platelet surface glycoproteins which occurs in the setting of viremia. Shingrix recombinant zoster vaccine does not contain live virus but rather contains zoster glycoprotein E combined with adjuvant ASO1B to promote sustained immune response. It stands to reason that this vaccine would induce a similar immune response as is seen in varicella zoster infection and may therefore induce IgG and IgM directed against platelet surface glycoproteins resulting in acute ITP. The patient in this case achieved a complete remission of his acute ITP following treatment with dexamethasone and IVIG. The question of administration of future vaccines remains an issue of concern in patients with prior vaccine-induced ITP, particularly now in light of FDA Emergency-use Authorization of the SARSCoV-2 mRNA vaccines. A study examining a second dose of the MMR vaccine in children with prior MMR-induced ITP showed no increased risk for ITP relapse within 6 weeks of the second dose. Often the potential risks of contracting the disease far outweigh the risk for receiving the vaccine. Studies of the Pfizer/BioNTech vaccine did show significant CD4+/CD8+ T cell response which can confer long lasting immunity in some patients. The evidence of T cell mediated immunity may be a reason to encourage patients to pursue vaccination despite asplenia or recent anti-CD20 therapy if they are thought to be at particularly high risk for complications from Covid-19 infection.