Discussion:
ITP is an autoimmune entity characterized by autoantibodies directed against platelet antigens leading to platelet destruction and thrombocytopenia. Clinical manifestations range from asymptomatic presentation, spontaneous petechiae and purpura, mucocutaneous hemorrhage to fatal complications such as gastrointestinal bleeding or intracranial hemorrhage which usually occur when platelet count is below 10x109/L.2
Vaccination as an etiology for secondary ITP was previously reported with influenza, hepatitis A and B, measles, mumps and rubella (MMR) and diphtheria tetanus acellular pertussis (DTaP) vaccines. It is hypothesized that pathogenesis of ITP is mainly secondary to molecular mimicry, a phenomenon in which antigens of host are recognized as antigens of immunization, provoking the development of autoantibodies. These antibody-coated platelets may undergo reticuloendothelial phagocytosis resulting in reduced platelet survival. It is also proposed that vaccine associated autoimmunity can stem not only form antigen mediated responses but also contributed by constituents of vaccine such as adjuvants, preservatives or diluents.1,3
Lee et al described 20 patients who developed thrombocytopenia after receiving COVID vaccination with either Moderna or Pfizer vaccine. Sixteen of these patients did not report history of thrombocytopenia prior to their vaccination. Onset of symptoms from the date of vaccination ranged from 1-23 days. Similarly, our patient had normal platelet counts prior to this presentation however ITP developed on day 26 after the second vaccine was given which differs from cases reported by Lee et al. 4 It is not clear how the immunologic mimicry happens after SARS-CoV2 vaccination, nor what the immunologic target is. Immune response to vaccines are highly variable between different individuals and populations, and there may be other factors implicated such as the microbiome impact on vaccine immunity.5 Most common treatments received in these patients were corticosteroids, IVIG along with platelet transfusions. Outcomes were reported in 16 patients of which 13 responded to initial treatment with IVIG, steroids or platelet transfusion, one patient received Rituximab, thrombopoietin receptor agonist, vincristine along with steroids and IVIG and one patient developed severe thrombocytopenia and intracranial hemorrhage despite receiving corticosteroids, IVIG and Rituximab. In our case thrombocytopenia was refractory to initial treatment with dexamethasone and IVIG. Due to her presentation with massive and multi-site bleeding, there was concern for imminent intracranial hemorrhage in this young and otherwise healthy female, and a rapid response to treatment of her refractory ITP seemed critical. Commonly used options for refractory ITP, such as rituximab, single agent thrombopoietin stimulating agent (TSA), spleen tyrosine kinase inhibitor fostamatinib seemed either to be too delayed or insufficient in their response rates for this case. Splenectomy was prohibited due to bleeding risk and would increase lifelong susceptibility to encapsulated bacteria. 6
Promising activity for MMF in the treatment of de novo and refractory ITP has emerged over the recent years, and after careful consideration and in detail discussion with the patient and her family, we decided to combine MMF with the TSA Romiplostim. The combination of immunosuppressants with IVIG and TSA has been reported in a small series to be efficacious and safe.7,8 The response to this combination was rapid and vigorous.
As COVID 19 pandemic persists concerns for vaccine related side effects remain both among care givers and general population. As of June 26,2021 around 46.4% of United states population received full vaccination against COVID 19 and the risk of serious adverse events remains extremely low. Like primary ITP, vaccine related ITP can have a broad spectrum of presentation ranging from mild bleeding and petechiae to fatal bleeding manifestations. When patients present with ITP, a thorough vaccination history is needed. ITP after COVID 19 vaccination is rare and the potential association is often overlooked and missed. With neither of the clinical trials studying Moderna or Pfizer vaccination had documented cases of thrombocytopenia,9it is worthwhile to note that possibility of reported thrombocytopenia post vaccination could be merely a coincidence rather than causative factor. Nevertheless, we are probably just now only at the beginning of our understanding of the plethora and complexity of side effects and immunological impact of the SARS-CoV 2 directed vaccination and the virus itself. Continued vigilance and reporting of the possible side effects with vaccinations is needed, and we believe this should not preclude individuals from getting vaccinated given rarity of these events and the proven effectiveness of vaccine in mitigating this horrendous pandemic.
Further studies on the aggressive management with combination regimens including immunosuppressants and thrombopoietin agonist, especially among patient’s refractory thrombocytopenia and bleeding complications is warranted.