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.