In this issue of the e-news


CONTENTS:


SARS-CoV-2 Vaccination and Immune Thrombocytopenia in De Novo and Pre-Existing ITP

mRNA Vaccine bottle

This study was a collaboration between several of PDSA’s medical advisors, PDSA’s research team, and world-renowned ITP experts. Data was analyzed from the PDSA patient-centered ITP Natural History Study Registry, the United Kingdom (UK) ITP Support Association’s COVID-19 survey, the Vaccine Adverse Events Reporting Systems (VAERS), and a ten-center retrospective analysis of the SARS-CoV-2 vaccination impact on adults with ITP. Most individuals included in the study received an mRNA vaccine (either Moderna or Pfizer-BioNTech). The authors concluded that the vaccines can be given safely to most individuals, including those with pre-existing ITP.

Some patients presented with what appeared to be a new diagnosis of ITP; most presented with a platelet count less than 10,000 and mild to moderate bleeding symptoms 3-13 days following vaccination. There was no significant difference between the incidence of ITP according to the vaccine manufacturer or the time between vaccination and when low platelet counts or symptoms developed; the increased incidence was not more than 1 per 50,000-100,000 people, or perhaps 25% above the ‘natural’ incidence of ITP. Those individuals who required treatment responded to corticosteroids and/or IVIG, returning to their pre-vaccination platelet count ranges within 2-4 weeks without major bleeding. Study results after the second vaccination were very similar to those after the first vaccine dose. Prior splenectomy did not alter the frequency of thrombocytopenia post-vaccination, but the fall in platelet count was greater on average. In fact, 44% of those presenting with ITP after the first dose had a similar response in platelet count change after receiving a second dose. For those who experienced no change in their platelet count or who had an increase in platelet count following dose one, 80% experienced the same response after receiving the second dose.

Overall, vaccination against SARS-CoV2 vaccine can be associated with the onset of what appears to be new ITP and a fall in the platelet count is seen in about one-third of those with a known diagnosis of ITP. However, the decrease in platelet count is generally not substantial. Individuals at higher risk to experience a larger drop in platelet count included those with previous splenectomy or had received five or more previous lines of treatment. The authors concluded SARS-CoV-2 vaccines can be given safely to most individuals with pre-existing ITP even if they developed thrombocytopenia after the first dose. However, close monitoring by a hematologist experienced in treating ITP is especially indicated for individuals who are at a higher risk for developing severe thrombocytopenia. This data will be presented next month at the upcoming American Society of Hematology (ASH) meeting.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8483984/

Comments from PDSA’s Medical Advisors:

This article represents a collaboration of many of the leading figures in the world of ITP. The study provides important information about the risk, severity, and management of thrombocytopenia after vaccination for SARS-COv2. The data suggest that platelet counts may fall in some patients with ITP because vaccination induces an immune/inflammatory state that can increase platelet clearance or stimulate platelet antibody production to a greater extent that it stimulates platelet production. The balance of these and other processes will determine what actually happens to the count. We suspect that in certain patients the count may increase and then decrease or vice-versa. It would take very frequent platelet counts to sort this out.

Three issues surfaced regarding patients who carry a diagnosis of ITP. One was that about one-third of patients with ITP experienced a fall in platelet count that either did not require treatment or was managed successfully with steroids and IVIG. Second, relatively severe ITP was more likely to develop in those individuals who had undergone splenectomy and/or had received 5 or more previous therapies. Third, patients who did not develop substantially worse thrombocytopenia after the first vaccination were less likely to develop substantially worse thrombocytopenia following re-vaccination.

The study provided a great deal of important information but did not answer a number of additional questions, such as whether a reaction to a previous vaccination to another agent had any relationship to what would happen with COVID vaccination. Also, the study provides data for patients who received the Moderna and Pfizer mRNA vaccines but did not provide information on those who received the Johnson and Johnson or Astra-Zeneca adenoviral vaccines. Third, the study did not examine the long-term effects of vaccination on pre-existing or de novo ITP.

Other studies published recently include one from David Kuter at Massachusetts General Hospital (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239625/) and a French collaboration led by Bertrand Godeau and Marc Michel (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7404899/).
Their results reinforce those reported in this article and suffer from the same limitations.


Immune Thrombocytopenia (ITP) Risks with AstraZeneca COVID-19 Vaccine

COVID vaccine bottles

In a small study from Australia, the relationship between the AstraZeneca and Pfizer BioNTech vaccinations against Covid-19 and risk of developing ITP was analyzed. Forty-seven cases of thrombocytopenia (defined as a platelet count less than 150,000) were identified post-vaccination; 6 cases were excluded based on blood clots in the patient, and 20 additional cases were excluded for pseudo-thrombocytopenia or other causes of a low platelet count. 21 cases of “true” ITP remained and were included in this study. Of these, 17 followed the AstraZenca vaccine and 4 the Pfizer vaccine. Fifteen of the 17 cases occurred following the first dose.

Of the 17 ITP cases diagnosed following receipt of AstraZeneca, 16 were classified as newly diagnosed, and one was an individual who had chronic ITP. Two of the 17 had unexplained bruising prior to receiving the vaccine and in retrospect may have had ITP. The diagnosis of ITP was made within 28 days following vaccine receipt, apart from one individual who reported developing ITP 78 days later.

Of the four ITP cases following the Pfizer vaccine, two were newly diagnosed ITP cases, and two had chronic ITP. Three of the ITP diagnoses were made following receipt of the second Pfizer dose. The study did not comment on the interval between vaccination and diagnosis in patients receiving Pfizer.

Most cases (94%) of ITP following vaccination were treated with corticosteroids, and some received IVIG therapy. Three were refractory to first-line treatments and required a TPO agent. Some (29%) required on-going therapy to maintain their platelet counts. There was one death following the development of ITP post-vaccination with a platelet count of 76,000.

Overall, the authors concluded that the AstraZeneca vaccine appeared to carry a greater risk for “causing” ITP than the Pfizer vaccine. However, it is important to note that although the development of ITP following vaccination is significant, the risk of developing ITP overall was noted to be 8 per million doses for AstraZeneca and 4.1 per million doses for the Pfizer vaccine.

https://www.sciencedirect.com/science/article/pii/S0264410X21013505?dgcid=author

Comments from PDSA’s Medical Advisors:

This small surveillance study was primarily looking at recipients of the Astra-Zeneca vaccine. The results suggest that the incidence of newly diagnosed ITP following Astra-Zeneca vaccination was greater than was seen with the Pfizer vaccines, confirming a previous study from Scotland (https://www.nature.com/articles/s41591-021-01408-4). The authors also found that there is a small transient spike in the incidence of seemingly de novo ITP in the weeks following vaccination. The medical community in general and the hematology community in particular, have done a good job identifying this side effect and publicizing these cases. The downside of this effort is that potential recipients in the general population and especially patients with ITP may delay or totally avoid vaccination despite these events being very rare and manageable. It must be emphasized that close monitoring of platelet counts and typical interventions have minimized the impact of post-vaccine falls in platelet counts. Furthermore, vaccine-induced thrombocytopenia tends to be transient, and that the risk of ITP and vaccine-induced thrombosis are far lower than the complications of COVID-19 infection which even when fatal or overtly severe may cause substantial problems for infected patients.

 

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