How Safe Is Vaccination Against SARS-CoV-2 for Patients With De Novo and Preexisting ITP?

A report describing the effects of SARS-CoV-2 vaccination on platelet counts of patients with de novo and preexisting immune thrombocytopenia (ITP), including findings of ITP development or exacerbation secondary to the administration of mRNA vaccines, was recently published in Blood. These findings support the safety of SARS-CoV-2 vaccines for patients with both de novo and preexisting ITP, as “the incidence of severe thrombocytopenia and bleeding is low and patients can be managed with standard and, occasionally, intensified approaches to therapy,” the authors wrote.

To identify potential cases of de novo ITP after SARS-CoV-2 vaccination, researchers led by Eun-Ju Lee, MD, of Weill Cornell Medicine in New York City, reviewed the Vaccine Adverse Event Reporting System (VAERS) using the following search terms:

  • immune thrombocytopenia
  • thrombocytopenia
  • decreased platelet count
  • intravenous immunoglobulin (IVIG) therapy
  • platelet transfusion

The investigators also obtained de-identified data on patients with preexisting ITP from a 10-center retrospective study of adults with ITP who were vaccinated against COVID-19 between December 2020 and March 2021 and who had a post-vaccination platelet count. Nine of the centers involved in the study were located in the U.S. The study defined ITP per American Society of Hematology and International Consensus Guidelines. Information collected from electronic medical records included patient demographics, duration of ITP, treatment history (including past use of rituximab or splenectomy, type of SARS-CoV-2 vaccine received, bleeding symptoms, and platelet counts).

Additionally, the researchers sourced data on patients with ITP from the Platelet Disorder Support Association (PDSA) National History Registry and the United Kingdom ITP Support Association survey.

Seventy-seven evaluable patients were identified in the VAERS analysis, all of whom had received either the Pfizer-BioNTech (n=37) or Moderna (n=40) vaccine. About one-third of patients (32%) reported premorbid autoimmune disease. In the 66 reports that specified onset of ITP after first or second vaccine dose, 51 patients (77%) developed thrombocytopenia after the first dose, and 15 patients (23%) after the second.

At a median of eight days following vaccination (range = 3-13), median platelet count was 3×109/L (range = 1-9×109/L). Symptoms included skin or oral mucosa bleeding (74%), genitourinary bleeding (n=6), gastrointestinal bleeding (n=5), and central nervous system bleeding (n=1). No significant difference in time to symptom onset or platelet count at diagnosis was found between recipients of the Pfizer-BioNTech versus Moderna vaccine.

Forty-six patients had records that specified treatment. Of these, all had received IVIG, corticosteroids, or platelet transfusions. Five patients received thrombopoietin receptor agonists (TPO-RAs), rituximab, or vincristine. Most of the 28 patients whose records included follow-up platelet count (93%) experienced an increase in platelet count to >30×109/L after treatment.

Eight patients with de novo ITP after the first vaccine dose contacted the study authors because their ITP was refractory and difficult to manage, but it is unknown whether these patients were included in the VAERS data. After additional treatment, all eight patients experienced improvements in their platelet counts.

Next, in the 10-center study of patients with preexisting ITP, researchers reported that patients were diagnosed a median of 12 years prior to ITP diagnosis (range = 4-23) and had received a median of three prior therapies (range = 2-4). Of the 117 patients, 69 were being treated for ITP at the time of vaccination, including 58 who were receiving a TPO-RA and 27 who had undergone splenectomy.

At the time of first vaccine dose, the median baseline platelet account among the 109 evaluable patients with preexisting ITP was 101×109/L (range = 60-199×109/L). By the time of the second vaccine dose, platelet counts remained relatively stable, at a median of 101×109/L (range = 60-186×109/L). After the second dose, the researchers observed that platelet counts rose in 24 patients (34%), remained stable in 25 patients (36%), and decreased in 21 patients (30%). Fourteen patients (20%) developing an exacerbation of ITP and nine requiring rescue treatment – all of whom had platelet counts that returned to pre-vaccination levels within two to four weeks.

Lastly, in the PDSA and U.K. studies, totaling 100 patients with ITP and post-vaccination platelet counts, 33 patients across both surveys reported lower post-vaccine platelet counts.

Regarding ITP treatment, the authors noted that splenectomy was associated with a higher risk of ITP exacerbation and decreased platelet counts post-vaccination across all three cohorts of patients with preexisting ITP.

“A critical question was whether platelet response to the first vaccine dose predicted platelet response to the second dose,” Dr. Lee and coauthors wrote. The observation that most patients who had decreased platelet counts after their first vaccine dose had stable or increased platelet counts after the second vaccine dose, suggesting that patients with ITP “who are eligible to receive additional vaccine doses, especially if they tolerated the first dose well, may safely do so,” Dr. Lee added. “A decrease in platelet count with a prior vaccine dose does not guarantee the same effect with a subsequent dose.”

No major bleeding was reported. “Whether this is also the case after booster doses will require further study,” the authors wrote.

Overall, “this report provides a factual basis to encourage SARS-CoV-2 vaccination for patients with ITP by describing the relatively infrequent adverse outcomes and their reversibility with treatment,” they concluded. “It also encourages receipt of both doses of two-dose vaccines, which appears to be particularly important as SARS-CoV-2 variants emerge.”

According to the authors, these findings are limited by the study’s retrospective design and reliance on information of undefined completeness from diverse sources. Additionally, voluntary participation in VAERS and the PDSA and U.K. surveys might have led to an increased number of adverse events or poor outcomes driving the choice to report.

Study authors report no relevant conflicts of interest.

Reference

Lee EJ, Moreira MB, Al-Samkari H, et al. SARS-CoV-2 vaccination and immune thrombocytopenia in de novo and pre-existing ITP patients [published online ahead of print, 2021 Sep 29]. Blood. doi: 10.1182/blood.2021013411.