key: cord-0919273-5zi49kyl
authors: Doyle, Andrew J.; Springell, Deborah; Dutt, Tina; Kenworthy, Jessica; Ling, Gavin; Desborough, Michael; Thomas, William; Hermans, Joannes; Vanveen, Joost; Cranfield, Tanya; Belsham, Edward; Hill, Quentin A.; Lester, Will; Scully, Marie
title: Acquired thrombotic thrombocytopenic purpura: A rare disease associated with BNT162b2 vaccine: Comment from Doyle et al.
date: 2022-02-26
journal: J Thromb Haemost
DOI: 10.1111/jth.15632
sha: 651f58332c11d079cbc7b4a4d2285c257947f15c
doc_id: 919273
cord_uid: 5zi49kyl

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Collaborators reviewed all diagnoses of de novo, clinical relapses, and ADAMTS13 relapses (ADAMTS13 activity <15% indicating consideration for elective anti-CD20 antibody therapy) of immune-mediated TTP at their centers from 1 January 2021 to 1 November 2021. The UK TTP registry is a prospective database of cases and treatment in the United Kingdom (Multicentre Research Ethics Committee: 08/H0810/54). Collaborators were asked to provide details on the patients' COVID-19 vaccination status including number of vaccines, manufacturer, and the time of vaccination in relation to presentation/treatment episode. Treatment was considered as plasma exchange with or without anti-CD20 therapy for de novo presentation and clinical relapse and anti-CD20 therapy alone for ADAMTS13 relapses.

We report on 90 patients requiring treatment for TTP at 10 hospital sites in England. A summary of these cases is described in The median time from vaccination to presentation with TTP requiring treatment was 87 days (interquartile range 32-120 days). Ten of 58 (17%) occurred within 28 days of receiving COVID-19 vaccination. Of those who presented within 28 days of vaccination, five were following first vaccination and five were following second vaccination. Four of these 10 cases were new presentations, one was a clinical relapse, and five were ADAMTS13 relapses. There was no difference in cases according to vaccine type.

We also assessed if the timing of de novo presentations and relapse episodes correlated to the vaccination program rollout. There Maayan et al. have expressed concern that the four cases of TTP they report are temporally related to COVID-19 vaccination, with two being de novo. They also highlight that there is a greater incidence of TTP cases than expected presenting in their health care system. From our UK experience, we identified four de novo cases. There were higher numbers of treatment episodes in the second half of 2021; however, the types of treatment episodes were not different between the two periods. This may be due to clinicians preferring to avoid immunosuppressants such as rituximab and steroids during the second wave of COVID-19 in early 2021 in the UK or allowing for an optimal immune response following vaccination which again was predominantly in early 2021.

Although we cannot exclude a causal relationship between TTP in four de novo patients seen in our described cohort similar to Maayan et al., reassuringly we did not see an increased number of presentations of TTP during the peak of the vaccination program when a larger and nationwide patient cohort was reviewed.

Additionally, the incidence of de novo cases of TTP was within an expected range of the population of England in 2021 with no perceived increased in demand for treatment of TTP by the authors.

Although we cannot exclude a link between COVID-19 vaccination and a small number of de novo presentations, it appears unlikely based upon these data. We would therefore support the ongoing use of COVID-19 vaccines in patients with TTP, particularly in those who have ongoing or an anticipated need for immunosuppression. We would also support the further reporting of de novo presentations of TTP within 1 month following COVID-19 vaccination to national reporting schemes to ensure detection of any future concerns. 

Acquired thrombotic thrombocytopenic purpura: a rare disease associated with BNT162b2 vaccine

First report of a de novo iTTP episode associated with an mRNA-based anti-COVID-19 vaccination

ChAdOx1 nCov-19 vaccine-induced thrombotic thrombocytopenic purpura successfully treated with plasmapheresis

Thrombotic thrombocytopenic purpura temporally associated with BNT162b2 vaccination in an adolescent successfully treated with caplacizumab

Thrombotic thrombocytopenic purpura: a new menace after COVID bnt162b2 vaccine

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Clinical features of vaccineinduced immune thrombocytopenia and thrombosis

Exacerbation of immune thrombocytopenia following COVID-19 vaccination

A case-control study to assess the risk of immune thrombocytopenia associated with vaccines