Page 186 - Haematologica May 2022

Letters to the Editor
Table 2. Demographics and clinical features of patients with relapsed chronic immune thrombocytopenia after COVID-19 vaccination.
Age Days COVID-19 Other Chronic Most Platelets WHO Bleeding First- Second- TTR TTCR Platelets Treatments Other
and after vaccine gender vaccination
94F 9 1stBNT 77M 2 1stChAd
antecedent ITP recent at bleeding line line at day 30 at day 30 vaccinations treatments platelets presentation score treatment treatment (x109/L)
prior to (x109/L) vaccination
(x109/L)
relevant history
73F 30 73M 31
1st ChAd 1st ChAd
Influenza None None
romiplostim
Stable off 188 treatment
Stable off 255 treatment
Stable off 120 treatment
6 1 11 2 5 1
Petechiae
Mild blood loss Petechiae
to ongoing romiplostim
Pred/IVIg None 3 8 144 IVIg None 3 5 215 Pred None 2 4 234
Pred 15 None mg daily
None None
None Stableon 86 12 0 None Nochange None 5 - 73 None None
Pred
10 mg DAT
Positive and ANA
ANA: antinuclear antibodies; BNT: BNT162b2 (Pfizer); ChAd: ChAdOx1 nCoV-19 (AstraZeneca); COVID-19: coronavirus disease 2019; DAT: direct antiglobulin test; Dex: dexamethasone; F: female; IVIg: intravenous immunoglobulin; M: male; Pred: prednisone; TTCR: time to complete response; TTR: time to response; WHO: World Health Organization.
assay for platelet factor 4 (PF4) was performed in six and all of these tested negative.
The median age of the patients was 75 years (range, 22-94), the median time to presentation after vaccination was 10 days (range, 2-31), and the platelet count at pres- entation was 7x109/L (range, 0-22x109/L). World Health Organization bleeding scores were mild: ten patients had grade 0 or 1, two patients had grade 2, and one patient each had grades 3 and 4.12
Ten cases had no prior history of ITP and all received treatment upfront: seven received prednisone, and three high-dose dexamethasone pulses. Eight patients also received between 1-2 g/kg intravenous immunoglobulins (IVIg) as part of first-line therapy. The median time to response was 3.5 days (range, 1-18). Ten evaluable patients achieved a complete response by a median of 9 days (range, 3-47). Day 30 data were available for nine of these ten patients without a prior history of ITP, as one left Australia: the median platelet count was 151x109/L (range, 8-259x109/L); eight were still on corticosteroids (median prednisone equivalent 20 mg daily), one was on eltrombopag (commenced as second-line treatment) and another was receiving mycophenolate mofetil that had been commenced in first-line treatment in combination with prednisone.
One 80-year-old female presented with life-threatening bleeding (influenza vaccination 1 day prior and ChAd 21 days prior to presentation) and after no initial response to escalating prednisone doses and IVIg, eltrombopag was commenced on day 15. Platelets began to respond by day 18, and the platelet count rose to 157x109/L by day 30 after presentation while only on prednisone.
One 82-year-old male presented with a platelet count of 3x109/L, and widespread bruising 9 days after his first ChAd vaccination. He was treated with high-dose dex- amethasone and platelets responded, reaching 97x109/L by day 16 (Figure 1A). He received influenza vaccination the following day, but his ITP relapsed by day 32. He responded promptly to a second pulse of high-dose dex- amethasone with a platelet ount of 65x109/L by day 36. He had never previously developed ITP despite numer- ous influenza vaccinations in the past.
One 83-year-old female presented with a platelet count of 10x109/L, facial petechiae, and upper chest ecchy-
moses 23 days after her first ChAd vaccination (Figure 1B). She responded promptly to a dexamethasone pulse 20 mg daily for 4 days and IVIg infusion 0.4 g/kg for 3 days. She relapsed on day 19 with platelets 23x109/L and new lower limb bruising, and was treated with another pulse of dexamethasone and IVIg 0.4 g/kg for 2 days.
In total, there were four patients with chronic ITP who relapsed following COVID-19 vaccination. Three patients receiving ChAd had stable chronic ITP, and were off ITP-directed therapies at the time of COVID-19 vac- cination. They were treated with standard first-line ther- apies and all responded within 3 days.
IVIg monotherapy alone was successful in one 72-year- old female with chronic ITP who presented with a platelet count of 11x109/L but responded by day 3, achieving a complete response on day 5; her day 30 platelet count was 215x109/L (Figure 1C), and she had no need for steroids at any time despite having had refracto- ry ITP requiring splenectomy in 1994. Her most recent prior platelet count was 255x109/L less than 3 weeks before vaccination. Her most recent prior ITP treatment had been rituximab monotherapy in 2011.
A second chronic ITP patient, a 77-year-old male who received influenza vaccination prior to ChAd vaccination, presented with a platelet count of 2x109/L, achieved a response and complete response by days 3 and 8 respec- tively, had a day 30 platelet count of 144x109/L, and was on a weaning schedule of prednisone at day 30 after ini- tially being treated with prednisone/IVIg upfront.
The third patient with chronic ITP, a 73-year-old male with a pre-vaccination platelet count of 120x109/L, was thrombocytopenic (platelet count, 5x109/L) 31 days after ChAd vaccination. He was started on prednisone monotherapy and achieved a response within 2 days, a complete response by day 4, and a platelet count of 234x109/L by day 30 while on prednisone 10 mg daily.
The fourth chronic ITP patient in this analysis was a 94-year-old female who received her first dose of BNT 9 days prior to presentation. She had previously enjoyed a stable platelet response on romiplostim for her chronic ITP with a recent platelet count of 86x109/L, falling to 12x109/L without any bleeding; her platelet count returned to baseline within 5 days of presentation. She proceeded to receive her second dose of BNT 21 days
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