Long-term follow-up after successful treatment of vaccine-induced prothrombotic immune thrombocytopenia

Thaler, Johannes; Jilma, Petra; Samadi, Nazanin; Roitner, Florian; Mikušková, Eva Ballová; Kudrnovsky-Moser, Stephan; Rettl, Joachim; Preiss, R.; Quehenberger, Peter; Pabinger, Ingrid; Knoebl, Paul; Ay, Cihan

doi:10.1016/j.thromres.2021.09.017

Cited by 17 publications

(18 citation statements)

References 8 publications

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“…Anticoagulation was changed to fondaparinux (7.5 mg: once daily subcutaneous for 5 days) following platelet count recovery before reverting to dabigatran (150 mg; twice daily) ( Figure 1A ). After 3 days, platelet count returned to normal range (190 × 10 9 /L), while D-dimer reduced significantly but remained elevated (3.12 mg/L) ( Figure 1A ), in keeping with other reports ( 11 ). The patient was discharged on day 9 with symptoms resolved and with continued dabigatran (150 mg: twice daily).…”

Section: Case Reportsupporting

confidence: 91%

Section: Case Reportsupporting

confidence: 85%

“…Follow-up assessments showed sustained platelet count and D-dimer within normal ranges (Figure 1A). Interestingly, anti-PF4 antibodies remained persistently high up to 90 days post admission (Figure 1B) as observed by others (10,11). Peripheral blood smears performed on day of admission (day 0) showed evidence of thrombocytopenia and revealed the presence of distinctive large, hypergranular platelets (Figure 2i), corresponding with the previously observed MPV at the upper limit of normal range on admission (Table 1).…”

Section: Case Reportsupporting

confidence: 82%

“…The same study also suggested pathogenic anti-PF4 antibodies may persist for >12 weeks in a small subgroup of patients, which necessitates further study to clarify if prolonged anticoagulation may be required. Thaler et al also reported similar observations, with anti-PF4 antibodies decreasing but at a very slow rate over several weeks (11). Due to these persistent anti-PF4 antibodies, in the United Kingdom it has been proposed that antibody levels be monitored weekly for the first 4 weeks and monthly for 6 months thereafter (12).…”

Section: (B)mentioning

confidence: 78%

“…It is believed that thrombosis in VITT, as in HIT, is caused by PF4/antibody complexes (formed following vaccination) which then bind the platelet membrane receptor FcγRIIA (CD32a), a low affinity Fc receptor, inducing platelet activation ( 8 , 9 ). Recently, there have been reports of prolonged, persistent anti-PF4 antibodies in VITT patients, but it is believed pathogenic (platelet-activating) antibodies decrease over time ( 10 ) and patients do not experience a relapse of the condition ( 11 ). To date, the majority of VITT cases have been reported in a minority of recipients of ChAdOx1 nCov-19 or Ad26.COV2.S (Janssen) adenoviral vector vaccines ( 12 ).…”

Section: Introductionmentioning

confidence: 99%

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Case Report: Hypergranular Platelets in Vaccine-Induced Thrombotic Thrombocytopenia After ChAdOx1 nCov-19 Vaccination

Comer

Chevillier

Szklanna

et al. 2022

Front. Cardiovasc. Med.

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BackgroundVaccine-induced thrombotic thrombocytopenia (VITT) post SARS-CoV-2 vaccination is characterized by thrombocytopenia and severe thrombosis. Platelet function during patient recovery in the medium-/long-term has not been investigated fully. Here, we undertook a 3-month study, assessing the recovery of a VITT patient and assessing platelet morphology, granule content and dense-granule release at two distinct time points during recovery.Case PresentationA 61 year-old female was admitted to hospital 15 days post ChAdOx1 nCov-19 vaccination. Hematological parameters and peripheral blood smears were monitored over 3 months. Platelet morphology and granule populations were assessed using transmission electron microscopy (TEM) at two distinct time points during recovery, as was agonist-induced platelet dense-granule release. Upon admission, the patient had reduced platelet counts, increased D-dimer and high anti-PF4 antibodies with multiple sites of cerebral venous sinus thrombosis (CVST). Peripheral blood smears revealed the presence of large, hypergranular platelets. Following treatment, hematological parameters returned to normal ranges over the study period. Anti-PF4 antibodies remained persistently high up to 90 days post-admission. Two days after admission, VITT platelets contained more granules per-platelet when compared to day 72 and healthy platelets. Additionally, maximal ATP release (marker of dense-granule release) was increased on day 2 compared to day 72 and healthy control platelets.ConclusionThis study highlights a previously unreported observation of platelet hypergranularity in VITT which may contribute to the thrombotic risk associated with VITT. Optimal approaches to monitoring recovery from VITT over time remains to be determined but our findings may help inform therapeutic decisions relating to anticoagulation treatment in this novel pathology.

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Section: Case Reportsupporting

confidence: 91%

Section: Case Reportsupporting

confidence: 85%

Section: Case Reportsupporting

confidence: 82%

Section: (B)mentioning

confidence: 78%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Case Report: Hypergranular Platelets in Vaccine-Induced Thrombotic Thrombocytopenia After ChAdOx1 nCov-19 Vaccination

Comer

Chevillier

Szklanna

et al. 2022

Front. Cardiovasc. Med.

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The path of uncovering a prothrombotic thrombocytopenic syndrome after viral vector‐based COVID‐19 vaccination: Where there is much light, the shadow is deep

Thaler

Knoebl

2021

Research and Practice in Thrombosis and Haemostasis

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Anti‐platelet factor 4 immunoglobulin G levels in vaccine‐induced immune thrombocytopenia and thrombosis: Persistent positivity through 7 months

Montague

Smith

Lodwick

et al. 2022

Research and Practice in Thrombosis and Haemostasis

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Background Anti‐platelet factor 4 (PF4) antibodies that activate platelets via FcγRIIA drive the pathophysiology of vaccine‐induced immune thrombocytopenia and thrombosis (VITT). Evolution of these antibodies and their ability to activate platelets after initial treatment remains unknown. Objectives To assess how clinical and platelet parameters, anti‐PF4 antibody levels, and patient serum reactivity changes during follow‐up after VITT presentation. Methods We describe cases of seven discharged VITT patients that were followed from diagnosis up to 280 days (range 199–280) after vaccination. We measured anti‐PF4 antibodies and PF4 levels in patient serum during follow‐up and tested the ability of patient serum to activate healthy donor platelets and patient platelets over time. Results Anti‐PF4 immunoglobulin G antibody levels are very high at diagnosis (0.9–2.6 OD) and remain relatively high (>1.0 OD) in all patients, except one treated with rituximab, at 7 months post vaccination. All patients were on direct oral anticoagulants throughout follow‐up and no patients had recurrent thrombosis. Patients’ platelets during follow‐up have normal FcγRIIA levels and responsiveness to platelet agonists. Patient diagnostic serum strongly activated control platelets, either alone or with PF4. Most follow‐up serum alone was weaker at stimulating donor and patient platelets. However, follow‐up serum beyond 150 days still strongly activated platelets with PF4 addition in three patients. Patient serum PF4 levels were lower than controls at diagnosis but returned within normal range by day 50. Conclusions Explanations for reduced platelet activation during follow‐up, despite similar total anti‐PF4 antibody levels, remains unclear. Clinical implications of persistent anti‐PF4 antibodies in VITT require further study.

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Long-term follow-up after successful treatment of vaccine-induced prothrombotic immune thrombocytopenia

Cited by 17 publications

References 8 publications

Case Report: Hypergranular Platelets in Vaccine-Induced Thrombotic Thrombocytopenia After ChAdOx1 nCov-19 Vaccination

Case Report: Hypergranular Platelets in Vaccine-Induced Thrombotic Thrombocytopenia After ChAdOx1 nCov-19 Vaccination

The path of uncovering a prothrombotic thrombocytopenic syndrome after viral vector‐based COVID‐19 vaccination: Where there is much light, the shadow is deep

Anti‐platelet factor 4 immunoglobulin G levels in vaccine‐induced immune thrombocytopenia and thrombosis: Persistent positivity through 7 months

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