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SARS-CoV-2 vaccines have been associated with various dermatological adverse events including bullous eruptions (Tomayko M, Damsky W, Fathy R et al. Subepidermal blistering eruptions, including bullous pemphigoid, following COVID-19 vaccination. J Allergy Clin Immunol 2021;148: 750- 751;Gambichler T, Boms S, Susok L et al. Cutaneous findings following COVID-19 vaccination: review of world literature and own experience. J Eur Acad Dermatol Venereol 2021;36: 172- 80). Certainly, the association could be coincidental, or it is also possible that a subclinical bullous pemphigoid (BP) was unmasked by vaccination. We present a unique case of BP-like eruption after COVID-19 mRNA vaccine that also posed a dilemma of further suitable vaccination in a patient with platelet disorder. A 57-year-old woman had her first dose of the Pfizer COVID-19 vaccine on 2 February 2021 on her left arm and within 24 h of receiving it she developed bruising of the entire arm. The patient was hospitalized for further investigations when she developed a bullous rash on her left arm that eventually involved her face and legs. Treatment with systemic steroids was commenced. Owing to her complex medical history including platelet disorder and Ehlers-Danlos syndrome, we were posed with a dilemma of a further suitable vaccination. After a multidisciplinary team meeting, the patient has been encouraged to receive a Moderna vaccine for the second dose. Clinicians should be aware of BP-like disease that may develop after COVID-19 mRNA vaccination. However, with the underlying cause of BP being uncertain, the rarity of its occurrences and the greater risks of SARS-CoV-2 infection, it is important to encourage full vaccination including completion in those with blisters after the first dose. Further studies are required to study the natural history of BP-like disease associated with the COVID-19 vaccines.
ABSTRACT
Basingstoke and North Hampshire hospital is part of the Southern Haemophilia Network (SHN) and is the Comprehensive Care Centre for the network. It spans a wide area and also receives regional referrals for further investigations of suspected platelet disorders. Platelet aggregation is a second-line test to investigate patients with possible bleeding disorders. It is usually performed after clotting factors are established to be normal and there is still concern about an underlying bleeding disorder. The aim of this study was to assess whether platelet aggregation studies led to a formal diagnosis of a platelet disorder. Further outcomes were to assess how many bleeding assessment tool (BAT) scores were documented and whether these corresponded with diagnostic rates. Patient records were retrospectively analysed over 13 months (from 20 June to 21 July). Seventy-two patients were identified who underwent platelet aggregation studies. These included regional and local referrals. Patients identified had their electronic records analysed for the appropriate information. Of note, platelet aggregation studies were stopped at the beginning of the COVID pandemic and only restarted in summer 2020. Therefore, these numbers may not be fully representative of a normal year due to a waiting list which developed during the suspension of this test. The 72 patients were made up of 78% females ( n = 56) and 22% males ( n = 16). Out of the 72 patients reviewed, 63% ( n = 45) were regional referrals and 37% were local referrals ( n = 27). The average age of this group was 31.89 years. Median age was 31 years (range 74). The youngest patient was 2 years old and the oldest was 76. BSH guidelines recommend using the BAT as a standardised tool for assessing bleeding history. However, it is not sensitive in determining which patients require further testing including platelet aggregometry. Only one patient had a documented BAT score out of the 72 referrals (1.39%). Platelet aggregometry did not go on and lead to a diagnosis in this patient. All the samples for platelet aggregometry were taken on site in keeping with national guidance. Three of the four cases of thrombocytopenia, (75%) had a blood film reviewed locally. Platelet aggregometry led to a diagnosis in 17% of patients ( n = 12) with a higher number of diagnoses in males than females. Forty-four per cent ( n = 7) of males seen were diagnosed with a platelet disorder compared to 9% ( n = 5) of females. Other diagnoses included connective tissue disease at 8% ( n = 6), drug induced/acquired defect 5% ( n = 4), thrombocytopenia 5% ( n = 4) and other bleeding disorders (such as VWF or Factor XI deficiency) at 4% ( n = 3). Out of the 12 diagnoses of bleeding disorders, 100% ( n = 12) were registered with the national database. In total 67% ( n = 48) of patients were discharged followed their platelet aggregations studies. In this study, platelet aggregometry had a low rate of diagnostic yield. There was a higher rate of diagnosis in the male population which likely reflects the that women are more heavily investigated due to menorrhagia . Despite the low diagnostic rates, platelet aggregation studies lead to a high number of discharges and reassurance to a number of patients that there is no underlying bleeding disorder. Therefore, they continue to have important role in the diagnosis and exclusion of underlying bleeding disorders.
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This report describes the case of a man affected by Myosin Heavy Chain 9 (MYH9)-related platelet disorder, with a recent history of SARS-CoV-2 pneumonia, who developed pulmonary embolism (PE). At the admittance the patient presented a marked thrombocytopenia. The rotational thromboelastometry (ROTEM) showed a reduction in maximum clot firmness. The CT scan showed a lobar PE while and no sign of superficial or deep venous thrombosis was found. Given the contraindication of anticoagulant therapy due to severe thrombocytopenia, after collegial evaluation of the case, an inferior vena cava filter was applied. The patient was discharged after 5 days of hospitalization, and fondaparinux 2.5 mg subcutaneously was prescribed for two months. Could MYH9 mutation contribute to thrombotic predisposition? Or rather the endothelial dysfunction induced by SARS-CoV-2 infection? The report presents a dissertation on the possible causes for the PE and describes the therapeutic strategy adopted. (www.actabiomedica.it).
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Introduction: Cases of de novo immune thrombocytopenia (ITP), including a fatality following SARS-CoV-2 vaccination in a previously healthy recipient, led to studying its impact in pre-existing ITP. Published reports are limited but suggest that most patients with ITP tolerate the COVID-19 vaccines well without frequent ITP exacerbations (Kuter, BJH, 2021). Data regarding risk factors for exacerbation and relationship of response to first dose to that of second dose are limited. Methods: Data for patients with pre-existing ITP were obtained via 3 sources. First, via a ten-center retrospective study of adults with ITP who received a SARS-CoV-2 vaccine between December 2020 and March 2021 and had a post-vaccination platelet count (n=117);9 centers were in the United States. Eighty-nine percent of patients received mRNA-based vaccines. The second and third sources of data were surveys distributed by the Platelet Disorder Support Association (PDSA) and the United Kingdom ITP Support Association. A 'stable platelet count' was defined as a post-vaccination platelet count within 20% of the pre-vaccination level. ITP exacerbation was defined as any one or more of: platelet decrease ≥ 50% compared to pre-vaccination baseline, platelet decrease by >20% compared to prevaccination baseline with platelet nadir < 30x10 9/L, receipt of rescue therapy for ITP. Continuous variables were described as mean ±SD or median [interquartile range];categorical variables were described as n (%). Relative risks and 95% confidence interval were calculated to estimate strength of association. Results: Among 117 patients with pre-existing ITP from 10 centers who received a SARS-CoV-2 vaccine, mean age was 63±17 years, 62% were female, with median 12 [4-23] years since diagnosis of ITP;patients had received a median of 3 [2-4] prior medical treatments. Sixtynine patients were on ITP treatment at the time of vaccination (Table 1). There was an almost even distribution of platelet count response following each vaccine dose. In 109 patients with data for dose 1, platelet counts increased in 32 (29%), were stable in 43 (39%), and decreased in 34 (31%);in 70 patients following dose 2, platelet counts increased in 24 (34%), were stable in 25 (36%), and decreased in 21 (30%) (Figure 1). Nineteen (17%) patients experienced an ITP exacerbation following the first dose and 14 (20%) of 70 after a second dose. In total, fifteen patients received and responded to rescue treatments (n = 6 after dose 1, n = 8 after dose 2, n = 1 after both doses). Of 7 patients who received rescue treatment after dose 1, 5 received dose 2 and only 1/5 received rescue treatment again. Rescue consisted of increased dose of ongoing medication, steroids, IVIG, and rituximab. Splenectomized persons and those who received 5 or more prior lines of medical therapy were at highest risk of ITP exacerbation. Only 1 of 47 patients who had neither undergone splenectomy nor received 5 or more lines of therapy developed ITP exacerbation after dose 1. There were 14 patients offtreatment at the time of dose 1 and 7 patients at time of dose 2;1 patient in each group developed ITP exacerbation with both these having had normal counts prior to vaccination and having undergone splenectomy. In 43 patients whose platelet counts were stable or increased after dose 1 and received dose 2, only 6 (14%) had platelet decreases to <50 x10 9/L after dose 2. Age, gender, vaccine type, and concurrent autoimmune disease did not impact post-vaccine platelet counts. In surveys of 57 PDSA and 43 U.K. ITP patients, similar rates of platelet change were seen (33% of participants reported decreased platelet count in both surveys) and prior splenectomy was significantly associated with worsened thrombocytopenia in each. Conclusions: Thrombocytopenia may worsen in pre-existing ITP post-SARS-CoV2-vaccination but when ITP exacerbation occurred, it responded well to rescue treatment. No serious bleeding events were noted. Rescue treatment was needed in 13% of patients. Proactive vaccination surveillance of patien s with known ITP, especially those post-splenectomy and with more refractory disease, is indicated. These findings should encourage patients with ITP to not only be vaccinated, but to receive the second dose when applicable to ensure optimal immunization. Rituximab interferes with vaccination response and ideally would be held until a minimum of 2 weeks after completion of vaccination.
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BACKGROUND Digital pathology and artificial intelligence (AI) are areas of growing interest in pathology. A number of institutes have already integrated digital imaging into routine workflow, relying on AI algorithms for the detection of various cancers and mitotic activity quantification. Despite the use of whole slide imaging (WSI) for tissue evaluation, the field of hematology has lagged behind. While many hospitals rely on limited technologies for automated peripheral blood evaluation (e.g. CellavisionTM), the Scopio LabsTM X100 digital scanner provides high resolution oil-immersion level dynamic images of large scanned areas (https://scopiolabs.com/hematology/). With recent FDA-clearance and newly implemented AI capabilities, the Scopio Labs scanner allows for clear and accurate cytomorphologic characterization and cell quantification for peripheral blood smears (PBS). To this end, we aimed to be one of the few pioneering institutes in the United States to adopt early and implement this technology into our routine workflow as a 'hub and spoke' model for optimized case assessment, data sharing and result reporting across multiple satellite locations within our hospital health system. DESIGN A Scopio x100 digital scanner was deployed at our main hospital site, with an anticipated secondary scanner for installment at a satellite laboratory. PBS flagged for hematopathologist review from two satellite laboratories were scanned, and full-field digitalized slides were evaluated by hematopathologists following AI automated analyses. RESULTS 311 peripheral smears were scanned since April 2021 and representative slides were digitalized at 100x magnification (Figure 1, weblink: https://demo.scopiolabs.com/#/view-scan/9231acaf-f898-4649-950d-a41c26c2baaa) with rapid monolayer, monolayer, fullfield, and full-field cytopenia scan options available. The automated AI capabilities classified cells into lineage-specific categories with quantification based on cytomorphologic features (Figure 2). Other AI features include additional cell assignment, cell annotation and comments accessible to all users, finalized report PDF generation, export, upload into our current PowerPath TM software with linkage to the corresponding flow cytometry and bone marrow biopsy reports;and the ability to share digitalized slides with clinicians, laboratory personnel and trainees using uniquely generated weblinks. Images can be used for lectures and tumor boards. Additionally, an 80-case study set for PBS was created for medical students, residents and fellow teaching purposes, including cases displaying acute B-cell lymphoblastic leukemia (B-ALL), acute myelomonocytic leukemia (AMML), hypersegmented neutrophils in COVID-19(+) patients, myelodysplastic syndrome (MDS), atypical lymphocytes, hemoglobinopathies, platelet disorders and various lymphomas. Overall improvements were made to the following areas: CLINICAL WORK/DIAGNOSIS 1. Time-saving due to pre-categorization of cells into lineage-specific groups for pathologist review 2. Minimizes subjectivity in cell counting and cellularity assessment EDUCATION 1. Case-based collection with flow and molecular being maintained here 2. Efficient case retrieval with retained annotations/comments for teaching purposes 3. Wide array of digitalized images for hematology atlas and publications ARCHIVING 1. Collection of reference images (intra/inter departmental) for an array of morphological entities for clinical reference and refined diagnosis (e.g. Bethesda reference images for pap by ASC) 2. Digital catalogue for long-term case follow-up and retrospective review CONCLUSION The Scopio Labs X100 digital system provides an efficient and cost-effective web-based tool to streamline clinical workflow and enhance PBS evaluation. With its recent AI capabilities of cell quantification, lineage-assignment and report-generation, we aim to continue our efforts to fully integrate Scopio Labs into our routine daily clinical workflow for reviewing PBS specimens. CONFLICT OF INTEREST STATEMENT The authors have nothing to isclose with regard to the submitted work (Figure Presented).