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BACKGROUND: Early damage control resuscitation and massive transfusion (MT) protocol activations improve outcomes in trauma patients with hemorrhagic shock, where scores to guide MT prediction are used including: the Assessment of Blood Consumption (ABC), Shock Index (SI), and Revised Assessment of Bleeding and Transfusion (RABT) scores. Our aim was to validate the RABT score in patients from two level I trauma centers in Canada. METHODS: A retrospective review of adult patients meeting trauma team activation criteria receiving >1 unit of red blood cells (RBCs) within 24 h of admission, from 2015 to 2020, was conducted. A RABT score ≥ 2, ABC score ≥ 2, and Shock Index (SI) ≥ 1 was used to predict MT using both research (≥10 RBCs in 24 h) and clinical (≥3 RBCs in 3 h) definitions. Scores were assessed and compared using sensitivity, specificity, and the area under the receiver operating characteristic (AUROC). RESULTS: We analyzed 514 patients with a mean age of 44.4 (19.2) years and a median injury severity score of 29 [18-38]. For both MT definitions, the RABT score trended towards higher sensitivity and lower specificity compared to ABC score and SI. For both research and clinical definitions of MT, the AUROC for the RABT score was not significantly higher (Research - RABT: 0.673 [0.610-0.735], ABC: 0.642 [0.551-0.734], SI 0.691 [0.625-0.757]; Clinical - RABT: 0.653 [0.608-0.698], ABC: 0.646 [0.600-0.691], SI 0.610 [0.559-0.660]). CONCLUSION: The RABT score is a valid tool for predicting the need for MTPs, performing similarly with a trend towards higher sensitivity when compared to the ABC score and SI.

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Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare complication after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) adenoviral vector vaccination. In British Columbia (BC), Canada, a provincial clinical care pathway was developed to guide clinicians in evaluating for VITT among patients who present with thrombocytopenia or thrombosis symptoms within 4 to 28 days after adenoviral vector vaccine exposure. All patients had enzyme-linked immunosorbent assay (ELISA) testing for platelet factor 4 (PF4) antibodies, and all cases with positive PF4-ELISA or d-dimer levels ≥2.0 mg/L fibrinogen equivalent units (FEU) had further testing for platelet-activating PF4 antibodies using a modified serotonin release assay (SRA). Between 1 May and 30 June 2021, 37% of 68 patients investigated for VITT had thrombosis, but only 3 had VITT confirmed by PF4-ELISA and SRA. Platelet counts, d-dimer levels, and ELISA optical density values were significantly different between those with and without VITT. Three patients had thrombocytopenia and thrombosis with d-dimer levels >4.0 mg/L FEU but had negative PF4-ELISA and SRA results. Patients with VITT were treated successfully with IV immunoglobulin, nonheparin anticoagulants, and corticosteroids. Our pathway demonstrated that thrombosis is common among patients investigated for VITT and that PF4-ELISA testing is necessary to confirm VITT in those presenting with thrombosis and thrombocytopenia.

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Hemophagocytosis refers to ingestion of hematopoietic elements or mature blood cells by another cell, typically by cells conventionally associated with phagocytic capacity. Although the finding of hemophagocytosis as a prominent feature in a patient's bone marrow might prompt consideration of a hemophagocytic syndrome (HPS) such as hemophagocytic lymphohistiocytosis (HLH) in a clinician's or pathologist's differential diagnosis, this morphologic feature can be nonspecific in the absence of other clinical and laboratory features of pathologic immune activation, which is the sine qua non of HPS/HLH. We describe three patients whose clinical presentations included transfusion-dependent anemia and whose bone marrow aspirates showed unexpectedly brisk hemophagocytosis of mature red blood cells. Despite striking morphologic hemophagocytosis, no patient met criteria for diagnosis of an HPS. Transfusion-associated hemophagocytosis and hyperferritinemia must be carefully distinguished from HLH through clinical and laboratory assessment. Biomarkers of pathologic immune activation are important diagnostic aids.

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AIMS: Mucosal squamous cell carcinomas are the most common head and neck malignancies. We hypothesised that over-expression of intracellular signalling proteins and decreased expression of desmoglein molecules would be associated with aggressive tumour behaviour in patients with head and neck squamous cell carcinoma. METHODS: Seventy-eight cases of head and neck squamous cell carcinoma were immunohistochemically stained for desmoglein 1, desmoglein 2, desmoglein 3, p53, bcl-2, vimentin, cyclin D1, p16, p21, p27, E-cadherin, and E2F-1 in paraffin-embedded tissue blocks in a microarray. RESULTS: The disease-specific survival was 56% at 5 years and 49% at 10 years. Expression of the desmoglein isotypes correlated positively with each other except for desmoglein 2 and desmoglein 3, which did not show a significant correlation. Desmoglein 1 and E-cadherin expression also correlated. On univariate analysis, only expression of desmoglein 1 correlated with patient outcome; lack of expression of desmoglein 1 was associated with a significantly worse disease-specific survival (p = 0.035). Hierarchical clustering analysis identified a subgroup of three patients with an immunophenotype distinct from the other tumours, characterised by co-expression of p16, p27, E2F-1 and bcl-2. Further statistical analysis of the prognostic significance of this small subgroup was not possible, but these three patients are alive and well. CONCLUSIONS: Decreased expression of desmoglein 1 is associated with a worse prognosis in head and neck squamous cell carcinoma patients. Examination of an extended panel of immunomarkers revealed a rare subtype of squamous cell carcinoma characterised by the expression of multiple proliferation-associated markers and the anti-apoptotic protein, bcl-2; determination of the prognostic significance of this subgroup will require study of a larger case series.

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