Treatment changes in hemophilia A with chromogenic factor VIII assay implementation.

Background: The one-stage assay (OSA) and the chromogenic assay (CSA) are 2 factor VIII (FVIII) assays used for the diagnosis and classification of hemophilia A. Discrepancies between the 2 assays exist in approximately one-third of patients with mild hemophilia A. Objectives: The objectives of this study were to report the proportion of patients with mild or moderate hemophilia A and OSA-CSA discrepancies and to report the observed changes in treatment approach prompted by the presence of assay discrepancy. The study aimed to identify OSA:CSA ratio associated with the highest sensitivity for identification of patients in whom modification of treatment approach may be recommended. Methods: This is a retrospective cohort study including adult (>18-year-old) patients with mild or moderate hemophilia A who were followed up at the Adult British Columbia Hemophilia Program between January 2013 and March 2019. Results: A total of 75 patients with mild and 23 with moderate hemophilia A based on baseline OSA were included. Overall, 52% of study patients had OSA-CSA discrepancies, and change in treatment approach was observed in 27% of patients with OSA-CSA discrepancy. The OSA:CSA ratio of 1.8 to 3.5 demonstrated the highest area under the receiver operating characteristics curve and sensitivity for identification of patients in which modification of treatment approach may be recommended (AUC 0.75; sensitivity 71%). Conclusion: In our population, OSA-CSA discrepancy was observed in 52% of patients with mild or moderate hemophilia A, and the treatment approach in 27% of these patients had to be modified.

VEXAS syndrome: A review of bone marrow aspirate and biopsies reporting myeloid and erythroid precursor vacuolation.

Myeloid and erythroid precursor vacuolation is a common dysplastic finding associated with myeloid malignancies, toxins, drug, and nutritional deficiencies. It has been described as a core morphologic feature in VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. We sought to determine the number of cases attributable to VEXAS syndrome in bone marrow biopsies and aspirates (BAMB) reporting myeloid precursor vacuolation. We reviewed 1318 individual BAMB reports from January 2020 to July 2021 where "vacuole(s)," "vacuolation," or "vacuolated" was reported. Bone marrow biopsies with vacuolation confined to blasts or those completed as routine workup prior to stem cell transplant or post induction chemotherapy for AML (acute myeloid leukemia) were excluded. Myeloid and erythroid precursor vacuolation was noted in 219 reports representing 210 patients. The most common etiology was myelodysplastic syndrome (MDS) (38.6%), AML (16.7%), lymphoproliferative disorders and multiple myeloma (7.6%), drug or toxin exposure (5.2%) myeloproliferative neoplasm (MPN) or MPN/MDS overlap syndrome (4.3%). VEXAS syndrome was determined to be the etiology in 2.9% of patients. Two additional cases of VEXAS syndrome with bone marrow biopsies reported in the specified time frame did not explicitly report myeloid or erythroid precursor vacuolation but were identified based on clinical suspicion and repeat BAMB review. Myeloid and erythroid precursor vacuolation is a dysplastic feature attributable to VEXAS syndrome in at least 2.9% of cases. Standardized reporting of vacuolization, triaging of molecular sequencing and optimal treatment of this disorder are critical issues facing those seeing patients with suspected VEXAS syndrome.

A young woman with persistent sore throat, Epstein-Barr virus, lymphadenopathy, and aberrant CD4 + CD7- T-cells.

A young woman with persistent EBV viremia and lymphocytosis had an abnormal CD4- T cell population with aberrant loss of CD7. She had a diagnosis of chronic active EBV (CAEBV), a lymphoproliferative disorder for which she ultimately required allogeneic hematopoietic stem cell transplantation.

Evaluation of immunoglobulin replacement therapy in secondary immunodeficiency at three British Columbia hospitals.

BACKGROUND AND OBJECTIVES: Immunoglobulin (Ig) usage has ongoing shortage concerns. Secondary immunodeficiencies (SIDs) account for a major proportion of usage of Igs in Canada. We audited Ig usage in patients with SID at three British Columbia hospitals to determine whether more stringent local guidelines are necessary. MATERIALS AND METHODS: A retrospective chart review was performed for patients who had Ig ordered between 1 January 2018 and 31 December 2019 for any SID indication. Cohorts were stratified into chronic and new users, and the Australian BloodSTAR guidelines were used as the benchmark at the time of conception. Having an eligible primary diagnosis, meeting SID criteria, an appropriate dosage and follow-up immunoglobulin G (IgG) levels encompassed appropriate usage. RESULTS: There were no demographic differences between chronic (N = 81) and new (N = 33) cohorts. The new cohort had a higher rate of appropriate usage (45.7% vs. 66.7%, p = 0.06). The most common reason for inappropriate usage in both groups was the lack of follow-up IgG level at 6 or 12 months. Factors, displayed by relative risk (RR), associated with appropriateness included the dispensing hospital (RR: 6.60), use of subcutaneous Ig (RR: 3.84), having an IgG level before starting therapy (RR: 3.51) and documentation of clinical benefit (RR: 4.70). CONCLUSION: There are high rates of inappropriate Ig usage in SID patients in both new and chronically treated groups. More stringent local guidelines and processes for assessing initial and ongoing Ig replacement are warranted.

Clinical care pathway for the evaluation of patients with suspected VITT after ChAdOx1 nCoV-19 vaccination.

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.

Lactate and glucose as additional considerations to the plasma sodium level-corrected erythrocyte mean corpuscular volume report when using the Sysmex XE-2100.

BACKGROUND: Mean corpuscular volume (MCV) can be artefactually inflated, by variation in sodium concentration, on the Sysmex XE-2100. We report that severe hyperglycemia and modest lactic acidemia can also spuriously increase MCV. To catch and correct such inaccurate MCV measurements, we propose to flag them using commonly assayed biomarkers. MATERIALS AND METHODS: We examined the relationship between delta MCV (uncorrected MCV minus corrected MCV), plasma osmolality, and levels of plasma glucose, lactate, and sodium in 60 samples from emergency room patients. Based on these biomarkers, we developed and tested a preliminary composite flag system to identify high delta MCV on 105 ER samples. Finally, we evaluated a revised composite flagging system optimized to improve the positive predictive value. RESULTS: Plasma osmolality, glucose and lactate are each correlated with delta MCV. The revised composite flag system - based on ≥ 5.0 mmol/L of plasma lactate, > 32 mmol/L of glucose, or > 150 mmol/L of sodium - identified twice as many patients with spuriously elevated MCV as the vendor recommended MCHC flagging system. The associated positive predictive value of 31%, while lower than the vendor flagging system (62%), was considered adequate for implementation in our laboratory. CONCLUSIONS: We recommend reporting clinically significant corrected MCVs, based on sample pre-dilution with the Sysmex buffer, when the proposed composite metabolic flag is triggered.