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.

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.

Evaluation of activated partial thromboplastin time coagulation waveform analysis for identification of patients with acquired factor VIII inhibitors.

INTRODUCTION: Activated partial thromboplastin time (PTT) coagulation waveforms produced by optical detection system coagulation analyzers provide additional potentially useful and routinely underutilized information for the evaluation of a patient's coagulation system. We aimed to identify features of PTT coagulation waveforms, available for all PTT assays performed in our hospital laboratories, that may prove useful in directing early investigations in patients with unexplained prolonged PTT. METHODS: We retrospectively reviewed 211 PTT coagulation waveforms from patient testing and categorized them based on the underlying hemostatic abnormality: normal, therapeutic anticoagulation, lupus anticoagulant, congenital factor deficiency, or acquired factor VIII inhibitor. We compared quantitative waveform parameters and the frequency of qualitatively abnormal double-peaked first derivative waveform curves between these groups. RESULTS: Partial thromboplastin time and derivative curve maxima and minima differed significantly between acquired factor VIII inhibitors and other diagnostic categories, and the second derivative curve minimum demonstrated the highest area under the receiver operator characteristic curve for identification of acquired factor VIII inhibitors (0.860; maximum accuracy: 79.5% for 2Dmin> -39.3 mAbs/s2 [sensitivity 90.5%; specificity 77.2%]). The presence of an abnormal double-peaked first derivative curve had a sensitivity of 83.3% and specificity of 81.6% for identification of acquired factor VIII inhibitors in cases with PTT >50 seconds. CONCLUSION: Partial thromboplastin time coagulation waveform analysis can aid in identification of patients with acquired factor VIII inhibitors and may be of clinical utility in directing early laboratory investigations to identify patients at risk of severe bleeding without prompt intervention.