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Background: Mass spectrometry methods are emerging as tools to detect M-proteins in the serum of multiple myeloma patients with increased sensitivity and specificity compared to traditional electrophoretic methods., Methods: A liquid handling system, the Agilent AssayMAP Bravo, with liquid chromatography high-resolution quadrupole-time-of-flight (LC-QTOF) mass spectrometry to analyze intact light chains was compared to immunofixation electrophoresis (IFE) for M-protein analysis. 210 patient serum samples were analyzed in a split sample comparison (LC-QTOF vs. IFE). LC-QTOF and IFE were interpreted by different individuals in a blinded fashion and results were grouped into four categories: IFE+/QTOF+, IFE+/QTOF-, IFE-/QTOF+, or IFE-/QTOF-., Results: The LC-QTOF method is able to determine the isotype of M-proteins in a similar fashion to IFE. The estimated limit of detection was ∼ 35 mg/L for adalimumab. For split patient samples, 168 were QTOF+/IFE+, 25 were QTOF-/IFE-, 14 were QTOF+/IFE-, and three were QTOF-/IFE + . Excluding the QTOF+/IFE- results due to the improved sensitivity of the LC-QTOF method, the concordance of LC-QTOF with IFE was ∼ 98 %. The LC-QTOF method also offers improved specificity compared to electrophoretic methods due to inclusion of the accurate mass of the light chains., Conclusions: The LC-QTOF method was deemed fit for clinical use as a qualitative test with increased sensitivity and specificity compared to IFE. The LC-QTOF can also better resolve therapeutic and multiple myeloma IgG-kappa M-proteins, which present a challenge for electrophoretic methods. Future work will determine suitability of this method as an assessment of minimal residual disease status., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Canadian Society of Clinical Chemists. All rights reserved.)

Background: Patients with hematological cancers have increased COVID-19 morbidity and mortality, and these patients show attenuated vaccine responses. This study aimed to characterize the longitudinal humoral immune responses to COVID-19 vaccination in patients with hematological malignancies., Patients and Methods: We conducted a prospective cohort study, collecting samples from March 2021 to July 2022, from patients seen at a cancer treatment center in London, Ontario, Canada, who met the following eligibility criteria: age ≥18 years, diagnosed with a hematological malignancy, recipient of a COVID-19 vaccine during the study period, and able to provide informed consent., Results: Median anti-S titers (MST) were 0.0, 64.0, and 680.5 U/mL following first (V1), second (V2), and third (V3) vaccine doses, respectively. Patients with lymphoid malignancies' response to vaccination was attenuated compared to myeloid malignancy patients after V2 and V3 (P < .001, P < .01). Active treatment was associated with lower antibody titers (MST 10) compared to treatment 12-24 months (MST 465, P = .04367) and >24 months (MST 1660.5, P = .0025) prior to vaccination. V3 significantly increased antibody titers compared to V2 for patients less than 3 months from treatment. Increasing age was associated with smaller antibody response following V2 (P < .05), but not following V3. Patients receiving anti-CD20 therapy did not demonstrate increased antibody titer levels after V3 (V2 MST 0, V3 MST 0; P > .05)., Conclusion: We report an attenuated serologic response to COVID-19 vaccination in our study population of patients with hematological malignancy. The immune response to vaccination was affected by patient age, diagnosis, treatment, and timing of treatment exposure., Competing Interests: Disclosures None of the authors have any competing interests to disclose., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Hemophilia B is a coagulation disorder that puts patients at an increased risk of bleeding. Factor (F) IX replacement therapy is traditionally used in such cases to maintain hemostasis. Nonacog beta pegol (N9-GP; Refixia) is a glycoPEGylated, extended half-life, recombinant FIX product that has demonstrated safety and efficacy when used to manage persons with hemophilia B., Key Clinical Question: Given the limited real-world evidence, we aimed to explore the role of N9-GP in maintaining hemostasis in persons with hemophilia B undergoing surgery., Clinical Approach: In this case series, we report real-world clinical experience with N9-GP to maintain hemostasis in persons with hemophilia B undergoing major and minor surgeries., Conclusion: The majority of cases presented in this case series had an excellent or very good hemostatic response, with no reported surgical complications related to the use of N9-GP., (© 2023 The Authors.)

We report a case of a patient with recurrent hematomas while on anticoagulation for a pulmonary embolism and a prolonged hospital stay due to a delayed diagnosis for acquired hemophilia A. Acquired hemophilia A is a rare autoimmune bleeding disorder with autoantibodies directed against coagulation factor VIII (FVIII), leading to an acquired FVIII deficiency. A prolonged isolated activated partial thromboplastin time (aPTT) in a bleeding patient warrants workup for acquired hemophilia A. This is specifically challenging in patients with thrombosis on anticoagulation and can lead to significant delays in diagnosis and associated morbidities. The case highlights the need for further awareness of this disease, potential laboratory pitfalls when conducting and interpreting coagulation assays, and the management considerations in a patient with a simultaneous thrombotic and hemorrhagic condition., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2023, MacNeill et al.)

Background: The Canadian Bleeding Disorders Registry (CBDR) captures data from 24 hemophilia treatment centers and patients directly. Nonacog beta pegol (N9-GP) was approved in Canada in 2018., Objectives: To assess treatment outcomes following switching to N9-GP in a real-world setting., Methods: CBDR data for Canadian male patients (aged 7-72 years) with hemophilia B receiving prophylactic N9-GP for ≥6 months as of March 31, 2021, were included. To allow comparison with the previously used products, only patients for whom data were available in the CBDR for at least 6 months before the switch to N9-GP were included in this retrospective analysis., Results: Forty-two patients were included in the analysis (total observation period: 148.0 patient-years). The distribution of disease severity was 62% severe, 36% moderate, 2% mild, with 62% of patients previously receiving recombinant factor IX-Fc-fusion protein (rFIXFc) and 38% previously receiving standard half-life (SHL) recombinant factor IX (rFIX). During a median follow-up period of 2.3 years on N9-GP prophylaxis, 232 bleeds were reported in 30 patients, 29% of patients reported zero bleeds. The median overall annualized bleeding rate on N9-GP was 0.73 for patients switching from rFIXFc (previously 1.44) and 2.10 for patients switching from SHL rFIX (previously 6.06). Median total annualized factor consumption (IU/kg) was lower with N9-GP than with previous SHL rFIX (2152 vs 3018) and previous rFIXFc (1766 vs 2278)., Conclusions: Results from this first real-world study of N9-GP in patients with hemophilia B suggest optimal bleeding control with low factor consumption after switching to N9-GP, irrespective of the previous product., (© 2022 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)

Background: We aim to determine the clinical utility of reflex coagulation investigations (RCI) for prolonged lupus insensitive activated partial thromboplastin time (aPTT) at our institution., Methods: We retrospectively reviewed all potential RCI (lupus insensitive aPTT of ≥32s) from April 2014 to June 2019. Our diagnostic algorithm requires completion of RCI only if samples had no interfering medications to explain a prolonged aPTT and were either from a preoperative sample or from a patient presenting with unexplained bleeding. Appropriate RCI samples undergo further investigations with one-stage factor activity testing for factors 8(FVIII), 9(FIX), and 11(FXI) reflexively. Data were obtained through electronic medical records to capture clinical characteristics, laboratory findings, prophylactic hemostatic replacement, and bleeding outcomes., Results: Three thousand and three hundreds seventeen samples from 2940 distinct patients were considered as potential RCI during the study period. 263/3317 (8%) samples had RCI completed. Of those, 55/263 (21%) had abnormal factor testing, with the majority from preoperative setting (43/55; 78%). 5/43 (12%) patients were referred to hematology for preoperative evaluation. 5/43 patients received preoperative hemostatic support. A total of 5 patients (5/43) developed postop bleeding. Six patients (6/55) had RCI for unexplained bleeding, and five patients (83%) had a newly identified clinically significant bleeding disorder., Conclusion: Reflex coagulation investigations benefited patients presenting with unexplained bleeding as this expedited the diagnosis and management of clinically significant bleeding disorders. RCI for preoperative evaluation infrequently led to additional hemostatic support/referral to hematology. The lack of additional workup for an abnormal factor activity level suggests laboratory alert fatigue as a potential contributory factor., (© 2021 John Wiley & Sons Ltd.)

Competing Interests: Intérêts concurrents: Chai Phua a reçu des honoraires personnels d’Hemalytic, d’Amgen, de Gilead, de Teva, de Takeda et Shire, de Roche, de Novo Nordisk, de Novartis, d’Octapharma, de Bristol Myers Squibb et Celgene, de Pfizer, de Bayer, de Janssen, de Sanofi et Bioverativ, et d’AstraZeneca, indépendamment des travaux soumis. Aucun autre intérêt concurrent n’a été déclaré.

Competing Interests: Competing interests: Chai Phua has received personal fees from Hemalytic, Amgen, Gilead, Teva, Takeda/Shire, Roche, NovoNordisk, Novartis, Octapharma, Bristol Myers Squibb/Celgene, Pfizer, Bayer, Janssen, Sanofi/Bioverativ and AstraZeneca, outside the submitted work. No other competing interests were declared.

Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder (PCSM-LPD) is a rare indolent disorder often associated with a favourable prognosis. It typically presents as a solitary skin lesion, mainly in the head, neck, or upper trunk region. Multifocal PCSM-LPD is a rare entity, with no standard treatment approaches available. In this article, we present the case of a 56-year-old male patient with multifocal biopsy-proven PCSM-LPD that was treated with methotrexate orally at 10 mg/m 2 body surface area weekly and successfully achieved full clinical resolution by the 10th week of therapy. A review of the literature indicates the efficacy of combination chemotherapy. However, due to the indolent nature of this disorder and the undesired side effects from combination chemotherapy, our treatment method involved oral methotrexate alone, and it was successful. Oral methotrexate is a potential therapeutic option in the management of multifocal PCSM-LPD and it warrants further investigations., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2020, Dimassi et al.)

: The management of a patient with hemophilia undergoing cardiovascular surgery relies on accurate coagulation test results. Both unfractionated heparin (UFH) and protamine sulfate used during cardiac surgery can interfere with factor and inhibitor assays. Here we describe the effects of UFH and protamine sulfate on routine coagulation, factor activity, and inhibitor assays. Pooled normal plasma (PNP) with UFH, PNP with protamine sulfate, PNP with both protamine sulfate and UFH were tested for the activated partial thromboplastin time (aPTT), prothrombin time (PT), thrombin time (TT), UFH anti-Xa, one-stage factor VIII (FVIII) activity, one-stage factor IX (FIX) activity, and Bethesda inhibitor assays for FVIII and FIX. UFH had a dose-dependent effect with TT, aPTT, and PT. On Bethesda inhibitor testing, FIX inhibition was detected at 1 U/ml UFH and 3 U/ml UFH for FVIII. Increasing protamine sulfate concentration in PNP prolonged the PT and aPTT in a dose-dependent manner, decreased FVIII and FIX activity and did not affect TT or UFH anti-Xa. At protamine sulfate doses of at least 200 μg/ml there was weak FVIII and FIX inhibition detected. At lower ratios of protamine sulfate to UFH (0.6 : 1-0.8 : 1), the aPTT decreased, suggesting reversal of UFH. However, at protamine sulfate to UFH ratios of 1.0 : 1 and higher, aPTT prolongation was observed. Inhibition of FVIII and FIX was detected at low ratios of protamine sulfate to UFH (below 0.4 : 1) and disappeared at higher ratios. UFH and protamine sulfate, alone or in combination, impact factor activity and inhibitor testing for both FVIII and FIX. Hence, factor activity and inhibitor assay results should be interpreted with caution when UFH or protamine sulfate are present.

The goal of treating Von Willebrand Disease (VWD) is to replace deficient or dysfunctional Von Willebrand Factor (VWF) protein. However, the choice of treatment has to be considered carefully in view of patient factors and the unique properties of replacement products. Tailoring a treatment plan to an individual patient's bleeding challenge is an intricate process. This review describes personalization of treatment selection for desmopressin (DDAVP), VWF replacement concentrates, including the newly available recombinant VWF (rVWF) and prophylaxis as a treatment approach in VWD., (Copyright © 2019. Published by Elsevier Ltd.)

We describe the case of a 67-year-old female patient presenting with constitutional symptoms and rapid decline. Two bone marrow core biopsies were performed, with spindled cells identified and thought to represent marrow involvement by systemic mastocytosis on the first biopsy. A diagnosis of metastatic vascular malignancy with sarcomatoid features was favored on the second core biopsy. The patient rapidly deteriorated and passed away. The post-mortem examination revealed a splenic angiosarcoma with metastasis to the liver and bone marrow. Splenic angiosarcoma is a rare, aggressive entity, with bone marrow metastasis even more uncommon. This report perceives this as a diagnostic consideration on bone marrow biopsies with spindled cells and explores the diagnostic dilemma and overlapping features of systemic mastocytosis and angiosarcoma., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2019, Plantinga et al.)

Background: Adults who require long-term anticoagulation with low-molecular-weight heparin (LMWH) such as cancer patients or the elderly may be at increased risk of fractures., Objective: To determine the effects of LMWH therapy of at least 3 months' duration on fractures and bone mineral density (BMD) in non-pregnant adult populations., Methods: We systematically reviewed electronic databases (e.g., MEDLINE, EMBASE), conferences and bibliographies until June 2015 and included comparative studies in non-pregnant adult populations that examined the effects of LMWH (≥3 months) on fractures and BMD. We synthesized evidence qualitatively and used random-effects meta-analysis to quantify the effect of LMWH on fractures., Results: Sixteen articles reporting 14 studies were included: 10 clinical trials (n = 4865 participants) and four observational cohort studies (3 prospective, n = 221; 1 retrospective, n = 30). BMD and fractures were secondary outcomes in the majority of trials, while they were primary outcomes in the majority of observational studies. In participants with venous thromboembolism and underlying cardiovascular disease or cancer (5 RCTs, n = 2280), LMWH for 3-6 months did not increase the relative risk of all fractures at 6-12 months compared to unfractionated heparin, oral vitamin K antagonists or placebo [pooled risk ratio (RR) = 0.58, 95 % CI: 0.23-1.43; I(2) = 12.5 %]. No statistically significant increase in the risk of fractures at 6-12 months was found for cancer patients (RR = 1.08, 95 % CI: 0.31-3.75; I(2) = 4.4 %). Based on the data from two prospective cohort studies (n = 166), LMWH for 3-24 months decreased mean BMD by 2.8-4.8 % (depending on the BMD site) compared to mean BMD decreases of 1.2-2.5 % with oral vitamin K antagonists., Conclusions: LMWH for 3-6 months may not increase the risk of fractures, but longer exposure for up to 24 months may adversely affect BMD. Clinicians should consider monitoring BMD in adults on long-term LMWH who are at increased risk of bone loss or fracture.