D-dimer testing: A narrative review.

D-dimer containing species are soluble fibrin degradation products derived from plasmin-mediated degradation of cross-linked fibrin, i.e., 'D-dimer'. D-dimer can hence be considered a biomarker of in vivo activation of both coagulation and fibrinolysis, the leading clinical application in daily practice of which is ruling out venous thromboembolism (VTE). D-dimer has been further evaluated for assessing the risk of VTE recurrence and helping define optimal duration of anticoagulation treatment in VTE, for diagnosing disseminated intravascular coagulation (DIC), and for screening those at enhanced risk of VTE. D-dimer assays should however be performed as intended by regulatory agencies, as their use outside these indications might make them a laboratory-developed test (LDT). This narrative review is aimed at: (1) reviewing the definition of D-dimer, (2) discussing preanalytical variables affecting D-dimer measurement, (3) reviewing and comparing the assays performance and some postanalytical variables (e.g., different units and age-adjusted cutoffs), and (4) discussing the interest of D-dimer measurement across different clinical settings, including pregnancy, cancer, and coronavirus disease 2019 (COVID-19).

Assessing research collaboration networks and social media use among venous thromboembolism researchers during the COVID-19 pandemic

Background: The ways in which research collaborations are formed and strengthened have evolved during the COVID-19 pandemic due to restrictions limiting in-person meetings. Given the need to rapidly adapt to online communication, and to accelerate COVID-19 venous thromboembolism (VTE) research, social media has played an important role in all aspects of these interactions. Aim(s): (1) Assess the size and geographic breadth of VTE researchers' project collaborations before and during the early stages of the COVID-19 pandemic;(2) Characterize how social media platforms are used by VTE researchers. Method(s): An online survey about research collaborations and social media use was distributed in June 2020 to VTE researchers via Twitter, CanVECTOR (n = 59) and INVENT (n = 389) research network websites and email lists. Research collaboration data were analyzed using ego-centred social network analytic techniques to assess the size and composition of researchers' VTE-and COVID-related collaboration networks. Result(s): Over half of respondents (23/45, 51%) reported leading at least one collaborative VTE research project in the past 2 years, with 16 (36%) currently leading COVID-related VTE research. Eighteen (78%) respondents who led VTE research projects also contributed as a collaborator to VTE research projects over the past 2 years, with 17 (74%) contributing to COVID-related VTE research. Research in the VTE field is inter-institutional and international, but early COVID-related collaborations tended to be more local (Table 1). Social media platforms were used primarily by VTE researchers to collect and disseminate COVID-19 VTE research information. Conclusion(s): Research in the VTE field is inter-institutional and international, but early COVID-related VTE research collaborations tended to be more local. Social media platforms may be useful in strengthening international collaborations between VTE researchers with similar interests. (Table Presented).

Evaluation of patients' experience and related qualitative outcomes in venous thromboembolism: A scoping review

Background: Venous thromboembolism (VTE) is a prevalent disease with high morbidity and mortality. VTE has well-documented physical sequelae, however the psychological and emotional experience of patients is seldom evaluated in randomized controlled trials. Aim(s): We conducted a scoping review of published qualitative studies aiming to understand the physical, psychological, and emotional impact of VTE as reflected from patients' perspectives. This scoping review is part of a larger initiative to develop a core outcome set for VTE treatment studies. This research is funded by the Canadian Institutes of Health Research and CanVECTOR. Method(s): A systematic literature search was conducted to identify qualitative studies assessing patient experience of VTE. Two authors independently screened titles and s using Covidence systematic review software. Full text reviews were conducted independently by two study team members. QSR International NVivo 12 software was used to perform systematic line-by- line coding of the Results and Discussion from all included articles. A modified method of thematic synthesis was used to collate themes upon reading and re-reading of the publications. Result(s): Our search strategy returned a total of 4944 citations;28 were ultimately included in the analysis. The studies were conducted across 13 countries and representative of 436 participants including a spectrum of VTE sub-populations. There were seven major themes identified;Acute Impacts: An Unforeseen Blow, Sustained Psychological Distress, Loss of Self: Life is Changed, Challenges of Thrombosis Management, Balancing Coping and Control, Negative Experience with the Medical System, and VTE in the Context of Other Conditions. Each major theme was comprised of additional subthemes (Figure 1). Conclusion(s): The physical, psychological, and emotional impacts of VTE extend beyond the quantitative outcomes typically evaluated in clinical trials. An improved understanding of the outcomes most important to patients will improve patient-centered research and care in VTE.

Rivaroxaban for Improvement in Thromboembolism Outcomes in Patients with Multiple Myeloma on Lenalidomide-Based Therapy: The Rithmm Feasibility Pilot Trial

Introduction:The association between thrombosis (TE) and cancer has been well established. The risk for thrombosis in Multiple Myeloma (MM) is further compounded by therapy-related factors, which increase the risk for both arterial and venous TE. Lenalidomide + dexamethasone (Ld) is the most widely used backbone therapy for MM and may increase the risk of TE. The current standard TE prophylaxis for patients on Ld is low dose aspirin (ASA) for low risk patients or low molecular weight heparin for high risk patients. Direct oral anticoagulants have been used empirically and have been evaluated in small prospective cohort studies with promising results. Methods: RithMM is an ongoing open label Canadian multicenter pilot feasibility RCT to assess the efficacy and safety of daily oral rivaroxaban 10 mg (Riva) versus ASA 81 mg in patients with MM on Ld-based therapy. Our primary objective is to assess the feasibility of accrual of patients with MM starting on Ld-based therapy. Patients not on therapeutic anticoagulation or antiplatelet agents for another indication (e.g. atrial fibrillation) are eligible for RithMM. Primary clinical endpoints are major cardiovascular (CV) events or major bleeding as per the ISTH criteria. The study will be considered feasible if 86 patients in 4 Canadian sites (London, Ottawa, Halifax, Niagara) can be enrolled in 12 months after each site activation. Sites are expected to accrue an average of 1.8 patients per month. Patients are randomly assigned to receive ASA (control) or Riva (intervention) using a simple randomization sequence run by the Redcap system, utilizing an automated assignment procedure. Patients enter the study at the time of anticoagulant initiation and are followed for 6 months, or until they withdraw from the study;die or develop a primary clinical outcome;whichever comes first. Herein we present the interim analysis of RithMM after study completion in 2 of 4 sites. Feasibility assessment: 17 patients were randomized to ASA and 17 to Riva (1 patient did not take the study drug). Feasibility assessment was severely impacted by the temporary but prolonged research activity closures secondary to the COVID-19 pandemic that limited direct patient accrual and led to significant delays in REB approval of the participating sites. The first patient was enrolled in January 2019 in London. Ottawa opened in October 2019, Halifax in December 2020 and Niagara in May 2021. A total of 34 patients have been enrolled: 22 London, 11 Ottawa and 2 Halifax. London was the only site actively accruing for 12 consecutive months. Ottawa opened for 3 months, held accrual for 9 months, then reopened for 7 months. Halifax was open for only 1 month. Niagara opened in May 2021, the time of study data lock for this . In addition, 7 potentially eligible patients were not screened given that they were enrolled in a MM treatment trial that did not permit enrolment in another trial. The accrual rate was excellent for London (105%) and Ottawa (52% in 10 months). The drop-out rate was 6% (2 patients) and drug compliance 100%. Clinical Outcomes: Baseline characteristics are depicted in the table. One patient in the ASA arm developed a proximal deep vein thrombosis 2 months after starting treatment, and another developed a clinically relevant nonmajor bleeding 6 weeks after starting ASA. Discussion: This is the interim analysis of the RithMM pilot trial that aims to evaluate the feasibility of accrual of MM patients on Ld -base therapy to assess the efficacy and safety of Riva versus ASA in preventing TE complications. The study was initiated during the COVID-19 pandemic turmoil, which severely impacted in the proper activation of 3 of the 4 participating sites. Despite this significant limitation, 2 sites were able to maintain the accrual of patients. Only 1 site remained opened according to the pre-specified consecutive 12- month study period. Despite this barrier, we could still attain an excellent accrual rate of 39.5% in 2 sites (London and Ottawa). The incidence of TE or bleeding was low, with o difference between ASA and Riva. However, the study was not powered to assess these outcomes. Lastly, Ld is the most widely used backbone therapy in MM, both in upfront and relapsed settings. Our group does not anticipate any barriers to achieving successful completion of accrual provided the hospital's activities remain safe and research activities open. [Formula presented] Disclosures: Louzada: Celgene: Honoraria;Janssen: Honoraria;Pfizer: Honoraria;Amgen: Honoraria. McCurdy: Sanofi: Honoraria;GSK: Consultancy, Honoraria;Takeda: Consultancy, Honoraria;Janssen: Consultancy, Honoraria;Amgen: Consultancy, Honoraria;Celgene: Consultancy, Honoraria. Phua: Pfizer: Honoraria;Amgen: Honoraria;AstraZeneca: Honoraria;Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees;NovoNordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees;Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Le Gal: Aspen: Honoraria;Bayer: Honoraria;Pfizer: Honoraria;LEO Pharma: Honoraria;BMS: Honoraria;Sanofi: Honoraria. Lam: Bristol-Meyers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees;Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees;AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees;Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees;Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees;Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees;Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees;Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees;AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees;Beigene: Honoraria, Membership on an entity's Board of Directors or advisory committees;Hoffmann-La Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees;Johnson & Johnson: Honoraria, Membership on an entity's Board of Directors or advisory committees;Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees;Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees;SeaGen: Honoraria, Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: Rivaroxaban 10 mg oral daily for thrombosis prophylaxis in myeloma patients on lenalidomide-based therapy. Health Canada approved the off label use for study purposes

Thrombocytopenia with and without Thrombosis Following COVID-19 Vaccination

Introduction: Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) were rapidly developed during the COVID-19 pandemic. There is emerging evidence of adverse hematologic effects including thrombocytopenia, for recipients of both mRNA and adenovirus-vector vaccines. We report findings in 9 patients diagnosed with thrombocytopenia following administration of an approved COVID-19 vaccine and managed according to the ASH COVID-19 Thrombosis with Thrombocytopenia Syndrome (TTS) recommendations [https://www.hematology.org/covid-19/vaccine-induced-immune-thrombotic-thrombocytopenia]. Methods: The study population included adults >18 years of age presenting to a large Canadian tertiary care centre, between April 1 st, 2021 and May 31 st, 2021, with new-onset thrombocytopenia within 31 days of receiving COVID-19 vaccination. Vaccines approved during this time period in Canada included BNT162b2 (Pfizer-BioNTech, mRNA) vaccine, mRNA-1273 (Moderna, mRNA) vaccine, and ChAdOx1-S (AstraZeneca (AZ), adenovirus vector-based) vaccine. We report on the initial presentation, management and 90-day outcomes. Results: Among 9 patients with thrombocytopenia included in this cohort, the median age was 55 years (range 24 to 73), and 5 patients (56%) were female. Seven patients received AZ and 2 had Pfizer vaccines. All events occurred after the first dose of COVID-19 vaccine with a median of 11 days between vaccination and presentation to hospital (range 2 to 31). All patients admitted to hospital tested negative for COVID-19 by PCR. Four patients developed TTS, as confirmed on both HIT ELISA and serotonin release assay, following AZ vaccination. Two patients presented with headaches and were diagnosed with cerebral vein thrombosis (CVT);and 2 presented with dyspnea and were diagnosed with venous thromboembolism (VTE). Platelet counts at presentation ranged 14-136 and D-dimer ranged 4000 to >44,000. HIT ELISA optical densities were persistently elevated. Three patients were admitted to hospital and received non-heparin parenteral anticoagulation, IVIG, and steroids. One patient had refractory thrombocytopenia with extension of CVT prompting use of therapeutic plasma exchange. Two patients had recurrent thrombocytopenia within 30 days of discharge and responded to repeat IVIG treatment. Five patients developed immune thrombocytopenic purpura (ITP), four without associated thrombosis and one patient with history of ITP and splenectomy, maintained on Revolade, presented with ITP flare and deep vein thrombosis. Presenting complaints included petechial rash and minor bleeding such as epistaxis. Platelet counts ranged from undetectable to 67;D-dimer levels were normal in all at presentation. Four patients were admitted to hospital and received IVIG +/- steroids. Two patients had recurrent severe thrombocytopenia within 14 days of discharge, requiring repeat steroid pulse. See Table for summary of all patients. Conclusion: In summary, application of the ASH TTS guidance to patients presenting with thrombocytopenia, with and without thrombosis, following COVID-19 vaccination was instrumental in the early identification and successful management of these complications. [Formula presented] Disclosures: Carrier: Sanofi: Honoraria;Pfizer: Honoraria, Research Funding;Servier: Honoraria;Bayer: Honoraria;Leo Pharma: Honoraria, Research Funding;BMS: Honoraria, Research Funding. Le Gal: BMS: Honoraria;Aspen: Honoraria;Bayer: Honoraria;LEO Pharma: Honoraria;Pfizer: Honoraria;Sanofi: Honoraria. Castellucci: BMS: Honoraria;Pfizer: Honoraria;Amag Pharmaceuticals: Honoraria;The Academy: Honoraria.