Three patients with severe manifestations of VITT after Covid-19 vaccination had a poor response to initial therapy with anticoagulants and intravenous immune globulin. Their conditions improved ...after therapeutic plasma exchange was initiated, and they were able to leave the hospital.
Older patients are significantly underrepresented in cancer clinical trials. A literature review was undertaken to identify the barriers that impede the accrual of this vulnerable population onto ...clinical trials and to determine what specific strategies are needed to improve the representation of older patients in research studies.
A systematic literature search was undertaken using several different strategies to identify relevant articles.
Nine of 31 relevant papers from 159 citations were included. Age is a significant barrier to recruitment; only a quarter to one third of potentially eligible older patients are enrolled onto trials. Physicians' perceptions, protocol eligibility criteria with restrictions on comorbid conditions, and functional status to optimize treatment tolerability are the most important reasons resulting in the exclusion of older patients. Other barriers include the lack of social support and the need for extra time and resources to enroll these patients. Conversely, older patients do not view their age as an important reason for refusing trials.
Specific clinical trials confined to older patients should be conducted to evaluate tumor biology, treatment tolerability, and the effect of comorbid conditions. Protocol designs need to stratify for age and be less restrictive with respect to exclusions on functional status, comorbidity, and previous cancers, such that results are generalizable to older patients. Physician education to dispel unfounded perceptions, improved access to available clinical trials, and provision of personnel and resources to accommodate the unique requirements of an older population are possible solutions to remove the barriers of ageism.
Viscoelastic assays (VEAs) that include thromboelastography and rotational thromboelastometry add value to the investigation of coagulopathies and goal-directed management of bleeding by providing a ...complete picture of clot formation, strength, and lysis in whole blood that includes the contribution of platelets, fibrinogen, and coagulation factors. Conventional coagulation assays have several limitations, such as their lack of correlation with bleeding and hypercoagulability; their inability to reflect the contribution of platelets, factor XIII, and plasmin during clot formation and lysis; and their slow turnaround times. VEA-guided transfusion algorithms may reduce allogeneic blood exposure during and after cardiac surgery and in the emergency management of trauma-induced coagulopathy and hemorrhage. However, the popularity of VEAs for other indications is driven largely by extrapolation of evidence from cardiac surgery, by the drawbacks of conventional coagulation assays, and by institution-specific preferences. Robust diagnostic studies validating and standardizing diagnostic cutoffs for VEA parameters and randomized trials comparing VEA-guided algorithms with standard care on clinical outcomes are urgently needed. Lack of such studies represents the biggest barrier to defining the role and impact of VEA in clinical care.
Despite the fact that direct oral anticoagulants (DOACs) are favoured over warfarin for stroke prevention in patients with non-valvular atrial fibrillation (NVAF), physicians need to maintain ...competence in using and monitoring warfarin since many patients have contraindications or other barriers to using DOACs. Unlike DOACs, warfarin therapy requires regular blood testing to ensure that it is within a target range to ensure efficacy and safety. There is limited real-world data on the adequacy of warfarin control and the cost and burden of monitoring warfarin therapy in Canadian NVAF patients.
In a large cohort of Canadian patients with NVAF on warfarin we assessed time in therapeutic range (TTR), determinants of TTR, process of care, direct costs, health related quality of life and loss of work time and productivity related to warfarin therapy.
Five hundred and fifty one patients with NVAF, either newly initiated or stable on warfarin were prospectively enrolled across 9 Canadian provinces from primary care practices and anticoagulant clinics. Participating physicians provided baseline demographic and medical information. Patients completed diaries for 48 weeks, capturing information about International Normalized Ratio (INR) test results, test locations, process of INR monitoring, direct costs of travel, health-related quality of life and work productivity measures. TTR was estimated using linear interpolation of INR results and linear regression used to investigate associations between TTR and factors (defined a priori).
Four hundred and eighty (87.1%) patients had complete follow-up with an overall TTR of 74.4% based on 7,175 physician-reported INR values from 501 patients. 88% of this cohort were monitored through routine medical care (RMC). The average number of INRs per patient during the 48-week period was 14.1 (standard deviation (SD) = 8.3) tests with a mean duration of 23.8 (SD = 11.1) days between tests. We did not find a relationship between TTR and age, sex, presence of major comorbidities, patient's province of residence or rural vs. urban residence. 12% of patients monitored through anticoagulant clinics had significantly better TTR than patients monitored through RMC (82% vs. 74%; 95% confidence interval: -13.8, -1.2; p = 0.02). Health related quality of life utility values were high and remained consistent throughout the study. The majority of patients reported no impact on either work productivity or impairment of regular activities due to being on long-term warfarin treatment.
We showed excellent overall TTR in an observed Canadian cohort, with monitoring through a dedicated anticoagulant clinic being associated with a statistically and clinically significant improvement in TTR. The burden of warfarin therapy on patients' health related quality of life or daily work and activities was low.
Objective To assess the validity of fibrinogen assay of rotational thromboelastometry (FIBTEM)-derived estimates of fibrinogen in samples collected during cardiopulmonary bypass in cardiac surgical ...patients by comparison to Clauss method fibrinogen concentration. Design Retrospective observational study. Setting Single university hospital center. Participants Human participants. Interventions Retrospectively obtained laboratory assays including rotational thromboelastometry (ROTEM) and Clauss fibrinogen assay. Measurements and Main Results A retrospective review was performed of anesthesia records at a single university teaching hospital during a 1-year period. From paired samples taken near the end of cardiopulmonary bypass, fibrinogen concentrations (Clauss method) were compared with FIBTEM-derived measures of maximal clot firmness (MCF) and clot amplitude at 10 minutes (A10) using Spearman’s rank correlation, linear regression, and receiver operating characteristic curve analysis. The study included 1,077 patients. Clauss fibrinogen was correlated strongly with FIBTEM amplitudes (r = 0.78 for MCF and A10; p<0.01). The correlation was related inversely to hemoglobin concentration (p<0.01). The area under the receiver operating characteristic curve was 0.95; the optimal FIBTEM A10 cutoff for diagnosis of a fibrinogen concentration of<1.5 g/L was≤8 mm. Conclusions The FIBTEM was a valid point-of-care method for estimating the fibrinogen concentration during cardiopulmonary bypass and may be used for prediction of hypofibrinogenemia before separation from the extracorporeal circuit.
Although venous thromboembolism (VTE) is an important cause of morbidity and mortality in critical care unit patients, the risk of VTE and its prevention have been poorly characterized in this ...population. Evidence-based thromboprophylaxis guidelines are also not available for these critically ill patients.
To review the prevalence of VTE, to summarize the available clinical trials of thromboprophylaxis, and to outline a practical approach to the prevention of VTE in critical care unit patients.
Systematic review of the relevant literature.
Most patients in critical care units have at least one major risk factor for VTE, and many patients have multiple risk factors. Objectively confirmed deep-vein thrombosis (DVT) rates varied from 13 to 31% among the four prospective studies in which critical care unit patients did not receive prophylaxis. We were able to identify only three randomized trials of thromboprophylaxis conducted in critical care units. The results of these studies suggest that both low-dose heparin and low-molecular-weight heparin are efficacious in preventing DVT compared with no prophylaxis. Fourteen studies reported that compliance with some form of thromboprophylaxis occurred in 33 to 100% of critically ill patients.
There is a paucity of data assessing the risks and prevention of VTE in critical care settings. Selection of prophylaxis for these challenging patients involves a consideration of the thromboembolic and bleeding risks, both of which may vary in the same patient from day to day.
BACKGROUND:Excessive bleeding carries a heavy burden of illness in cardiac surgery. Although platelet dysfunction is considered to be an important cause, it is not routinely measured. Our objective ...was to explore the relationship between platelet dysfunction and blood loss in cardiac surgery.
METHODS:In 100 consenting patients undergoing cardiac surgery requiring cardiopulmonary bypass, platelet function was measured before, during, and after bypass with a point-of-care device that compares platelet counts before and after exposure to an agonist. Clinicians were blinded to the results of testing. Patients whose calculated blood loss was part of the highest quartile for the cohort were classified as having had high blood loss. The independent relationship between platelet function and high blood loss was measured with the aid of multivariable Poisson regression modeling (with a robust error variance) that controlled for patients’ overall risk of high blood loss.
RESULTS:Calculated blood loss was negatively skewed with a median of 798 mL (25th and 75th percentiles of 380 and 1775 mL). Patients whose blood loss exceeded 1770 mL were classified as having had high blood loss, and 25 patients met this criterion. There was 1 death in the high blood loss group unrelated to hemorrhage. After adjusting for bleeding risk, each 10 × 10/L increase in collagen-activated functional platelet count during rewarming and postprotamine, respectively, was associated with a relative risk of 0.89 (95% confidence interval, 0.82–0.97; P = 0.006) and 0.87 (95% confidence interval, 0.78–0.98; P = 0.02) for high blood loss.
CONCLUSIONS:Platelet dysfunction, as measured by a point-of-care method during rewarming and postprotamine, is independently associated with high blood loss in cardiac surgery. Additional studies are needed to determine whether the incorporation of this assay into blood management algorithms might help rationalize blood transfusion therapy, potentially reducing blood loss and improving clinical outcomes.
Coagulation testing provides a prime opportunity to make an impact on the reduction of unnecessary laboratory test ordering, as there are clear indications for testing. Despite the prothrombin ...time/international normalized ratio and activated partial thromboplastin time being validated for specific clinical indications, they are frequently ordered as screening tests and often ordered together, suggesting a gap in understanding of coagulation.
Based on a needs assessment, we developed an online educational module on coagulation for trainees, incorporating education on testing cost, specificity, and sensitivity. Fifty participating resident physicians and medical students completed a validated premodule quiz, postmodule quiz after completion of the module, and a latent quiz 3 to 6 months after to assess longer‐term knowledge retention. Trainees provided responses regarding their subjective laboratory test‐ordering practices before and after module completion.
The median premodule quiz score was 67% (n = 50; range, 24%‐86%) with an increase of 24% to a median postmodule quiz score of 91% (n = 50; range, 64%‐100%). There was evidence of sustained knowledge acquisition with a latent quiz median score of 89% (n = 40; range, 67%–100%). Trainees were more likely to consider the sensitivity, specificity, and cost of laboratory investigations before ordering them following completion of the educational module.
Using the expertise of medical educators and incorporating trainee feedback, we employed a novel approach to the teaching of coagulation to maximize its approachability and clinical relevance. We found sustained knowledge retention regarding coagulation and appropriate coagulation test ordering, and a subjective change to trainee ordering habits following participation in our educational intervention.
Idarucizumab, a monoclonal antibody fragment that reverses the anticoagulant effect of dabigatran, was approved for use in Canada in 2016.
Our objective was to assess the safety of idarucizumab among ...patients who received the drug within the first 3 years of its use in Canada.
We performed a retrospective health records review of all idarucizumab use, excluding use in those <18 years of age, between May 16, 2016, and August 1, 2019, at six Ontario tertiary care hospitals. The primary outcome was mortality. The secondary outcomes were in‐hospital arterial thrombotic event (ATE), in‐hospital venous thromboembolism (VTE), length of hospital stay, and length of critical care stay.
A total of 85 patients received idarucizumab during the study period for the following indications: 37 (43.5%) for spontaneous bleeding, 28 (32.9%) for traumatic bleeding, 11 (12.9%) for emergency surgeries/procedures, 5 (5.9%) for elective surgeries/procedures, and 4 (4.7%) for other indications. Nineteen patients (22.4%; 95% confidence interval CI, 14.8%‐32.3%) did not survive their hospitalization. During hospitalization, two patients (2.4%; 95% CI, 0.7%‐8.2%) had ATE, and three patients (3.5%; 95% CI, 1.2%‐9.9%) had VTE. The median length of stay was 8 (interquartile range IQR, 2.5‐13) days in hospital and 3 (IQR, 2‐5) days in critical care.
Compared with clinical trial data, we found a numerically higher rate of mortality and similar rate of ATE and VTE among patients treated with idarucizumab in the real world.
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