Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)has led to a worldwide pandemic, and patients with the infection are referred to as having COVID-19. Although COVID-19 is commonly considered a respiratory disease, there is clearly a thrombotic potential that was not expected. The pathophysiology of the disease and subsequent coagulopathy produce an inflammatory, hypercoagulable, and hypofibrinolytic state. Several observational studies have demonstrated surprisingly high rates of venous thromboembolism (VTE) in both general ward and intensive care patients with COVID-19. Many of these observational studies demonstrate high rates of VTE despite patients being on standard, or even higher intensity, pharmacologic VTE prophylaxis. Fibrinolytic therapy has also been used in patients with acute respiratory distress syndrome. Unfortunately, high quality randomized controlled trials are lacking. A literature search was performed to provide the most up-to-date information on the pathophysiology, coagulopathy, risk of VTE, and prevention and treatment of VTE in patients with COVID-19. These topics are reviewed in detail, along with practical issues of anticoagulant selection and duration. Although a number of international organizations have produced guideline or consensus statements, they do not all cover the same issues regarding anticoagulant therapy for patients with COVID-19, and they do not all agree. These statements and the most recent literature are combined into a list of clinical considerations that clinicians can use for the prevention and treatment of VTE in patients with COVID-19.
The American College of Clinical Pharmacy charged the Clinical Practice Affairs Committee to review and update the College's 1995 White Paper, "Rewards and Advancements for Clinical Pharmacy Practitioners." Because of the limited data on the present state of rewards and advancements for clinical pharmacists, an online survey of "front-line" clinical pharmacists and pharmacy managers was conducted (1126 total respondents, 14% response rate). The resulting White Paper discusses motivators and existing systems of rewards and advancements for clinical pharmacists, as well as perceived barriers to implementation of these systems. Clinical pharmacists reported work-life balance, a challenging position, and opportunities for professional advancement as the most important factors for career success. At the time of the survey, financial rewards appeared not to be a major motivator for clinical pharmacists. Managers underestimated the importance that clinical pharmacists place on work-life balance and favorable work schedules. Although almost two thirds of the clinical pharmacists surveyed had not developed a professional development plan, 84% indicated an interest in career planning. Both clinical pharmacists and managers rated the lack of a clear reward and advancement structure as the most important barrier to effective systems of rewards and advancements. Pharmacy managers and administrators are encouraged to develop effective systems of rewards and advancements for clinical pharmacists that positively impact patient care and the institution's mission; these systems will benefit the clinical pharmacist, the health care institution, and the patient.
The introduction of oral direct anti-Xa anticoagulants apixaban and rivaroxaban has significantly impacted the treatment and prevention of thromboembolic disease. Clinical scenarios exist in which a quantitative assessment for degree of anticoagulation due to these agents would aid management. The purpose of this work was to evaluate the chromogenic antifactor Xa assay calibrated with heparin standards at our institution for assessment of intensity of anticoagulation with rivaroxaban or apixaban in addition to its current use for unfractionated heparin or low-molecular-weight heparin. We also aimed to propose expected steady state peak and trough antifactor Xa activities for these agents based upon dosing regimens approved for nonvalvular atrial fibrillation. Antifactor Xa activity correlated very strongly with apixaban and rivaroxaban concentration in both spiked samples and treated patient plasma samples (r (2) = .99, P < .001). This correlation was observed over a broad range (20-500 ng/mL) of drug concentrations, as sample dilution with pooled normal plasma significantly extended the range of quantitative assessment. Based on drug concentrations previously published in pharmacokinetic studies, the expected steady state peak and trough antifactor Xa activity ranges for apixaban are 1.80 to 2.20 IU/mL and 0.70 to 1.10 IU/mL, respectively. For rivaroxaban, these ranges are 3.80 to 6.20 IU/mL and 0.60 to 1.00 IU/mL, respectively. In conclusion, our findings demonstrate that heparin-calibrated antifactor Xa activity correlates strongly with apixaban and rivaroxaban concentration. The dilution of samples allowed for this correlation to be extended over the majority of on-therapy drug concentrations.
Background: Clinical practice guidelines recommend that cerebral venous thrombosis (CVT) be managed with long-term anticoagulant therapy using warfarin or low-molecular-weight heparin (LMWH) for 3 to 12 months. However, oral factor Xa inhibitors may offer preferable alternative treatment options for these patients. Objective: The primary objective was to determine the effectiveness and safety of rivaroxaban or apixaban compared with warfarin or enoxaparin as long-term anticoagulation therapy for patients with a new diagnosis of CVT. Methods: This was a single-center retrospective review of patients with newly diagnosed CVT who received acute and maintenance anticoagulation treatment. Study groups compared patients who received warfarin, enoxaparin, or an oral factor Xa inhibitor as their maintenance anticoagulant. The primary outcome was recurrent thrombotic events while on anticoagulation. Secondary outcomes included modified Rankin Scale, improved cerebral venous sinus opacification, duration of anticoagulant therapy, bleeding events during anticoagulant therapy, and adverse effects. Results: A total of 119 patients were included in the analysis: warfarin (89), enoxaparin (11), and oral factor Xa inhibitor (19). The risk of recurrent thrombotic events were 11.2%, 0%, and 10.5% in the warfarin, enoxaparin, and oral factor Xa inhibitor treatment groups, respectively ( P = 0.7635). There were no significant between-group differences observed regarding any of the secondary outcomes. Conclusions: Although the sample size is limited, these findings indicate that oral factor Xa inhibitors are a reasonable treatment option for patients with CVT. There was a trend toward more persistent symptoms in patients on warfarin, suggesting a potential improvement in recovery among patients that received an oral factor Xa inhibitor.
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