Evaluation of the Clinical Impact of Thromboprophylaxis in Patients With COVID-19 Following Hospital Discharge.

BACKGROUND: Data are limited regarding the incidence of thromboembolism post-hospital discharge among COVID-19 patients. Guidelines addressing the role of extended thromboprophylaxis for COVID-19 patients are limited and conflicting. OBJECTIVE: The purpose of this study was to evaluate the incidence of post-discharge thromboembolic and bleeding events and the role of thromboprophylaxis among COVID-19 patients. METHODS: A retrospective analysis was conducted of hospitalized patients with symptomatic COVID-19 infection who were discharged from a University of Colorado Health (UCHealth) hospital between March 1, 2020, and October 31, 2020. The primary outcome was objectively confirmed thromboembolism within 35 days post-discharge. The main secondary outcome was the incidence of bleeding events within 35 days post-discharge. Outcomes were compared between those who received extended prophylaxis and those who did not. RESULTS: A total of 1171 patients met the study criteria. A total of 13 (1.1%) of patients had a documented thromboembolic event and 10 (0.9%) patients had a documented bleeding event within 35 days post-discharge. None of the 132 patients who received extended prophylaxis had a thromboembolic event compared to 13 of 1039 who did not receive extended prophylaxis (0 and 1.3%, respectively; P = .383). The incidence of bleeding was higher among patients who received extended prophylaxis compared to those who did not (3.0% vs 0.6%, P = .019). CONCLUSIONS AND RELEVANCE: These results suggest that post-discharge extended prophylaxis may be beneficial for select COVID-19 patients, while carefully weighing the risk of bleeding. Application of our findings may assist institutions in development of thromboprophylaxis protocols for discharged COVID-19 patients.

Direct oral anticoagulants versus warfarin in patients with single or double antibody-positive antiphospholipid syndrome.

Warfarin is recognized as the standard treatment for thrombotic antiphospholipid syndrome (APS); however, direct oral anticoagulants (DOACs) represent appealing therapeutic alternatives given their lack of monitoring and limited drug interactions. A few randomized controlled trials comparing rivaroxaban with warfarin showed an increased risk of recurrent thromboembolism, specifically arterial thrombosis, in patients with high risk forms of APS such as those that are triple antibody positive. We conducted a single-center, retrospective cohort study of all patients within our health system from 2015 to 2020 with a diagnosis of APS (single or double antibody positive) and history of venous thromboembolism. We sought to compare the proportion of patients with a recurrent thrombosis when prescribed a DOAC versus warfarin. Among 96 patients included, 57 were prescribed warfarin and 39 were prescribed a DOAC (90% rivaroxaban). The proportion of patients with a recurrent thromboembolism was almost three times higher in the DOAC group (15.4%) compared to the warfarin group (5.3%), although this was not statistically significant (p = 0.15). Major bleeding was not different between groups. Our findings suggest that rivaroxaban may pose an increased risk for recurrent thromboembolism in low risk APS patients that are single or double-antibody positive compared to warfarin. Results of our study should be cautiously applied to DOACs besides rivaroxaban given their small representation in this study.

Evaluation of safety and efficacy outcomes of direct oral anticoagulants versus warfarin in normal and extreme body weights for the treatment of atrial fibrillation or venous thromboembolism.

Despite evolving evidence, the use of direct oral anticoagulants (DOACs) in patients with extremes of body weight remains controversial. This study aimed to measure the impact of DOACs compared to warfarin on safety and efficacy outcomes in extreme body weight patients. This multi-center, health system, retrospective study examined the outcomes of patients with all body weights and extreme body weights prescribed a DOAC (rivaroxaban, apixaban, dabigatran, edoxaban) or warfarin for atrial fibrillation or venous thromboembolism over a 9-year period. The primary outcome was a composite of thromboembolism, symptomatic recurrent VTE, or severe bleeding; analyzed by pre-determined BMI cutoffs. A total of 19,697 patients were included in the study: 11,604 in the DOAC group and in the 8093 in the warfarin group. 295 patients were underweight and 9108 patients were pre-obese to obese class 3. After adjusting for potential confounders, warfarin patients had higher odds of experiencing the composite outcome compared to DOAC patients (OR 1.337, 95% CI 1.212-1.475). Additionally, obese patients were 24.6% more likely to experience the outcome compared to normal BMI patients. Adjusted modeling showed that warfarin patients experienced higher bleed rates compared to DOAC patients (OR 1.432, 95% CI 1.266-1.620). Obese patients were less likely to be diagnosed with a bleed (OR 0.749, 95% CI 0.658-0.854), and underweight patients were more likely to be diagnosed with a bleed (OR 1.522, 95% CI 1.095-2.115) compared to normal BMI patients. In conclusion, DOACs for atrial fibrillation or VTE in patients with extreme body weights appear safe and effective when compared to warfarin.

Evaluation of a patient specific, targeted-intensity pharmacologic thromboprophylaxis protocol in hospitalized patients with COVID-19.

Patients with COVID-19 are at higher risk of thrombosis due to the inflammatory nature of their disease. A higher-intensity approach to pharmacologic thromboprophylaxis may be warranted. The objective of this retrospective cohort study was to determine if a patient specific, targeted-intensity pharmacologic thromboprophylaxis protocol incorporating severity of illness, weight, and biomarkers decreased incidence of thrombosis in hospitalized patients with COVID-19. Included patients were hospitalized with COVID-19 and received thromboprophylaxis within 48 h of admission. Exclusion criteria included receipt of therapeutic anticoagulation prior to or within 24 h of admission, history of heparin-induced thrombocytopenia, extracorporeal membrane oxygenation, pregnancy, or incarceration. Per-protocol patients received thromboprophylaxis according to institutional protocol involving escalated doses of anticoagulants based upon severity of illness, total body weight, and biomarker thresholds. The primary outcome was thrombosis. Secondary outcomes included major bleeding, mortality, and identification of risk factors for thrombosis. Of 1189 patients screened, 803 were included in the final analysis. The median age was 54 (42-65) and 446 (55.5%) were male. Patients in the per-protocol group experienced significantly fewer thrombotic events (4.4% vs. 10.7%, p = 0.002), less major bleeding (3.1% vs. 9.6%, p < 0.001), and lower mortality (6.3% vs. 11.8%, p = 0.02) when compared to patients treated off-protocol. Significant predictors of thrombosis included mechanical ventilation and male sex. Post-hoc regression analysis identified mechanical ventilation, major bleeding, and D-dimer ≥ 1500 ng/mL FEU as significant predictors of mortality. A targeted pharmacologic thromboprophylaxis protocol incorporating severity of illness, body weight, and biomarkers appears effective and safe for preventing thrombosis in patients with COVID-19.

Evaluation of direct oral anticoagulant use on thromboelastography in an emergency department population.

BACKGROUND: Direct oral anticoagulant (DOAC) use presents a challenge to all providers involved in emergency care of patients since widely accepted laboratory tests to assess the level of anticoagulation for such medications are lacking. Viscoelastic tests such as thromboelastography (TEG) tests are increasingly used throughout major trauma centers to help guide resuscitation efforts in patients presenting with trauma and/or hemorrhagic shock. OBJECTIVE: The primary outcome compared TEG parameters between emergency department trauma patients reporting DOAC therapy and known normal TEG parameter values. The secondary outcome evaluated patients who reported time of last known DOAC dose within a preferred time frame of <12 h for once daily dosing DOAC therapy or < 6 h for twice daily dosing DOAC therapy. METHODS: This single-center, retrospective cohort study assessed TEG values in patients receiving DOAC therapy and compared these to institution TEG ranges considered normal. TEG values of reaction time (R time), kinetics (K), alpha angle (AA), maximum amplitude (MA), and percent lysis in 30 min (LY30) were collected for patients reporting DOAC therapy. RESULTS: 40 patients were included in this study. 19 patients reported apixaban therapy and 21 reported rivaroxaban therapy. 5 (12.5%) patients had an elevated R time and 1 (2.5%) patient had a reduced MA. All other TEG values did not suggest hypocoagulability. For the secondary outcome assessing patients reporting last known dose within the preferred time frame, only the R time was elevated in 2 (14.3%) patients. Lastly, in a subgroup analysis of patients with elevated low-molecular-weight heparin (LMWH) orAnti- Xa levels, the R time was the only parameter affected in 25% of patients. CONCLUSION: TEG values were typically not affected by rivaroxaban or apixaban use in an emergency department trauma population suggesting that TEG is not sensitive for Xa inhibitor detection and should not be relied upon for assessing anticoagulation in such settings.

A Single-Center Retrospective Evaluation of the Use of Oral Factor Xa Inhibitors in Patients With Cerebral Venous Thrombosis.

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.

Evaluation of intravenous direct thrombin inhibitor monitoring tests: Correlation with plasma concentrations and clinical outcomes in hospitalized patients.

The parenterally administered direct thrombin inhibitors (DTIs) argatroban and bivalirudin are effective anticoagulants for acute heparin-induced thrombocytopenia (HIT) treatment. The activated partial thromboplastin time (aPTT) has classically been used as the monitoring test to assess degree of anticoagulation, however concerns exist with using aPTT to monitor DTI therapy. In this observational study plasma samples from DTI treated patients were analyzed by aPTT, dilute thrombin time (dTT) and ecarin chromogenic assay (ECA) to delineate results into concordant and discordant groups. Discordant samples were further analyzed via liquid chromatography with tandem mass spectrometry (LC MS/MS). In total 101 patients with 198 samples were evaluated. Discordance between tests were frequent (59% of DTI treated patients). Bivalirudin aPTT vs dTT discordance was observed in 45% (57/126) of samples. Amongst bivalirudin samples with test discordance dTT results were more likely to be concordant with LC MS/MS than the aPTT (77% vs 9%, p < 0.0001). Argatroban aPTT vs dTT discordance was observed in 43% (31/72) and aPTT vs ECA discordance was observed in 40% (29/72) of samples. Amongst argatroban samples with test discordance both the dTT and ECA tests were more likely to have concordant results with LC MS/MS than the aPTT (88% vs 9%, p < 0.0001 for both dTT and ECA tests). There were no differences between discordant and concordant patient groups in a composite outcome of bleeding/thrombosis rate (23% vs 27%, p = 0.689). Further investigation is warranted to elucidate the effect of suitable monitoring assays on patient outcomes in the setting of DTI therapy.

Multi-centered evaluation of a novel fixed-dose four-factor prothrombin complex concentrate protocol for warfarin reversal.

INTRODUCTION: Previous studies have shown fixed-dose 4PCC to be as effective as standard-dose 4PCC for warfarin reversal. However, certain patient populations such as those with high total body weight (TBW) or elevated baseline INR may be at increased risk for treatment failure. The purpose of this study was to validate the efficacy of a novel fixed-dose 4PCC protocol for warfarin reversal. METHODS: This was a multi-centered observational comparison of patients who received 4PCC for warfarin reversal. Fixed-dose patients received 1500 units of 4PCC with the dose increased to 2000 units in patients with a baseline INR ≥ 7.5, a TBW ≥ 100 kg, or for intracranial hemorrhage (ICH). Standard-dosing followed manufacturer recommendations. The primary outcome was achievement of a post-4PCC INR of ≤1.4. Secondary outcomes included target INR achievement among patients with a baseline INR ≥ 7.5, a TBW ≥ 100 kg, or neurologic bleeding indications; hospital length of stay; cost of therapy; and thromboembolic complications. RESULTS: A total of 116 patients were included in the standard-dose group and 75 in the fixed-dose group. There was no difference in the primary outcome (65% vs 57%, p = 0.32). There was no difference in secondary outcomes aside from cost of therapy in which fixed-dose 4PCC was less expensive than standard-dose 4PCC. CONCLUSION: A fixed-dose 4PCC regimen for warfarin reversal of 1500 units, with an increased dose of 2000 units for select patients, is as effective as standard-dose 4PCC for INR reversal.

Management of Venous Thromboembolism: Recent Advances in Oral Anticoagulation Therapy.

OBJECTIVE: To review clinical data on direct oral anticoagulants (DOACs) used in the acute treatment of venous thromboembolism (VTE) as well as practical considerations when using these products. DATA SOURCES: Searches of PubMed and Google Scholar for VTE, deep vein thrombosis, pulmonary embolism, and relevant drug international nonproprietary names were conducted. Additional online searches were conducted for prescribing information. STUDY SELECTION AND DATA EXTRACTION: Relevant articles on dabigatran, rivaroxaban, apixaban, and edoxaban for the management of VTE compared with oral vitamin K antagonists (VKAs; published between 1966 and December 2015) were reviewed and summarized, together with information on dosing, pharmacokinetics/pharmacodynamics, and drug-drug interactions. DATA SYNTHESIS: The DOACs have the potential to circumvent many of the disadvantages of VKAs. At a minimum, they greatly increase the available therapeutic options, thus providing a greater opportunity for clinicians to select a management option that best fits the needs of individual patients. Despite the significant advance that DOACs represent, they are not without risk and require careful consideration of a number of clinical issues to optimize safety and efficacy. CONCLUSIONS: The emergence of DOACs for the management of thromboembolic disorders represents a paradigm shift from oral VKAs. The DOACs provide similar efficacy and improved safety in selected patients as compared with VKAs. Clinicians treating VTE need to be familiar with the intricacies involved in using these agents, including the appropriate dose selection for the relevant indication, avoidance of drug-drug and drug-disease interactions, and consideration of dose adjustments in specific clinical situations, such as organ dysfunction.

The role of prothrombin complex concentrates in reversal of target specific anticoagulants.

Over the past several years a new era for patients requiring anticoagulation has arrived. The approval of new target specific oral anticoagulants offers practitioners several advantages over traditionally used vitamin K antagonist agents including predictable pharmacokinetics, rapid onset of action, comparable efficacy and safety, all without the need for routine monitoring. Despite these benefits, hemorrhagic complicates are inevitable with any anticoagulation treatment. One of the major disadvantages of the new oral anticoagulants is lack of specific antidotes or reversal agents for patients with serious bleeding or need for urgent surgery. As use of the new target specific oral anticoagulants continues to increase, practitioners will need to understand both the pharmacodynamics and pharmacokinetic properties of the agents, as well as, the available literature with use of non-specific therapies to reverse anticoagulation. Four factor prothrombin complex concentrates have been available for several years in Europe, and recently became available in the United States with approval of Kcentra. These products have shown efficacy in reversing anticoagulation from vitamin K antagonists, however their usefulness with the new target specific oral anticoagulants is poorly understood. This article will review the properties of dabigatran, rivaroxaban and apixaban, as well as the limited literature available on the effectiveness of prothrombin complex concentrates in reversal of their anticoagulant effects. Additional studies are needed to more accurately define the role of prothrombin complex concentrates in patients with life threatening bleeding or who require emergent surgery, as current data is both limited and conflicting.

Practical considerations in emergency management of bleeding in the setting of target-specific oral anticoagulants.

The recent arrival of the target-specific oral anticoagulants (TSOACs) offers potential advantages in the field of anticoagulation. However, there are no rapid and accurate and routinely available laboratory assays to evaluate their contribution to clinical bleeding. With the expanding clinical indications for the TSOACs, and the arrival of newer reversal agents on the market, the emergency clinician will need to be familiar with drug specifics as well as methods for anticoagulation reversal. This review offers a summary of the literature and some practical strategies for the approach to the patient taking TSOACs and the management of bleeding in these cases.

The future of inpatient anticoagulation management.

Anticoagulation therapy management has evolved dramatically in both the outpatient and inpatient arenas over the last 30 years in the interest of optimizing patient safety and outcomes. With the advent of target specific oral anticoagulants and next generation antiplatelet agents, a new world of "antithrombosis management" is quickly becoming evident. Additionally, significant changes to the healthcare system in the United States are anticipated with the implementation of the Healthcare Affordability Act. Collectively, these changes constitute the next major evolution in the management of patients on antithrombotic therapy. This article is intended to serve as a call to action for inpatient anticoagulation management services and specialists to familiarize themselves with potential changes, consider the impact they may have and proactively optimize their structure and services to be better able to embrace and capitalize on change.

Approaches to Precision-based Anticoagulation management in the critically Ill.

Anticoagulant therapy is commonly associated with a high incidence of avoidable adverse events, especially in the acute care setting. This has led to several initiatives by key national health care stakeholders, including specific attention to The Joint Commission's National Patient Safety Goals, to improve anticoagulation management. The subject of special populations has long been identified as challenging by clinicians with the use of anticoagulants. This is driven in part by numerous variables that can contribute to hard outcomes such as bleeding, thrombosis, length of stay, hospital re-admission, morbidity, and mortality. Despite the notable effort to improve the use of anticoagulants with numerous clinical trials, guidelines, guidance statements, and other sources of published evidence, notable difficulties continue to challenge practitioners in managing this class of medications. This is especially the case with very diverse critically ill populations where countless variables exist, many of which were never explored in trials or have historically been frequently excluded. Trials evaluating anticoagulation therapy often can only account for small portions of variables that may affect thrombosis and hemostasis, and study methods often do not reflect the constantly changing dynamic conditions seen in unique critically ill patients. Clinicians providing care to the numerous critically ill populations are faced with conditions that lead to relatively small therapeutic windows, which makes designing safe optimal anticoagulation management plans difficult when dealing with complex patients and mechanical support devices. The approach to crafting a successful management plan for anticoagulant therapy must incorporate the numerous variables that are continuously assessed and revised during the patient's time in the intensive care unit. We explore considerations and approaches when developing, assessing, and implementing an individualized or precision-based management plan that involves the use of anticoagulants in the critically ill. The skills and thought process provided will assist clinicians in managing this unique, variable, and challenging population.

Prospective, randomized, controlled, trial to assess ASA DOSing by body mass index in HEalthy volunteers (DOSE study).

STUDY OBJECTIVE: Aspirin (ASA) has demonstrated inconsistent results in primary prevention of cardiovascular disease (CVD). Guidelines are also inconsistent in the recommendation of routine ASA use for primary prevention of CVD, but advocate dosing as a "one-size-fits-all" approach. DESIGN: An intention-to-treat, double-blind, randomized, controlled, clinical trial comparing three treatment arms of ASA 81, 325, and 500 mg daily dosed for 14 days were evenly randomized across the dosing categories to measure the impact of dosing by body mass index (BMI) (20-24.9, 25-29.9, ≥30 kg/m2 ) on ASA anti-platelet effects. SETTING: University Ambulatory Clinic. PATIENTS: Healthy volunteers defined as individuals who were medication free without acute or chronic significant health problems. INTERVENTION: Change in ASA reactivity unit (ARU), salicylate levels, and thromboxane B2 (TxB2) levels were measured across BMI dosing categories and time. MAIN RESULTS: Fifty-four participants with a mean (±SD) age of 34.4 ± 10.9 years (M:F; 23:31) completed the study. Baseline ARU and TxB2 levels were not significantly different between obese and non-obese individuals. BMI was not a predictor of platelet inhibition. There was no interaction between gender and platelet activation at baseline or following ASA treatment. ASA 81 mg was associated with a lower ARU response (approximate 50% lower response) than either the 325-mg or the 500-mg doses of ASA. TxB2 and salicylate levels exhibited lower trends at 81 mg compared with higher doses. CONCLUSIONS: In healthy male and female participants administered ASA for 14 days, obesity is not associated with increased basal platelet activation or ASA resistance. ASA 81 mg was significantly less effective in reducing platelet aggregation compared with ASA 325 and 500 mg, independent of BMI.

Evaluation of empiric versus nomogram-based direct thrombin inhibitor management in patients with suspected heparin-induced thrombocytopenia.

The aim of this study was to evaluate a direct thrombin inhibitor (DTI) titration protocol in patients with suspected HIT. This observational study compared patients treated with argatroban or bivalirudin according to the University of Colorado Hospital DTI titration protocol versus a control group treated prior to protocol implementation. Protocol patients had DTI initial doses based on organ function and fixed dosage adjustments of 10, 25, or 50%. Initial doses and titrations in the control group were made per physician discretion. A total of 130 patients were enrolled: 47 in the protocol group and 83 in the control group (median age 54 years, 63% male, 78% critically ill, and 54% received argatroban). Goal aPTT was achieved with initial DTI dose in 64% of protocol patients and 46% of control patients (P = 0.07). Median (IQR) time to goal aPTT was reduced in the protocol group compared to the control group [5 hr (2-10 hr) vs. 13 hr (6-29 hr); P < 0.0001]. Median time to dose stabilization was 10 hr (6-27 hr) and 22 hr (13-40 hr) in the protocol and control groups, respectively; P < 0.0001. Median number of titrations to goal was 0 (0-1) versus 1 (0-4), respectively; P = 0.02. Median percentage of aPTT values in goal was 67% (41-100%) versus 53% (33-76%), respectively; P = 0.027. The DTI titration protocol shortened time to achieve goal aPTT, reduced time to dose stabilization, decreased the number of titrations required to achieve aPTT goal, and improved the percentage of aPTT values in goal range.

Health care disparities in the acute management of venous thromboembolism based on insurance status in the U.S.

Acute venous thromboembolism (VTE) is common, costly, and potentially lethal. Therapeutic anticoagulation requires timely, closely monitored medical follow-up. If ineffective, clinical outcomes worsen and resource utilization increases. This risk may be magnified in uninsured patients. This study examined VTE care in hospital patients and investigated differences based on insurance status. We performed a retrospective chart review on medical VTE patients at an academic teaching hospital between December 1, 2007 and April 30, 2009. We reviewed medical records for demographics, insurance, admission status, length of stay (LOS), and 30-day Emergency Department (ED) recidivism and hospital readmission. Measured outcomes were analyzed based on payer source. We identified 234 medical VTE patients; 67 patients were uninsured (28.6%). 106 patients (45.3%) presented with deep vein thrombosis only. Most VTE patients were admitted to the hospital (171; 73.1%), including all 128 pulmonary embolism patients. Admitted uninsured patients averaged a LOS of 5.5 versus 3.7 days for insured (P = 0.03), with ED recidivism rates of 26.1 versus 11.3%, respectively (P = 0.02). Average cost for all VTE care in uninsured patients was $12,297 versus $7,758 for insured patients (P = 0.04). This study identified disparities in medical care and resource utilization for medical VTE patients based on insurance. Uninsured VTE patients were hospitalized nearly two additional days and were more than two times as likely to return to the ED within 30 days compared to insured patients. Additional research is needed to explain these disparities, and to explore system improvements for the uninsured VTE patient.

Evaluation of Medication Administration Timing-Are We Meeting Our Goals?

BACKGROUND: Per the Centers for Medicare and Medicaid Services (CMS) Code of Federal Regulations (CFR) 482.23(c) regarding medication administration, hospital policies and procedures must identify time-critical scheduled medications which must be administered within 30 minutes either before or after the scheduled dosing time, for a total administration window of 1 hour. OBJECTIVE: The general objective of this analysis was to determine whether there was a difference in meeting medication administration goals when comparing time-critical to non-time-critical scheduled medication administration in both intensive care units (ICUs) and general medical floors at a large, academic medical center. METHODS: Data were collected in 6 inpatient nursing units (3 general medical units and 3 ICUs) during the month of June 2017. Electronic medical record charge data for medications were used to evaluate timeliness of medication administration. RESULTS: In total, 69,794 medication administrations were evaluated. Of 389 administrations of time-critical scheduled medications, 268 (69%) were administered on time. Of 69,405 administrations of non-time-critical scheduled medications, 58,099 (84%) were administered on time (P < 0.001). ICUs had a higher percentage of on-time administrations than general medical units (89% vs 77%, P < 0.001), and nurses had a higher percentage of on-time administrations than respiratory therapists (84% vs 63%, P < 0.001). CONCLUSIONS: Non-time-critical scheduled medications were more commonly administered on time compared with time-critical scheduled medications. Staff education and optimizations to the electronic health record (EHR) are interventions that may improve administration of time-critical scheduled medications.

Retrospective Comparison of Andexanet Alfa and 4-Factor Prothrombin Complex for Reversal of Factor Xa-Inhibitor Related Bleeding.

The aim of this retrospective study was to compare andexanet alfa and 4-factor prothrombin complex (4F-PCC) for reversal of factor Xa (FXa)-inhibitor bleeding. Patients that received andexanet alfa for reversal were included. An equivalent number of patients administered 4F-PCC for FXa-inhibitor bleeding were randomly selected as historical controls. The primary outcome was effective hemostasis achievement within 12 h, defined using ANNEXA-4 criteria. Thromboembolic events and mortality within 30 days were also evaluated. A total of 32 patients were included. Baseline characteristics were not statistically different between andexanet alfa (n = 16) and 4F-PCC (n = 16). Intracranial bleeding was the primary reversal indication in 43.8% versus 62.5% of patients, respectively. Effective hemostasis was reached in 75.0% of andexanet alfa patients compared to 62.5% of 4F-PCC patients (P = .70). Thromboembolic events occurred in 4 (25.0%) patients and 3 (18.8%) patients, respectively (P = .99). Mortality incidence was 12.5% and 31.3%, respectively (P = .39). Andexanet alfa and 4F-PCC attained hemostasis in a majority of patients. A high, but a similar rate of thromboembolic events was seen with both treatments. Prospective studies are needed to elucidate comparative risks and benefits of the 2 agents.

Optimizing anticoagulation for patients receiving Impella support.

Anticoagulation of patients treated with the Impella percutaneous mechanical circulatory support (MCS) devices is complex and lacks consistency across centers, potentially increasing the risk of complications. In order to optimize safety and efficacy, an expert committee synthesized all available evidence evaluating anticoagulation for patients receiving Impella support in order to provide consensus recommendations for the management of anticoagulation with these devices. The evidence synthesis led to the creation of 42 recommendations to improve anticoagulation management related to the use of the Impella devices. Recommendations address purge solution management, intravenous anticoagulation, monitoring, evaluation and management of heparin-induced thrombocytopenia (HIT), and management during combination MCS support. The use of a heparinized, dextrose-containing purge solution is critical for optimal device function, and a bicarbonate-based purge solution may be an alternative in certain situations. Likewise, intravenous (ie, systemic) anticoagulation with heparin is often necessary, although evidence supporting the optimal assay and target range for monitoring the level of anticoagulation is generally lacking. Patients treated with an Impella MCS device may develop HIT, which is more difficult to evaluate and treat in this setting. Lastly, the use of Impella with extracorporeal membrane oxygenation or for biventricular support creates additional anticoagulation challenges.

Coagulopathy, Venous Thromboembolism, and Anticoagulation in Patients with COVID-19.

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 many international organizations have produced guidelines 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.