Safety and Effectiveness of an Anti-Xa-based Unfractionated Heparin Protocol for Impella Percutaneous Ventricular Assist Devices.

Background: Impella devices are used for mechanical circulatory support in patients with cardiogenic shock or those undergoing high-risk percutaneous coronary intervention (PCI). Anticoagulation protocols in this population are not well established and are complicated by concomitant use of purge solutions containing unfractionated heparin (UFH) and intravenous UFH continuous infusion (CI) for systemic anticoagulation. Objectives: To evaluate thrombotic and bleeding complications when using a novel UFH protocol with a reduced initial UFH CI dose of 6 units/kg/hour targeting an anti-Xa goal of 0.3 to 0.5 units/mL in patients receiving Impella support. Methods: This single-center, retrospective study included 41 patients on Impella support who received an UFH purge solution and/or an IV UFH infusion. The primary outcome was overall composite bleeding. Secondary outcomes included thrombotic events and systemic UFH exposure. An exploratory analysis was performed to identify risk factors for bleeding. Results: Anti-Xa values were in therapeutic range 46% of the time while on support (interquartile range 16.6%-75%), with a median IV UFH dose of 6 units/kg/hour. The overall bleeding rate was 29.2%, with 6 minor bleeds and 2 major bleeds with no fatal bleeding or intracranial hemorrhage. Rate of overall thrombosis was 4.9%, including 1 ischemic stroke and 1 occurrence of limb ischemia. Conclusion: Use of a modified UFH protocol to target an anti-Xa goal of 0.3 to 0.5 units/mL resulted in bleeding and thrombotic event rates similar to previous literature. This protocol utilizing an initial rate of 6 units/kg/hour may be a useful approach to achieve therapeutic anticoagulation while accounting for UFH exposure from the purge solution and minimizing need for frequent calculations.

Effectiveness and Safety of High-Dose Thromboprophylaxis in Morbidly Obese Major Trauma Patients.

BACKGROUND: Trauma increases risk for venous thromboembolism (VTE) and obesity is a known independent risk factor for VTE development. Currently, no consensus on an optimal prophylactic dosing strategy for morbidly obese trauma patients exists. The objective of this study is to evaluate the effectiveness and safety of a BMI-stratified dosing strategy for VTE prophylaxis in morbidly obese trauma patients. METHODS: This was a single center, retrospective cohort study of adult major trauma patients with a body mass index (BMI) of ≥40 kg/m2 admitted to the surgical-trauma intensive care unit from April 2014 to July 2020. Patients included were those who received enoxaparin 40 mg subcutaneously (SQ) every 12 hours (Q12H) for BMI of 40 to 49.9 kg/m2 or 60 mg SQ Q12H BMI ≥ 50 kg/m2 (per protocol), or enoxaparin 40 mg SQ Q12H for BMI of 40 to 49.9 kg/m2 (non-protocol). The primary endpoint was confirmed incidence of VTE. Secondary endpoints included occurrence of deep vein thrombosis (DVT) or pulmonary embolism (PE) during hospitalization, bleeding events, intensive care unit (ICU) and hospital length of stay (LOS) and hospital mortality. RESULTS: One hundred forty-five morbidly obese major trauma patients were included, with 123 patients (84.8%) in the per-protocol group. The primary outcome of in-hospital VTE did not occur in any patients in this group. Bleeding events occurred in 3 patients (2.7%) with a BMI of 40 to 49.9 kg/m2 and in 2 patients (16.7%) with a BMI of ≥50 kg/m2 (P = .064). Twenty-two patients in the non-protocol group were reviewed. One VTE event (4.5%) and no bleeding events occurred in this group. Median ICU LOS was 5 days, and hospital LOS was 11 days for the entire study group. CONCLUSIONS: Administration of enoxaparin 40 mg SQ Q12H to morbidly obese major trauma patients with a BMI of 40 to 49.9 kg/m2 and enoxaparin 60 mg SQ Q12H in those with a BMI of ≥50 kg/m2 resulted in low rates of VTE and bleeding events in the current study. However, future larger studies using this BMI-stratified dosing strategy are necessary to confirm these findings.

Hemostatic Efficacy and Safety of 4-Factor Prothrombin Complex Concentrate in Doac-Associated Intracranial Hemorrhage.

Background: Factor Xa (FXa) inhibitor use has increased over the last decade and though associated rates of major bleeding are lower compared to warfarin, outcomes from intracranial hemorrhage (ICH) are still significant. Targeted FXa inhibitor reversal agent became available in 2018, however use of 4-factor prothrombin complex concentrate (4F-PCC) for FXa inhibitor-associated ICH continues at many institutions. Objective: Evaluate the safety and hemostatic efficacy of 4F-PCC for FXa inhibitor-associated ICH. Methods: Single-center, retrospective study of patients who received 4F-PCC for FXa inhibitor-associated ICH. The primary efficacy endpoint was hemostasis and thrombosis was the main safety endpoint. Secondary endpoints included in-hospital mortality and discharge disposition. Results: 76 patients on apixaban or rivaroxaban were included. Good or excellent hemostasis was achieved in 80.3% of patients. Five patients experienced a thrombotic event. Favorable discharge disposition and lower in-hospital mortality was more likely in patients who achieved excellent hemostasis. Conclusion: 4F-PCC is safe and effective for FXa inhibitor associated ICH.

Prothrombin Complex Concentrate Use in Intracranial Hemorrhage Patients With Cirrhosis Not on Prior Anticoagulation.

BACKGROUND/OBJECTIVE: Patients with intracranial hemorrhage (ICH) have a 30-day mortality rate up to 52%, and the risk of mortality is increased in patients with disease-induced coagulopathy such as cirrhosis. The objective of this study was to evaluate whether 4F-PCC administration mitigates hematoma expansion in ICH patients with cirrhosis not currently receiving anticoagulation therapy compared to standard of care therapies. METHODS: This was a single-center, retrospective study comparing adult patients with ICH and history of cirrhosis who received 4F-PCC versus standard of care therapies. The primary outcome was rate of ICH expansion within 24 hours after admission. RESULTS: A total of 58 patients were included with 21 who received 4FPCC vs 37 who received standard of care therapies. The 4F-PCC group had a significantly higher number of patients with Child Pugh Class C cirrhosis (85.7% vs. 48.6%, P = 0.006), higher baseline INR (1.7 vs. 1.4, P = 0.001) and more patients with a spontaneous cause of hemorrhage (61.9% vs. 29.7%, P = 0.01). Stable follow-up head CT was achieved in 68.4% of patients who received 4F-PCC versus 72.7% of patients treated with standard of care therapies (P = 0.11). Patients who received 4F-PCC had a significantly greater change in INR within 24 hours (-0.2 vs. 0, P = 0.02) and higher rate of mortality (61.9% vs. 18.9%, P = 0.001). Baseline INR > 2 and surgical evacuation for ICH were associated with decreased odds of stable follow-up head CT in the multivariate logistic regression model. CONCLUSIONS: A single dose of 4F-PCC did not significantly improve the rate of stable head CT at 24 hours in patients with ICH and cirrhosis. Randomized clinical trials with larger patient populations are warranted to fully determine the role of 4F-PCC in this unique population.

The Impact of Rivaroxaban and Apixaban on Tacrolimus Trough Levels.

The solid organ transplant community is slow to adopt the routine practice of using direct oral anticoagulants. Rivaroxaban and apixaban share common metabolic pathways with tacrolimus. This study aimed to clarify the impact of rivaroxaban/apixaban on tacrolimus troughs. Fifty solid organ transplant recipients with concomitant use of tacrolimus and rivaroxaban/apixaban were retrospectively assessed for changes in tacrolimus troughs and dose. Average dose-adjusted tacrolimus troughs and average tacrolimus total daily doses prior to and after rivaroxaban/apixaban initiation were compared. Subgroup analyses evaluating rivaroxaban and apixaban individually were performed. Rivaroxaban was prescribed to 18 recipients, and apixaban was prescribed to 32 recipients. Transplanted organs included kidney (n = 22), lung (n = 18), liver (n = 7), simultaneous pancreas and kidney (n = 1), and simultaneous kidney and liver (n = 2). The median doseadjusted tacrolimus trough and tacrolimus total daily dose prior to rivaroxaban/apixaban initiation was 2.15 ng/mL/mg (IQR 1.17, 3.37) and 4 mg (IQR 1.88, 6.25), respectively. The median dose-adjusted tacrolimus trough and tacrolimus total daily dose after rivaroxaban/apixaban initiation was 2.16 ng/mL/mg (IQR 1.24, 4.10) and 3.55 mg (IQR 1.5, 6.35), respectively. No significant difference was found between average dose-adjusted tacrolimus troughs or tacrolimus total daily doses before and after rivaroxaban/apixaban initiation or in the individual subgroup analyses for rivaroxaban/apixaban. It is unlikely that initiating rivaroxaban/apixaban affects tacrolimus troughs or requires tacrolimus dose adjustment. This study does not elucidate if tacrolimus affects rivaroxaban/apixaban pharmacokinetics or pharmacodynamics.

Surveillance Ultrasound in the Neuro Intensive Care Unit: Time to Deep Vein Thrombosis Diagnosis.

BACKGROUND/OBJECTIVES: Deep vein thrombosis (DVT) and pulmonary embolism (PE) are complications of hospitalization leading to increased morbidity and mortality. Routine surveillance ultrasound has become common practice in some intensive care units (ICU) to detect DVT early and initiate anticoagulation, preventing complications. However, initiating anticoagulants for asymptomatic DVT treatment may increase risk of hemorrhage. The objective of this study was to investigate the value of routine surveillance ultrasound in early DVT diagnosis in Neuro ICU patients. METHODS: This is a retrospective review of patients diagnosed with DVT during admission to the Neuro ICU at University Hospital from January 1, 2012, through December 31, 2017. Patients were identified through International Classification of Diseases 9th and 10th Revision codes for DVT and PE, screened for inclusion criteria, and then classified as surveillance group or symptom-driven group based on intervention received. Primary outcome was time to DVT diagnosis. Secondary outcome included clinically significant hemorrhage identified by anticoagulation treatment discontinuation for suspected hemorrhage or new or expanding hemorrhage on head computerized tomography (CT). RESULTS: A total of 116 patients were identified, with 50 included: 27 were classified as surveillance and 23 as symptom-driven. Seven patients (surveillance = 3 and symptom-driven = 4) were diagnosed with only PE and were excluded from primary outcome. Median time to DVT diagnosis was similar at 148 h for surveillance versus 172 h for symptom driven (p = 0.2). There was no difference in treatment discontinuation rates (surveillance 21% vs symptom 31%; p = 0.4). Of the 27 patients with follow-up head CT, two in the surveillance group and two in the symptom-driven group showed a new or expanding hemorrhage. CONCLUSION: Routine surveillance ultrasound did not lead to significantly earlier DVT diagnosis. Hemorrhagic events were not different between groups. Utility of surveillance ultrasound in this population should be evaluated in large, prospective trials before routine use can be recommended.

Clinical Pharmacy Discharge Counseling Service and the Impact on Readmission Rates in High-Risk Patients.

Background: A number of patient safety and transition of care initiatives have highlighted the benefits of incorporating a clinical pharmacist in the discharge medication process. Numerous studies have identified the prominent and consequential role of medication therapy errors occurring at hospital discharge. Objective: The objective of this study was to evaluate the effects of a discharge medication counseling service on readmission rates, emergency department (ED) visits, and days to first readmission or ED visit in patients deemed high risk for hospital readmission. Methods: A retrospective chart review was conducted from October 2014 to December 2014 in adult patients admitted to a general medicine unit and identified as being at high risk for readmission. Endpoints were compared between patients who received discharge counseling (study group) and those who did not (control group). Results: Eighty-nine high-risk patient charts were reviewed. Forty-four patients were in the study group and 45 patients were in the control group. There were no differences between the baseline characteristics of both groups. There were no differences between the study and control groups in 30-day readmission rates (18.2% vs 26.7%; P = .45) and in 30-day ED visits (4.6% vs 11.1%; P = .43). The number of days to first readmission or ED visit between the study and control groups was 22 versus 12 (P = .26). Conclusion: Although no statistical difference was found between groups in this study, integration of a clinical pharmacist as part of an interdisciplinary approach in the discharge medication process resulted in numerical improvements in outcomes. Additional investigation is warranted to further highlight the potential benefits of this service.