A case study of 10 patients administered HBOC‐201 in high doses over a prolonged period: outcomes during severe anemia when transfusion is not an option

Hemoglobin-Based Oxygen Carriers (HBOCs) can act as an "oxygen bridge" in acute severe anemia when transfusion is indicated, but not possible. We present data on 10 Expanded Access (EA) patients treated with high cumulative doses of Hemopure (HBOC-201), to assess the ability of HBOC-201 to safely treat life threatening anemia in situations where high volumes of product were administered over an extended period of time. Inclusion in this study required that the patient receive at least 10 units of HBOC-201 between 2014 and 2017 under the FDA-sanctioned EA program. Depending on a patient's geographical location, treatment with HBOC-201 was obtained through either a single patient emergency Investigational New Drug (IND) application, or an intermediate size population IND. Of the 41 patients who were treated during this period, 10 patients received 10 or more units of the product. Data were obtained from medical records. Treatments with HBOC-201 started within 24 hours of signing consent and were administered at an average rate of 1.99 (SD 0.17) units per day over a mean of 8.2 days (SD 2.9), during which patients received on average 16.2 units (SD 5.7 units) of HBOC-201. The median pre-treatment nadir corpuscular hemoglobin (Hb) concentration was 3.3 (SD 0.9) g/dL and post-treatment Hemoglobin was 7.3 (SD 1.7) g/dL. Common side effects included methemoglobinemia, gastrointestinal symptoms, and hypertension. However, no product-related serious adverse events (SAEs) were noted. All patients survived. Administration of HBOC-201 over an extended period is a feasible and safe oxygen bridge for severely anemic patients who cannot be transfused with RBC

Patient Satisfaction with Extended-Interval Warfarin Monitoring

Extended-interval monitoring of warfarin has been proposed to reduce follow-up burden and improve patient satisfaction. We aimed to make an initial assessment of anticoagulation satisfaction before and after an extended-interval warfarin monitoring intervention. We conducted a translational prospective single-arm pilot study of extended-interval warfarin monitoring in five pharmacist-managed anticoagulation clinics. Patients meeting CHEST guideline criteria for extended-interval warfarin monitoring began progressive extended-interval follow-up (6, 8, and 12 weeks thereafter). The Duke Anticoagulation Satisfaction Scale (DASS) was administered at baseline and at end-of-study or study removal (in patients no longer appropriate for extended interval follow-up). Forty-six patients had evaluable pre- and post-intervention DASS survey data. Mean age of patients was 66.5 years, 74 % were non-Hispanic whites, and 48 % were men. Patients completed a mean ± SD of 34 ± 22 weeks of follow-up. Mean ± SD total DASS score at baseline was 45.2 ± 14.2 versus 49.1 ± 14.9 at end-of-study (mean change, +3.9 [95 % CI -0.6-8.4; p = 0.09]), indicating no benefit-and trending toward decrement-to anticoagulation satisfaction. Change in anticoagulation satisfaction varied substantially following extended-interval monitoring, with no evidence of improved satisfaction. Plausible reasons for patients not preferring extended-interval monitoring include increased anxiety and disengagement from self-management activities, both potentially related to less frequent feedback and reassurance during extended interval-monitoring. Additional research is needed to identify who is likely to benefit most from extended-interval monitoring. Anticoagulation satisfaction should be considered with clinical factors and shared-decision making when implementing extended-interval warfarin monitoring

Feasibility of Extended-interval Follow-up for Patients Receiving Warfarin

AIMS: The 2012 American College of Chest Physician Evidence-Based Management of Anticoagulant Therapy guidelines suggest an international normalized ratio (INR) testing interval of up to 12 weeks, rather than every 4 weeks, for patients with consistently stable INRs while taking vitamin K antagonists. We aimed to examine the feasibility of extended-interval follow-up in a real-world setting. METHODS: Patients receiving stable warfarin therapy for ≥ 12 weeks at baseline began extended-interval follow-up with visits occurring at 6 weeks, 14 weeks, and every 12 weeks thereafter to a maximum of 68 weeks or until they were no longer suitable for extended-interval follow-up. A single INR excursion \u3e0.3 from goal was permitted if a reversible precipitating factor was identified and the INR was expected to return to goal without dose adjustment. The primary outcome was the proportion of patients completing all study follow-up visits. RESULTS: Of 48 patients enrolled, 47 had evaluable data. The most common indication for anticoagulation was atrial fibrillation/flutter (53.2%). At baseline, mean prior warfarin treatment duration was 6.7 ± 6 years and median number of weeks on a stable regimen was 24 weeks (IQR, 19-37.5). Eleven patients (23%) completed all study follow-up visits, whereas 17 (36%) did not maintain a stable INR past the 14-week follow-up. CONCLUSION: A large proportion of patients with previously stable (≥ 3 months) INRs were not able to maintain stable INRs during extended-interval follow-up. More research is needed to identify patient characteristics predictive of success with extended-interval follow-up prior to broad implementation

A Patient-Centered Emergency Department Management Strategy for Sickle-Cell Disease Super-Utilizers

Introduction:A subpopulation of sickle-cell disease patients, termed super-utilizers, present frequently to emergency departments (EDs) for vaso-occlusive events and may consume disproportionate resources without broader health benefit. To address the health care needs of this vulnerable patient population, we piloted a multidisciplinary intervention seeking to create and use individualized patient care plans that to alter utilization through coordinated care. Our goals were to assess feasibility primarily, and to assess resource use secondarily.Methods: We evaluated the effects of a single-site interventional study targeted at a population of adult sickle-cell disease super-utilizers using a pre- and post-implementation design. The pre-intervention period was 06/01/13 to 12/31/13 (7 months) and the post-intervention period was 01/01/14 to 02/28/15 (14 months). Our approach included: patient-specific best practice advisories (BPA); an ED management protocol (figure 1); formation of a "medical home" for these patients.Results: For 10 subjects targeted initially we developed and implemented coordinated care plans; after deployment, we observed a tendency toward reduction in ED and inpatient utilization across all measured indices. Between the annualized pre- and post-implementation periods: ED visits decreased by 16.5 visits/pt-yr (95% CI, -1.32 to 34.2); ED length of state (LOS) decreased by 115.3 hours/pt-yr (95% CI, -82.9 to 313.5); in-patient admissions decreased by 4.20 admissions/pt-yr (95% CI, -1.73 to 10.1); in-patient LOS decreased by 35.8 hours/pt-yr (95% CI, -74.9 to 146.7); and visits where the patient left before treatment was reduced by an annualized total of 13.7 visits. We observed no patient mortality in our 10 subjects and no patient required admission to the ICU care 72 hours following discharge. Conclusion: This effort suggests that a targeted approach is both feasible and potentially effective, laying a foundation for broader study

Successful Implementation of a Packed Red Blood Cell and Fresh Frozen Plasma Transfusion Protocol in the Surgical Intensive Care Unit

<div><p>Background</p><p>Blood product transfusions are associated with increased morbidity and mortality. The purpose of this study was to determine if implementation of a restrictive protocol for packed red blood cell (PRBC) and fresh frozen plasma (FFP) transfusion safely reduces blood product utilization and costs in a surgical intensive care unit (SICU).</p><p>Study Design</p><p>We performed a retrospective, historical control analysis comparing before (PRE) and after (POST) implementation of a restrictive PRBC/FFP transfusion protocol for SICU patients. Univariate analysis was utilized to compare patient demographics and blood product transfusion totals between the PRE and POST cohorts. Multivariate logistic regression models were developed to determine if implementation of the restrictive transfusion protocol is an independent predictor of adverse outcomes after controlling for age, illness severity, and total blood products received.</p><p>Results</p><p>829 total patients were included in the analysis (PRE, n=372; POST, n=457). Despite higher mean age (56 vs. 52 years, p=0.01) and APACHE II scores (12.5 vs. 11.2, p=0.006), mean units transfused per patient were lower for both packed red blood cells (0.7 vs. 1.2, p=0.03) and fresh frozen plasma (0.3 vs. 1.2, p=0.007) in the POST compared to the PRE cohort, respectively. There was no difference in inpatient mortality between the PRE and POST cohorts (7.5% vs. 9.2%, p=0.39). There was a decreased risk of urinary tract infections (OR 0.47, 95%CI 0.28-0.80) in the POST cohort after controlling for age, illness severity and amount of blood products transfused.</p><p>Conclusions</p><p>Implementation of a restrictive transfusion protocol can effectively reduce blood product utilization in critically ill surgical patients with no increase in morbidity or mortality.</p></div

Multivariate Analysis of early transfusion and urinary tract infection rates.

<p>Abbreviations. RR, relative risk; CI, confidence interval.</p><p>Abbreviations. APACHE, Acute Physiology and Chronic Health Evaluation; PRBC, packed red blood cells; FFP, fresh frozen plasma; CI, confidence interval.</p><p>Multivariate Analysis of early transfusion and urinary tract infection rates.</p

Restrictive transfusion protocol for FFP.

<p>Restrictive transfusion protocol for FFP.</p

Restrictive transfusion protocol for PRBC.

<p>Restrictive transfusion protocol for PRBC.</p