Warfarin dosage in a postpartum woman while breastfeeding: A case report.

Warfarin is the only oral anticoagulant recommended in women who are breastfeeding. Although warfarin is a compatible and recommended agent in the postpartum period and during lactation, little is known regarding changes to warfarin dose requirements in this patient population. Here, we report the case of a 40-year-old woman who transitioned from enoxaparin monotherapy back to warfarin at 2 months postpartum, while she was breastfeeding. Despite resuming warfarin at her previously therapeutic dose, her international normalized ratio (INR) remained subtherapeutic and required multiple dose increases. She ultimately required a 100% increase in her warfarin dose postpartum, compared to pre-pregnancy, to achieve a therapeutic INR. This case suggests patients may require higher warfarin doses postpartum, compared to pre-pregnancy, especially if breastfeeding. Clinicians should closely monitor these patients and adjust warfarin doses as necessary.

Comparison of thrombotic and clinical outcomes in SARS-CoV-2-pneumonia versus other viral pneumonia in an urban academic medical center.

BACKGROUND: Infection with viral pneumonia (PNA) is known to offset the coagulation cascade. Recent studies assessing novel SARS-CoV-2 infection observed a high frequency of systemic thrombotic events resulting in ambiguity if severity of infection or specific viral strain drive thrombosis and worsen clinical outcomes. Furthermore, limited data exists addressing SARS-CoV-2 in underrepresented patient populations. OBJECTIVES: Assess clinical outcomes events and death in patients diagnosed with SARS-CoV-2 pneumonia compared to patients with other types of viral pneumonia. METHODS: Retrospective cohort study evaluated electronic medical records in adult patients admitted to University of Illinois Hospital and Health Sciences System (UIHHSS) with primary diagnosis of SARS-CoV-2 PNA or other viral (H1N1 or H3N2) PNA between 10/01/2017 and 09/01/2020. Primary composite outcome was the following event incidence rates: death, ICU admission, infection, thrombotic complications, mechanical ventilation, renal replacement therapy, and major bleeding. RESULTS: Of 257 patient records, 199 and 58 patients had SARS-CoV-2 PNA and other viral PNA, respectively. There was no difference in primary composite outcome. Thrombotic events (n = 6, 3%) occurred solely in SARS-CoV-2 PNA patients in the ICU. A significantly higher incidence of renal replacement therapy (8.5% vs 0%, p=0.016) and mortality (15.6% vs 3.4%, p=0.048) occurred in the SARS-CoV-2 PNA group. Multivariable logistic regression analysis revealed age, presence of SARS-CoV-2, and ICU admission, aOR 1.07, 11.37, and 41.95 respectively, was significantly associated with mortality risk during hospitalization; race and ethnicity were not. CONCLUSION: Low overall incidence of thrombotic events occurred only in the SARS-CoV-2 PNA group. SARS-CoV-2 PNA may lead to higher incidence of clinical events than those observed in H3N2/H1N1 viral pneumonia, and that race/ethnicity does not drive mortality outcomes.

Clinically stable covid-19 patients presenting to acute unscheduled episodic care venues have increased risk of hospitalization: secondary analysis of a randomized control trial.

BACKGROUND: Assessment for risks associated with acute stable COVID-19 is important to optimize clinical trial enrollment and target patients for scarce therapeutics. To assess whether healthcare system engagement location is an independent predictor of outcomes we performed a secondary analysis of the ACTIV-4B Outpatient Thrombosis Prevention trial. METHODS: A secondary analysis of the ACTIV-4B trial that was conducted at 52 US sites between September 2020 and August 2021. Participants were enrolled through acute unscheduled episodic care (AUEC) enrollment location (emergency department, or urgent care clinic visit) compared to minimal contact (MC) enrollment (electronic contact from test center lists of positive patients).We report the primary composite outcome of cardiopulmonary hospitalizations, symptomatic venous thromboembolism, myocardial infarction, stroke, transient ischemic attack, systemic arterial thromboembolism, or death among stable outpatients stratified by enrollment setting, AUEC versus MC. A propensity score for AUEC enrollment was created, and Cox proportional hazards regression with inverse probability weighting (IPW) was used to compare the primary outcome by enrollment location. RESULTS: Among the 657 ACTIV-4B patients randomized, 533 (81.1%) with known enrollment setting data were included in this analysis, 227 from AUEC settings and 306 from MC settings. In a multivariate logistic regression model, time from COVID test, age, Black race, Hispanic ethnicity, and body mass index were associated with AUEC enrollment. Irrespective of trial treatment allocation, patients enrolled at an AUEC setting were 10-times more likely to suffer from the adjudicated primary outcome, 7.9% vs. 0.7%; p < 0.001, compared with patients enrolled at a MC setting. Upon Cox regression analysis adjustment patients enrolled at an AUEC setting remained at significant risk of the primary composite outcome, HR 3.40 (95% CI 1.46, 7.94). CONCLUSIONS: Patients with clinically stable COVID-19 presenting to an AUEC enrollment setting represent a population at increased risk of arterial and venous thrombosis complications, hospitalization for cardiopulmonary events, or death, when adjusted for other risk factors, compared with patients enrolled at a MC setting. Future outpatient therapeutic trials and clinical therapeutic delivery programs of clinically stable COVID-19 patients may focus on inclusion of higher-risk patient populations from AUEC engagement locations. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04498273.

Effect of Thromboprophylaxis on Clinical Outcomes After COVID-19 Hospitalization.

BACKGROUND: Patients hospitalized with COVID-19 have an increased incidence of thromboembolism. The role of extended thromboprophylaxis after hospital discharge is unclear. OBJECTIVE: To determine whether anticoagulation is superior to placebo in reducing death and thromboembolic complications among patients discharged after COVID-19 hospitalization. DESIGN: Prospective, randomized, double-blind, placebo-controlled clinical trial. (ClinicalTrials.gov: NCT04650087). SETTING: Done during 2021 to 2022 among 127 U.S. hospitals. PARTICIPANTS: Adults aged 18 years or older hospitalized with COVID-19 for 48 hours or more and ready for discharge, excluding those with a requirement for, or contraindication to, anticoagulation. INTERVENTION: 2.5 mg of apixaban versus placebo twice daily for 30 days. MEASUREMENTS: The primary efficacy end point was a 30-day composite of death, arterial thromboembolism, and venous thromboembolism. The primary safety end points were 30-day major bleeding and clinically relevant nonmajor bleeding. RESULTS: Enrollment was terminated early, after 1217 participants were randomly assigned, because of a lower than anticipated event rate and a declining rate of COVID-19 hospitalizations. Median age was 54 years, 50.4% were women, 26.5% were Black, and 16.7% were Hispanic; 30.7% had a World Health Organization severity score of 5 or greater, and 11.0% had an International Medical Prevention Registry on Venous Thromboembolism risk prediction score of greater than 4. Incidence of the primary end point was 2.13% (95% CI, 1.14 to 3.62) in the apixaban group and 2.31% (CI, 1.27 to 3.84) in the placebo group. Major bleeding occurred in 2 (0.4%) and 1 (0.2%) and clinically relevant nonmajor bleeding occurred in 3 (0.6%) and 6 (1.1%) apixaban-treated and placebo-treated participants, respectively. By day 30, thirty-six (3.0%) participants were lost to follow-up, and 8.5% of apixaban and 11.9% of placebo participants permanently discontinued the study drug treatment. LIMITATIONS: The introduction of SARS-CoV-2 vaccines decreased the risk for hospitalization and death. Study enrollment spanned the peaks of the Delta and Omicron variants in the United States, which influenced illness severity. CONCLUSION: The incidence of death or thromboembolism was low in this cohort of patients discharged after hospitalization with COVID-19. Because of early enrollment termination, the results were imprecise and the study was inconclusive. PRIMARY FUNDING SOURCE: National Institutes of Health.

Prescribing Pattern of Oral Anticoagulants in Patients With Obesity.

INTRODUCTION: There is limited efficacy and safety data for direct oral anticoagulants (DOACs) in patients with obesity, and it has been suggested to avoid DOACs in this patient population. OBJECTIVE: Describe the prescribing pattern of oral anticoagulants in obese patients in an urban university setting and assess efficacy, safety, and adherence. METHODS: Retrospective, cohort study in patients ≥18 years with a history of VTE and/or atrial fibrillation. Patients with a BMI >40 kg/m2 and/or weight >120 kilograms and a prescription for warfarin or a DOAC from August 25, 2014 until August 25, 2017 are included. The primary outcome is the number of warfarin or DOAC prescriptions. Secondary outcomes include thromboembolism and bleeding events. Patient adherence was evaluated using time in therapeutic range (TTR), adherence rate to clinic appointments, and medication possession ratio (MPR). RESULTS: Of the 276 patients who met eligibility criteria, 158 (57.2%) were prescribed warfarin and 118 (42.8%) were prescribed a DOAC. There was no difference in the rate of stroke or recurrent VTE between groups (3.2% vs. 3.4%, p = 0.944). There was also no difference in the rate of bleeding between groups (16.1% vs. 17.8%, p = 0.707). The TTR for the warfarin group was 44.8 ± 23%, and appointment adherence was 78.6 ± 20%. The MPR for the DOAC group was 0.93 ± 0.24. CONCLUSIONS: Despite limited data in obese patients, DOACs are prescribed in this population. Results suggest no difference in safety and efficacy compared to warfarin, but barriers to quality anticoagulation may exist in this population.

Outpatient Randomized Controlled Trials in the Covid-19 Era and Beyond.

Outpatient Trials in the Covid-19 Era and BeyondA group of investigators had a meeting at the National Heart, Lung, and Blood Institute in May 2020 to discuss ways to decrease thrombotic complications among symptomatic outpatients with Covid-19. The investigators discuss their approach to three specific challenges: conducting a trial remotely, working through regulatory hurdles, and recruiting a diverse population of participants.

Recruitment in a research study via chatbot versus telephone outreach: a randomized trial at a minority-serving institution.

Chatbots are software applications to simulate a conversation with a person. The effectiveness of chatbots in facilitating the recruitment of study participants in research, specifically among racial and ethnic minorities, is unknown. The objective of this study is to compare a chatbot versus telephone-based recruitment in enrolling research participants from a predominantly minority patient population at an urban institution. We randomly allocated adults to receive either chatbot or telephone-based outreach regarding a study about vaccine hesitancy. The primary outcome was the proportion of participants who provided consent to participate in the study. In 935 participants, the proportion who answered contact attempts was significantly lower in the chatbot versus telephone group (absolute difference -21.8%; 95% confidence interval [CI] -27.0%, -16.5%; P < 0.001). The consent rate was also significantly lower in the chatbot group (absolute difference -3.4%; 95% CI -5.7%, -1.1%; P = 0.004). However, among participants who answered a contact attempt, the difference in consent rates was not significant. In conclusion, the consent rate was lower with chatbot compared to telephone-based outreach. The difference in consent rates was due to a lower proportion of participants in the chatbot group who answered a contact attempt.

Effect of Antithrombotic Therapy on Clinical Outcomes in Outpatients With Clinically Stable Symptomatic COVID-19: The ACTIV-4B Randomized Clinical Trial.

Importance: Acutely ill inpatients with COVID-19 typically receive antithrombotic therapy, although the risks and benefits of this intervention among outpatients with COVID-19 have not been established. Objective: To assess whether anticoagulant or antiplatelet therapy can safely reduce major adverse cardiopulmonary outcomes among symptomatic but clinically stable outpatients with COVID-19. Design, Setting, and Participants: The ACTIV-4B Outpatient Thrombosis Prevention Trial was designed as a minimal-contact, adaptive, randomized, double-blind, placebo-controlled trial to compare anticoagulant and antiplatelet therapy among 7000 symptomatic but clinically stable outpatients with COVID-19. The trial was conducted at 52 US sites between September 2020 and June 2021; final follow-up was August 5, 2021. Prior to initiating treatment, participants were required to have platelet count greater than 100 000/mm3 and estimated glomerular filtration rate greater than 30 mL/min/1.73 m2. Interventions: Random allocation in a 1:1:1:1 ratio to aspirin (81 mg orally once daily; n = 164), prophylactic-dose apixaban (2.5 mg orally twice daily; n = 165), therapeutic-dose apixaban (5 mg orally twice daily; n = 164), or placebo (n = 164) for 45 days. Main Outcomes and Measures: The primary end point was a composite of all-cause mortality, symptomatic venous or arterial thromboembolism, myocardial infarction, stroke, or hospitalization for cardiovascular or pulmonary cause. The primary analyses for efficacy and bleeding events were limited to participants who took at least 1 dose of trial medication. Results: On June 18, 2021, the trial data and safety monitoring board recommended early termination because of lower than anticipated event rates; at that time, 657 symptomatic outpatients with COVID-19 had been randomized (median age, 54 years [IQR, 46-59]; 59% women). The median times from diagnosis to randomization and from randomization to initiation of study treatment were 7 days and 3 days, respectively. Twenty-two randomized participants (3.3%) were hospitalized for COVID-19 prior to initiating treatment. Among the 558 patients who initiated treatment, the adjudicated primary composite end point occurred in 1 patient (0.7%) in the aspirin group, 1 patient (0.7%) in the 2.5-mg apixaban group, 2 patients (1.4%) in the 5-mg apixaban group, and 1 patient (0.7%) in the placebo group. The risk differences compared with placebo for the primary end point were 0.0% (95% CI not calculable) in the aspirin group, 0.7% (95% CI, -2.1% to 4.1%) in the 2.5-mg apixaban group, and 1.4% (95% CI, -1.5% to 5.0%) in the 5-mg apixaban group. Risk differences compared with placebo for bleeding events were 2.0% (95% CI, -2.7% to 6.8%), 4.5% (95% CI, -0.7% to 10.2%), and 6.9% (95% CI, 1.4% to 12.9%) among participants who initiated therapy in the aspirin, prophylactic apixaban, and therapeutic apixaban groups, respectively, although none were major. Findings inclusive of all randomized patients were similar. Conclusions and Relevance: Among symptomatic clinically stable outpatients with COVID-19, treatment with aspirin or apixaban compared with placebo did not reduce the rate of a composite clinical outcome. However, the study was terminated after enrollment of 9% of participants because of an event rate lower than anticipated. Trial Registration: ClinicalTrials.gov Identifier: NCT04498273.

Development of pulmonary embolism in a nonhospitalized patient with COVID-19 who did not receive venous thromboembolism prophylaxis.

PURPOSE: Coronavirus disease 2019 (COVID-19) has been associated with thrombotic complications such as stroke and venous thromboembolism (VTE), and VTE prophylaxis for hospitalized patients with COVID-19 is recommended. However, extended postdischarge VTE prophylaxis and VTE prophylaxis for nonhospitalized patients with COVID-19 are not routinely recommended due to uncertain benefit in these populations. SUMMARY: Here we report development of a pulmonary embolism (PE) in a young patient without other VTE risk factors who was treated for COVID-19 in an emergency department (ED) and discharged home without VTE prophylaxis, which was consistent with current recommendations. The patient presented to the ED 12 days later with complaints of chest pain for 1 day and was found to have a PE within the segmental and subsegmental branches of the left lower lobe. CONCLUSION: This case suggests that nonhospitalized patients with COVID-19 may be at higher risk for VTE than patients with other medical illnesses and warrants further research into the risk of VTE in outpatients with COVID-19.

Implementation of a Direct Oral Anticoagulation Screening Service at a Large Academic Medical Center Provided by a Pharmacist-managed Antithrombosis Clinic as a Method to Expand Antithrombotic Stewardship Efforts.

BACKGROUND: How and when to monitor direct oral anticoagulants (DOACs) for safety and efficacy is a question many anticoagulation clinics are trying to answer. A pharmacist-led antithrombosis clinic (ATC) initiated a clinical service to provide oversight for all prescribed DOACs. OBJECTIVE: Describe the implementation and outcomes of a DOAC screening service. METHODS: The service was initiated utilizing a daily electronic prescribing report of DOAC prescriptions. Prescriptions were reviewed by clinical pharmacists to assess patient insurance, eligibility, and accuracy of prescribed doses. RESULTS: In the first year since service implementation in April 2016, 317 new prescriptions and 595 refill prescriptions were reviewed. A DOAC service pharmacist was able to reach 125 (39.4%) of 317 patients about their new prescription and 59 (9.9%) of 595 refill patients to provide education and follow-up on management as needed. Interventions were performed for 79 (28%) of 317 new prescriptions and 86 (14.5%) of 595 refill prescriptions. Common interventions with new prescriptions include contacting the prescriber for a medication or dose change (25.4%), assistance with medication access (21.5%), and coordinating appropriate lab and provider follow up (21.5%). Common interventions with refill prescriptions include recommending appropriate follow-up (50%) and contacting the prescriber for medication or dosage change (24.4%). CONCLUSION: Implementation of a DOAC screening service identified and resolved dosing errors, improved medication access, provided patient education, and improved follow-up.

Assessment of venous thromboembolism treatment in patients with cancer on low molecular weight heparin, warfarin, and the direct oral anticoagulants.

BACKGROUND: Direct oral anticoagulants (DOACs) are not recommended for venous thromboembolism (VTE) treatment in patients with cancer because their safety and efficacy have not been compared to low molecular weight heparin (LMWH) in large trials. Routine anti-Xa monitoring in cancer patients on LMWH is also not recommended due to limited data correlating anti-Xa levels and outcomes. OBJECTIVE: Compare the safety and efficacy of DOACs to LMWH and warfarin and assess the relationship of anti-Xa monitoring and outcomes in patients with cancer taking LMWH in an urban university setting. METHODS: This retrospective, cohort study analyzed the recurrence of VTE and number of bleeding events in patients with cancer. RESULTS: There were 131 patients included in the analysis. There was no difference seen in the rate of recurrent VTEs between the LMWH, warfarin and DOAC groups (9.3%, 5.9%, 9.1%, p = 0.89). There was also no difference in the rate of bleeding between groups (10.5%, 14.7%, 9.1%, p = 0.576). There was an increased rate of mortality seen in the LMWH group (26.7% vs. 2.9% vs. 18.2%, p = 0.006). There was no difference seen in recurrent VTE (10.3% vs. 8.5%, p = 0.53) or bleeding (10.3% vs. 10.7%, p = 0.661) between the monitored and unmonitored LMWH patients. CONCLUSION: Results of this analysis suggest DOACs may be as safe and effective as LMWH and warfarin for the treatment of VTE in patients with cancer, and there may be no clinical benefit to routine anti-Xa monitoring in patients on LMWH treatment. However, larger studies are needed to confirm these observations.

Implementation of a New Clinic-Based, Pharmacist-Managed PCSK9 Inhibitor Consultation Service.

BACKGROUND: The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors alirocumab and evolocumab were approved by the FDA in 2015. In anticipation of provider interest and a potential increase in referrals to the on-site specialty pharmacy, we created a pharmacist-managed consultation service. PROGRAM DESCRIPTION: The development of a clinic-based pharmacist-managed consultation service for the management of the PCSK9 inhibitor agents alirocumab and evolocumab is described. Key implementation steps included (a) creation of a pharmacy team and collaboration with cardiology; (b) completion of a needs assessment; (c) service creation; (d) collaboration with the on-site specialty pharmacy; (e) development of an electronic consult order and consult pool; (f) personnel training; and (g) service approval and marketing. The service development occurred over 9 months (July 2015-April 2016) and was implemented hospital-wide in May 2016. OBSERVATIONS: The University of Illinois Hospital and Health Sciences System PCSK9 inhibitor consultation service successfully integrated the benefits of a clinical review process, information technology capabilities of an electronic medical record system, and collaboration with the on-site specialty pharmacy to provide a comprehensive service that aimed to facilitate appropriate medication management from prescribing to patient administration and provide monitoring for this class of specialty medications. IMPLICATIONS/RECOMMENDATIONS: The PCSK9 pharmacist-managed consultation service provides a method for complex therapies to be managed comprehensively through the collaboration of ambulatory care clinics and outpatient specialty pharmacies. DISCLOSURES: No outside funding supported this study. Groo reports speaker bureau fees from Pfizer and Bristol-Myers Squibb. The other authors have nothing to disclose. All the authors contributed to study concept and design. Atande took the lead in data collection, and data interpretation was performed by Groo and Atanda. The manuscript was written by Atanda and revised by all the authors.

Upper-Extremity Deep-Vein Thrombosis: A Retrospective Cohort Evaluation of Thrombotic Risk Factors at a University Teaching Hospital Antithrombosis Clinic.

BACKGROUND: Upper-extremity deep-vein thrombosis (UEDVT) causes significant morbidity and mortality and is not well characterized in the existing literature, particularly in underrepresented minorities such as African Americans. OBJECTIVE: To describe the characteristics of a cohort of patients with UEDVT seen at an urban academic medical center. METHODS: This was a retrospective cohort study among patients with a confirmed UEDVT at the University of Illinois Hospital and Health Sciences System between 1996 and 2011. Patients were identified by ICD-9 code for UEDVT. Variables collected include thrombotic risk factors and outcomes, including recurrent thrombosis and bleeding. RESULTS: We identified 229 patients with UEDVT; 71% were African American, and 11% were diagnosed with sickle cell disease. The average number of UEDVT risk factors was 4.40 ± 1.5, the most common being central venous catheter (CVC) use (178, 78%). In the year following UEDVT, 13% experienced recurrent thrombosis, and 6% experienced major bleeding. Of 181 patients receiving warfarin after an UEDVT, 36% of international normalized ratio (INR) values were therapeutic. Patients with sickle cell disease had a lower proportion of INRs within the target range (25% vs 38%, P < 0.01), and were more likely to be lost to follow-up (67% vs 46%, P = 0.05) and experience a recurrent thrombotic event (29% vs 11%, P = 0.02). CONCLUSION: A CVC is the most common risk factor for UEDVT; however, patients with sickle cell disease demonstrate additional unique demographics and risk factors. Patients included in this underrepresented demographic cohort had a low quality of anticoagulation control, particularly those with sickle cell disease.

Recommendations for Aligning PGY2 Pharmacy Residency Training and Pharmacy Specialist Board Certification.

With the increased focus and anticipated growth in specialty training and certification within the profession of pharmacy, it is important for the profession to step back and evaluate the manner in which its adopted education and certification systems interface. As a result of specialty practice development, significant growth is occurring in both postgraduate year two (PGY2) pharmacy residency programs and individuals seeking certification by the Board of Pharmacy Specialties. As the profession continues to evolve its specialty training and credentialing systems, it is important to consider the inherent relationship between these systems. This paper considers the current landscape of specialty training and certification, including issues related to the quality of PGY2 training, consistent application of standards across and within PGY2 programs, credentialing of preceptors and program directors, and alignment of training with specialty certification examination content domains. We outline recommendations across three areas: (1) creating consistency between specialty training and certification, (2) aligning qualifications of PGY2 residency program directors and preceptors with the designated specialty area, and (3) assessing program quality in the context of the expectations of specialists established by the profession. The goal of this paper is to stimulate professional dialogue on these issues. Establishing both formal and informal connections between specialty training and certification can serve as the foundation for a rational approach to professional development and the credentialing that will be recognized by stakeholders outside the pharmacy profession. Establishing these connections will also support and advance the profession's mission of meeting the medication needs of patients.

Critical Review and Update on the Treatment of Acute and Chronic Pulmonary Embolism.

Pulmonary embolism (PE), can be life-threatening without rapid appropriate therapy and often leads to chronic disease and disability. The ambiguity of symptoms makes PE difficult to diagnose, and available imaging strategies have their limitations. Treatment options for acute PE include fibrinolytics, surgical embolectomy, catheter-directed treatment, or vena cava filter placement as well as traditional parenteral anticoagulants, used alone or as a bridge to a vitamin K antagonist (VKA). The direct oral anticoagulants (DOACs) rivaroxaban and apixaban allow for single drug therapy, eliminating the need for initial parenteral anticoagulation, while dabigatran and edoxaban are initiated after a short course of parenteral therapy. The DOACs serve as a viable alternative to warfarin for chronic management for PE. Pulmonary embolism provoked from transient risk factors often requires a short-term course of anticoagulation (3 months). Unprovoked events, and those that occur in the presence of continuing risk factors such as cancer, or clinical markers such as residual vein thrombosis and elevated d-dimers can predict a higher risk of recurrent events and warrant extended anticoagulation. This review evaluates current recommendations for the treatment of PE, including dosing strategies, duration of therapy, and special populations such as renal impairment, malignancy, and obesity.

Balance of academic responsibilities of clinical track pharmacy faculty in the United States: a survey of select American College of Clinical Pharmacy Practice and Research Network Members.

STUDY OBJECTIVES: To characterize the balance of clinical and academic responsibilities of clinical track pharmacy faculty in the United States and evaluate organizational structures that promote satisfactory balance between these responsibilities. DESIGN: Prospective cross-sectional survey. SETTING: A 22-item online survey was developed and distributed via Qualtrics software. PARTICIPANTS: Clinical faculty members of the American College of Clinical Pharmacy Adult Medicine, Ambulatory Care, Cardiology, Critical Care, Gastrointestinal/Liver/Nutrition, Immunology/Transplantation, Infectious Disease, and Pediatrics Practice and Research Networks (PRNs) were invited to participate via the PRN electronic mailing list. MEASUREMENTS AND MAIN RESULTS: The survey comprised questions related to demographics, organizational structure, and balance of clinical and academic responsibilities. A total of 344 participants responded to some or all of the survey questions. The demographics were relatively equally balanced between faculty at state and private academic institutions, academic rank, and practice setting. Expected and actual effort allocations were similar for each of the clinical and academic responsibilities, with direct patient care and clinical teaching representing more than 50% effort allocation cumulatively. Clinical faculty at state institutions devoted a larger proportion of time to clinical service, whereas clinical faculty at private institutions devoted a greater proportion of time to didactic teaching. When asked about time constraints, 157 (69.8%) of the 225 survey participants responding to this question did not believe they had sufficient time to fulfill their nonclinical academic needs. Clinical faculty who were provided "protected time" away from clinical service had a significantly more favorable opinion of this question. CONCLUSION: Most of the clinical track pharmacy faculty indicated that they have insufficient time to fulfill their nonclinical academic responsibilities. Provision of protected time may alleviate some of these time constraints.

Association of the GGCX (CAA)16/17 repeat polymorphism with higher warfarin dose requirements in African Americans.

OBJECTIVE: Little is known about genetic contributors to higher than usual warfarin dose requirements, particularly for African Americans. This study tested the hypothesis that the γ-glutamyl carboxylase (GGCX) genotype contributes to warfarin dose requirements greater than 7.5 mg/day in an African American population. METHODS: A total of 338 African Americans on a stable dose of warfarin were enrolled. The GGCX rs10654848 (CAA)n, rs12714145 (G>A), and rs699664 (p.R325Q); VKORC1 c.-1639G>A and rs61162043; and CYP2C9*2, *3, *5, *8, *11, and rs7089580 genotypes were tested for their association with dose requirements greater than 7.5 mg/day alone and in the context of other variables known to influence dose variability. RESULTS: The GGCX rs10654848 (CAA)16 or 17 repeat occurred at a frequency of 2.6% in African Americans and was overrepresented among patients requiring greater than 7.5 mg/day versus those who required lower doses (12 vs. 3%, P=0.003; odds ratio 4.0, 95% confidence interval, 1.5-10.5). The GGCX rs10654848 genotype remained associated with high dose requirements on regression analysis including age, body size, and VKORC1 genotype. On linear regression, the GGCX rs10654848 genotype explained 2% of the overall variability in warfarin dose in African Americans. An examination of the GGCX rs10654848 genotype in warfarin-treated Caucasians revealed a (CAA)16 repeat frequency of only 0.27% (P=0.008 compared with African Americans). CONCLUSION: These data support the GGCX rs10654848 genotype as a predictor of higher than usual warfarin doses in African Americans, who have a 10-fold higher frequency of the (CAA)16/17 repeat compared with Caucasians.

Dosing and monitoring of low-molecular-weight heparin in high-risk pregnancy: single-center experience.

STUDY OBJECTIVE: To evaluate dosing requirements and monitoring patterns of low-molecular-weight heparin (LMWH) when used in high-risk pregnancy. DESIGN: Retrospective, observational, cohort study. SETTING: University-affiliated medical center. PATIENTS: Forty-nine women treated with LMWH between 2001 and 2005 for either prophylaxis or treatment of venous thromboembolism during pregnancy and monitored with antifactor Xa activity. MEASUREMENTS AND MAIN RESULTS: Data were obtained on 53 pregnancies in the 49 women. The primary outcome was change in dosing requirements of LMWH throughout pregnancy as determined by the corresponding antifactor Xa activity peak levels. Mean starting doses of twice-daily enoxaparin and doses most proximate to delivery were 39.2 mg (range 30-60 mg) and 55.0 mg (range 30-100 mg, p=0.06), respectively, for the prophylaxis group and 83.0 mg (range 30-180 mg) and 85.7 mg (range 30-160 mg, p=0.41), respectively, for the therapeutic group. Weight-based mean starting doses and doses most proximate to delivery were 0.46 and 0.62 mg/kg (p=0.03), respectively, for the prophylaxis group and 0.90 and 0.87 mg/kg (p=0.29), respectively, for the therapeutic group. Dose changes were required in 9 (69%) of 13 pregnancies and 21 (55%) of 38 pregnancies (data from two of the 40 pregnancies were excluded-one in a patient receiving dalteparin, and one in a patient with mitral valve replacement who had higher antifactor Xa goals) in the prophylaxis and therapeutic groups, respectively, to achieve target antifactor Xa activity. The weight-based prophylactic dose was consistently 0.6 mg/kg in all three trimesters, achieving a mean ± SD target antifactor Xa activity of 0.39 ± 0.18 units/ml, whereas the therapeutic dose was 0.9 mg/kg to maintain antifactor Xa activity of 0.71 ± 0.22 units/ml. CONCLUSION: Dose changes for LMWH throughout pregnancy as guided by antifactor Xa activity were common. A significant increase in the LMWH dose requirements in the prophylactic group suggests that more frequent monitoring of antifactor Xa activity may be appropriate in pregnant patients to maintain target anticoagulant levels.

Association of apolipoprotein E genotype with duration of time to achieve a stable warfarin dose in African-American patients.

STUDY OBJECTIVE: To test the hypothesis that genotypes for proteins affecting vitamin K availability influence the duration of time required to achieve a stable warfarin dose in African-American patients. DESIGN: Retrospective cohort study. SETTING: Pharmacist-managed antithrombosis clinic. PATIENTS: Ninety-two African-American adults whose warfarin therapy was initiated between September 2, 1999, and July 8, 2009. MEASUREMENTS AND MAIN RESULTS: During a routine anticoagulation clinic visit, a sample was collected from each patient for genetic analysis. genotyping was performed for the following variants: apolipoprotein E ε2, ε3, and ε4; NAD(P)H:quinone oxidoreductase (NQO1)*2; cytochrome P450 (CYP) 4F2 V433M; CYP2C9*2, *3, *5, *8, and *11; and vitamin K epoxide reductase complex 1 (VKORC1) -1639G>A. Patients' medical records were then reviewed, and data were collected retrospectively for each anticoagulation clinic visit during the first 6 months of warfarin therapy or until dose stabilization. The median time required to reach a stable warfarin dose, defined as the dose that produced therapeutic anticoagulation for three consecutive clinic visits, was 83 days. Compared with the 46 patients who achieved a stable warfarin dose within 83 days, the 46 patients who required longer durations for dose stabilization had a higher frequency of the apolipoprotein E ε3/ε3 genotype (37% vs 59%, p=0.037). Sixty-one percent of patients with the ε3/ε3 genotype versus 40% of those with an ε2 or ε4 allele had a delay in achieving a stable dose (p=0.037). Neither the CYP4F2 nor NQO1 genotype was associated with warfarin dose stabilization. CONCLUSION: Our data support the hypothesis that the apolipoprotein E genotype is associated with duration of time to reach a stable warfarin dose in African-American patients. Further insight into the genetic effects on warfarin dose stabilization could reveal novel methods to improve anticoagulation control during the warfarin initiation period.

Bleeding incidence with concomitant use of antidepressants and warfarin.

INTRODUCTION: Bleeding is the major complication associated with warfarin therapy. Some antidepressants are also associated with increased bleeding risk. Warfarin and antidepressants are used frequently in combination, but it is unclear whether concomitant use increases the risk of bleeding beyond that with warfarin alone. The primary goal of this study was to determine whether the use of warfarin and an antidepressant increases the risk for bleeding outcomes compared with the use of warfarin alone. The secondary goal was to characterize the risk of bleeding in warfarin-treated patients taking one specific class of antidepressant, selective serotonin reuptake inhibitors (SSRIs). MATERIALS AND METHODS: This was a retrospective, single-center, study of warfarin-treated patients prescribed (n = 46) and not prescribed (n = 54) an antidepressant. Medical records over 6 months were reviewed for international normalized ratio values, medical history, bleeding type and incidence, and hospitalization due to bleeding. Patients were included in the antidepressant group if they were taking concomitant warfarin and antidepressant therapy consistently for a period of 6 months and in the control group if they were not taking an antidepressant with warfarin. RESULTS: The use of any antidepressant with warfarin was not associated with the incidence of any bleeding or major bleeding during the 6-month period. However, the use of an SSRI with warfarin was associated with an increase in any bleeding event (odds ratio 2.6, 95% confidence interval, 1.01-6.4 P = 0.04). The use of an SSRI remained a significant predictor of bleeding after accounting for other factors associated with bleeding risk. CONCLUSIONS: Based on these data, it is important to clarify the interaction between warfarin and SSRIs in regard to bleeding risk given the high frequency of their concomitant use.