Acute Portal and Superior Mesenteric Vein Thrombosis with Topical Testosterone Therapy: An Adverse Drug Event Case Report.

This is a case report of a 55-year-old Caucasian male prescribed topical testosterone therapy for 12 months prior to admission, when he was diagnosed with acute thrombosis in the portal vein (PVT) and superior mesenteric vein (SMV). The patient had a negative thrombophilia workup, including Factor V Leiden, Prothrombin G20210A, and JAK2 V617F mutations. There were no other pertinent laboratory markers that raised concern for the cause of thrombus. No strong familial history of venous thromboembolism (VTE) was reported during the patient's initial workup. With this in mind, the patient's use of topical testosterone therapy was considered the most likely risk factor for the PVT and SMV thrombus. During hospitalization, the patient was initiated on therapeutic anticoagulation with a heparin drip and discharged to home on apixaban for 3 months with extended therapy to be determined by outpatient hematologist. With no other identified VTE risk factors, probability that this patient's VTE was attributed to testosterone was evaluated using the Naranjo scale with a calculated score of 6, which classifies the adverse reaction as "likely." Clinicians should be aware of the possibility that topical testosterone therapy may be a risk factor for venous thrombosis in unusual sites.

Trends and Outcomes of Oral Anticoagulation With Direct Current Cardioversion for Atrial Fibrillation/Flutter at an Academic Medical Center.

Background: Increasing reports suggest the safe use of direct oral anticoagulants (DOACs) in electrical cardioversion. The aim of this study was to assess the trends and 30-day outcomes associated with anticoagulation for cardioversion. Methods: Patients who underwent electrical cardioversion from January 2015 to October 2020 with a 30-day follow-up were included; and outcomes including stroke, transient ischemic attack, intracranial hemorrhage (ICH), and major gastrointestinal bleeding were recorded. Results: Of the 515 patients, 351 (68%) were men and 164 (32%) were women, with a mean CHA2DS2VASc score of 2.6 ± 1.6. Outpatient apixaban use increased from 10% in 2015 to 46% in 2020 (P < 0.001) with a decline in the use of warfarin from 24% in 2015 to 10% in 2020 (P = 0.023). Apixaban use peri-procedurally for cardioversion increased from 32% in 2015 to 35% in 2020 (P = 0.317), while warfarin use decreased from 23% in 2015 to 14% in 2020 (P = 0.164). At discharge, apixaban prescriptions increased from 21% in 2015 to 61% in 2020 (P < 0.001), while warfarin prescriptions declined from 30% in 2015 to 13% in 2020 (P = 0.009). No ICH was recorded in the 30 days after cardioversion. Ischemic stroke occurred in four (0.7%) patients with one (0.29%) of the 338 patients on a DOAC, one (0.8%) of the 124 patients on warfarin and two (5.5%) of the 36 patients not receiving anticoagulation post cardioversion. There were seven (1%) major gastrointestinal bleeding events in patients on oral anticoagulation, of which four (3%) were on warfarin and three (0.8%) were on DOACs. Conclusions: Our study shows the increasing and safe use of DOACs for the purpose of cardioversion. The rates of 30-day ischemic stroke post cardioversion were low and only occurred in patients admitted in the intensive care unit.

Modes of Failure in Venous Thromboembolism Prophylaxis.

Venous thromboembolism (VTE) is associated with potentially preventable in-hospital morbidity and mortality. Although evidence-based guidelines are widely available, their application in clinical practice varies markedly. VTE prophylaxis involves a multistep dynamic process that can fail at various points during hospital stay. Our aim was to identify defects in VTE prophylaxis. Upon admission, our patients undergo VTE risk stratification and orders for prophylaxis are entered. All patients that fulfill the criteria for the Patient Safety Indicator (PSI)-12, as defined by the Agency for Healthcare Research and Quality, are prospectively entered in a database. From a review of 138 PSI-12 patients, only 21 had correct risk stratification and appropriate chemoprophylaxis during their hospital stay; 70 had been incorrectly stratified, with 28 of these patients receiving incorrect prophylaxis due to incorrect stratification, thus delaying the correct administration of chemoprophylaxis for >24 h. Inadequate application of mechanical prophylaxis was noted in 114 patients. VTE prophylaxis relies on correct risk stratification, ordering appropriate pharmacomechanical measures and, finally, the delivery of this treatment throughout the hospital stay. A large percentage of patients who had a thromboembolic complication received inadequate prophylaxis. This study identifies potential areas for intervention to improve VTE prophylaxis.

Evaluation of Bivalirudin as the Primary Anticoagulant in Patients Receiving Extracorporeal Membrane Oxygenation for SARS-CoV-2-Associated Acute Respiratory Failure.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a potential option for the management of severe acute respiratory failure secondary to COVID-19. Conflicting the use of this therapy is the known coagulopathy within COVID-19, leading to an incidence of venous thrombotic events of 25% to 49%. To date, limited guidance is available on optimal anticoagulation strategies in this population. OBJECTIVE: The purpose of this study was to evaluate the utilization of a pharmacist-driven bivalirudin dosing protocol for anticoagulation in the setting of ECMO for COVID-19-associated respiratory failure. METHODS: This was a single-center retrospective chart review over a 9-month period of patients receiving bivalirudin while on ECMO. All patients with acute respiratory failure requiring ECMO with a positive SARS-CoV-2 polymerase chain reaction were included. Bivalirudin was dosed via aPTT monitoring after a starting dose of 0.2 or 0.3 mg/kg/h. RESULTS: There were 33 patients included in this study, all receiving mechanical ventilation. The most common starting dose of bivalirudin was 0.2 mg/kg/h, with an average time to therapeutic range of 20 hours. Compared to previous reports, rates of bleeding were low at 15.1%, and 6.1% of patients developed a new venous thromboembolic event while on ECMO. ECMO survival was 51.5%, with an ICU mortality rate of 48.5%. CONCLUSION AND RELEVANCE: In the first published report of its use within this population, bivalirudin was found to be a viable choice for anticoagulation in those patients on ECMO for severe respiratory failure secondary to COVID-19.

Intravenous phytonadione administered orally in reducing warfarin-related coagulopathy.

INTRODUCTION: The cost of phytonadione tablets has increased markedly and is significantly higher than the intravenous formulation. The intravenous formulation given orally is a potential alternative but has not been directly evaluated in comparison to the commercially available tablet. The objective of this study was to evaluate the efficacy of phytonadione intravenous solution given orally compared to commercially available phytonadione tablets for reversal of coagulopathy related to warfarin. METHODS: We conducted a retrospective, observational study of adult patients who received phytonadione tablets and the IV formulation orally for warfarin-related coagulopathy. The international normalized ratio (INR) was measured before and after phytonadione administration. The primary outcome was INR <1.5 at 24 h after phytonadione administration. RESULTS: From January 1, 2015 to August 1, 2018 a total of 200 patients were identified. In total, 58% (n = 116) patients received IV phytonadione solution given orally and 42% (n = 84) patients received the tablets. The primary outcome of INR <1.5 at 24 h was not significantly different between groups (p = 0.321). DISCUSSION: The IV phytonadione solution given by mouth and the tablet formulation performed similarly.

Interhospital Transfer of Patients With Acute Pulmonary Embolism: Challenges and Opportunities.

Acute pulmonary embolism (PE) is associated with significant morbidity and mortality. The management paradigm for acute PE has evolved in recent years with wider availability of advanced treatment modalities ranging from catheter-directed reperfusion therapies to mechanical circulatory support. This evolution has coincided with the development and implementation of institutional pulmonary embolism response teams (PERT) nationwide and internationally. Because most institutions are not equipped or staffed for advanced PE care, patients often require transfer to centers with more comprehensive resources, including PERT expertise. One of the unmet needs in current PE care is an organized approach to the process of interhospital transfer (IHT) of critically ill PE patients. In this review, we discuss medical optimization and support of patients before and during transfer, transfer checklists, defined roles of emergency medical services, and the roles and responsibilities of referring and receiving centers involved in the IHT of acute PE patients.

Value-based assessment of implementing a Pulmonary Embolism Response Team (PERT).

PERTs are a new, multidisciplinary approach to PE care. They were conceived to efficiently identify and risk stratify PE patients and standardize care delivery. More research needs to be conducted to assess the effects that PERTs have had on PE care. This study sought to determine the effects of a PERT on quality and overall value of care. This was a retrospective study of all patients 18 years of age or older who presented with a principal diagnosis of an acute PE based on available ICD codes from January 1, 2010 to December 31, 2018. Patients who did not have an imaging study, i.e., CTPA or ECHO, available were excluded. Patients were divided into pre- (before October 2015) and post-PERT eras (after October 2015) and stratified based on the presence of right heart strain/dysfunction on imaging. All quality outcomes were extracted from the EMR, and cost outcomes were provided by the financial department. 530 individuals (226 pre-PERT and 304 post-PERT) were identified for analysis. Quality outcomes improved between the eras; most notably in-hospital mortality decreased (16.5 vs. 9.6) and hospital LOS decreased (7.7 vs. 4.4) (p < 0.05). Total cost of care also decreased a statistically significant amount between the eras. The implementation of a PERT improved quality and cost of care, resulting in improved value. We hypothesize that this may be due to more timely identification and risk stratification leading to earlier interventions and streamlined decision making, but further research is required to validate these findings in larger cohorts.

Venous thromboembolism (VTE) risk stratification in general medical patients at an academic medical center.

Hospital-acquired venous thromboembolism (VTE) is still a concern for general medical patients. Pharmacologic prophylaxis can reduce VTE incidence, but there is the potential for adverse effects. Therefore, determining which patients should receive VTE prophylaxis via risk scoring tools is essential. Limited evidence exists for the ideal venous thromboembolism risk assessment model (RAM) in hospitalized medical patients, as compared to other hospitalized patient subgroups such as surgical patients. The primary objective was to investigate the utilization and appropriateness of our institution-based VTE RAM and comparison to the Padua Prediction Score (PPS). This would allow for a gauge of provider risk assessment accuracy as well as appropriate predictive potential of the PPS or whether an alternative to the PPS should be considered. A total of 330 adult general medicine patients were included in this retrospective chart review. When compared to our institution-based VTE RAM, providers predominately stratified patients at a higher VTE risk than the institution-based VTE RAM. VTE incidence was 0.3%, which was lower than predicted. Significant discordance exists between providers' VTE risk assessment and that predicted by RAMs. Our institution-based VTE RAM appears comparable to PPS; however, it was not being utilized by providers, resulting in potentially unnecessary use of pharmacologic prophylaxis. The most appropriate venous thromboembolism risk assessment model for general medicine patients is undetermined. Our providers generally assess patients as moderate or high VTE risk, despite our institution-based RAM which typically recommends a lower risk category than provider selection. Because of provider risk assessment, more patients received pharmacologic VTE prophylaxis than would have been recommended by the RAM, which might correlate to the low incidence of VTE which was < 0.5%, although bleeding complications were not assessed in this study. A prospective study utilizing the Padua Prediction Score (or similar RAM) in general medicine patients is warranted in order to decipher the best method of predicting VTE risk.

Comparison of Low- Versus High-Dose Four-Factor Prothrombin Complex Concentrate (4F-PCC) for Factor Xa Inhibitor-Associated Bleeding: A Retrospective Study.

BACKGROUND: Although andexanet alfa was recently approved as a specific reversal agent for apixaban and rivaroxaban, some providers still elect to administer 4-factor prothrombin complex concentrate (4F-PCC) instead, due to concerns surrounding efficacy, thrombotic risk, administration logistics, availability, and cost. Previous studies have described success with 4F-PCC doses ranging from 25 to 35 U/kg, with some guidelines recommending 50 U/kg. OBJECTIVES: The purpose of this study was to compare hemostasis between patients receiving low- (20-34 U/kg) versus high-dose (35-50 U/kg) 4F-PCC for the urgent reversal of apixaban and rivaroxaban. PATIENTS/METHODS: We performed a retrospective cohort study at a level one trauma center and comprehensive stroke center between January 2015 and December 2018. Main exclusion criteria included patients receiving less than 20 U/kg or if postreversal imaging were unavailable. Outcomes assessed included hemostasis for critical bleeding associated with apixaban or rivaroxaban and postoperative bleeding for reversal for emergent procedures. RESULTS: The low-dose strategy was administered to n = 57 (57.6%) patients at a mean dose of 26.6 U/kg. The high-dose strategy was used in n = 42 (42.4%) patients at a mean dose of 47.6 U/kg. There was no difference in hemostasis by dosing strategy (75.4% vs 78.6%, P = .715) or hospital mortality (19.3% vs 35.7%, P = .067). No difference was found for secondary end points, including thrombotic events (5.3% vs 2.4%, P = .635) and hospital length of stay (11.3 vs 12.5 days, P = .070). CONCLUSIONS: Our comparison addresses a gap in the literature surrounding optimal dosing and supports a similar efficacy profile between dosing low- versus high-dose treatment.

Diagnosis and Treatment of Pulmonary Embolism During the Coronavirus Disease 2019 Pandemic: A Position Paper From the National PERT Consortium.

The coexistence of coronavirus disease 2019 (COVID-19) and pulmonary embolism (PE), two life-threatening illnesses, in the same patient presents a unique challenge. Guidelines have delineated how best to diagnose and manage patients with PE. However, the unique aspects of COVID-19 confound both the diagnosis and treatment of PE, and therefore require modification of established algorithms. Important considerations include adjustment of diagnostic modalities, incorporation of the prothrombotic contribution of COVID-19, management of two critical cardiorespiratory illnesses in the same patient, and protecting patients and health-care workers while providing optimal care. The benefits of a team-based approach for decision-making and coordination of care, such as that offered by pulmonary embolism response teams (PERTs), have become more evident in this crisis. The importance of careful follow-up care also is underscored for patients with these two diseases with long-term effects. This position paper from the PERT Consortium specifically addresses issues related to the diagnosis and management of PE in patients with COVID-19.

Reduced dose thrombolysis with ultrasound-facilitated catheter-directed administration for acute pulmonary embolism reduces length of stay.

The optimal dose and duration of tissue plasminogen activator (tPA) administered with ultrasound-facilitated catheter-directed thrombolysis (USCDT) to patients with acute PE remains to be determined. Our institution recently adopted a shorter duration (4 h) of USCDT and lower dosing strategy (tPA 1 mg/h) based on data from the OPTALYSE PE Trial. The purpose was to evaluate the implementation at our institution of shorter duration (4 h) of USCDT and lower dosing strategy (tPA 1 mg/h) as outlined by OPTALYSE PE Trial. This was a retrospective, single-center, observational study included patients from 01/01/2017 to 12/31/2018 in a large, academic medical center. Group 1 represented patients who underwent USCDT prior to 01/18/18. Group 2 represented patients who underwent USCDT after 01/18/18 and received 4 h of USCDT and tPA 1 mg/h/catheter. The primary outcome was intensive care unit (ICU) length of stay (LOS). Secondary outcomes were the proportion of patients experiencing a composite of major adverse events (death, recurrent PE, major bleeding, or stroke), change in right ventricle size/function and pulmonary artery pressures, need for mechanical respiratory or hemodynamic support, hospital LOS and drug cost. A total of 31 patients were included in the study: twenty patients in Group 1 and eleven patients in Group 2. Median ICU LOS was 3.5 days in Group 1 and 1 day in Group 2. Group 2 had reduced MACE, requirement for mechanical respiratory or hemodynamic support, hospital LOS, drug costs and adverse events. Implementation of a shorter duration of USCDT and lower dosing strategy for tPA in patients with acute PE may be one strategy to reduce the total ICU LOS and costs associated with care.

Diagnosis, Treatment and Follow Up of Acute Pulmonary Embolism: Consensus Practice from the PERT Consortium.

Pulmonary embolism (PE) is a life-threatening condition and a leading cause of morbidity and mortality. There have been many advances in the field of PE in the last few years, requiring a careful assessment of their impact on patient care. However, variations in recommendations by different clinical guidelines, as well as lack of robust clinical trials, make clinical decisions challenging. The Pulmonary Embolism Response Team Consortium is an international association created to advance the diagnosis, treatment, and outcomes of patients with PE. In this consensus practice document, we provide a comprehensive review of the diagnosis, treatment, and follow-up of acute PE, including both clinical data and consensus opinion to provide guidance for clinicians caring for these patients.

The implementation of a pulmonary embolism response team in the management of intermediate- or high-risk pulmonary embolism.

BACKGROUND: Massive and submassive pulmonary embolism (PE) can be life-threatening. Treatment options include anticoagulation, fibrinolysis, catheter-directed or open surgical thrombus removal, and extracorporeal membrane oxygenation. With increasing patient complexity and advanced therapeutic options, the approach to optimal care for patients with intermediate- to high-risk PE is not clearly established. Multidisciplinary, rapid response teams can optimize risk stratification and expedite management. A PE response team (PERT) composed of specialists from cardiology, vascular surgery, emergency medicine, pulmonary and critical care, interventional radiology, cardiac surgery, hospital medicine, and pharmacy was created at our institution. The team is tasked with evaluating and treating patients with massive and submassive PE by use of a risk stratification and treatment algorithm. We describe our initial experience with this approach. METHODS: The records of patients treated by the PERT since inception in October 2015 through May 2017 were reviewed (intervention group). The diagnoses codes of the PERT patients were retrieved from the Vizient database. A retrospective control cohort group was created using these specific diagnoses and a matching set of demographics (age, sex), Medicare Severity Diagnosis Related Group, admission severity of illness, and admission risk of mortality. Statistical analysis was performed using the Fisher exact test, the Pearson χ2 statistic, Student t-test, and Cochran-Cox approximation. P < .05 was considered significant. RESULTS: During the time interval, 77 patients with massive or submassive PE were treated by PERT activation; 992 patients included in the control group were treated at the discretion of an attending physician without use of the algorithm from October 2013 to 2016. Both groups had similar demographics, similar distribution of risk of mortality and severity of illness, and similar average Medicare Severity Diagnosis Related Group weighting. There was no statistically significant difference in the mortality rate between the two groups. The PERT group had significantly lower intensive care unit stay and overall length of stay. No difference was seen in direct cost between the two groups despite higher use of interventional treatment modalities in the PERT group. CONCLUSIONS: In our institution, assembly of a dedicated team to treat patients with massive or submassive PE according to a clinical algorithm resulted in expedited treatment and reduced variation of care. Intensive care unit stay and overall length of stay were reduced by this approach, with no impact on direct cost despite the use of advanced modalities of treatment. We believe that this paradigm can be of potential value in other disease entities, particularly when multiple disciplines are involved.

Factor VIIa administration in orthotopic heart transplant recipients and its impact on thromboembolic events and post-transplant outcomes.

Recombinant, activated factor VIIa (rFVIIa) is used during cardiac surgeries to mitigate refractory coagulopathic bleeding. The purpose of this study was to examine whether rFVIIa use in orthotopic heart transplant (OHT) recipients was associated with a higher incidence of thromboembolic (TE) events compared to patients who did not. A single-center, retrospective, cohort study was performed on OHT recipients who received rFVIIa for refractory coagulopathic bleeding from January 2013 to December 2015. Patients were evaluated for up to 6 months after transplantation and assessed for TE events, rejection, readmissions, graft survival, and patient survival. Categorical variables were analyzed using the Chi square test while student's t or ANOVA testing was utilized for continuous variables. Of the 62 patients who met inclusion criteria, 27 patients received rFVIIa, and 35 patients were selected for the control group. The overall incidence of TE events was not significantly different between patients who received rFVIIa compared to patients in the control group (14.8% vs 11.4%) (p = 0.69). Within 14 days, 14.81% of rFVIIa patients suffered a TE event compared to 5.7% of the control group (p = 0.23). Rejection, readmissions, graft survival, and patient survival were not significantly different at any time points. Use of rFVIIa in heart transplantation showed no difference in the overall rate of TE events, however, there was a nonsignificant trend toward higher risk of early TE development in the rFVIIa group compared to the control group.

Oral factor Xa inhibitors for the treatment of left ventricular thrombus: a case series.

Left ventricular thrombus (LVT) formation usually necessitates short term anticoagulation for thrombus resolution and to prevent embolic events. Historically, vitamin K antagonist therapy has been the treatment of choice. However, with the advent of direct acting anticoagulants, their role in the management of LVT is not clear. Patients were included if they had received rivaroxaban or apixaban for more than 1 day for LVT documented on imaging. The primary objective was resolution of LVT at 3 months based on assessment by an independent cardiologist review of initial and subsequent imaging results. The principle safety objective was to assess major or clinically relevant non-major bleeding using GUSTO, TIMI, and BARC bleeding criteria. During the 2-year study period seven patients were treated with rivaroxaban and three with apixaban. Two patients who had received apixaban and one on rivaroxaban were lost to follow up. In those with an initial and follow-up ECHO (n = 6) the median time to follow up imaging was 214 (IQR 33-414) days and complete LVT resolution was observed in 83% of patients. One patient on rivaroxaban had a bleeding events that was minimal (TIMI), Type 2 (BARC), or classified as mild (GUSTO) due to pulmonary hemorrhage. In those deemed not to be a candidate for vitamin K antagonist the use of rivaroxaban or apixaban may be a considered in the treatment of LVT. Further research in this area is needed to assess the efficacy and safety of using FXAI for treatment of LVT.

Delayed hematologic toxicity following rattlesnake envenomation unresponsive to crotalidae polyvalent antivenom.

North American rattlesnake envenomations are known to produce coagulopathies and thrombocytopenia. However, the occurrence of delayed hematologic toxicity (less than seven days after envenomation) is poorly characterized in the medical literature. While the recurrence of hematologic derangements has been documented following envenomation, it is usually in the absence of clinically significant bleeding. Although commonly recommended to treat delayed coagulopathies, the effectiveness of crotalidae polyvalent immune Fab ovine (CroFab®) in managing this condition remains in question and warrants further investigation and exploration. We describe the case of a 19-year-old male who presented following rattlesnake envenomation at a church service who was treated with antivenin for 48 h and discharged home only to return four days later with profound thrombocytopenia, coagulopathy, and clinically significant bleeding.