Rural-urban differences in pulmonary embolism mortality by race-ethnicity and sex in the United States, 1999-2020.

INTRODUCTION: Racial and ethnic differences in pulmonary embolism (PE) mortality within rural and urban regions in the U.S. have not previously been described. PE mortality may vary across regions and urbanization given disparities in social and structural determinants and comorbid disease. METHODS: Using surveillance data from the Centers for Disease Control and Prevention, age-adjusted mortality rates (AAMR) related to PE were calculated for rural and urban regions in the U.S., in non-Hispanic Black and White women and men, between 1999 and 2020. RESULTS: Among 137,946 deaths in urban regions and 41,333 deaths in rural regions due to PE during this period, AAMR decreased 1.8% per year in urban regions from 3.1 to 100,000 in 1999 to 2.2 per 100,000 in 2020, and decreased 1% per year in rural regions from 4.3 to 100,000 in 1999 to 3.3 per 100,000 in 2020. Since 2008, AAMR from PE increased in non-Hispanic White males in rural and urban regions, decreased in non-Hispanic Black females in rural regions, and otherwise remained stagnant in all other race-sex groups. CONCLUSIONS: AAMR from PE was higher in rural compared with urban individuals, with differences by race and sex. Mortality rates remained stagnant over the last decade in non-Hispanic Black adults and non-Hispanic White females and increased in non-Hispanic White males.

Hereditary thrombotic thrombocytopenic purpura acquired through liver transplantation: A case report.

A 62-year-old received orthotopic liver transplantation. Three weeks later, thrombotic microangiopathy developed. Testing revealed thrombotic thrombocytopenic purpura (TTP) characterized by low ADAMTS13 (A Disintegrin-like Metallopeptidase with ThromboSpondin type 1 motif 13) activity and no inhibitor of ADAMTS13 protein. Retrospective attainment of donor records revealed a TTP diagnosis, presumably hereditary TTP (hTTP), as an ADAMTS13 protein inhibitor was not mentioned. As the grafted liver does not produce ADAMTS13 protein, the recipient now functionally has hTTP and will likely need plasma transfusions indefinitely. While hTTP is extremely rare, it should be considered a contraindication to liver donation outside of exceptional circumstances. If a potential liver donor has TTP listed on medical history, attempts should be made to determine whether it is autoimmune or hereditary. An accurate medical history is critical as it is the only reliable way to identify hTTP, as outside of acute exacerbations of TTP, donors with hTTP can have normal laboratory values, including normal hemoglobin, platelets, and renal function.

A safe and effective use of caplacizumab in pregnancy-related acquired thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura (TTP) is not uncommonly seen in pregnancy, either with the first episode or with the exacerbation of known disease. The management of TTP in pregnancy can be challenging if there is refractoriness to the use of therapeutic plasma exchange (TPE) and high-dose corticosteroids. Caplacizumab, a vWF-directed humanized antibody fragment, is approved for the treatment of acquired TTP but there is sparse data on its use in pregnant patients. Antenatal and peripartum haemorrhage is a theoretical concern with the use of the medication in the obstetric population. However, as options for treatment of TTP in the patients who have refractory disease are significantly limited, off-label use of caplacizumab to achieve disease control and prevent maternofetal morbidity and mortality is a reasonable consideration. This article described the successful use of caplacizumab in a pregnant patient with acquired TTP and the associated favourable outcome. The patient suffered an exacerbation following initial TPE and became refractory to both plasma exchange and high-dose corticosteroids. Off-label use of caplacizumab resulted in hematologic recovery and successful delivery of a healthy neonate. This case represents a contribution to the sparse literature on the use of this effective medication in an often-challenging clinical situation.

DOAC compared with warfarin for VTE in patients with obesity: a retrospective cohort study conducted through the VENUS network.

The effectiveness and safety of direct oral anticoagulants (DOAC) compared with warfarin remains uncertain in obese patients. We assessed the comparative effectiveness and safety of DOACs with warfarin for the treatment of VTE among obese patients. This multi-center retrospective cohort study included adults with a BMI ≥ 35 kg/m2 or weight ≥ 120 kg prescribed either DOAC (apixaban, dabigatran, edoxaban, rivaroxaban) or warfarin for a VTE diagnosis. The primary outcome was the 12-month rate of recurrent VTE. The secondary outcome was the 12-month rate of major bleeding. Among 5626 patients, 67% were prescribed warfarin and 33% were prescribed a DOAC. The 12-month VTE recurrence rate was 3.6% (67/1823) for patients treated with DOAC compared with 3.8% (143/3664) for patients treated with warfarin [odds ratio for recurrent VTE on warfarin versus DOAC (OR) (95% CI).07 (0.80, 1.45)]. The 12-month major bleeding rate was 0.5% (10/1868) for patients on DOAC versus 2.4% (89/3758) on warfarin [OR 4.25 (2.19, 8.22)]. Similar proportions of recurrent VTE occurred across BMI thresholds on DOAC and warfarin: for BMI ≥ 35 kg/m2 (N = 5412), 3.6% versus 3.8%, respectively [OR 1.08 (0.80, 1.46)]; for BMI ≥ 40 kg/m2 (N = 2321), 4.4% versus 3.5%, respectively [OR 0.80 (0.51, 1.26)]; and for BMI ≥ 50 kg/m2 (N = 560), 3.1% versus 3.7%, respectively [OR 1.18 (0.39, 3.56)]. Similar proportions of recurrent VTE occurred in patients with obesity treated for VTE with DOACs and warfarin. DOACs were associated with lower major bleeding compared to warfarin in patients with obesity and VTE.

Differences in referral to a chronic thromboembolic pulmonary hypertension center following acute pulmonary embolism: a locoregional experience.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a treatable complication of acute pulmonary embolism (PE). Identification of factors that impact referral to a comprehensive CTEPH center may improve disease awareness and patient outcomes. We conducted a study of patients with acute PE. Cases were identified through a natural language processing algorithm. ICD coding was used to assess clinical documentation for dyspnea or CTEPH placed at least 90 days after their acute PE diagnosis. We analyzed characteristics of patients who were referred vs. not referred, as well as referral patterns for "at risk" patients. 2454 patients with acute PE were identified, of which 4.9% (120/2454) were referred for CTEPH evaluation. Patients who were not referred were older (61 vs. 54 years, p < 0.001), had higher rates of cancer (28% vs. 10%, p < 0.001), and lived further from the referral center (9.1 miles vs. 6.7 miles, p = 0.03). Of 175 patients identified as "at risk," 12% (21/175) were referred. In the 'at risk' cohort, distance from referral center among referred and not referred was significant (5.7 miles vs. 8.8 miles, p = 0.04). There were low rates of referral to CTEPH center in post-PE patients, and in patients with symptoms who may be at higher risk of CTEPH. Age, co-morbid conditions, distance from comprehensive center, and presence of a primary care provider contribute to differences in referral to a comprehensive CTEPH center. Clinician education about CTEPH is important to ensure optimal care to patients with or at risk for chronic complications of acute PE.

From Budd-Chiari syndrome to acquired von Willebrand syndrome: thrombosis and bleeding complications in the myeloproliferative neoplasms.

Thrombotic and hemorrhagic complications are prevalent in patients with essential thrombocythemia, polycythemia vera, and myelofibrosis. Given the impact on morbidity and mortality, reducing the risk of thrombosis and/or hemorrhage is a major therapeutic goal. Historically, patients have been risk stratified on the basis of traditional factors, such as advanced age and thrombosis history. However, multiple factors contribute to the thrombotic tendency, including gender, mutational profile, inflammatory stress, and abnormal cell adhesion. Management includes cardiovascular risk reduction and use of antiplatelet therapy, depending on myeloproliferative neoplasm subtype and mutational status. Anticoagulation is a mainstay of therapy for those with venous thrombosis, but practice patterns remain heterogeneous. Cytoreduction is indicated for higher-risk patients, but efficacy may depend on the involved vascular bed. Management of special situations, such as unusual site thrombosis, bleeding, the perioperative period, and pregnancy, are especially challenging. In this article, risk factors and treatment strategies for myeloproliferative neoplasm thrombosis and bleeding, including special situations, are reviewed. Insights gained from recent studies may lead to the development of a more precise risk classification and tailored therapy.

Cancer-Associated Venous Thromboembolic Disease, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology.

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Cancer-Associated Venous Thromboembolic Disease focus on the prevention, diagnosis, and treatment of patients with cancer who have developed or who are at risk for developing venous thromboembolism (VTE). VTE is a significant concern among cancer patients, who are at heightened risks for developing as well as dying from the disease. The management of patients with cancer with VTE often requires multidisciplinary efforts at treating institutions. The NCCN panel comprises specialists from various fields: cardiology, hematology/hematologic oncology, internal medicine, interventional radiology, medical oncology, pharmacology/pharmacy, and surgery/surgical oncology. This article focuses on VTE prophylaxis for medical and surgical oncology inpatients and outpatients, and discusses risk factors for VTE development, risk assessment tools, as well as management methods, including pharmacological and mechanical prophylactics. Contraindications to therapeutic interventions and special dosing, when required, are also discussed.

How I treat patients with inherited bleeding disorders who need anticoagulant therapy.

Situations that ordinarily necessitate consideration of anticoagulation, such as arterial and venous thrombotic events and prevention of stroke in atrial fibrillation, become challenging in patients with inherited bleeding disorders such as hemophilia A, hemophilia B, and von Willebrand disease. There are no evidence-based guidelines to direct therapy in these patients, and management strategies that incorporate anticoagulation must weigh a treatment that carries a risk of hemorrhage in a patient who is already at heightened risk against the potential consequences of not treating the thrombotic event. In this paper, we review atherothrombotic disease, venous thrombotic disease, and atrial fibrillation in patients with inherited bleeding disorders, and discuss strategies for using anticoagulants in this population using cases to illustrate these considerations.

Multicenter analysis of the use of transjugular intrahepatic portosystemic shunt for management of MPN-associated portal hypertension.

BCR-ABL1-negative myeloproliferative neoplasms (MPNs) are clonal stem cell disorders defined by proliferation of one or more myeloid lineages, and carry an increased risk of vascular events and progression to myelofibrosis and leukemia. Portal hypertension (pHTN) occurs in 7-18% of MPN patients via both thrombotic and nonthrombotic mechanisms and portends a poor prognosis. Transjugular intrahepatic portosystemic shunt (TIPS) has been used in the management of MPN-associated pHTN; however, data on long-term outcomes of TIPS in this setting is limited and the optimal management of medically refractory MPN-associated pHTN is not known. In order to assess the efficacy and long-term outcomes of TIPS in MPN-associated pHTN, we performed a retrospective analysis of 29 MPN patients who underwent TIPS at three academic medical centers between 1997 and 2016. The majority of patients experienced complete clinical resolution of pHTN and its clinical sequelae following TIPS. One, two, three, and four-year overall survival post-TIPS was 96.4%, 92.3%, 84.6%, and 71.4%, respectively. However, despite therapeutic anticoagulation, in-stent thrombosis occurred in 31.0% of patients after TIPS, necessitating additional interventions. In conclusion, TIPS can be an effective intervention for MPN-associated pHTN regardless of etiology. However, TIPS thrombosis is a frequent complication in the MPN population and indefinite anticoagulation post-TIPS should be considered.

Heparin-induced thrombocytopenia testing is over-utilized in cirrhosis & correlates with poor clinical outcomes.

INTRODUCTION: Heparin-induced thrombocytopenia (HIT) is a serious complication seen in hospitalized, medically-ill patients. Evaluation for HIT using a commercially-available ELISA-based test has become increasingly common; however, it does have a high false positive rate. Implications of HIT testing in patients with cirrhosis have not yet been reported. MATERIAL AND METHODS: We conducted a single-institution, retrospective review of all patients with cirrhosis admitted over a 29-month period. The student's t-test and the χ2 test were used for comparisons. We performed a stratified survival analysis using Kaplan-Meier and log rank testing. RESULTS: A total of 1,305 patients had a HIT Ab sent during the study period. Of these patients, 106 had cirrhosis and were included in the study. Eighteen (17%) of the patients with cirrhosis were HIT Ab positive and four of the eighteen had a positive Serotonin Release Assay (SRA) confirmatory test. No difference was found in platelet nadir, thrombotic rate, length of stay, and patient survival between patients with positive HIT Ab and negative HIT Ab testing. No consistent treatment was used among patients who were HIT Ab positive, despite hematology service consultation. Patients who were HIT Ab negative were more likely to have undergone liver transplantation compared to those who were positive (27 vs. 5.5%, respectively; p = 0.048). CONCLUSION: Our data suggest that HIT Ab testing is over-used in patients with cirrhosis and is poorly predictive of outcomes. With a poor positive predictive value, HIT testing may add unnecessary complexity to an already complicated patient population.

Preventing venous thromboembolism for ambulatory patients with cancer: Developing the form and content of implementation strategies.

Background: For ambulatory cancer patients receiving systemic chemotherapy, adherence is low to recommended venous thromboembolism (VTE) prevention interventions. Previously, we identified implementation strategies to address barriers to adherence, including (1) conducting clinician education and training; (2) developing and distributing educational materials for clinicians; (3) adapting electronic health records to provide interactive assistance; and (4) developing and distributing educational materials for patients. The objective of this study was to develop these implementation strategies' form (i.e., how and when) and content (i.e., information conveyed) as a critical step for implementation and dissemination. Methods: To design and develop the form and content of the implementation strategies, we conducted multidisciplinary stakeholder panels with oncology clinicians, pharmacists, and hematologists. Over several panel discussions, we developed a low fidelity prototype. Participants performed preliminary usability testing, simulating patient care encounters. We also conducted interviews with three patients who provided additional feedback. Results: The form and content for each strategy, respectively, included (1) concise training with a slide deck; (2) succinct summary of evidence for the interventions and support for anticoagulation management; (3) automated VTE risk-assessment and clinical decision support, including bleeding risk assessment and anticoagulation options; and (4) patient education resources. During development, audit and feedback was identified as an additional strategy, for which we created report cards to implement. Conclusion: With stakeholder input, we successfully developed the form and content needed to put the implementation strategies into practice. The next step is to study the effect on the uptake of ambulatory VTE prevention recommendations in oncology clinics.

Venous thromboembolism prevention program implementation in a community oncology practice: a cohort study.

Background: While national guidelines recommend Venous Thromboembolism (VTE) risk assessment in cancer outpatients and consideration of pharmacologic prophylaxis in high-risk patients, prophylaxis rates are low in community oncology practices. A successful model for guideline implementation (the Vermont Model, VM) is validated in an academic tertiary oncology setting. We undertook an implementation study to determine the success of this model in a multi-site community oncology practice. The study objectives were to: 1) adapt the VM to the community practice setting; 2) implement the adapted VM into practice; and 3) evaluate clinical and implementation outcomes. Methods: The study was carried out in three phases: (1) Pre-implementation, a multidisciplinary team addressed the need to adapt the VM to the local context including electronic medical record (EMR) optimisation and clinician education; (2) implementation of the strategies adapted to the local context, informed by VM and adapted based on stakeholder feedback; (3) prospective evaluation of clinical and implementation outcomes at six months after implementation. Findings: Following creation of a comprehensive initiation roadmap for the adaptation of VM program to the community practice, 302 cancer outpatients initiating new treatment met inclusion criteria over a 6 month implementation period. VTE risk education was provided to 100% of patients, and 98% (296) of patients received a VTE risk assessment. Of 52 patients (18%) who scored as high risk based on a modified Khorana (Protecht) score, 14 (27%) initiated prophylaxis. Barriers to program adaptation included EMR optimization challenges and practice-level responsibility assignment, time constraints, concern about potential drug interactions, and financial & insurance issues. Interpretation: Implementation of a multidisciplinary VTE prevention model in the community-based oncology setting successfully increased VTE education and risk assessment rates. AC prophylaxis rates were modestly increased, highlighting the need to understand and address barriers to anticoagulant prophylaxis prescribing in this setting. Funding: Northern New England Clinical Oncology Society Research Funding Program.

When Direct Oral Anticoagulants Should Not Be Standard Treatment: JACC State-of-the-Art Review.

For most patients, direct oral anticoagulants (DOACs) are preferred over vitamin K antagonists for stroke prevention in atrial fibrillation and for venous thromboembolism treatment. However, randomized controlled trials suggest that DOACs may not be as efficacious or as safe as the current standard of care in conditions such as mechanical heart valves, thrombotic antiphospholipid syndrome, and atrial fibrillation associated with rheumatic heart disease. DOACs do not provide a net benefit in conditions such as embolic stroke of undetermined source. Their efficacy is uncertain for conditions such as left ventricular thrombus, catheter-associated deep vein thrombosis, cerebral venous sinus thrombosis, and for patients with atrial fibrillation or venous thrombosis who have end-stage renal disease. This paper provides an evidence-based review of randomized controlled trials on DOACs, detailing when they have demonstrated efficacy and safety, when DOACs should not be the standard of care, where their safety and efficacy are uncertain, and areas requiring further research.

Improving Judicious Use of Heparin-Induced Thrombocytopenia Testing Through Electronic Health Record-Based Intervention.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is an immune-mediated drug reaction that can cause thromboembolism in the setting of thrombocytopenia. An enzyme-linked immunosorbent assay (ELISA)-based assay to screen for HIT antibodies (HAb) is available but has relatively low specificity and a correspondingly high false positive rate. The 4Ts score has been validated to determine the pretest probability of HIT. The authors hypothesized that an electronic health record (EHR)-based clinical decision support (CDS) tool incorporating the 4Ts score would reduce the volume of HAb orders. METHODS: After implementing a CDS tool into the EHR, the researchers retrospectively evaluated the impact from November 2019 to October 2021, compared to a preintervention period (January to October 2019). The primary outcome was average tests per month. Secondary outcomes included rates of tests ordered per total inpatient encounters and proportion of HAb sent despite low 4Ts score in the postintervention study period. RESULTS: Of 1,833 HAb sent during the study period, 1,217 occurred in the postintervention period. In the postintervention period compared with the preintervention period, the average orders per month was 50.5 (standard deviation [SD] 9.7) vs. 61.6 (SD 7.2) (p = 0.003), and the order incidence rate was 8.0 per 1,000 patient encounters postintervention vs. 9.2 per 1,000 patient encounters preintervention (rate ratio [RR] 0.87, 95% confidence interval [CI] 0.79-0.96, p = 0.002). Postintervention, 252 (20.7%) had a 4Ts score calculated as low probability, 759 (62.4%) as intermediate probability, and 131 (10.8%) as high probability, and 75 had no associated 4Ts score. CONCLUSION: Implementation of a simple CDS tool reduced the rate of HAb orders, reducing unnecessary HAb testing.

Venous thromboembolism prevention in cancer care: implementation strategies to address underuse.

Background: Evidenced-based interventions have been developed to prevent venous thromboembolism (VTE) in ambulatory patients with cancer, including VTE-risk assessment for all patients and targeted primary thromboprophylaxis for high-risk patients. Despite supportive evidence and recommendations, oncologists rarely assess VTE risk or provide primary prophylaxis. Our previous work identified barriers and facilitators to using VTE prevention interventions in oncology practice. Objectives: To identify potential strategies that address the identified barriers and leverage facilitators to achieve successful implementation of evidence-based interventions for VTE prevention in oncology practice. Methods: We used the Implementation Research Logic Model, an implementation science framework, to map the relationships among barriers and facilitators, feasible and effective implementation strategies, and implementation and clinical outcomes that will be used to evaluate the implementation strategies. Results: We identified 12 discrete implementation strategies (eg, conducting clinician education and training and staged implementation scale-up) that address barriers and leverage facilitators through their mechanisms of action (eg, increased clinician awareness of evidence and targeting the highest effectiveness). We identified key implementation (eg, penetration, adoption, acceptability, fidelity, appropriateness, and sustainability), system (eg, integration of VTE-risk assessment into clinical workflow), and clinical (eg, lower VTE rates) outcomes targeted by the selected strategies. Conclusion: Using the Implementation Research Logic Model framework and building on our knowledge of barriers and facilitators, we identified implementation strategies and important outcomes to evaluate these strategies. We will use these results to test and measure the strategies to improve the uptake of evidence-based recommendations for VTE prevention in oncology practice.