Avatrombopag for adults with early versus chronic immune thrombocytopenia.

Avatrombopag is a newer thrombopoietin receptor agonist (TPO-RA) currently approved to treat chronic ITP (duration >12 months). No studies have yet evaluated the safety and effectiveness of avatrombopag in newly diagnosed ITP (duration <3 months) or persistent ITP (duration 3-12 months), and so its use in these populations is presently off-label worldwide. We hypothesize that avatrombopag has similar safety and effectiveness irrespective of ITP disease phase. To evaluate this, we performed a multicenter observational cohort study of adults with ITP treated with avatrombopag, comparing patient outcomes by disease phase (newly diagnosed/persistent versus chronic). Seventy-five patients were included, 23 with newly diagnosed/persistent ITP (17.7 patient-years of avatrombopag treatment) and 52 with chronic ITP (65.3 patient-years of avatrombopag treatment). On avatrombopag, 91% of newly diagnosed/persistent patients versus 96% of chronic patients (p = .58) achieved a platelet response (≥50 × 109 /L) and 86% versus 81% of patients (p = .78) achieved a complete response (≥100 × 109 /L). Median platelet counts on avatrombopag were similar between the two groups (165 × 109 /L vs. 129 × 109 /L, p = .57). Response durability was high and similar in both groups. No patients in the newly diagnosed/persistent group had a major bleeding event, thromboembolic event or avatrombopag discontinuation for adverse events, compared with 4, 1, and 2, respectively, in the chronic group. Thrombocytosis (platelets ≥400 × 109 /L) incidence was similar in the two groups. No other drug-related adverse events occurred in either group. Avatrombopag was safe and effective in patients with newly diagnosed and persistent ITP, with outcomes numerically, statistically, and clinically similar to patients receiving avatrombopag for chronic ITP.

Burnout in US hematologists and oncologists: impact of compensation models and advanced practice provider support.

Burnout is prevalent throughout medicine. Few large-scale studies have examined the impact of physician compensation or clinical support staff on burnout among hematologists and oncologists. In 2019, the American Society of Hematology conducted a practice survey of hematologists and oncologists in the AMA (American Medical Association) Masterfile; burnout was measured using a validated, single-item burnout instrument from the Physician Work-Life Study, while satisfaction was assessed in several domains using a 5-point Likert scale. The overall survey response rate was 25.2% (n = 631). Of 411 respondents with complete responses in the final analysis, 36.7% (n = 151) were from academic practices and 63.3% (n = 260) from community practices; 29.0% (n = 119) were female. Over one-third (36.5%; n = 150) reported burnout, while 12.0% (n = 50) had a high level of burnout. In weighted multivariate logistic regression models incorporating numerous variables, compensation plans based entirely on relative value unit (RVU) generation were significantly associated with high burnout among academic and community physicians, while the combination of RVU + salary compensation showed no significant association. Female gender was associated with high burnout among academic physicians. High advanced practice provider utilization was inversely associated with high burnout among community physicians. Distinct patterns of career dissatisfaction were observed between academic and community physicians. We propose that the implementation of compensation models not based entirely on clinical productivity increased support for women in academic medicine, and expansion of advanced practice provider support in community practices may address burnout among hematologists and oncologists.

Facial Nerve Preservation With Inferior Long-Axis Dissection of Large Vestibular Schwannomas.

OBJECTIVE: To describe a tumor resection using the inferior long-axis (ILA) technique for cisternal facial nerve dissection in large vestibular schwannomas (VS). STUDY DESIGN: Retrospective case series from 2018 to 2021. SETTING: Tertiary academic medical center. PATIENTS: Patients who underwent surgical resection with ILA facial nerve dissection of VS (>2.0 cm measured parallel to the petrous ridge) and had at least 3-month follow-up. INTERVENTIONS: Cisternal facial nerve dissection during retrosigmoid or translabyrinthine approach using standardized ILA technique developed by author R.N. MAIN OUTCOME MEASURES: Immediate postoperative and last follow-up facial nerve function with House-Brackmann scores of I to II defined as "good" facial nerve function and House-Brackmann scores III to VI defined as "poor" function. Extent of resection was also assessed. RESULTS: A total of 48 patients underwent large VS resection with ILA dissection of tumor off of the facial nerve from 2018 to 2021. Mean (standard deviation) tumor size was 3.11 (0.76) cm. Mean (standard deviation) follow-up was 9.2 (9.0) months. Gross-total resection or near-total resection were achieved in 75% (radiographic estimate) to 83% (surgeon estimate) of cases. End-of-case facial nerve stimulation at 0.05 mAmp with a response of at least 240 mV was achieved in 80.4% of patients. Good facial nerve function was observed in 72% immediately postoperatively, 70% 1-month postoperatively, and 82% of patients at last follow-up. CONCLUSIONS: The ILA technique is now the method of choice of the senior surgeon (R.N.) when performing microsurgical dissection of the cisternal facial nerve, with which he has achieved high rates of total or near-total resection with excellent facial nerve preservation.

Assessing and Addressing the Risk of Venous Thromboembolism Across the Spectrum of Gender Affirming Care: A Review.

OBJECTIVE: Accumulating evidence demonstrates that gender affirming hormone therapy (GAHT) improves mental health outcomes in transgender persons. Data specific to the risks associated with GAHT for transgender persons continue to emerge, allowing for improvements in understanding, predicting, and mitigating adverse outcomes while informing discussion about desired effects. Of particular concern is the risk of venous thromboembolism (VTE) in the context of both longitudinal GAHT and the perioperative setting. Combining what is known about the risk of VTE in cisgender individuals on hormone therapy (HT) with the evidence for transgender persons receiving HT allows for an informed approach to assess underlying risk and improve care in the transgender community. OBSERVATIONS: Hormone formulation, dosing, route, and duration of therapy can impact thromboembolic risk, with transdermal estrogen formulations having the lowest risk. There are no existing risk scores for VTE that consider HT as a possible risk factor. Risk assessment for recurrent VTE and bleeding tendencies using current scores may be helpful when assessing individual risk. Gender affirming surgeries present unique perioperative concerns, and certain procedures include a high likelihood that patients will be on exogenous estrogens at the time of surgery, potentially increasing thromboembolic risk. CONCLUSIONS AND RELEVANCE: Withholding GAHT due to potential adverse events may cause negative impacts for individual patients. Providers should be knowledgeable about the management of HT in transgender individuals of all ages, as well as in the perioperative setting, to avoid periods in which transgender individuals are off GAHT. Treatment decisions for both anticoagulation and HT should be individualized and tailored to patients' overall goals and desired outcomes, given that the physical and mental health benefits of gender affirming care may outweigh the risk of VTE.

Surgical management of patients with von Willebrand disease: summary of 2 systematic reviews of the literature.

von Willebrand disease (VWD) is the most common inherited bleeding disorder. The management of patients with VWD who are undergoing surgeries is crucial to prevent bleeding complications. We systematically summarized the evidence on the management of patients with VWD who are undergoing major and minor surgeries to support the development of practice guidelines. We searched Medline and EMBASE from inception through October 2019 for randomized clinical trials (RCTs), comparative observational studies, and case series that compared maintaining factor VIII (FVIII) levels or von Willebrand factor (VWF) levels at >0.50 IU/mL for at least 3 days in patients undergoing major surgery, and those with options for perioperative management of patients undergoing minor surgery. Two authors screened and abstracted data and assessed the risk of bias. We conducted meta-analyses when possible. We evaluated the certainty of the evidence using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. We included 7 case series for major surgeries and 2 RCTs and 12 case series for minor surgeries. Very-low-certainty evidence showed that maintaining FVIII levels or VWF levels of >0.50 IU/mL for at least 3 consecutive days showed excellent hemostatic efficacy (as labeled by the researchers) after 74% to 100% of major surgeries. Low- to very-low-certainty evidence showed that prescribing tranexamic acid and increasing VWF levels to 0.50 IU/mL resulted in fewer bleeding complications after minor procedures compared with increasing VWF levels to 0.50 IU/mL alone. Given the low-quality evidence for guiding management decisions, a shared-decision model leading to individualized therapy plans will be important in patients with VWD who are undergoing surgical and invasive procedures.

Speech Recognition Outcomes in Adults With Slim Straight and Slim Modiolar Cochlear Implant Electrode Arrays.

OBJECTIVE: To compare differences in audiologic outcomes between slim modiolar electrode (SME) CI532 and slim lateral wall electrode (SLW) CI522 cochlear implant recipients. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary academic hospital. METHODS: Comparison of postoperative AzBio sentence scores in quiet (percentage correct) in adult cochlear implant recipients with SME or SLW matched for preoperative AzBio sentence scores in quiet and aided and unaided pure tone average. RESULTS: Patients with SLW (n = 52) and patients with SME (n = 37) had a similar mean (SD) age (62.0 [18.2] vs 62.6 [14.6] years, respectively), mean preoperative aided pure tone average (55.9 [20.4] vs 58.1 [16.4] dB; P = .59), and mean AzBio score (percentage correct, 11.1% [13.3%] vs 8.0% [11.5%]; P = .25). At last follow-up (SLW vs SME, 9.0 [2.9] vs 9.9 [2.6] months), postoperative mean AzBio scores in quiet were not significantly different (percentage correct, 70.8% [21.3%] vs 65.6% [24.5%]; P = .29), and data log usage was similar (12.9 [4.0] vs 11.3 [4.1] hours; P = .07). In patients with preoperative AzBio <10% correct, the 6-month mean AzBio scores were significantly better with SLW than SME (percentage correct, 70.6% [22.9%] vs 53.9% [30.3%]; P = .02). The intraoperative tip rollover rate was 8% for SME and 0% for SLW. CONCLUSIONS: Cochlear implantation with SLW and SME provides comparable improvement in audiologic functioning. SME does not exhibit superior speech recognition outcomes when compared with SLW.

Impact of Hematology Electronic Consultations on Utilization of Referrals and Patient Outcomes in an Integrated Health Care System.

INTRODUCTION: Electronic consultations (e-consults) may be a valuable tool in the current era of increased demand for hematologists. Despite the increasing use of e-consults in hematology, their optimal utilization and impact on patient outcomes and workload are largely unknown. METHODS: In this retrospective cohort study, we studied the hematology consult experience at Veterans Affairs Connecticut from 2006 to 2018. We included 7,664 hematology consults (3,240 e-consults and 4,424 face-to-face [FTF] consults) requested by 1,089 unique clinicians. RESULTS: We found that e-consults were rapidly adopted and used equally among physicians of different degrees of experience. The number of FTF consults did not decrease after the introduction of e-consult services. E-consults were preferentially used for milder laboratory abnormalities that had been less likely to result in a consult before their availability. Referring clinicians used e-consults preferentially for periprocedural management, anemia, leukopenia, and anticoagulation questions. Eighty-three percent of e-consults were resolved without needing an FTF visit in the year after the consult. Consults for pancytopenia, gammopathy, leukocytosis, and for patients with known malignancy were less likely to be resolved by e-consult. Among patients who were diagnosed with a new hematologic malignancy after their consult, having an e-consult before an FTF visit did not adversely affect survival. CONCLUSION: In summary, e-consults safely expanded delivery of hematology services in our health care system but increased total consult volume. We report novel data on what types of consults may be best suited to the electronic modality, the impact of e-consults on workload, and their optimal use and implementation.

How to manage bleeding disorders in aging patients needing surgery.

With improvements in medical care, the life expectancy of patients with bleeding disorders is approaching that of the general population. A growing population of older adult patients with bleeding disorders is at risk of age-related comorbidities and in need of various elective and emergent age-related procedures. The increased risk of thrombosis and volume overload in older adults complicates perioperative hemostatic management. Furthermore, antithrombotic treatment such as antiplatelet or anticoagulant therapy, which is frequently required for various cardiovascular interventions, requires a meticulous individualized approach. Evidence-based guidelines for the management of aging patients with bleeding disorders are lacking, largely due to the underrepresentation of older adult patients in clinical trials as well as the rarity of many such bleeding disorders. We discuss the current guidelines and recommendations in the perioperative hemostatic management of older adult patients with hemophilia and von Willebrand disease as well as other rare bleeding disorders. The optimal management of these patients is often complex and requires a thorough multidisciplinary and individualized approach involving hematologists, surgeons, anesthesiologists, and the specialists treating the underlying disorder.

Bleeding assessment tools in the diagnosis of VWD in adults and children: a systematic review and meta-analysis of test accuracy.

Von Willebrand disease (VWD) can be associated with significant morbidity. Patients with VWD can experience bruising, mucocutaneous bleeding, and bleeding after dental and surgical procedures. Early diagnosis and treatment are important to minimize the risk of these complications. Several bleeding assessment tools (BATs) have been used to quantify bleeding symptoms as a screening tool for VWD. We systematically reviewed diagnostic test accuracy results of BATs to screen patients for VWD. We searched Cochrane Central, MEDLINE, and EMBASE for eligible studies, reference lists of relevant reviews, registered trials, and relevant conference proceedings. Two investigators screened and abstracted data. Risk of bias was assessed using the revised tool for the quality assessment of diagnostic accuracy studies and certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework. We pooled estimates of sensitivity and specificity. The review included 7 cohort studies that evaluated the use of BATs to screen adult and pediatric patients for VWD. The pooled estimates for sensitivity and specificity were 75% (95% confidence interval, 66-83) and 54% (29-77), respectively. Certainty of evidence varied from moderate to high. This systematic review provides accuracy estimates for validated BATs as a screening modality for VWD. A BAT is a useful initial screening test to determine who needs specific blood testing. The pretest probability of VWD (often determined by the clinical setting/patient population), along with sensitivity and specificity estimates, will influence patient management.

Acquired von Willebrand Syndrome.

Acquired von Willebrand syndrome can occur in the setting of myeloproliferative neoplasms; plasma cell dyscrasias and other lymphoproliferative disorders; autoimmune conditions; and causes of increased shear forces, such as aortic stenosis or other structural heart disease and mechanical circulatory support. The depletion of von Willebrand factor, especially high-molecular-weight multimers, can lead to mucocutaneous bleeding and the formation of arteriovenous malformations, particularly in the gastrointestinal tract. Management focuses on correction of the underlying cause when possible, but may include intravenous immunoglobulins, von Willebrand factor concentrate, rituximab, or antiangiogenic therapy depending on the clinical context.

ASH ISTH NHF WFH 2021 guidelines on the management of von Willebrand disease.

BACKGROUND: von Willebrand disease (VWD) is a common inherited bleeding disorder. Significant variability exists in management options offered to patients. OBJECTIVE: These evidence-based guidelines from the American Society of Hematology (ASH), the International Society on Thrombosis and Haemostasis (ISTH), the National Hemophilia Foundation (NHF), and the World Federation of Hemophilia (WFH) are intended to support patients, clinicians, and health care professionals in their decisions about management of VWD. METHODS: ASH, ISTH, NHF, and WFH formed a multidisciplinary guideline panel. Three patient representatives were included. The panel was balanced to minimize potential bias from conflicts of interest. The University of Kansas Outcomes and Implementation Research Unit and the McMaster Grading of Recommendations Assessment, Development and Evaluation (GRADE) Centre supported the guideline development process, including performing and updating systematic evidence reviews (through November 2019). The panel prioritized clinical questions and outcomes according to their importance to clinicians and patients. The panel used the GRADE approach, including GRADE Evidence-to-Decision frameworks, to assess evidence and make recommendations, which were subject to public comment. RESULTS: The panel agreed on 12 recommendations and outlined future research priorities. CONCLUSIONS: These guidelines make key recommendations regarding prophylaxis for frequent recurrent bleeding, desmopressin trials to determine therapy, use of antiplatelet agents and anticoagulant therapy, target VWF and factor VIII activity levels for major surgery, strategies to reduce bleeding during minor surgery or invasive procedures, management options for heavy menstrual bleeding, management of VWD in the context of neuraxial anesthesia during labor and delivery, and management in the postpartum setting.

Pregnancy outcomes, risk factors, and cell count trends in pregnant women with essential thrombocythemia.

Pregnancy in essential thrombocythemia (ET) is associated with increased risk of obstetric complications. We retrospectively evaluated risk factors in 121 pregnancies in 52 ET women seen at 3 affiliate hospitals. Univariable and multivariable analyses were performed at the α = 0.10 level. Cell counts were characterized throughout pregnancy and correlated with outcomes using logistic modeling. The overall live birth rate was 69 %. 48.7 % of all women experienced a pregnancy complication, the most common being spontaneous abortion, which occurred in 26 % of all pregnancies. Maternal thrombosis and hemorrhage rates were 2.5 % and 5.8 %. On multivariable analysis, aspirin use (OR 0.29, p = 0.014, 90 % CI 0.118-0.658) and history of prior pregnancy loss (OR 3.86, p = 0.011, CI 1.49-9.15) were associated with decreased and increased pregnancy complications, respectively. A Markov model was used to analyze the probability of a future pregnancy complication based on initial pregnancy outcome. An ET woman who suffers a pregnancy complication has a 0.594 probability of a subsequent pregnancy complication, compared to a 0.367 probability if she didn't suffer a complication. However, despite this elevated risk, overall prognosis is good, with a >50 % probability of a successful pregnancy by the third attempt. Platelet counts decreased by 43 % in ET during pregnancy, with nadir at delivery and prompt recovery in the postpartum period. Women with larger declines in gestational platelet counts were less likely to suffer complications (p = 0.083). Our study provides important guidance to physicians treating ET women during pregnancy, including counseling information regarding risk assessment and expected trajectory of platelet levels.

Systems-based hematology: highlighting successes and next steps.

Systems-based hematology is dedicated to improving care delivery for patients with blood disorders. First defined by the American Society of Hematology in 2015, the idea of a systems-based hematologist arose from evolving pressures in the health care system and increasing recognition of opportunities to optimize the quality and cost effectiveness of hematologic care. In this review, we begin with a proposed framework to formalize the discussion of the range of initiatives within systems-based hematology. Classification by 2 criteria, project scope and method of intervention, facilitates comparison between initiatives and supports dialogue for future efforts. Next, we present published examples of successful systems-based initiatives in the field of hematology, including efforts to improve stewardship in the diagnosis and management of complex hematologic disorders (eg, heparin-induced thrombocytopenia and thrombophilias), the development of programs to promote appropriate use of hematologic therapies (eg, blood products, inferior vena cava filters, and anticoagulation), changes in care delivery infrastructure to improve access to hematologic expertise (eg, electronic consultation and disorder-specific care pathways), and others. The range of projects illustrates the broad potential for interventions and highlights different metrics used to quantify improvements in care delivery. We conclude with a discussion about future directions for the field of systems-based hematology, including extension to malignant disorders and the need to define, expand, and support career pathways.

Associations between hematology/oncology fellows' training and mentorship experiences and hematology-only career plans.

As the adult hematology and oncology fellowship training pathways have merged in the United States and concerns have arisen about the aging of practicing hematologists, the American Society of Hematology and hematology education leaders are looking to improve their understanding of the factors that contribute to fellows' plans to enter hematology-only careers. With the support of the American Society of Hematology, we collected and analyzed data from a survey of hematology/oncology fellows (n = 626) to examine the relationship between training and mentorship experiences and fellows' plans to enter hematology-only careers. Fellows who planned to enter hematology-only careers were significantly more likely to report having clinical training and mentorship experiences in hematology throughout their training relative to fellows with oncology-only or combined hematology/oncology career plans. After controlling for prior interest in hematology and demographic characteristics, exposure to hematology patients in medical school and fellowship, hematology research experiences, and hematology mentorship (research collaboration and career coaching) were positively and significantly associated with hematology-only career plans. These findings suggest that increasing opportunities for exposure to hematology patients, research opportunities and mentors throughout training could be helpful in building a strong pipeline of potential hematologists.

Cost-effectiveness of edoxaban versus dalteparin for the treatment of cancer-associated thrombosis.

Malignancy is a well-established risk factor for venous thromboembolism and while low-molecular-weight heparin therapy has been standard of care for cancer-associated thrombosis for many years, many patients find injection therapy burdensome. The direct oral anticoagulant edoxaban has been shown to be noninferior to dalteparin for the treatment of cancer-associated thrombosis. In a Markov simulation model, edoxaban with 6-month time horizon and a United States societal perspective with 2017 US dollars, edoxaban was the preferred strategy in the general cancer population (6-month cost $6061 with 0.34 quality adjusted life years) and in a subgroup of patients with gastrointestinal malignancy (6-month cost $7227 with 0.34 quality adjusted life years). The incremental cost effectiveness ratio of dalteparin compared to edoxaban was $1,873,535 in the general oncology population and $694,058 in the gastrointestinal malignancy population.

Imatinib-induced drug reaction with eosinophilia and systemic symptoms in solid tumors: a patient with dermatofibrosarcoma protuberans and successful desensitization management.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe, potentially life-threatening drug-induced hypersensitivity reaction, characterized by cutaneous eruptions, fever, diffuse lymphadenopathy, along with hypereosinophilia, and elevated liver function tests, which in severe cases may lead to fulminant hepatic failure and death. Although DRESS syndrome has been associated with over 50 different drugs including imatinib, it has never been reported in association with imatinib treatment in solid tumors. We recently treated a patient with metastatic dermatofibrosarcoma protuberans, a rare cutaneous mesenchymal tumor characterized by constitutive activation of the PDGFß receptor and high sensitivity to imatinib therapy, who had a DRESS reaction to imatinib. Given an initial dramatic clinical and radiological response to treatment and lack of effective alternative targeted therapies, following imatinib discontinuation and resolution of DRESS, we cautiously reintroduced imatinib therapy using a desensitization protocol under the care of the allergy and immunologic clinic. Imatinib was carefully titrated from an initial dose of 50 mg to a target dose of 400 mg daily, while tapering down the prednisone dose. The patient was able to tolerate the treatment without recurrent episodes of DRESS or interruptions, and gained additional 6 months of clinical benefit from imatinib treatment. Although suspected causative drugs should not be reintroduced in DRESS whenever possible, in this case of metastatic disease and lack of effective alternative treatments, a carefully designed drug rechallenge helped minimize the risk of overt clinical reaction and resulted in an overall clinical benefit.