How I treat the co-occurrence of venous and arterial thromboembolism: anticoagulation, antiplatelet therapy, or both?

ABSTRACT: Arterial and venous thromboses are classically considered distinct disease states, with arterial thrombosis mediated predominantly by platelets and therefore, treated with antiplatelet therapy, and venous thrombosis mediated by the plasmatic coagulation system and treated with anticoagulation. However, co-occurrence of arterial and venous events is common, and there is increasing evidence of shared risk factors and pathophysiologic overlap. This presents a management challenge: does the patient with venous and arterial thrombosis, require anticoagulation, antiplatelet therapy, or both? Herein, we present a structured approach to the evaluation and management of patients with venous thrombosis who are also at risk for or have a history of an arterial thromboembolic event. We emphasize the importance of defining the indications for antithrombotic therapy, as well as the evaluation of factors that influence both thrombotic and bleeding risk, including disorder-specific and patient-specific factors, as well as the inherent risk balance of antithrombotic therapy regimens. We illustrate this approach in 4 cases, discussing the unique considerations and recent updates in the management of venous thrombosis, acute noncardioembolic ischemic stroke, coronary artery disease and acute myocardial infarction, and peripheral artery disease after revascularization.

NCCN Guidelines® Insights: Systemic Mastocytosis, Version 3.2024.

Mastocytosis is a heterogeneous group of disorders comprising cutaneous mastocytosis, systemic mastocytosis, and mast cell sarcoma. It is associated with a variety of symptoms related to the release of mast cell mediators and mast cell tissue infiltration. Referral to specialized centers with expertise in the management of mastocytosis and multidisciplinary collaboration with subspecialists (eg, allergists for the management of anaphylaxis and drug hypersensitivities, anesthesiologists for invasive procedures or surgery, high-risk obstetrician for pregnancy) is recommended. The NCCN Guidelines for Systemic Mastocytosis provide evidence- and consensus-based recommendations for the diagnosis and comprehensive care of patients with systemic mastocytosis. The multidisciplinary panel of experts convenes at least once a year to review requested changes to the guidelines from both internal and external entities as well as to discuss data on existing and new therapies. These NCCN Guidelines Insights focus on some of the recent updates to the guidelines.

How I treat unexplained arterial thrombosis.

Most arterial thrombotic events have a clear atherosclerotic or cardioembolic etiology, but hematologists are frequently asked to assist in the diagnosis and management of a patient with a nonatherosclerotic and noncardioembolic arterial event, referred to here as an unexplained arterial thrombosis. Because there is an assorted list of factors that can precipitate an arterial event, we present a systematic diagnostic approach to ensure consideration of not only primary hypercoagulable disorders, but also pro-thrombotic medications or substances, vascular and anatomic abnormalities, and undiagnosed systemic disorders, such as malignancy and autoimmune diseases. We also review existing literature of the role of hypercoagulable disorders in arterial thrombosis and discuss our approach to thrombophilia workup in patients after an unexplained arterial event. We conclude with 3 representative cases to both illustrate the application of the outlined diagnostic schema and discuss common management considerations, specifically the selection of anticoagulation vs antiplatelet therapy for secondary prevention.

Oncology Patient Smoking Cessation Treatment Preferences: Perceptions Across Former and Current Cigarette Smokers.

Although the benefits of smoking cessation following a cancer diagnosis have been well-established, up to 50% of cancer patients continue to smoke. Continued smoking through oncology treatment leads to increased risk of adverse events including reduced effectiveness of treatment, recurrence of additional malignancies, and reduced survival rates. Upon the cancer diagnosis, oncology healthcare providers become the primary trusted source of information and support, which represents a great opportunity to assist these patients to quit smoking. However, it remains unclear how oncology healthcare providers can best address smoking cessation from a patient-centered perspective. The present study surveyed oncology patients from Birmingham, AL, classified as either former (n = 174) or current smokers (n = 81) to identify their perceptions regarding the role of oncology healthcare providers in their smoking cessation efforts. Current smokers were more likely to be younger, received their cancer diagnosis within the past 3 years, and have a cancer diagnosis with high smoking-related public awareness (i.e., head, neck, or lung) compared to former smokers. Additionally, 81% of current smokers reported experiencing smoking cessation discussions with their oncology healthcare providers with the most prominent recommendations being use of nicotine replacement therapies (46.9%) and medication (35.8%). These smoking cessation experiences align with patient preferences. However, despite the frequency of smoking cessation discussions, current smokers demonstrated an ambivalence in understanding the risks of continued smoking during their medical treatment. Overall, this study highlights the important role of oncology healthcare providers on implementing smoking cessation intervention for their patients who continue to smoke.

An open-label, pilot study of veliparib and lapatinib in patients with metastatic, triple-negative breast cancer.

BACKGROUND: Poly (ADP-ribose)-polymerase inhibitors (PARPi) have been approved for cancer patients with germline BRCA1/2 (gBRCA1/2) mutations, and efforts to expand the utility of PARPi beyond BRCA1/2 are ongoing. In preclinical models of triple-negative breast cancer (TNBC) with intact DNA repair, we have previously shown an induced synthetic lethality with combined EGFR inhibition and PARPi. Here, we report the safety and clinical activity of lapatinib and veliparib in patients with metastatic TNBC. METHODS: A first-in-human, pilot study of lapatinib and veliparib was conducted in metastatic TNBC (NCT02158507). The primary endpoint was safety and tolerability. Secondary endpoints were objective response rates and pharmacokinetic evaluation. Gene expression analysis of pre-treatment tumor biopsies was performed. Key eligibility included TNBC patients with measurable disease and prior anthracycline-based and taxane chemotherapy. Patients with gBRCA1/2 mutations were excluded. RESULTS: Twenty patients were enrolled, of which 17 were evaluable for response. The median number of prior therapies in the metastatic setting was 1 (range 0-2). Fifty percent of patients were Caucasian, 45% African-American, and 5% Hispanic. Of evaluable patients, 4 demonstrated a partial response and 2 had stable disease. There were no dose-limiting toxicities. Most AEs were limited to grade 1 or 2 and no drug-drug interactions noted. Exploratory gene expression analysis suggested baseline DNA repair pathway score was lower and baseline immunogenicity was higher in the responders compared to non-responders. CONCLUSIONS: Lapatinib plus veliparib therapy has a manageable safety profile and promising antitumor activity in advanced TNBC. Further investigation of dual therapy with EGFR inhibition and PARP inhibition is needed. TRIAL REGISTRATION: ClinicalTrials.gov , NCT02158507 . Registered on 12 September 2014.

Current Practice and Clinical Utility of Thrombophilia Testing in Hospitalized Patients with Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Testing for thrombophilic disorders is often performed in patients after cryptogenic ischemic stroke in an attempt to identify a hematologic explanation for the event. However, the role of commonly tested thrombophilias in ischemic stroke is poorly defined. There is limited evidence to quantify how these disorders affect ischemic stroke risk and testing practices are highly variable. METHODS: Retrospective evaluation of thrombophilia testing practices and clinical outcomes was performed in hospitalized patients with acute ischemic stroke (n = 1898) at a large academic hospital over a two-year period. Variables assessed included testing components, timing of testing, number of abnormal results, and frequency of change in clinical management prompted by abnormal results. A provider survey was also performed to assess perceptions of current testing practices and provider understanding of testing indications. RESULTS: Thrombophilia testing was performed in 190 (10%) patients admitted for acute ischemic stroke. Of those tested, 137 (72.1%) had at least one abnormal result, but this decreased to 37.4% when elevated factor VIII activity was excluded. An abnormal result prompted initiation of anticoagulation in only 4 patients (2%). The provider survey indicated that all providers (100%) were selecting thrombophilia tests using a pre-existing order set and were interested in additional education on testing indications and interpretation. Comparison to similar studies at other institutions revealed significant variation in testing practices, and a small proportion of patients in which testing prompted a change in management (1-8%). CONCLUSIONS: Thrombophilia testing is frequently obtained in hospitalized patients with acute ischemic stroke, yet testing only changed management in 2% of patients. Efforts to improve provider education and the stewardship of testing are needed to ensure appropriate evaluation and treatment of patients with acute ischemic stroke.

Severe platelet transfusion refractoriness after thoracoabdominal aneurysm repair.

Severe thrombocytopenia after thoracoabdominal aortic aneurysm repair poses a significant clinical risk in the immediate postoperative period. Understanding the mechanisms of refractoriness to platelet transfusion is relevant to supporting thrombocytopenic patients postoperatively. We present the case of a 76-year-old woman with refractory thrombocytopenia secondary to alloimmunization following open repair of a Crawford extent IV thoracoabdominal aneurysm. The patient provided written informed consent for the report of her case details and imaging studies.

Iron Deficiency Among Hospitalized Patients With Congestive Heart Failure.

INTRODUCTION: Studies have demonstrated the efficacy of intravenous (IV) iron when administered to patients with congestive heart failure (CHF) and iron deficiency (ID). We aimed to better understand the adherence of treatment for ID among a population with CHF, with particular interest in high-risk groups not often studied due to inadequate recruitment. METHODS: A retrospective chart review at our institution was conducted from January 1, 2012, to July 7, 2021. Analysis included hospitalized patients with CHF and ID and dividing these patients into two time periods based on changes in iron treatment patterns and treatment between sexes. RESULTS: Four thousand eight hundred thirteen patients were included in this study. During the "early era," 7.0% of patients with CHF and ID received IV iron compared with 20.9% of "late-era" patients. Female patients with ID were statistically less likely to receive IV iron when compared with male patients, both unadjusted (0.66, confidence interval [CI] 0.55-0.79, p < .0001) and adjusted (0.72, CI 0.59-0.87, p < .0001) for covariates. CONCLUSION: This study illustrates improved adherence to treatment for ID among hospitalized population with CHF and ID over time but persistent undertreatment remains. Future studies will need to identify the barriers to treating female patients with CHF and ID to reduce these disparities.

Heparin-induced thrombocytopenia: An illustrated review.

Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse drug effect from unfractionated or low-molecular-weight heparin that results in thrombocytopenia and potentially catastrophic thrombosis. HIT occurs due to the development of platelet-activating antibodies against multimolecular complexes of platelet factor 4 and heparin. Given the frequency of thrombocytopenia and heparin use among hospitalized patients, calculation of the 4Ts Score is recommended to identify patients at increased likelihood of HIT and direct further evaluation. In patients with an intermediate or high probability 4Ts Score, an immunoassay and functional assay are recommended to confirm or refute the diagnosis of HIT. Heparin avoidance and initiation of nonheparin anticoagulation are the mainstays of acute HIT management. In this illustrated review, we provide visual summaries of the diagnosis and management of HIT, highlighting connections between pathophysiology and clinical care as well as summarizing efforts in quality improvement in the field. We further emphasize common pitfalls and pearls in diagnosis and management to encourage evidence-based care. We include graphical representation of the unique challenges of HIT with cardiopulmonary bypass and also delineate autoimmune HIT and its subtypes.

Quality improvement approaches to heparin-induced thrombocytopenia: a scoping review.

Background: Heparin-induced thrombocytopenia (HIT) is a relatively uncommon condition characterized by 2 exceedingly common phenomena in hospitalized patients: thrombocytopenia and heparin exposure. Consequently, HIT is frequently overdiagnosed and inappropriately treated. These issues are the focus of many quality improvement (QI) initiatives. Objectives: In this scoping review, we identified and characterized all published QI studies on improving the diagnosis and management of HIT. Methods: We conducted a systematic literature search through April 2022 for studies reporting on QI interventions regarding the diagnosis, treatment, and/or prevention of HIT. Results: Thirty studies were included in the final review. Studies were separated into 5 groups based on the focus of the interventions: increasing HIT recognition, reducing HIT incidence, reducing HIT overdiagnosis, promoting safer HIT management, and creating HIT task forces. Nine studies focused on the implementation of 4Ts score calculator into electronic medical record orders for HIT testing, while only 1 evaluated the impact of reducing unfractionated heparin use in favor of low-molecular-weight heparin. Six studies focused on the implementation of direct thrombin inhibitor management protocols, while none evaluated the use of alternative anticoagulants in HIT management. Conclusion: The bulk of published HIT QI research focused on reducing overdiagnosis and promoting safer direct thrombin inhibitor therapy, while minimal attention has been devoted to HIT prevention and the use of evidence-based alternative HIT therapies.

Challenges in the diagnosis of thrombotic thrombocytopenic purpura.

INTRODUCTION: Immune-mediated TTP (iTTP) is a rare condition without pathognomonic signs and symptoms. For this reason, the diagnosis of iTTP may be delayed or even missed, with potentially catastrophic consequences. AREAS COVERED: The authors performed an extensive literature review on the diagnosis of iTTP and its challenges combined with their own experience in a referral center for patients with iTTP. EXPERT OPINION: Although a definitive diagnosis of iTTP depends on the ADAMTS13 activity result, timely testing is rarely available at many centers to which patients present. If less complex tests were to become available, they would decrease the chances of late and/or missed diagnoses of iTTP throughout the world. While clinical scores to estimate the likelihood of iTTP exist, they are not well known, and can be misleading if used in the wrong context. Furthermore, the three scoring systems (PLASMIC, Bentley, and French) only moderately correlate with each other, which further complicates the landscape. The existence of these scores and how they should be used in practice is but one opportunity that can be seized through more robust programs to educate nonspecialist clinicians on how to recognize and treat patients with iTTP.

From Activated Partial Thromboplastin Time to Antifactor Xa and Back Again.

OBJECTIVES: Monitoring is essential to safe anticoagulation prescribing and requires close collaboration among pathologists, clinicians, and pharmacists. METHODS: We describe our experience in the evolving strategy for laboratory testing of unfractionated heparin (UFH). RESULTS: An intrainstitutional investigation revealed significant discordance between activated partial thromboplastin time (aPTT) and antifactor Xa (anti-Xa) assays, prompting a transition from the former to the latter in 2013. With the increasing use of oral factor Xa inhibitors (eg, apixaban, rivaroxaban, edoxaban, betrixaban), which interfere with the anti-Xa assay, we adapted our protocol again to incorporate aPTT in patients admitted on oral Xa inhibitors who require transition to UFH. CONCLUSIONS: Our experience demonstrates key challenges in anticoagulation and highlights the importance of clinical pathologists in helping health systems adapt to the changing anticoagulation landscape.

Pitfalls in Diagnosing Thrombotic Thrombocytopenic Purpura in Sickle Cell Disease.

Thrombotic thrombocytopenia purpura is characterised by microangiopathic haemolytic anaemia and red cell fragmentation on the peripheral smear, neurological involvement and thrombocytopenia. Diagnosis in the context of sickle cell disease can be challenging due to the inherent haemolytic state and the multitude of other associated complications of the latter. Specifically, fat embolism syndrome characterised by respiratory failure, neurological impairment and thrombocytopenia can be misdiagnosed this way. Confirmation of a diagnosis of thrombotic thrombocytopenic purpura requires demonstration of very low levels (<10%) of the metalloproteinase ADAMTS13 which in fat embolism syndrome is normal. Existing scoring systems used to estimate the pre-test probability for thrombotic thrombocytopenic purpura cannot be applied in patients with sickle cell disease due to the chronic underlying haemolysis. Here, we analyse the diagnostic approach in published cases of thrombotic thrombocytopenic purpura affecting patients with sickle-cell disease. The vast majority of cases were characterised by severe respiratory failure before any other manifestation, a feature of fat embolism syndrome but not of thrombotic thrombocytopenic purpura, and all received red cell transfusion prior to receiving therapeutic plasma exchange. Despite the potential overestimation of the pre-test probability using the existing scoring systems, a large number of cases still scored low. There were no cases with documented low ADAMTS13. In the majority this was not tested, while in the 3 cases that ADAMTS13 was tested, levels were normal. Our review suggests that due to many overlapping clinical and laboratory features thrombotic thrombocytopenic purpura may be erroneously diagnosed in sickle cell disease instead of other complications such as fat embolism syndrome and confirmation with ADAMTS13 testing is essential.

Impact of COVID-19 on Hematology-Oncology Trainees: A Quantitative and Qualitative Assessment.

PURPOSE: Graduate medical and research training has drastically changed during the COVID-19 pandemic, with widespread implementation of virtual learning, redeployment from core rotations to the care of patients with COVID-19, and significant emotional and physical stressors. The specific experience of hematology-oncology (HO) fellows during the COVID-19 pandemic is not known. METHODS: We conducted a mixed-methods study using a survey of Likert-style and open-ended questions to assess the training experience and well-being of HO fellows, including both clinical and postdoctoral trainee members of the American Society of Hematology and ASCO. RESULTS: A total of 2,306 surveys were distributed by e-mail; 548 (23.8%) fellows completed the survey. Nearly 40% of fellows felt that they had not received adequate mental health support during the pandemic, and 22% reported new symptoms of burnout. Pre-existing burnout before the pandemic, COVID-19-related clinical work, and working in a primary research or nonclinical setting were associated with increased burnout on multivariable logistic regression. Qualitative thematic analysis of open-ended responses revealed significant concerns about employment after training completion, perceived variable quality of virtual education and board preparation, loss of clinical opportunities to prepare for independent clinical practice, inadequate grant funding opportunities in part because of shifting research priorities, variable productivity, and mental health or stress during the pandemic. CONCLUSION: HO fellows have been profoundly affected by the pandemic, and our data illustrate multiple avenues for fellowship programs and national organizations to support both clinical and postdoctoral trainees.