Houghton, Damon E

Myeloproliferative neoplasm (MPN) patients are at risk of splanchnic vein thromboses (SVT). Prior studies have failed to demonstrate a benefit of hydroxyurea therapy in preventing recurrent thrombosis after SVT, but are limited by small sample sizes and inability to account for starting, stopping, or switching of cytoreductive therapies. To better assess the impact of cytoreductive therapy on thrombosis recurrence, we performed a retrospective cohort study of MPN-SVT patients from the international GASTRO-MPN Consortium, treating cytoreductive therapy as a time-dependent covariate. We identified 757 patients, of which 43% were treated with cytoreductive therapy. During a median follow-up of 7.4 years, 256 patients (34%) had thrombosis recurrence; 145 (19%) had SVT extension/recurrence/TIPS thrombosis, 138 (18%) an thrombosis recurrence outside the splanchnic bed (74% were venous). Additionally, 262 patients (35%) experienced clinically relevant bleeding and 170 (22%) died. After adjusting for age, sex, prior thrombosis, timing of MPN diagnosis relative to SVT, anticoagulation initiation within 30 days of SVT diagnosis, MPN type, JAK2 status, other cancers and cirrhosis, cytoreductive therapy was associated with a decreased risk of recurrent thrombosis (HR 0.67 95%CI 0.50-0.89, p=0.01). This was driven by a lower risk of SVT extension/recurrence (HR 0.62 95%CI 0.42-0.90, p=0.01) but not by extra-splanchnic thrombosis recurrence (HR 0.97 95%CI 0.72-1.30, p=0.82). In a subgroup of patients without erythrocytosis/thrombocytosis at initial SVT (n=275), cytoreductive therapy was associated with a HR 0.65 (95%CI 0.40-1.07, p=0.09) for recurrent thrombosis. These data support the use of cytoreductive therapy in MPN-SVT patients to prevent recurrent thrombosis, particularly SVT extension/recurrence.

Background: Chronic venous insufficiency (CVI) can be evaluated using Duplex ultrasonography (US) and air plethysmography (PG), yet comparative performance remains unclear. Methods: We retrospectively identified patients who underwent venous insufficiency US and PG within a 90-day interval from March 1, 2015 through July 31, 2024. CVI severity was classified by the clinical (C) component of the Clinical, Etiologic, Anatomic, and Pathophysiologic (CEAP) classification system and categorized as mild (C0–2), moderate (C3), or severe (C4–6). PG and insufficiency US findings were compared across categories and machine learning models were trained to predict severe CVI. Results: We analyzed 1478 limbs from 839 patients who were predominantly women (62%) with a mean age of 61 years (± 14 years). Severe CVI was present in 32.3% of limbs. US detected venous incompetence in 67.4% of limbs overall and in 75.3% of severe CVI limbs. Abnormal PG findings occurred in 72.9% of limbs overall and in 88.5% of severe CVI limbs. PG parameters in machine learning models outperformed US parameters in predicting severe CVI (area under the receiver operating characteristic curve [AUROC] 0.82 vs 0.65). The top PG model (multilayer perceptron [MLP]) achieved an AUROC of 0.82, versus the best US model (gradient boosting) with an AUROC of 0.65. Limiting PG data to incompetence and obstruction parameters modestly reduced performance but remained higher than US (logistic regression AUROC 0.72). Conclusion: Our findings indicate that PG assessment in CVI offers superior performance compared to US. Overall, these results validate the quantitative whole-limb hemodynamic approach using PG, which provides a more complete understanding of the pathology behind CVI.

Post-pulmonary embolism syndrome (PPES) encompasses a diverse spectrum of long-term complications that are associated with persistent dyspnea, exercise intolerance, and a decrease in quality of life. The PPES constellation ranges from life-threatening conditions such as chronic thromboembolic pulmonary hypertension (CTEPH) to nonlife-threatening but still debilitating conditions such as chronic thromboembolic pulmonary disease (CTED) or post-PE deconditioning. The safety and efficacy of exercise and cardiopulmonary rehabilitation programs to prevent and manage these symptoms in PPES has not been well established. Herein, we review contributors to PPES and synthesize the evidence for exercise training after PE to treat and prevent PPES.

Abstract Immune thrombocytopenia (ITP) carries an increased risk of thrombosis, which may be further amplified by splenectomy and thrombopoietin receptor agonists (TPO-RAs). Although each intervention has been individually studied for its thrombotic risk, data are lacking on the safety of postsplenectomy TPO-RA use. We conducted a retrospective cohort study of adult patients with ITP who underwent splenectomy between 2011 and 2024. Patients were stratified on the basis of postsplenectomy TPO-RA use. The primary outcome was incidence of thrombosis. Secondary outcomes included bleeding, mortality, and hematologic response. Time-to-event analyses and multivariate Cox regression were performed. Among 88 patients, 37 (42%) patients received TPO-RAs after splenectomy. Thrombosis occurred in 17 patients in the TPO-RA group vs 14 patients in the non–TPO-RA group (P = .07). The 10-year cumulative incidence of thrombosis was numerically higher in the TPO-RA group (57% vs 36%), with clustering of events within the 3 months of postsplenectomy TPO-RA initiation. Venous events predominated; arterial events were rare. No significant differences were observed in bleeding or mortality rates between groups. Platelet counts alone did not independently affect bleeding or thrombosis. TPO-RA use after splenectomy was not significantly associated with increased thrombosis risk. However, early initiation may coincide with a high-risk period, and the sustained numerical difference in cumulative incidence throughout follow-up highlights potential clinical relevance. These findings support the need for individualized thromboprophylaxis and prospective evaluation of TPO-RA safety in this setting.

Background: The use of validated risk stratification tools for the workup of suspected pulmonary embolism (PE) is a recommendation of the American Society of Hematology and the American College of Emergency Physicians. Methods: We designed and implemented electronic clinical pretest probability (PTP) tools for use in emergency departments (ED). Overall, 38 EDs (tertiary and regional EDs) in the United States were involved across three health systems. PTP use was analyzed between September 12, 2022 and January 11, 2023 in 270,247 ED visits. PTP use was examined in terms of the percentage of visits for which patients underwent computed tomography pulmonary angiography (CTPA). Each site chose the 3-tier Wells’ score for implementation and Site 2 designed a combined Wells’, pulmonary embolism rule-out criteria (PERC), and YEARS score. Results: At Site 3, forced use resulted in documented PTP scores in 49–53% of ordered CTPAs. At Sites 1 and 2, where PTP scores were optional, documented PTP scores occurred in 2–3% and 1–3% of CTPA orders, respectively. At Site 1, the use of PTP increased slightly over the study period, with signs that PE yield on imaging was also increasing (3.4–5.9%). At Site 2, PE yield on imaging was 9–10%, and it remained similar, with similar use of PTP tools over the study period. PE yield (6–8%) on imaging also remained similar throughout the study at Site 3. Conclusions: Guideline-endorsed PTP scores for PE at three independent health systems in the United States did not increase PE yield on imaging. Novel implementation strategies involving interdisciplinary teams are urgently needed.

Background: The calf muscle pump is an understudied contributor to venous return from the lower extremity. This study aimed to determine if calf pump function (CPF) is independently associated with the severity of chronic venous disease classified by CEAP (Clinical-Etiology-Anatomy-Pathophysiology). Methods: The Mayo Clinic Vascular Laboratory database was analyzed from January 2015 through September 2023. Ambulatory adults who underwent venous air plethysmography were included. Venous plethysmography assessed the severity of venous incompetence, and CPF was measured as ejection fraction (EF) per leg. The clinical component (C0 through C6) of the CEAP score was evaluated for each extremity at the time of the study. Results: A total of 7760 limbs from 3733 patients were analyzed. The mean age was 62 years, with 62% women. Venous obstruction was detected in 3.2% of limbs. Venous incompetence severity was categorized as normal (44%), mild (26%), moderate (19%), and severe (10%). A significant trend of reduced CPF was observed with higher CEAP scores ( p < 0.001). Multivariable logistic regression, adjusted for age, sex, degree of venous incompetence, and obstruction showed reduced CPF was a significant predictor (odds ratio 1.84, CI: 1.5–2.2) of active/prior ulcer (C5 or C6). In contrast to more severely reduced CPF, mildly reduced CPF (EF 40–49%) was not associated with active/prior ulcers. Conclusion: This large contemporary study demonstrates that decreased CPF is associated with worse chronic venous disease. Importantly, we demonstrate for the first time that CPF is independently associated with active/prior venous ulcers after accounting for other venous physiologic parameters and demographics.