Paget-Schroetter Syndrome Research Articles

A Rare Cause of Upper Extremity Thrombosis: Paget-Schroetter Syndrome

Upper extremity deep vein thrombosis (UEDVT) is extremely rare in children and adolescents. Paget - Schroetter Syndrome (PSS) is the primary, spontaneous thrombosis of the subclavian venous (SV) axillary tract. Herein, we report on PSS in two children who did regular body building exercises. 16-year-old two male patients admitted with complaints of swelling, coldness and pain on the right upper extremity. Their recent history disclosed that they have been doing advanced body building exercises for the last year. Physical examination revealed a difference of 4 cm and 5 cm in the diameter of each arm, as well as coldness and venous engourgement in the upper extremities. An acute thrombus was present in the proximal right SV lumen and no flow was detected on upper extremity venous doppler ultrasaund. Surgical treatment was performed in addition to medical thrombosis treatment. Early diagnosis and treatment of PSS is important for better outcomes. PSS should be considered in young patients with UEDVT, especially those with a history of vigorious exercise.

Early Diagnosis of Upper Extremity Deep Venous Thrombosis Using Emergency Department Point-of-Care Ultrasound: A Case Report

Introduction: Upper extremity deep vein thrombosis (UEDVT) is a serious condition associated with fatal complications. It necessitates careful consideration and prompt intervention. Despite the proven effectiveness of point-of-care ultrasonography (POCUS) in detecting UEDVT, it is rarely utilized in the Emergency Department (ED). Purpose: To highlight the role of POCUS in the early diagnosis of UEDVT in the ED. Case Summary: A 65-year-old female, actively undergoing chemotherapy via a right subcutaneous port for known left breast cancer, presented to the ED exhibiting throat irritation, facial swelling, and itchiness. These symptoms surfaced the day after her latest chemotherapy session. She typically experienced similar reactions post-chemotherapy, managed by routine oral antihistamines and steroids, yet this instance persisted despite medication. On examination, she appeared flushed, with a plethoric and erythematous face, accompanied by swelling extending from her neck to the left arm, along with tender left axillary lymph nodes. A POCUS of the left upper arm revealed soft tissue edema, a non-compressible brachial vein, and a hypoechoic floating luminal lesion (Figure 1). Subsequent computed tomography (CT) confirmed upper limb deep venous thrombosis extending into the left subclavian and internal jugular vein, partially non-occlusive in the proximal superior vena cava (Figure 2. A & B). Notably, she had a known contrast allergy, requiring pre-treatment with steroid and diphenhydramine before contrast injection. Based on CT findings, therapeutic enoxaparin was initiated in the ED and patient was admitted under oncology care, subsequently discharged on rivaroxaban. Discussion: Based on previous studies, the reliance on radiologists' availability for vascular imaging to diagnose UEDVT within the ED led to significant delays, extending up to two hours. Notably, the utilization of POCUS by Emergency Physicians resulted in a marked reduction in both diagnosis and intervention times. Furthermore, insights from six prospective studies confirm the accuracy of color-Doppler sonographic imaging in diagnosing UEDVT, showcasing sensitivity ranging between 78% to 100% and specificity from 82% to 100%. This compelling evidence strongly advocates for the broader integration of POCUS in EDs, emphasizing its credibility in enhancing diagnostic accuracy and expediting timely intervention for UEDVT. Applying these findings to this specific patient case, reliance on POCUS could have avoided the risks associated with radiation and contrast exposure Conclusion: Integrating POCUS into the ED's diagnostic protocol for UEDVT enables early detection and intervention, and mitigates risks associated with contrast agents and excessive radiation exposure.

Thoracic Outlet Syndrome and Thrombosis: A Case of Paget-Schroetter Syndrome Triggered by Prolonged Strap-Holding.

Thoracic Outlet Syndrome and Thrombosis: A Case of Paget-Schroetter Syndrome Triggered by Prolonged Strap-Holding.

Giant Subclavian Artery Aneurysm

Subclavian artery aneurysms are rare peripheral aneurysms. A giant subclavian artery aneurysm can lead to compression of the trachea or brachial plexus, erosion of the lung causing hemoptysis, hoarseness of voice, dysphagia, Horner’s syndrome, and upper extremity deep vein thrombosis. Compression of the trachea and inability to ventilate the patient can be a real challenge for the anesthesiologist and must be anticipated. Computed tomographic angiography is a useful imaging modality for its diagnosis and to rule out additional aneurysms in the body.

Management of catheter-related upper extremity deep vein thrombosis in patients with cancer: a systematic review and meta-analysis

BackgroundPatients with cancer commonly require a central venous catheter, which is associated with an increased risk of venous thromboembolism (VTE). Despite the frequent occurrence, the optimal anticoagulation management and outcomes for patients with cancer and catheter-related upper extremity deep vein thrombosis (DVT) are unclear. ObjectiveWe performed a systematic review and meta-analysis to evaluate the rates of recurrent VTE and bleeding in patients with cancer and catheter-related upper extremity DVT. MethodsWe searched MEDLINE, Embase, Scopus, and CENTRAL from inception to June 2, 2023. The primary efficacy outcome was recurrent VTE, and the primary safety outcome was major bleeding. The incidence rates (with 95% CI) of outcomes were pooled using random effects model. ResultsWe included 29 studies (N = 2,836), among which 5 were prospective. The duration of follow-up and anticoagulation varied considerably. The main long-term anticoagulant used was low molecular weight heparin, followed by direct oral anticoagulants. The pooled 3-month recurrent VTE rate from 14 studies (N = 1,128) was 0.56% (95% CI, 0.10%-3.01%; I2 = 0%). The pooled 3-month major bleeding rate from 10 studies (N = 834) was 2.34% (95% CI, 1.14%-4.76%; I2 = 0%). We were unable to pool event rates beyond 3 months, given high heterogeneity. All studies had serious risk of bias. ConclusionsOur study demonstrated a relatively low rate of recurrent VTE and moderate rate of major bleeding events within the first 3 months in patients with cancer and catheter-related upper extremity DVT. However, there was significant heterogeneity in the management and reporting after 3 months.

A Survey of Clinician Perspectives on the Management of Catheter-Related Upper Extremity Deep Vein Thrombosis in Patients with Cancer

Background: Central venous catheters (CVCs) are commonly used in cancer patients to facilitate blood draws, administration of chemotherapy or other supportive care treatment. Catheter-related upper extremity deep vein thrombosis (DVT) is a major complication of CVCs, with studies reporting a rate of symptomatic venous thromboembolism (VTE) of 7% over 3 months in patients with active cancer and a new CVC. Despite the frequent occurrence, the optimal management in patients with cancer and catheter-related upper extremity DVT is unclear, given the lack of high-quality data. Objective: We conducted a survey aiming to characterize practice patterns and perceptions of clinicians who treat patients with cancer and catheter-related upper extremity DVT. Methods: An online survey was distributed to international clinicians who manage patients with cancer and catheter-related upper extremity DVT. The survey explored the type and duration of anticoagulation, focusing on the management after the initial 3 months of anticoagulation, as well as treatment strategies upon catheter removal and interests in future clinical studies. Descriptive statistics was used to summarize survey responses. Results: The survey was generated on LimeSurvey ® in English and publicized by Twitter ® and email communications via multiple international organizations of hematologists, oncologists, and/or thrombosis specialists, including the International Society on Thrombosis and Haemostasis (ISTH), Thrombosis Canada, the Canadian Venous Thromboembolism Research Network (CanVECTOR), and more. As of July 30, 2023, 115 clinicians from 26 countries had completed the survey. The majority of the respondents specialized in thrombosis (N=72, 62.6%) and/or hematology (N=60, 52.2%), followed by internal medicine (N=38, 33.0%) and oncology (N=14, 12.2%) (multiple selection was permitted for this question). For the initial management of a patient without unresected gastrointestinal (GI) or genitourinary (GU) cancer, thrombocytopenia, or relevant drug-drug interactions, 75% of clinicians would prescribe a direct oral anticoagulant (DOAC) and 25% would give low-molecular-weight heparin (LMWH). On the other hand, in patients with unresected GI/GU cancer, the majority (N=105, 91.3%) of respondents chose to initiate LMWH. After the initial 3 months of anticoagulation, if the CVC remains in place in a patient with active cancer, the majority (N=112/114, 98.2%) of clinicians would continue anticoagulation, but with variable doses (57% and 43% chose therapeutic and prophylactic dosing, respectively). If the CVC remains in place but the cancer is in remission, fewer (70%) respondents would continue anticoagulation, and more would continue prophylactic as compared to therapeutic dosing (73% vs. 27%) in this setting. Practice variation further increases upon catheter removal, especially in the presence of active cancer (Figures 1 and 2). The majority of respondents (N=111, 96.5%) agree that there is a need for prospective studies to evaluate the management of patients with cancer and catheter-related upper extremity DVT, and over 91% (N=105) would consider enrolling their patients in a study to evaluate prophylactic dosing of anticoagulation for secondary prevention of VTE in patients with cancer and catheter-related upper extremity DVT. To help plan such a study, we evaluated respondents' perception on the maximal “tolerable” recurrent VTE rate between 3 and 6 months (as the main interest is in the management strategy after the initial 3 months), and 2% and 3% were the most common responses (41.2% and 31.6% of the respondents, respectively). Conclusions: Our survey demonstrates that current practice in managing patients with cancer and catheter-related upper extremity DVT is heterogenous, especially after the initial 3 months of anticoagulation and upon catheter removal. Well-conducted prospective studies in this population are needed, which is supported by most clinicians.

Management of Catheter-Related Upper Extremity Deep Vein Thrombosis in Patients with Cancer: A Systematic Review and Meta-Analysis

Background: Patients with cancer commonly require a central venous catheter (CVC) for delivery of cancer therapies and/or supportive care. The presence of a CVC is associated with an increased risk of venous thromboembolism (VTE). Despite the frequent occurrence, the optimal anticoagulation management and outcomes for patients with cancer and catheter-related upper extremity deep vein thrombosis (DVT) are unclear. Objective: We performed a systematic review and meta-analysis to evaluate the rates of recurrent VTE and bleeding complications in patients with cancer and catheter-related upper extremity DVT. Methods: We searched MEDLINE, Embase, Scopus, and CENTRAL (Cochrane) from inception to June 2, 2023. We aimed to include randomized controlled trials (RCTs) (if any), prospective and retrospective cohort studies, and case-control studies (including ≥ 10 patients) evaluating adult patients with cancer and catheter-related upper extremity DVT. The primary efficacy outcome was recurrent VTE, and the primary safety outcome was major bleeding as defined by individual studies. Secondary outcomes included clinically relevant non-major bleeding, total bleeding events, and all-cause mortality. By using R software (version 4.0.3), the incidence rates (with 95% confidence interval [CI]) of recurrent VTE and bleeding outcomes at different time points were pooled using random effects model. Results: After screening 4,264 records, we included 29 studies (N=2,848 patients) in the systematic review. There were no RCTs, 5 prospective cohort studies (including 260 patients), and 24 retrospective cohort studies. Most studies had modest sample size (N<100). Overall from 24 studies with reported tumor types, the most common malignancy was hematological malignancy (50.4%), followed by gastrointestinal (13.6%), breast (10.2%), and lung (5.5%) cancers. The median or mean follow-up duration varied widely from 1 to 20 months. Duration of anticoagulation also varied considerably with median or mean duration of 20 days to 6 months. The main long-term anticoagulant used was low-molecular-weight heparin (58.1%), followed by direct oral anticoagulants (24.3%). Only two studies (N=87 patients) specifically reported the management and associated outcomes after catheter removal. Thirteen studies (N=1105 patients) reported a 3-month recurrent VTE rate, with the pooled rate of 1% (95% CI 0-3%, I 2 = 0%) (Figure 1). Nine studies (N=811 patients) reported a 3-month major bleeding rate, with the pooled rate of 2% (95% CI 1-5%, I 2 = 0%) (Figure 2). We were unable to pool event rates beyond 3 months given high degree of heterogeneity in the follow-up duration, bleeding definition, and duration of anticoagulation. Conclusions: Our systematic review and meta-analysis demonstrated relatively low rates of recurrent VTE and major bleeding events within the first 3 months in patients with cancer and catheter-related upper extremity DVT. However, there was significant heterogeneity in the management and reporting after 3 months, and available data are poor to guide treatment strategies and duration of anticoagulation. The optimal management after catheter removal was also unclear. Future large prospective studies are needed.

Overall Survival of Warfarin Compared to LMWH/Doacs in Cancer-Associated Venous Thromboembolism: VA Cohort Study

Background: Warfarin has been shown in pre-clinical models to have anti-neoplastic activity. In a population-based study using the SEER-Medicare Linked Database warfarin was associated with improved survival compared to low molecular weight heparin (LMWH) or direct oral anticoagulants (DOACs) in the treatment of cancer-associated thrombosis (CAT). To assess whether the observed survival advantage is consistent in other large cohorts, we performed a matched cohort study utilizing the Veterans Affairs (VA) database. The VA is a large, integrated health care system with comprehensive data for their patients at the individual level, which provides the optimal observational cohort to confirm the novel hypothesis warfarin confers a mortality benefit over LMWH. Method: Using the retrospective data from the VA health care system from 2000-2021, we identified patients with CAT who were > 18 years, had available prescription data for anticoagulation within 30 days of venous thromboembolism (VTE), and survived > 14 days after the index VTE event. Patients were excluded if they had prior diagnosis of VTE or had any anticoagulation prescription prior to the first coded VTE event. The primary outcome was overall survival (OS). Patients were matched 1:1 using nearest neighbor matching on the propensity score. The matching variables included cancer site, cancer stage, date of cancer diagnosis, date of VTE diagnosis, age at VTE diagnosis, gender, race, BMI, Elixhauser-based weighted comorbidity score, and rurality of residential status. Cox proportional-hazards regression was performed to estimate hazard ratios (HR) and 95% confidence intervals. Log-rank test was utilized to estimate the p-value. Subgroup analyses were performed in the largest groups of cancer available in the data set including prostate cancer, lung cancer, gastrointestinal cancer (excluding hepatobiliary cancer), and malignant hematologic neoplasms (including myeloid malignancy, lymphoid malignancy, and multiple myeloma). Finally subgroup analysis was also performed on localized cancer and metastatic disease based on AJCC stage grouping. Result: There were a total of 20,078 patients that met the inclusion and exclusion criteria without missing data. The warfarin cohort consistent of 8383 patients while non-warfarin cohort comprised 11696 patients. Among the non-warfarin cohort, 54% of the patients were prescribed LMWH exclusively and 38% of the patients were prescribed DOAC exclusively within 30days of the VTE diagnosis. The most common malignancies in the cohort included prostate (29.4%), lung (20.9%), gastrointestinal (15.7%) and hematologic malignancies (10.3%). Of patients with solid tumors, 22% had metastatic cancer. Among the VTE events, 33.3% were acute lower extremity deep vein thrombosis, 48.4% were acute pulmonary embolism, and 18.3% were acute upper extremity deep vein thrombosis. After propensity score matching, 8,383 patients were included in the warfarin arm and 8,383 patients in the non-warfarin arm. The median age at VTE diagnosis of the matched cohort was 69 [IQR 63 - 75] and the majority of the patients (96.7%) were male. Warfarin was associated with a significant improvement in OS compared to non-vitamin K antagonists (median OS, 1204 days [95% CI, 1137-1276 days] vs 703 days [95% CI, 665-747 days]; HR 0.79 [95% CI 0.76 - 0.82]; p-value <2x10 -16) (Figure1). The difference was also preserved in gastrointestinal malignancy (HR 0.8 v95% CI 0.73-0.87), lung cancer (HR 0.8, 95% CI 0.79-0.92) and prostate cancer (HR 0.71, 95% CI 0.65-0.77). The survival advantage was preserved in patients with metastatic (HR 0.86, 95% CI 0.78-0.83) and localized cancer (HR 0.80, 95% CI 0.76-0.84) (Figure 2). Conclusion and Relevance: In a population level propensity matched study, warfarin for the treatment of CAT was associated with significantly improved survival over non-vitamin K antagonist anticoagulation in CAT. These provocative finding confirm the previous observation in SEER-Medicare database and have important implications on patient care and health care costs. Further investigation into the biological basis of these findings could potentially lead to biomarker and drug discovery for cancer therapies and prognostication.

Use and Outcomes of Secondary Anticoagulation in Patients

Background: Although the rate of venous thromboembolism (VTE) recurrence is low among pediatric patients with provoked VTE, children with a history of VTE who have persistent prothrombotic risk factors such as central venous catheters (CVCs), thrombophilia and cancer have been shown to have increased risk for recurrent VTE (e.g., Brandao et al., Lancet Hematology 2020). Prospective multicenter data on the use of secondary anticoagulation in patients with a first provoked VTE are limited. Objective: We sought to characterize the use and outcomes of secondary anticoagulation in patients <21 years old with provoked VTE, via the multinational Kids-DOTT trial. We hypothesized that older patient age is associated with use of secondary anticoagulation among patients with provoked VTE who have persistent prothrombotic risk factors following completion of a primary course of anticoagulation for treatment of acute provoked VTE, and that frequencies of clinically relevant bleeding and recurrent VTE are low in this setting. Methods: We conducted a secondary analysis of patients enrolled in the NIH-sponsored, multinational randomized controlled Kids-DOTT trial (NCT00687882; Goldenberg et al., JAMA 2022) who received secondary anticoagulation. We defined secondary anticoagulation as anticoagulant use beyond the initial treatment period of 6-12 weeks for the purpose of secondary VTE prevention, as captured in case report forms. “Chronic” secondary anticoagulation was defined as that which began within 2 weeks of the prescribed treatment course; otherwise, secondary anticoagulation was defined as “episodic”. The presence of new and/or recurrent prothrombotic risk factors was captured in association with each episode. Variables were summarized as counts and percentages for categorical variables and medians with interquartile ranges (IQR) for continuous variables. To compare groups that did versus did not receive secondary anticoagulation, Mann-Whitney U test was used for continuous variables and chi-square, or Fisher's exact test was used for categorical variables, with alpha <0.05 considered significant. All statistical analyses were performed using R version 4.1.2 (R Core Team, 2021). Results: Among 532 patients enrolled in the Kids-DOTT trial, 18 (3.4%) received secondary anticoagulation, all of whom had persistence or recurrence of prothrombotic risk factors (Table 1). The most frequent prothrombotic risk factors associated with use of secondary anticoagulation were a new or persistent central venous catheter (28%, N=5) and infection (17%, N=3). Despite having persistence or recurrence of prothrombotic risk factors, only 1 patient who received secondary anticoagulation developed recurrent VTE and 2 patients experienced clinically relevant bleeding during a median follow-up of 1.99 years [IQR 1.06-2.02], none of which was temporally related to secondary anticoagulation use. As shown in Table 2, patients who received secondary anticoagulation were older (median 12.9 years [IQR 7.6-15.5 years] vs. 8 years [1-15 years], P=0.05) and more likely to have upper extremity deep vein thrombosis (50% vs. 29%; P=0.003) when compared to those who did not receive secondary anticoagulation. Conclusion: These findings suggest that use of secondary anticoagulation is low among patients <21 years old with provoked VTE. However, among those who receive secondary anticoagulation for persistent or recurrent prothrombotic risk factors, the risks of recurrent VTE and clinically relevant bleeding may be low. Furthermore, focused study of use and outcomes of chronic and episodic secondary anticoagulation is warranted to inform future practice on secondary prevention in children, adolescents, and young adults with a history of provoked VTE.

Risk of Recurrent Venous Thromboembolism in Patients with Acute Isolated Subsegmental Pulmonary Embolism - a Single Center Chart Review

Introduction: The incidence of pulmonary embolism (PE) has been increasing, but its case-fatality rate is decreasing over time, suggesting overdiagnosis, a lesser severity of the illness and/or improvements in treatment strategies. Approximately 10-14% of all diagnosed PE are isolated to the subsegmental vessels. The risk of recurrent venous thromboembolism (VTE) in patients with an acute subsegmental pulmonary embolism (SSPE), managed with or without anticoagulant therapy, remains poorly understood. Methods and analysis: This is an observational, retrospective cohort study of adult patients diagnosed with an acute isolated SSPE (single or multiple) at The Ottawa Hospital, Ontario, Canada, from June 01, 2019, to August 31, 2022. Data on diagnosis and follow-up were collected through a retrospective review of the medical records. Among inclusion criteria, no selection was made on provoking factors or on presence/absence of symptoms at presentation. We excluded those patients with concomitant diagnosis of deep vein thrombosis (DVT) who were started on anticoagulation and those who had an indication for long-term anticoagulation at the time of SSPE diagnosis (e.g. atrial fibrillation). The primary outcome was recurrent VTE events other than SSPE, occurring after the diagnosis among patients managed without anticoagulation, and after treatment initiation among those treated with anticoagulation. Results: Overall, 120 patients with a diagnosis of acute SSPE were included in the analysis. The mean age of the participants was 59 +/- 3 years, 47% were women, the mean body weight was 76 +/- 4 kg, and 35% of them had active cancer. Seventy-nine patients (66%) were treated with anticoagulation, whereas 41 patients (34%) were not. The most frequent treatment was direct oral anticoagulant, being used in 64/79 patients (81%), whereas 15/79 patients (19%) received low molecular weight heparin. Most patients were treated for 3-6 months. Twenty-one (28%) of treated patients continued long-term anticoagulation for secondary prevention. Individuals with active cancer at time of SSPE diagnosis were 32/79 (41%) and 10/41 (24%), respectively among treated and not treated patients. Overall, duration of follow-up was 452 +/- 77 days; 7 patients were lost to follow-up. Recurrent VTE events occurred in 7/113 (6.2%) patients: 5/75 (6.7%, 95% CI 2.2 to 14.9) of them were diagnosed in the treatment group (2 occurred while on anticoagulation and 3 after discontinuation of treatment) and the other 2/38 (5.3%, 95% CI 0.6 to 17.8) were detected among patients managed without anticoagulation. Recurrences were mostly represented by more proximal PEs (5 patients), one patient had an upper extremity DVT and the other one was diagnosed with both DVT and proximal PE. Conclusions: In our retrospective cohort study, most patients diagnosed with an acute SSPE received anticoagulation. The prevalence of recurrent thromboembolic events detected over more than a year follow-up was relatively high, with 6.7% and 5.3%, respectively, among patients treated with anticoagulation and those managed without anticoagulation. Further data are needed to better understand the natural history of this thrombotic complication and to identify the right patients who would benefit from anticoagulation.

Venous Thromboembolism Outcomes Among Cancer and Non-Cancer Patients Managed with Patient-Centric Guideline-Driven Protocol

Purpose/Introduction: Patients with cancer and venous thromboembolism (VTE) have higher complication rates including thrombosis recurrence and bleeding. Real world prospective clinical outcome estimates of VTE management comparing cancer and non-cancer patients are limited. To assess VTE recurrence, major bleeding, and clinically relevant non-major bleeding (CRNMB) in patients with cancer and without cancer, the prospective Mayo Clinic Thrombophilia Clinic Registry was analyzed. Methods: Upon recruitment, consecutive patients with confirmed acute VTE (03/01/2013 - 04/30/2023) were treated in a standardized, guideline-sanctioned, protocol driven strategy incorporating shared patient-decision making. Patients were divided into groups based on cancer status. After enrollment, patients were actively followed at 3 month intervals, in person whenever feasible, by mailed questionnaire or scripted phone interview to assess vital status, medication compliance, VTE recurrence, major bleeding and CRNMB. Results: Over the study time-frame, 2,064 patients (53.8% male, 46.2% female) with a cancer and 2,647 patients (54.9% male, 45.1% female) without cancer were enrolled. The most common cancers were gastrointestinal (n=423, 20.5%), pancreatic (n=287, 13.9%), genitourinary (n=198, 9.6%), hematologic (n=171, 8.3%), and lung cancer (n=170, 8.2%). Patients with cancer were older, had lower weight and lower platelet counts compared to non-cancer patients (Table1). Pulmonary embolism (PE, 52.6% vs 43.7%, p<0.001), upper extremity DVT (9.1% vs 6.0%, p<0.001), and splanchnic DVT (11.1% vs 6.9%, p<0.001) were more frequent among cancer patients. In contrast, leg DVT was more frequent among non-cancer patients (65.4% vs.47.2%, p<0.001). While mean duration of anticoagulation was similar between groups, notable differences in 3 month and > 9 month durations were evident as were initial anticoagulant choices (Table 1). Despite a well-organized protocol driven and guideline sanctioned management strategy, patients with active cancer experienced a 2.2-fold higher rate of VTE recurrence (p<0.001) and a 1.8 fold higher rate of major bleeding (p<001) compared to non-cancer patients (Table 2). CRNMB rates did not differ by cancer status. Conclusions: In this large prospective, guideline-driven and patient-centric registry of VTE management, patients with cancer had significantly higher rate of VTE recurrence and major bleeding, compared to non-cancer patients. These data provide important estimates for power calculations for future randomized trials of VTE treatment.

Diagnosis, Management and Outcomes in Children with Paget Schroetter Syndrome: A Retrospective Cohort Study

Introduction Venous thoracic outlet syndrome occurs secondary to the extrinsic compression and impingement of the subclavian vein as it passes through the thoracic outlet, eventually resulting in upper extremity effort thrombosis, or Paget-Schroetter syndrome (PSS). This rare condition typically affects the dominant arm of athletic young adults with a history of repeated overhead activities. At Boston Children's Hospital (BCH), a multidisciplinary team of hematologists, interventional radiologists, and vascular surgeons manage these patients according to a standardized protocol including anticoagulation, pharmaco-mechanical thrombolysis, venoplasty, and decompressive rib-resection surgery. Herein we report the clinical and radiological outcomes of a cohort of patients with PSS managed at BCH. Objective The principle objective of this retrospective cohort study was to review the diagnosis, pharmacological, interventional radiology and surgical management, complications, and long-term outcomes of sequential pediatric patients (≤21 years) treated for PSS at BCH over a 3.5-year period of time (January 1, 2020 to July 31, 2023). Methods This study was performed as a part of an ongoing quality improvement initiative and was deemed exempt by the Institutional Review Board. Eligible patients were defined as children (≤21 years) with PSS per criteria established by the Society for Vascular Surgery. Clinical and demographic data, including post-thrombotic syndrome (PTS) scores of eligible patients were abstracted from their medical records. PTS evaluation at BCH is typically performed 6-12 months after DVT diagnosis using both the modified Villalta and Manco-Johnson instruments. Major bleeding, and recurrent/progressive thromboses were defined per published guidelines by the International Society on Thrombosis and Haemostasis. Standard statistical methods were used - median (range) for continuous variables and frequency with 95% CI for categorical data. Results The study cohort consisted of 20 patients (9 female). PSS was confirmed based on dynamic imaging with provocative maneuvers for all patients. Median (range) age at DVT diagnosis was 17 (15-21) years. Thirteen patients were diagnosed at an outside hospital and referred to BCH for further management. Fourteen patients received upfront anticoagulation with low molecular weight heparin of whom 13 patients were transitioned to a DOAC. Six patients were started on DOACs upfront. Fifteen subjects (75%) received upfront endovascular intervention at diagnosis. Median interval between DVT diagnoses to endovascular intervention was 5 (1-118) days. All patients underwent decompressive rib-resection surgery. Median interval between DVT diagnosis and surgery was 12 (7-39) weeks. Three patients (15%) developed major bleeding and 3 (15%) patients developed recurrent/progressive thrombosis after surgery. Two of the 3 patients who developed major bleeding were anticoagulated with a DOAC pre-operatively, which had been held for 48 hours before surgery. All subjects had a planned post-operative venogram, 14 (70%) of whom underwent completion venoplasty. Anticoagulation was discontinued in 18/20 (90%) patients with a median duration of therapy of 19.5 (14-60) weeks. Four patients (20%) were noted to have an underlying thrombophilia (Factor 5 R506Q [2]; Factor 2 G20210A [1]; Protein S deficiency [1]). End-of-therapy imaging was obtained for all patients - 17 (85%) had complete thrombus resolution, while two (10%) had partial thrombus resolution. Seventeen (85%) patients have undergone evaluation for PTS, of whom 12 (71%) were noted to have mild PTS and 2 (12%) have moderate-severe PTS as defined by the modified Villata instrument. Discussion Greater than 90% of pediatric patients with PSS who were treated per our institutional multi-disciplinary protocol had complete or partial thrombus resolution. Additionally, only 12% of patients reported moderate to severe PTS on follow-up and were prescribed sequential compression sleeves. Lastly, DOACs appear to be safe and efficacious in this cohort, though based on our internal data, we now interrupt DOACs for 72 hours before decompressive surgery.

A Transformer Natural Language Processing Algorithm for Cancer Associated Thrombosis Phenotype

Introduction: Cancer patients have high risk of venous thromboembolism (VTE). The ability to accurately capture VTE outcome in large electronic health record (EHR) is critical for both surveillance and risk stratification. We previously published a rule-based natural language processing (NLP) algorithm that relied on radiology reports alone with a precision (positive predictive value) of 89% and recall (sensitivity) of 69-78% (sTable 5 PMID36626707). The low recall metric was expected as VTE diagnosis that occur at outside hospital would not be captured by radiology reports. In the current study, we aimed to assess the performance of a machine learning NLP algorithm using both radiology and medical notes to detect cancer associated VTE longitudinally in a large cancer cohort. Methods: VTEwasdefined as symptomatic or incidental pulmonary embolism, lower or upper extremity deep vein thrombosis. Unusual thrombosis such as splanchnic vein thrombosis (mostly tumor thrombi) was classified as negative. Figure 1 details the study design: i) patient selection, ii) pre-annotation filtering, iii) gold standard annotation, iv) transformer model development. From a cohort of 9,769 patients with active cancer receiving first-line systemic therapy, we first pre-filtered all clinic progress notes, discharge summaries, and radiology reports to exclude sections with little clinical relevance (e.g. review of systems, physical exam), while maintaining sections with high clinical value (e.g. history of present illness, assessment/plan, hospital problems/course). Then, we kept notes with VTE keyword stems (e.g. VTE, PE, DVT, thromb, embol, clot, filling defect, phlebitis). We selected 808 patients with at least 1 keyword to determine the gold standard VTE date and location through independent chart review process. This cohort was randomly split into a training and testing cohort at an 7:1 ratio. In the training cohort (n=708), we further annotated all keyword-containing phrases within 30 days (d) from VTE date and from index date until 180d if no VTE (n=~2,000). The ~800 positive and ~1,200 negative keyword-containing phrases were used to train ClinicalBERT (bidirectional encoder representation transformer) large language model through split-sample cross validation to finetune the loss function and to determine the prediction threshold. Finally, we applied the entire trained model package to every available notes/reports (n=~2300) in the test cohort (n=100) to assess if the first positively predicted date would correlate with the gold standard VTE date. Results: The finetuned ClinicalBERT modelachieved 98% precision and 98% recall on the patient level in the training cohort (n=708). When applied on the 100-patient test cohort, the model accurately predicted first VTE events in 50/54 patients (93% precision) and captured 50/54 of patients with VTE (93% recall sensitivity) (Table 1). Most of the tumor thrombi and superficial venous thrombi were correctly classified as negative. The false positives were related to unusual sentences with both positive and negative findings such as “Thrombosis surrounding the left brachial catheter in basilic vein,” “CT chest with PE was done,” “Lovenox was initiated for UE DVT, but this was port thrombosis in the basilic vein.” The false negatives were related to isolated VTE diagnosis close to death or loss to follow-up. Notably, the precision and recall tradeoff can be further finetuned by changing the minimum number of positively predicted notes from the NLP. Conclusion: In conclusion, we successfully developed and tested a transformer NLP model to detect cancer associated VTE longitudinally using a combination of clinical notes and radiology reports that achieved a precision of 93% and recall of 93%. This represented an improvement over our original algorithm with radiology report alone. Further validation of the model in external cohorts and finetuning through federated or transferred learning are ongoing to ensure model generalizability and usability.

Non-O Blood Group and Pretreatment Risk of Venous Thromboembolism in Patients with Diffuse Large B-Cell Lymphoma

Introduction: Diffuse large B-cell lymphoma (DLBCL) is the most frequent aggressive non-Hodgkin lymphoma (NHL). It has been extensively documented that the risk of venous thromboembolism (VTE) is augmented in patients with aggressive lymphomas. The timing of VTE occurrence in this group of patients is highly variable and depends on diverse risk factors. Lately, it has been observed that ABO blood group type can have a prognostic impact on both thrombosis development and survival outcomes in patients with cancer. Therefore, the study aimed to examine the ABO blood group as a risk factor for VTE development in patients with DLBCL, to examine the relation between ABO blood groups and the timing of VTE development, and to investigate the association between ABO group type and treatment and survival outcomes. Methods: A total of 340 patients with DLBCL (newly diagnosed and relapsed) have been included in the study and all of them have been treated at the Lymphoma Center, Clinic for Hematology, University Clinical Center of Serbia. Data regarding VTE events were collected for all the patients included in the study, from the time of diagnosis to 3 months after the last cycle of therapy. ABO blood group has been determined before the treatment initialization. VTE was diagnosed objectively based on clinical examination, laboratory evaluation, and radiographic studies. Results: The median patients' age was 60 years (range, 19-89 years) and 52.9% were males. Newly diagnosed patients were dominant in the study population (94.4%). The majority of patients had advanced stage (stage III Ann Arbor 22.3% and stage IV 30.7%, respectively) of the disease. The median international prognostic index (IPI) was 2 (range, 0-5). Complete remission (CR) and partial remission (PR) were most commonly recorded (51.7% and 28.8%, respectively). The rate of VTE was 12.6% (43 patients), with the highest frequency of lower and upper extremity deep vein thrombosis (12 patients each). VTE was diagnosed before the initiation of specific hematological treatment in 54.5% of DLBCL patients, whilst 45.5% of DLBCL patients have been diagnosed with VTE following the hematological treatment initiation. The following distribution of ABO blood groups among DLBCL patients was detected: A blood group 39.4%, B blood group 17.6%, AB blood group 9.1%, and O blood group 33.8%. No significant association between VTE development and ABO group type was found (p=0.706) nor between VTE development and time of VTE development (p=0.895). The rate of VTE in DLBCL patients with A blood type was 4.7%, in B 2.1%, in AB 1.8%, and in O 4.1%, respectively (p=0.706). DLBCL patients with the non-O blood group developed VTE significantly more frequently prior to the hematological treatment commencement than after the treatment initiation (6.2% vs. 2.6%, p=0.003). Univariate logistic regression analysis showed that non-O blood type in DLBCL patients is a prognostic factor for VTE development prior to hematological treatment initiation (odds ratio (OR)=8.56, 95% confidence interval (CI): 1.92-38.21, p=0.005). Multivariate logistic regression model demonstrated that non-O blood type is an independent predictor of pretreatment VTE development in DLBCL patients (OR=18.33, 95% CI: 1.51-222.87, p=0.022). Therapy response of DLBCL patients was significantly associated with the ABO blood group (p=0.012) in the way that A and AB blood types were associated with unsatisfactory treatment response (no statistically significant association was found between ABO blood type and DLBCL patients' Ann Arbor stage, mediastinal involvement, bulky disease, extranodal disease, IPI, central nervous system involvement). Univariate regression analysis showed that A blood type is a predictor of unsatisfactory therapy response in patients with DLBCL (OR=1.85, 95% CI: 1.04-3.29, p=0.035). However, in multivariate regression model, this finding lost statistical significance. No significant association was observed regarding ABO blood type, progression-free survival, and overall survival in patients with DLBCL (p=0.398 and p=0.593, respectively). Conclusion: In DLBCL patients, non-O blood group is an independent predictor of VTE occurrence prior to initiation of a specific hematologic treatment. DLBCL patients with A blood group could be at risk of insufficient treatment response.

Incidence and Risk Factors for Thrombosis in Cancer Patients with COVID-19

Introduction: Cancer is a leading cause of morbidity and mortality in the United States, and cancer patients infected with COVID-19 are at increased risk of death. Given that cancer and COVID-19 are both risk factors for thrombosis, it has been hypothesized that cancer patients with COVID-19 may be at greater risk for thromboembolic events than patients with COVID-19 alone. This risk could necessitate the need for more vigilant thrombosis prophylaxis. However, studies investigating risk factors for thromboembolic events in this population are limited with mixed results. We aimed to determine the incidence and risk factors for thromboembolic events in patients with cancer and COVID-19. Methods: We performed a retrospective cohort review of all cancer patients hospitalized with COVID-19 at our institution between January 1, 2021 and April 1, 2023. Patients over the age of 18 who had previously been diagnosed with cancer, received treatment within the prior 6 months, and had been hospitalized due to COVID-19 were included in the study. We assessed whether patients had experienced a thromboembolic event during their hospital stay, which included thrombosis of the extracorporeal circuit, distal or proximal lower extremity deep venous thrombosis (DVT), upper extremity DVT, pulmonary embolism, superficial thrombophlebitis, ischemic stroke, or other arterial event. Information regarding comorbidities and clinical course was extracted from the patient's record. Descriptive analysis was performed, and association between qualitative variables was studied with the Chi-squared test and the Fisher Exact test, when appropriate. For quantitative variables, the t-test or the Mann-Whitney U test was performed. Multivariate logistic regression was used to assess variables predictive of thromboembolic events. Results: 456 patients with cancer and COVID-19 were included in the study. The median age was 69 years (IQR 62 - 78) and 55% of patients were male. The majority (85%) of patients were White. Most patients had either lung (19%) or bone marrow (17%) cancer, and 196 (43%) had received chemotherapy in the 6 months prior to hospitalization. 37 patients (8.1%) had thromboembolic events during their hospital stay. Age, race, receipt of chemotherapy, and history of hypertension, heart disease, obesity, and stroke were not predictive of thromboembolic events. Patients with thromboembolic events experienced significantly longer lengths of hospital stay than those without thromboembolic events (9 days vs 12 days, p<0.05). Conclusion: Thromboembolic events affect many cancer patients with COVID-19 and may complicate their treatment course during hospitalization. Patients who experienced a thromboembolic event had prolonged hospital stays, which may lead to increased financial and emotional burden in this patient population. Evidence-based strategies for preventing thrombosis, including pharmacologic and mechanical methods, should be emphasized in hospitalized cancer patients with COVID-19, which may decrease thrombotic complications. Further, methods of secondary thrombosis prophylaxis, such as early detection with screening methods or treatment of subclinical methods, should be encouraged. Future studies should promote risk classification in this patient population and optimal prophylaxis paradigms.

Development of a Combined Risk Assessment Model for Venous Thromboembolism and Bleeding in Hematopoietic Stem Cell Transplantation Patients

Background: Venous thromboembolism (VTE) and bleeding are common complications amongst allogeneic and autologous hematopoietic stem cell transplant (HSCT) patients. Balancing risk of bleeding and thrombosis in this population is particularly challenging as HSCT patients are concurrently pancytopenic and coagulopathic. However, risk factors for bleeding and thrombosis in HSCT patients are understudied. We aimed to derive a combined bleeding and VTE risk assessment tool to be used in the immediate post-transplant period (90 days). Methods: We conducted a retrospective cohort study of adult patients who underwent allogeneic or autologous HSCT between January 1, 2011 and December 31, 2021 at a tertiary care centre in Canada. The risk models patients were followed from transplant until occurrence of the event of interest with last follow up at Day 90 post-transplant, or death. Primary outcome for VTE was the occurrence of a confirmed thrombosis including proximal upper and lower extremity deep vein thrombosis, pulmonary embolism, or thrombosis of unusual sites, including cerebral and splanchnic. Primary outcome for bleeding was the occurrence of a major or clinically significant non-major bleeding event, not related to anticoagulation, as per the definition of the International Society of Thrombosis and Hemostasis. Group characteristics were compared using chi-square, Fisher's exact, or Student's T-tests as appropriate. Potential predictors for VTE and bleed amongst our patients were evaluated using single variable logistic regression and confirmed with multiple variable logistic regression with forward selection. For continuous variables, optimal cut-off points were estimated using ROC curves. Final VTE and bleed risk scores were derived based on weighted variables and compared using Cox regression with non-parametric bootstrapping used for internal validation. Results: A total of 476 patients (317 autologous, 159 allogeneic) were included. 47 patients (9.8%) suffered from VTE, and 32 patients (6.7%) suffered from bleed unrelated to anticoagulation within 90 days post-HSCT. A VTE risk assessment tool was derived, and internally validated, and it included: second central venous catheter insertion (due to complications from first central line) (2 points), and previous cancer treatment with steroids (1 point). The overall cumulative incidence of VTE was 31.8% in the high-risk group (>2 points) versus 7.6% in the low-risk group (0-1 points). The high-risk group was associated with higher mortality at 90 days (15.9% versus 3.2%, p <0.001; Figure 1). A bleeding risk assessment tool was also derived, and internally validated, and it included: baseline (day 0 of transplant) platelet count of <90 (1 point), and baseline hemoglobin of <96 (1 point). The overall cumulative incidence of bleed was 17.2% in the high-risk group (2 points), versus 4.3% in the low-risk group (0-1 points). The high-risk group was associated with higher mortality at 90 days (12.6% versus 2.6%, p<0.001). Amongst the low-risk bleed group, overall cumulative incidence of VTE was 10.03%, with 31.03% in the high-risk VTE group versus 8.33% in the low-risk VTE group (p<0.001). The positive VTE group was associated with higher mortality at 90 days (10.26% versus 1.72%, p=0.001; Figure 2). Amongst the high-risk bleed group, overall cumulative incidence of VTE was 9.19%, with 33.33% in the high-risk VTE group, versus 4.17% in the low-risk VTE group (p<0.001). The positive VTE group was associated with higher mortality at 90 days (37.5% versus 10.13%, p=0.026). Conclusion: We derived a predictive score, VTE and Bleeding in Marrow Transplant (VBMT) - risk score, for both VTE and bleeding in the immediate post-transplant period (90 days), to be used in conjunction with other criteria for bleeding and thrombosis. Amongst the low-risk bleed patients, we recommend strong consideration of chemical VTE prophylaxis, especially amongst the high-risk VTE group. These risk assessment models will help stratify patients based on bleed and thrombosis risk, and ultimately help guide VTE prophylaxis and surveillance strategies amongst HSCT patients.

Paget-Schroetter syndrome in a young female patient: a case report

Paget-Schroetter syndrome in a young female patient: a case report

Ability of Caprini and Padua risk-assessment models to predict venous thromboembolism in a nationwide Veterans Affairs study

ObjectiveVenous thromboembolism (VTE) is a preventable complication of hospitalization. Risk-stratification is the cornerstone of prevention. The Caprini and Padua are two of the most commonly used risk-assessment models (RAMs) to quantify VTE risk. Both models perform well in select, high-risk cohorts. Although VTE RAMs were designed for use in all hospital admissions, they are mostly tested in select, high-risk cohorts. We aim to evaluate the two RAMs in a large, unselected cohort of patients. MethodsWe analyzed consecutive first hospital admissions of 1,252,460 unique surgical and non-surgical patients to 1298 Veterans Affairs facilities nationwide between January 2016 and December 2021. Caprini and Padua scores were generated using the Veterans Affairs’ national data repository. We determined the ability of the two RAMs to predict VTE within 90 days of admission. In secondary analyses, we evaluated prediction at 30 and 60 days, in surgical vs non-surgical patients, after excluding patients with upper extremity deep vein thrombosis, in patients hospitalized ≥72 hours, after including all-cause mortality in a composite outcome, and after accounting for prophylaxis in the predictive model. We used area under the receiver operating characteristic curves (AUCs) as the metric of prediction. ResultsA total of 330,388 (26.4%) surgical and 922,072 (73.6%) non-surgical consecutively hospitalized patients (total N = 1,252,460) were analyzed. Caprini scores ranged from 0 to 28 (median, 4; interquartile range [IQR], 3-6); Padua scores ranged from 0-13 (median, 1; IQR, 1-3). The RAMs showed good calibration and higher scores were associated with higher VTE rates. VTE developed in 35,557 patients (2.8%) within 90 days of admission. The ability of both models to predict 90-day VTE was low (AUCs: Caprini, 0.56; 95% confidence interval [CI], 0.56-0.56; Padua, 0.59; 95% CI, 0.58-0.59). Prediction remained low for surgical (Caprini, 0.54; 95% CI, 0.53-0.54; Padua, 0.56; 95% CI, 0.56-0.57) and non-surgical patients (Caprini, 0.59; 95% CI, 0.58-0.59; Padua, 0.59; 95% CI, 0.59-0.60). There was no clinically meaningful change in predictive performance in any of the sensitivity analyses. ConclusionsCaprini and Padua RAM scores have low ability to predict VTE events in a cohort of unselected consecutive hospitalizations. Improved VTE RAMs must be developed before they can be applied to a general hospital population.

A Standardised Surgical Approach for Improved Outcomes in Paget-Schroetter Syndrome: Insights From A Comprehensive Meta-Analysis

A Standardised Surgical Approach for Improved Outcomes in Paget-Schroetter Syndrome: Insights From A Comprehensive Meta-Analysis

Midline catheters in patients with advanced chronic kidney disease.

Midline catheters (midlines) are increasingly used in patients with advanced chronic kidney disease (CKD). This study describes current practice and acute complications associated with midlines in CKD patients. Trained abstractors at 66 hospitals from the Michigan Hospital Medicine Safety (HMS) Consortium collected data on a sample of patients who received a midline during hospitalization. Patients were classified as having advanced CKD if their estimated glomerular filtration rate was <45 mL/min/1.73 m2 . Midline recipients with advanced CKD were compared to those without advanced CKD by patient, provider, and device characteristics, and by the occurrence of acute complications including major (e.g., upper extremity deep vein thrombosis [UE-DVT] and catheter-related bloodstream infection [CRBSI]) or minor (e.g., catheter occlusion, catheter dislodgement, infiltration, superficial thrombophlebitis, and leaking at insertion site) events. Multivariable mixed effects logistic regression was used to evaluate the association between catheter-related complications and stage of CKD. Of 21,415 midline recipients, 5272 (24.6%) had advanced CKD, while 16,143 (75.4%) did not. Most midlines were single lumen (90.5%) and remained in place for a median of 6 days. A major or minor midline complication occurred in 804 (15.3%) patients with and 2239 (14.4%) patients without advanced CKD (adjusted odds ratios = 1.04; 95% confidence interval: 0.94-1.14). Among patients with advanced CKD, CRBSI occurred in 13 patients (0.2%) and UE-DVT occurred in 65 patients (1.2%). The proportion of advanced CKD among midline recipients and the frequency of midline-related complications varied across hospitals (interquartile range [IQR] = 19.2% to 29.8% [median = 25.0%] and IQR = 11.0%-18.9% [median = 15.4%], respectively).