Venous Thromboembolism Characteristics and Outcomes Among RIETE Patients Tested & Untested for Inherited Thrombophilia.

Inherited thrombophilia (IT) workup is commonly pursued in venous thromboembolism (VTE) patients. Recent American Society of Hematology (ASH) guidelines recommend a selective approach to IT testing, nevertheless, evidence on whether thrombophilia testing can actually improve patient-important outcomes through tailored management is limited. Data from the large prospective RIETE registry was analyzed to compare VTE risk factors, management and outcomes between patients who were tested for IT and untested patients, during anticoagulant treatment and following its discontinuation. Among 103,818 patients enrolled in RIETE, 21,089 (20.3%) were tested for IT, 8,422 (8.1%) tested positive, and 82,729 (79.7%) were not tested. IT testing was more frequent in patients with VTE provoked by minor risk factors, and less common in those with major risk factors like surgery or active cancer. Choices of anticoagulant treatment did not differ based on IT testing results. Untested patients exhibited inferior outcomes across all VTE categories, with higher rates of VTE recurrence, major bleeding, mortality, and notably, cancer-related mortality. After treatment discontinuation, IT-negative patients with surgically provoked VTE showed lower recurrence rates. For immobilization-related VTE as well as in estrogen-related VTE, no significant differences in recurrence rates were observed between IT-negative and IT-positive patients. However IT-negative patients with pregnancy or postpartum-related VTE, had significantly lower recurrence rates. Patients with unprovoked VTE, particularly those testing positive for IT, had high recurrence rates post-treatment. These findings underscore the complex role of IT testing in managing VTE, supporting personalized treatment strategies that consider VTE risk factors and comorbidities.

Pediatric splenic infarction: Assessment of associated clinical conditions and outcome.

Pediatric splenic infarction (SI) is rare yet clinically significant. Publications regarding this complication are mostly limited to case reports. This is a retrospective study examining SI etiology, clinical presentation, management, and outcomes among children. Twenty-two patients (median age: 7.9 years) were included, mostly with pre-existing hematological diseases. Splenomegaly (72%), thrombocytopenia, and anemia were common. Most of the patients did not receive antithrombotic therapy yet only two patients experienced recurrences. During follow up 36% of patients died, however no fatalities were attributed to thrombotic or bleeding complications.

Outcomes of venous thromboembolism in patients with inherited thrombophilia treated with direct oral anticoagulants: insights from the RIETE registry.

While direct oral anticoagulants (DOACs) are frequently used to treat venous thromboembolism (VTE), the outcomes of patients with inherited thrombophilia (IT) receiving DOACs for VTE remain understudied. We used data from the international RIETE registry to compare the rates of VTE recurrences, major bleeding, and mortality during anticoagulant treatment in VTE patients with and without IT, grouped by the use of DOACs or standard anticoagulant therapy. Among 103,818 enrolled patients, 21,089 (20.3%) were tested for IT, of whom 8422 (39.9%) tested positive: Protein C deficiency 294, Protein S deficiency 726, Antithrombin deficiency 240, Factor V Leiden 2248, Prothrombin gene mutation 1434, combined IT 3480. Overall, 14,189 RIETE patients (6.2% with IT) received DOACs, and 89,629 standard anticoagulation (8.4% with IT), mostly with heparins followed by vitamin K antagonists. Proportions of patients receiving DOACs did not differ between IT-positive and IT-negative patients. Rates of VTE recurrence on anticoagulant treatment were highest in patients with AT deficiency (P < 0.01). Rates of on-treatment major bleeding and all-cause mortality were lowest among patients with Factor V Leiden (FVL) or PT G20210A mutations, compared with patients who tested negative. Patients with IT who received DOACs had lower rates of major bleeding than those receiving standard anticoagulation. Excluding FVL and Protein S deficiency, patients with IT had lower rates of VTE recurrence with DOACs than with standard anticoagulation. DOACs are equally safe and effective in VTE patients with IT, with lower bleeding rates than those on standard anticoagulation.

Emicizumab prophylaxis in infants: Single-centre experience.

The hallmark of haemophilia A (HA) therapy is prophylaxis, aimed at spontaneous bleeding prevention. Emicizumab provides a viable alternative to intravenous factor replacement therapy. However, data on its use in infants are limited. This single-centre open arm prospective study reports on emicizumab prophylaxis in infants. We included severe HA patients under 1 year who started emicizumab prophylaxis since 2018, with longitudinal follow-up. The study collected data on demographics, clinical and laboratory variables, the occurrence of bleeding events, surgeries and treatment outcomes. Of the 27 enrolled infants, whose median age at prophylaxis initiation was 7 months, 24 primarily choose to start emicizumab therapy (3/27 switched from FVIII prophylaxis due to development of FVIII inhibitors). The median age for prophylaxis initiation decreased to 3 months in 2023. Following emicizumab initiation, the median calculated ABR decreased, and no intracranial haemorrhages were observed. Thrombin generation showed a significant improvement in peak height and endogenous thrombin potential at steady state after a loading period. Our study highlights a shift towards early prophylaxis in the era of non-replacement therapies. It underscores the need for continuous evaluation and refinement of treatment approaches, emphasizing personalized care and diligent monitoring in the evolving field of paediatric haemophilia care.

Cancer-associated splanchnic vein thrombosis: Clinical implications and management considerations.

Splanchnic vein thrombosis (SVT), a thrombosis which involves the portal, mesenteric, and splenic veins, and the Budd-Chiari syndrome, represents an uncommon type of venous thromboembolism (VTE). Like with deep vein thrombosis of the lower extremities and pulmonary embolism, ample evidence suggests a significant association between SVT and cancer, particularly intra-abdominal solid malignancies (e.g. hepatobiliary and pancreatic cancers) and myeloproliferative neoplasms (MPN). Clinical symptoms of SVT in cancer patients can be ambiguous, and frequently attributed to the primary cancer itself. Alternatively, SVT may be asymptomatic and detected incidentally during cancer staging or follow-up evaluations. SVT can also precede the diagnosis of cancer and has been associated with poorer outcomes in patients with liver or pancreatic cancers. Therefore, an unprovoked SVT warrants a thorough evaluation for an underlying malignancy or MPN. Cancer-associated SVT carries a high risk of VTE extension, recurrence and bleeding. Extended anticoagulant treatment is often required in the absence of a high bleeding risk. Guidelines suggest treatment with either low molecular weight heparin (LMWH) or direct oral anticoagulants (DOACs), although available data on the safety and effectiveness of DOACs in these patients is limited. This comprehensive review outlines the epidemiology, pathogenesis, risk factors, and diagnosis of cancer-associated SVT and underscores the importance of comprehensive patient evaluation and evidence-based management.

Bleeding phenotype and hemostatic evaluation by thrombin generation in children with Noonan syndrome: A prospective study.

BACKGROUND: This study aimed to evaluate the bleeding phenotype and to conduct a comprehensive hemostatic evaluation in individuals with Noonan syndrome (NS), a dominantly inherited disorder caused by pathogenic variants in genes associated with the Ras/MAPK signaling pathway. METHODS: Children with a genetically confirmed diagnosis of NS underwent clinical evaluation, routine laboratory tests, platelet function testing, and thrombin generation (TG) assessment. RESULTS: The study included 24 children. The most frequently reported bleeding symptoms were easy bruising and epistaxis, while bleeding complications were observed in 15% of surgical procedures. Various hemostatic abnormalities were identified, including platelet dysfunction, von Willebrand disease, and clotting factor deficiencies. Abnormal platelet function was observed in 50% of the patients, and significantly lower TG parameters were found compared to controls. However, no significant correlation was observed between bleeding symptoms and TG results. CONCLUSIONS: The study suggests that the bleeding diathesis in NS is multifactorial, involving both platelet dysfunction and deficiencies of plasma coagulation factors. The potential role of TG assay as an ancillary tool for predicting bleeding tendencies in individuals with NS undergoing surgery warrants further investigation.

Management of surgery in persons with hemophilia A receiving emicizumab prophylaxis: data from a national hemophilia treatment center.

Background: Persons with hemophilia A may require surgical procedures. Real-world data on invasive procedures in persons with hemophilia A receiving emicizumab prophylaxis are limited. Objectives: To evaluate the safety of invasive procedures in persons with hemophilia A receiving emicizumab prophylaxis and their outcomes in a longitudinally followed cohort. Methods: Data from medical records of persons with hemophilia A with and without factor VIII (FVIII) inhibitors longitudinally followed at our tertiary center, who received emicizumab prophylaxis and underwent all types of invasive procedures, were retrieved. Outcomes of interest were bleeding and thrombotic complications. Results: Overall, 35 patients underwent 56 invasive procedures, 18 (32.1%) were major. The median age was 36.3 years (IQR, 8.8-55.9 years); 12 patients (34.3%) were younger than 18 years at the time of procedure; 17 (48.6%) were patients with FVIII inhibitors. Among major procedures, orthopedic surgeries prevailed. All patients who underwent major procedures received factor replacement with either recombinant activated factor VII (patients with inhibitors) or FVIII (patients without inhibitors). Factor concentrates were administered prior to 32 (84.2%) of the minor procedures. Repeated doses were given according to international expert opinion recommendations and patients' condition.There were 7 bleeding events in 6 patients, 5 were major bleeds, including 1 patient who underwent a minor procedure without factor replacement. None of the patients experienced a thrombotic complication. Conclusion: Invasive procedures can be performed safely in patients receiving emicizumab prophylaxis with close surveillance after surgery. Factor concentrates may be advised in selected patients undergoing minor procedures.

Factor VIII inhibitors in hemophilia A treated with emicizumab: longitudinal follow-up of outcomes.

Background: Using emicizumab in lieu of immune tolerance induction (ITI) for patients with hemophilia A (HA) and factor (F)VIII inhibitors has been well described. However, decisions regarding ITI initiation, regimen, and preservation of tolerance remain to be elucidated. Objectives: To study the course of FVIII inhibitors in patients with HA and a history of FVIII inhibitors receiving emicizumab prophylaxis. Methods: Patients with HA, with and without FVIII inhibitors, initiating emicizumab prophylaxis were prospectively followed up in our center. All patients with current or previous inhibitors were included in this analysis. Plasma samples for FVIII inhibitor assays were obtained every 3 to 6 months or following FVIII exposure. Patients documented annual bleeding rate and any FVIII exposure days (EDs). Results: Of 162 emicizumab-treated participants, 51 met the inclusion criteria. A decrease in annual bleeding rate was observed in all 51 participants followed up for a median of 3.3 years, with 31 breakthrough bleeding episodes reported in 22 of 51 participants. FVIII inhibitor level transiently increased following FVIII exposures in 5 of 15 failed ITI participants. Eight of 21 participants who did not undergo ITI were exposed to FVIII (1-2 EDs)), and 1 of these 8 participants demonstrated increased FVIII inhibitor levels after head trauma (following 1 ED). Among participants who underwent successful ITI, 8 of 15 patients were exposed to FVIII over a total of 13 EDs (1-2 ED(s) each) for traumatic breakthrough bleeds. In all these participants, inhibitor levels remained zero, indicating successful tolerance maintenance. Conclusion: Our longitudinal follow-up of emicizumab-treated patients with HA and FVIII inhibitors shows that occasional exposure to FVIII may induce a transient anamnestic response. Nonetheless, no FVIII inhibitor recurrence was noted following FVIII exposures in patients who underwent successful ITI.

Venous thromboembolism characteristics, treatment and outcomes in young adults: findings from the Registro Informatizado de Enfermedad TromboEmbólica registry.

BACKGROUND: Venous thromboembolism (VTE) is rare in patients aged <21 years. Young adults aged 18 to 21 years are frequently included in adult VTE studies, whereas pediatric VTE studies include patients aged up to either 18 or 21 years. The clinical characteristics of young adult patients with VTE have not been well defined. OBJECTIVES: We aimed to highlight any unique characteristics or treatment considerations that may apply to young adult patients with VTE. METHODS: Data from the prospective, international Registro Informatizado de Enfermedad TromboEmbólica registry were used. Patients were stratified into subcohorts according to age. The clinical characteristics, risk factors, management, and outcomes of young adult patients with VTE were compared with those of adolescents aged 12 to 18 years and adults aged >21 years. RESULTS: Of 104 253 Registro Informatizado de Enfermedad TromboEmbólica patients enrolled until August 2022, 234 were adolescents and 884 were young adults. Less cases of pulmonary embolism were reported in adolescents (P < .001). Estrogen use was a common risk factor, more prevalent in adolescents and young adults (P < .001), whereas active cancer and immobilization were uncommon in both. Most patients were initially treated with low-molecular-weight heparin. VTE recurrence, major bleeding, and all-cause mortality rates were comparably low among adolescents and young adults. None of the patients aged <21 years died from VTE recurrence. CONCLUSION: Young adults have some distinctive VTE risk factors. While VTE presentation may be similar among young adults and older patients, the outcomes of patients aged <21 years are more favorable.

Anticoagulant treatment for pediatric splanchnic vein thrombosis: a systematic review and meta-analysis.

BACKGROUND: The clinical characteristics of splanchnic vein thrombosis (SVT) in pediatric patients and its optimal treatment strategies are unknown. OBJECTIVES: This study aimed to assess the effectiveness and safety of anticoagulant therapy for pediatric SVT. METHODS: MEDLINE and EMBASE databases were searched up to December 2021. We included observational and interventional studies that enrolled pediatric patients with SVT and reported anticoagulant treatment and outcomes, including rates of vessel recanalization, SVT extension, venous thromboembolism (VTE) recurrence, major bleeding, and mortality. Pooled proportions of vessel recanalization were calculated with their 95% CI. RESULTS: A total of 506 pediatric patients (aged 0-18 years) across 17 observational studies were included. The majority of patients had portal vein thrombosis (n = 308, 60.8%) or Budd-Chiari syndrome (n = 175, 34.6%). Most events were triggered by transient provoking factors. Anticoagulation (heparins and vitamin K antagonists) was prescribed in 217 (42.9%) patients, and 148 (29.2%) patients underwent vascular interventions. The overall pooled proportions of vessel recanalization were 55.3% (95% CI, 34.1%-74.7%; I2 = 74.0%) among anticoagulated patients and 29.4% (95% CI, 2.6%-86.6%; I2 = 49.0%) among non-anticoagulated patients. SVT extension, major bleeding, VTE recurrence, and mortality rates were 8.9%, 3.8%, 3.5%, and 10.0%, respectively, in anticoagulated patients and 2.8%, 1.4%, 0%, and 50.3%, respectively, in non-anticoagulated patients. CONCLUSION: In pediatric SVT, anticoagulation appears to be associated with moderate recanalization rates and a low risk of major bleeding. VTE recurrence is low and comparable to that reported in pediatric patients with other types of provoked VTE.

The occurrence of thrombosis during intensive chemotherapy treatment for acute myeloid leukemia patients does not impact on long-term survival.

Venous thromboembolism (VTE) is frequently seen in acute myeloid leukemia (AML) patients and presents a significant clinical challenge. The association of VTE during intensive chemotherapy with risk models such as the Medical Research Council (MRC) cytogenetic-based assessment and the European LeukemiaNet (ELN) 2017 molecular risk model have not been rigorously evaluated. Additionally, there is a paucity of data pertaining to the long-term prognostic impact of VTE in AML patients. We performed an analysis of baseline parameters of AML patients diagnosed with VTE during intensive chemotherapy and compared them with patients without VTE. The analyzed cohort consisted of 335 newly diagnosed AML patients with a median age of 55 years. Thirty-five patients (11%) were classified as MRC favorable risk, 219 (66%) patients as intermediate risk, 58 patients (17%) as adverse risk. Per ELN 2017, 132 patients (40%) had favorable risk disease, 122 patients (36%) intermediate risk, and 80 patients (24%) had adverse risk. VTE was seen in 33 patients (9.9%), occurring mostly during induction (70%), and required catheter removal in 9 patients (28%). Baseline clinical, laboratory, molecular, and ELN 2017 parameters were not significantly different groups. However, MRC intermediate-risk group patients were significantly more likely to experience thrombosis compared to favorable risk and adverse risk patients (12.8% versus 5.7% and 1.7%, respectively; p = 0.049). Median overall survival was not significantly impacted by the diagnosis of thrombosis (3.7 years versus 2.2 years; p = 0.47). VTE is tightly associated with temporal and cytogenetic parameters in AML but does not significantly impact on long-term outcomes.

Burnout in Israeli medical students: a national survey.

INTRODUCTION: Professional burnout is characterized by loss of enthusiasm for work, cynicism, and a low sense of personal efficacy. Burnout may adversely affect medical professionalism. Burnout is common in clinicians and varying rates have been reported in medical students. No data exist regarding the prevalence of burnout among Israeli medical students. The aims of this study were to assess the rate of burnout in Israeli medical students and to identify students who were particularly susceptible to burnout. METHODS: A cross-sectional questionnaire design was employed, gathering data from medical students in all years of study across three medical schools. Burnout was measured using the Maslach Burnout Inventory Student Survey (MBI-SS), translated into Hebrew. RESULTS: Of the 2160 students in the participating medical schools, 966 (44.7%) completed MBI-SS and demographic questionnaires. The overall burnout rate was 50.6%. Multivariate logistic regression analysis yielded that female gender, age under 25, advanced year of study, studying at a specific medical school and not being a parent are all significantly correlated with higher levels of burnout. CONCLUSIONS: A high rate of burnout was found. The identification of young women who are not parents during advanced years of studies as being at-risk is important, in order to guide the development of burnout prevention interventions.

Association between Thrombin Generation and Clinical Characteristics in COVID-19 Patients.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) disease is associated with coagulopathy and an increased risk of thrombosis. An association between thrombin generation (TG) capacity, disease severity, and outcomes has not been well described. METHODS: We assessed the correlation of TG with sequential organ failure assessment (SOFA) and sepsis-induced coagulopathy (SIC) scores and clinical outcomes by analysis of plasma samples obtained from hospitalized COVID-19 patients. RESULTS: 32 patients (68.8% male), whose median age was 69 years, were assessed, of whom only 3 patients did not receive anticoagulant therapy. D-dimers were uniformly increased. During hospitalization, 2 patients suffered thrombosis, 3 experienced bleeding, and 12 died. TG parameters from anticoagulated COVID-19 patients did not significantly differ from the values obtained from non-anticoagulated healthy controls. Patients who received higher than prophylactic doses of anticoagulant therapy had increased lag time (p = 0.003), lower endogenous thrombin potential (ETP) (p = 0.037), and a reduced peak height (p = 0.006). ETP correlated with the SIC score (p = 0.038). None of the TG parameters correlated with the SOFA score or were associated with mortality. CONCLUSION: TG was not associated with disease severity among patients hospitalized with COVID-19. However, a correlation between ETP and the SIC score was noted and deserves attention.

50 Years of Pediatric Hemostasis: Knowledge, Diagnosis, and Treatment.

Studies from the past 50 years have contributed to the expanding knowledge regarding developmental hemostasis. This is a dynamic process that begins in the fetal phase and is characterized by physiological variations in platelet counts and function, and concentrations of most coagulation factors and the native coagulation inhibitors in early life, as compared with adulthood. The developmental hemostasis studies since the 1980 to 1990s established the laboratory reference values for coagulation factors. It was only a decade or two later, that thromboelastography (TEG) or (rotational thromboelastometry [ROTEM]) as well as thrombin generation studies, provided special pediatric reference values along with the ability to evaluate clot formation and lysis. In addition, global whole blood-based clotting assays provided point of care guidance for proper transfusion support to children hospitalized in intensive care units or undergoing surgery. Although uncommon, thrombosis in children and neonates is gaining increasing recognition, typically as a secondary complication in sick children. Bleeding in children, and particularly intracerebral hemorrhage in newborns, still represent a therapeutic challenge. Notably, our review will outline the advancements in understanding developmental hemostasis and its manifestations, with respect to the pathophysiology of thrombosis and bleeding complications in young children. The changes of transfusion policy and approach to thrombophilia testing during the last decade will be mentioned. Subsequently, a brief summary of the data on anticoagulant treatments in pediatric patients will be presented. Finally, we will point out the 10 most cited articles in the field of pediatric and neonatal hemostasis.

Coming soon to a pharmacy near you? FXI and FXII inhibitors to prevent or treat thromboembolism.

Anticoagulants have been in use for nearly a century for the treatment and prevention of venous and arterial thromboembolic disorders. The most dreaded complication of anticoagulant treatment is the occurrence of bleeding, which may be serious and even life-threatening. All available anticoagulants, which target either multiple coagulation factors or individual components of the tissue factor (TF) factor VIIa or the common pathways, have the potential to affect hemostasis and thus to increase bleeding risk in treated patients. While direct oral anticoagulants introduced an improvement in care for eligible patients in terms of safety, efficacy, and convenience of treatment, there remain unmet clinical needs for patients requiring anticoagulant drugs. Anticoagulant therapy is sometimes avoided for fear of hemorrhagic complications, and other patients are undertreated due to comorbidities and the perception of increased bleeding risk. Evidence suggests that the contact pathway of coagulation has a limited role in initiating physiologic in vivo coagulation and that it contributes to thrombosis more than it does to hemostasis. Because inhibition of the contact pathway is less likely to promote bleeding, it is an attractive target for the development of anticoagulants with improved safety. Preclinical and early clinical data indicate that novel agents that selectively target factor XI or factor XII can reduce venous and arterial thrombosis without an increase in bleeding complications.

Application of a clinical decision rule and laboratory assays in pediatrics: Adult heparin-induced thrombocytopenia.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is rare among pediatric patients. The diagnosis of HIT depends upon clinical decision tools to assess its pretest probability, supported by laboratory evidence of anti-platelet factor 4 (anti-PF4)/heparin antibodies. AIMS: To compare the use of the 4Ts score clinical decision tool, clinical characteristics, and laboratory findings between pediatric and adult patients with suspected HIT. METHODS: We compiled all pediatric patients in our center for whom HIT testing was performed during the years 2015-2021. These were compared with a cohort of consecutive adult patients. Laboratory diagnosis of HIT was performed with particle gel immunoassay (PaGIA) as screening test and confirmed by an automated latex-enhanced immunoturbidimetric assay (LIA) and/or by functional flow cytometry assay (FCA). RESULTS: The cohort included 34 children (under 18 years) and 105 adults. Adults mostly received heparins for thromboembolism prophylaxis and treatment (72.4%, n = 76), and were more frequently treated with low-molecular-weight heparin (LMWH). Children were mostly exposed during cardiopulmonary bypass and extracorporeal membrane oxygenation (ECMO, 61.8%, n = 21), and were more frequently treated with unfractionated heparin (UFH). Compared with adults, children had significantly higher 4Ts scores. Nevertheless, adults had a slightly higher rate of a positive diagnosis of HIT. Six out of 16 adults with confirmed HIT presented with thrombosis (37.5%), whereas all three pediatric patients with HIT presented with thrombosis (p = .087). CONCLUSIONS: 4Ts scores are higher in children compared with adult patients for whom laboratory tests for HIT were obtained. A potentially higher incidence of thrombosis in children with HIT may be attributable to the severity of underlying illness.

Anti-TFPI for hemostasis induction in patients with rare bleeding disorders, an ex vivo thrombin generation (TG) guided pilot study.

BACKGROUND: Rare bleeding disorders (RBD) are inherited coagulopathies, whose hemostatic control is based upon replacement therapy. Marstacimab (PF-06741086) is a human monoclonal IgG that targets the Kunitz2 domain of tissue factor pathway inhibitor [TFPI]. Marstacimab is currently in development for bleeding prophylaxis in patients with hemophilia. OBJECTIVES: To assess the potential impact of Marstacimab upon thrombin generation (TG) in RBD patients' plasma samples. RESULTS: Our cohort included 18 RBD patients, with severe deficiencies: 5 Von Willebrand Disease (VWD) type 3, 4 FVII, 3 FXI, 2 FXIII deficiency and 1 patient with: FX, FV + FVIII, Fibrinogen, combined vitamin K dependent factors' deficiency. Citrated samples from RBD patients were collected and spiked with Marstacimab, TG was measured by calibrated automated thrombogram. Among all patients a reduced baseline TG was observed as compared to controls. Improvement of median (lag time, peak and ETP was observed in Marstacimab spiked samples from 8 min, 99 nM, 1116 nMx min to 5.5 min, 194 nM,1614 nMx min, respectively. None of the values measured among RBD patients exceeded normal controls. CONCLUSION: These in vitro data suggest that Marstacimab may serve as a promising approach for restoring the hemostatic balance in various RBD, though potential clinical implications should be further investigated.

Management strategies and clinical outcomes in patients with inferior vena cava thrombosis: Data from GARFIELD-VTE.

BACKGROUND: Inferior vena cava (IVC) thrombosis is a rare form of venous thromboembolism (VTE). The optimal treatment strategies and outcomes are unclear in patients with this presentation. OBJECTIVE: We aimed to compare baseline characteristics, treatment patterns and 24-month outcomes in IVC thrombosis patients (n = 100) with lower extremity deep vein thrombosis (LEDVT) patients (n = 7629). METHODS: GARFIELD-VTE is a prospective, observational registry of 10 868 patients with objectively diagnosed VTE from 415 sites in 28 countries. RESULTS: IVC thrombosis patients were younger (51.9 vs. 59.8 years), more frequently had active cancer (26.0% vs. 8.9%) or history of cancer (21.0% vs. 12.2%), and less frequently had recent trauma or surgery than LEDVT patients. IVC thrombosis was more frequently treated with parenteral anticoagulants alone (35.1% vs. 15.9%), whereas patients with LEDVT more commonly received vitamin K antagonists (32.0% vs. 25.8%) or direct oral anticoagulants (49.0% vs. 35.1%). Thrombolysis (11.0% vs. 3.6%) and surgical/mechanical interventions (4.0% vs. 1.4%) were more frequent in IVC thrombosis. At 24-months, the rate per 100 person-years (95% confidence interval) of all-cause mortality was higher in patients with IVC thrombosis than LEDVT (13.28 [8.57-20.58] vs. 4.91 [4.55-5.3]); the incidence of cancer-associated mortality was comparable as was the incidence of VTE recurrence (4.11 [1.85-9.15] vs. 4.18 [3.84-4.55]). Major bleeding was slightly higher in IVC thrombosis (2.03 [0.66-6.31] vs. 1.66 [1.45-1.89]). CONCLUSION: In summary, IVC thrombosis patients have higher all-cause mortality rates than those with LEDVT, a finding only partly attributable to malignancy.

The Prognostic Role of Neutrophil-to-Lymphocyte Ratio in Patients Hospitalized with Acute Pulmonary Embolism.

Early risk stratification is essential for determining the appropriate therapeutic management approach of pulmonary embolism (PE). This study aimed to evaluate the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in patients hospitalized with acute pulmonary embolism by investigating its association with mortality in a large-scale population diagnosed and hospitalized with acute PE. We retrieved all consecutive patients hospitalized in an internal medicine department or an intensive care unit in a tertiary medical center from December 2007 to April 2021 with a discharge diagnosis of pulmonary embolism. A total of 2072 patients were included. Patients with above-median NLR (i.e., 5.12) had a higher 30-day mortality risk (adjusted odds ratio (aOR), 2.82; 95% confidence interval (CI) 2.14-3.70) and higher one-year mortality risk (aOR, 2.51; 95% CI 2.04-3.08). Similar trends were demonstrated in a sub-analysis of patients without cancer and hemodynamically stable (i.e., systolic blood pressure over 90 mmHg). Furthermore, the median hospital length of stay in patients with an elevated NLR was higher, and so was the in-hospital mortality rate. Elevated NLR in acute PE is associated with a worse short-term and long-term prognosis and with a longer duration of hospitalization.

Cancer-Associated Splanchnic Vein Thrombosis.

Splanchnic vein thrombosis (SVT), which includes portal, mesenteric, and splenic vein thrombosis and the Budd-Chiari syndrome, is an infrequent manifestation of venous thromboembolism (VTE). Like typical site VTE, SVT is also frequently associated with cancer, particularly intra-abdominal solid malignancies and myeloproliferative neoplasms (MPNs). The clinical presentation of SVT is nonspecific. Symptoms may be related to the underlying malignancy, and thrombosis is incidentally diagnosed by imaging studies for cancer staging or follow-up in a substantial proportion of cases. The occurrence of SVT predicts worse prognosis in patients with liver or pancreatic cancer and, not uncommonly, SVT may precede the diagnosis of cancer. Therefore, the occurrence of an apparently unprovoked SVT should prompt careful patient evaluation for the presence of an underlying malignancy or MPN. Cancer patients carry a high risk of VTE extension and recurrence and long-term anticoagulant treatment is suggested in the absence of high risk of bleeding. Either LMWH or direct oral anticoagulants (DOACs) are suggested for the treatment of patients with cancer-related SVT, although limited experience is available on the use of DOACs in these settings. Vitamin K antagonists (VKAs) are suggested for the short and long-term treatment of SVT associated with MPN. This review outlines the epidemiological aspects, pathogenesis, risk factors, and diagnosis of cancer-associated SVT, and addresses questions regarding the management of this challenging condition.