Thromboelastography characteristics in critically ill patients with liver disease.

OBJECTIVE: The purpose of this study was to determine how thromboelastography (TEG) parameters differ by various clinical conditions that commonly occur in patients with cirrhosis, including sepsis, acute on chronic liver failure (ACLF), alcohol-associated hepatitis (AAH) and portal vein thrombosis (PVT). BACKGROUND: TEG, a whole blood assay, is used to assess several parameters of coagulation and is becoming increasingly used in clinical practice. STUDY: This study was a retrospective chart review of 155 patients admitted to the ICU with decompensated cirrhosis from 2017 to 2019. RESULTS: The R time was significantly shorter in patients when they were septic compared to when they were not and longer in patients with vs. without ACLF grade 3. Alpha angle and maximum amplitude was decreased in patients with severe AAH compared to those without severe AAH; and maximum amplitude was increased in patients with acute PVT compared to those with chronic PVT. R time was positively correlated with Chronic Liver Failure Consortium Organ Failure and Chronic Liver Failure Consortium ACLF scores (rho = 0.22, P = 0.020), while alpha angle and maximum amplitude were negatively correlated with MELD-NA. CONCLUSION: Findings suggest TEG parameters vary in several clinical conditions in patients with decompensated cirrhosis who are admitted to the ICU. Prospective research is needed to confirm our findings and to determine how this knowledge can be used to guide clinical practice, as well as blood product transfusions in the setting of bleeding or prior to invasive procedures.

Recombinant von Willebrand factor and tranexamic acid for heavy menstrual bleeding in patients with mild and moderate von Willebrand disease in the USA (VWDMin): a phase 3, open-label, randomised, crossover trial.

BACKGROUND: Heavy menstrual bleeding occurs in 80% of women with von Willebrand disease and is associated with iron deficiency and poor response to current therapies. International guidelines indicate low certainty regarding effectiveness of hormonal therapy and tranexamic acid. Although von Willebrand factor (VWF) concentrate is approved for bleeds, no prospective trials guide its use in heavy menstrual bleeding. We aimed to compare recombinant VWF with tranexamic acid for reducing heavy menstrual bleeding in patients with von Willebrand disease. METHODS: VWDMin, a phase 3, open-label, randomised crossover trial, was done in 13 haemophilia treatment centres in the USA. Female patients aged 13-45 years with mild or moderate von Willebrand disease, defined as VWF ristocetin cofactor less than 0·50 IU/mL, and heavy menstrual bleeding, defined as a pictorial blood assessment chart (PBAC) score more than 100 in one of the past two cycles were eligible for enrolment. Participants were randomly assigned (1:1) to two consecutive cycles each of intravenous recombinant VWF, 40 IU/kg over 5-10 min on day 1, and oral tranexamic acid 1300 mg three times daily on days 1-5, the order determined by randomisation. The primary outcome was a 40-point reduction in PBAC score by day 5 after two cycles of treatment. Efficacy and safety were analysed in all patients with any post-baseline PBAC scores. The trial was stopped early due to slow recruitment on Feb 15, 2022, by a data safety monitoring board request, and was registered at ClinicalTrials.gov, NCT02606045. FINDINGS: Between Feb 12, 2019, and Nov 16, 2021, 39 patients were enrolled, 36 of whom completed the trial (17 received recombinant VWF then tranexamic acid and 19 received tranexamic acid then recombinant VWF). At the time of this unplanned interim analysis (data cutoff Jan 27, 2022), median follow-up was 23·97 weeks (IQR 21·81-28·14). The primary endpoint was not met, neither treatment corrected PBAC score to the normal range. Median PBAC score was significantly lower after two cycles with tranexamic acid than with recombinant VWF (146 [95% CI 117-199] vs 213 [152-298]; adjusted mean treatment difference 46 [95% CI 2-90]; p=0·039). There were no serious adverse events or treatment-related deaths and no grade 3-4 adverse events. The most common grade 1-2 adverse events were mucosal bleeding (four [6%] patients during tranexamic acid treatment vs zero during recombinant VWF treatment) and other bleeding (four [6%] vs two [3%]). INTERPRETATION: These interim data suggest that recombinant VWF is not superior to tranexamic acid in reducing heavy menstrual bleeding in patients with mild or moderate von Willebrand disease. These findings support discussion of treatment options for heavy menstrual bleeding with patients based on their preferences and lived experience. FUNDING: National Heart Lung Blood Institute (National Institutes of Health).

Building a CAT clinic - real-world systems approaches to prevention and treatment.

Cancer patients have an increased risk of developing venous thrombosis. The implementation of a cancer associated thrombosis clinic can be instrumental for the prevention, early recognition, and management of venous thromboembolism in this vulnerable population. Cancer thrombosis clinics rely on a multidisciplinary approach to care and require standardization along with a dedicated team of healthcare professionals. Cancer thrombosis clinics have the potential to improve patient outcomes and lower healthcare expenditure. Herein, we describe a successful model of a cancer thrombosis clinic and highlight the potential impact on clinical outcomes.

Thromboembolism in Patients with Metastatic Urothelial Cancer Treated with Immune Checkpoint Inhibitors.

BACKGROUND: Immunotherapy has become one of the mainstays for metastatic urothelial carcinoma treatment. Whether immune checkpoint inhibitor therapy increases thromboembolism (TE) risk is unknown. OBJECTIVE: We investigated the incidence of arterial thromboembolism (ATE) and venous thromboembolism (VTE) events and its associated outcomes in patients with metastatic urothelial cancer treated with immune checkpoint inhibitors. METHODS: Patients with urothelial cancer treated with immune checkpoint inhibitors at the Cleveland Clinic from 1/1/2015 to 12/31/2019 were identified. The Kaplan-Meier method estimated overall survival and Cox proportional hazards regression evaluated the impact of TE on overall survival. RESULTS: Of 279 patients, 72% were men with pure urothelial cancer (62%) who started atezolizumab (40%), nivolumab (3%), or pembrolizumab (57%). At a median follow-up of 5.6 months (range 0.3-51.6), 42 patients developed a TE (VTE n = 37, 13%, ATE n = 5, 2%). The cumulative incidence of TE after immune checkpoint inhibitor therapy was 9.1% (95% confidence interval 6.0-13.0) at 6 months and 13.6% (95% confidence interval 9.6-18.4) at 12 months. Most TE (VTE 62%, ATE 100%) occurred within 6 months of immune checkpoint inhibitor initiation (median doses 5, range 1-59), and the majority (VTE 81%, ATE 100%) resulted in hospitalization (median: 5 days, 4 days, respectively). Thromboembolism (hazard ratio 2.296, p = 0.0004), Bajorin score 1 or 2 (hazard ratio 1.490, p = 0.0315), and Bajorin score 2 (hazard ratio 3.50, p < 0.0001) were associated with worse overall survival. CONCLUSIONS: Immune checkpoint inhibitors are associated with a high TE risk. Thromboembolism is associated with worsened survival, among other poor outcomes. Further investigation into the mechanism behind immune checkpoint inhibitor-associated TE is needed.

COVID-19 and venous thromboembolism: A narrative review.

COVID-19 (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) is associated with coagulopathy through numerous mechanisms. The reported incidence of venous thromboembolism (VTE) in hospitalized patients with COVID-19 has varied widely, and several meta-analyses have been performed to assess the overall prevalence of VTE. The novelty of this coronavirus strain along with its unique mechanisms for microvascular and macrovascular thrombosis has led to uncertainty as to how to diagnose, prevent, and treat thrombosis in patients affected by this virus. This review discusses the epidemiology and pathophysiology of thrombosis in the setting of SARS-CoV-2 infection along with an updated review on the preventative and treatment strategies for VTE associated with SARS-CoV-2 infection.

Updated guidelines for immune thrombocytopenic purpura: Expanded management options.

The current American Society of Hematology (ASH) guidelines for the management of patients with immune thrombocytopenic purpura (ITP) are an update to the 2011 guidelines. The updates focus on treating patients with ITP without bleeding in both outpatient and inpatient settings, including those with newly diagnosed, persistent, and chronic ITP refractory to first-line therapy. Recommendations for therapy include corticosteroids, intravenous immunoglobulins, anti-D immunoglobulin, rituximab, splenectomy, and thrombopoietin-receptor agonists, as well as observation.

Building a CAT clinic - real-world systems approaches to prevention and treatment.

Cancer patients have an increased risk of developing venous thrombosis. The implementation of a cancer associated thrombosis clinic can be instrumental for the prevention, early recognition, and management of venous thromboembolism in this vulnerable population. Cancer thrombosis clinics rely on a multidisciplinary approach to care and require standardization along with a dedicated team of healthcare professionals. Cancer thrombosis clinics have the potential to improve patient outcomes and lower healthcare expenditure. Herein, we describe a successful model of a cancer thrombosis clinic and highlight the potential impact on clinical outcomes.

Thromboembolism in Patients with Metastatic Renal Cell Carcinoma Treated with Immunotherapy.

BACKGROUND: Metastatic renal cell carcinoma (mRCC) is associated with a high risk of thromboembolism (TE). OBJECTIVE: We investigated whether immunotherapy (IO) increases the hypercoagulable state in this high-risk population. PATIENTS AND METHODS: Patients with mRCC treated with IO between 1 January 2015 and 31 December 2019 at the Cleveland Clinic were identified. Cumulative incidence analysis calculated TE rates over time and Gray's test determined differences in TE rates among groups. The Kaplan-Meier method estimated survival, while Cox proportional hazard regression evaluated the impact of TE on OS. RESULTS: Of 351 patients, 75% were men with clear cell mRCC (81%) and International Metastatic Renal Cell Carcinoma (IMDC) intermediate- to poor-risk disease (77%). Patients received single-agent IO (52%), doublet IO (31%), or IO with non-IO therapy (17%). The median number of IO doses was 8 (range 1-81). At a median follow-up of 12.8 months, 12% of patients (n = 43) had a TE event (venous n = 37 [11%], arterial n = 6 [2%]). The cumulative TE incidence at 6 months was 4.4% (95% confidence interval [CI] 2.6-6.9) and 9.8% (95% CI 6.8-13.4) at 12 months. No factors, including IMDC or Khorana score, were identified to predict TE development. Seventy-two percent of TE resulted in hospitalization (9% TE-related mortality and 21% TE-related dose delay). TE (p < 0.0001), poor IMDC score (p < 0.0001), and Khorana score ≥ 2 (p < 0.0001) were associated with worse OS. CONCLUSIONS: Patients with mRCC treated with IO had a high incidence of TE. TE was associated with risk of treatment delay, hospitalization, and mortality, while TE, IMDC poor risk, and Khorana score ≥ 2 were associated with worse survival. Further investigations into IO-associated TE are needed to identify benefit from primary thromboprophylaxis.

Patients with advanced renal cell carcinoma carry an increased risk of clotting, both in their arteries and veins. Historically, risk scores such as the Khorana score were used to assess which patients with solid tumors would benefit from preventative blood thinning medications as they undergo chemotherapy. Whether the Khorana score can be applied to use with immunotherapy is not known. Currently, limited knowledge exists of the impact of immunotherapy on additional clotting in patients with renal cell carcinoma. This study shows an increased incidence of clotting under immunotherapy treatment in patients with advanced renal cancer compared with rates seen in the literature. This study highlights an associated risk of hospitalization, need to stop cancer therapy, as well as risk of death from clotting. Additionally, we determine that clotting, poor disease pathology (as assessed by the International Metastatic Renal Cell Carcinoma Database Consortium), and a Khorana score of ≥2 are predictors of a worse overall survival. This information will be useful in future studies that will address the usefulness of preventative blood thinner medications in this high-risk population.

Polyphosphate expression by cancer cell extracellular vesicles mediates binding of factor XII and contact activation.

Extracellular vesicles (EV) have been implicated in diverse biological processes, including intracellular communication, transport of nucleic acids, and regulation of vascular function. Levels of EVs are elevated in cancer, and studies suggest that EV may stimulate thrombosis in patients with cancer through expression of tissue factor. However, limited data also implicate EV in the activation of the contact pathway of coagulation through activation of factor XII (FXII) to FXIIa. To better define the ability of EV to initiate contact activation, we compared the ability of EV derived from different cancer cell lines to activate FXII. EV from all cell lines activated FXII, with those derived from pancreatic and lung cancer cell lines demonstrating the most potent activity. Concordant with the activation of FXII, EV induced the cleavage of high molecular weight kininogen (HK) to cleaved kininogen. We also observed that EVs from patients with cancer stimulated FXII activation and HK cleavage. To define the mechanisms of FXII activation by EV, EV were treated with calf intestinal alkaline phosphatase or Escherichia coli exopolyphosphatase to degrade polyphosphate; this treatment blocked binding of FXII to EVs and the ability of EV to mediate FXII activation. In vivo, EV induced pulmonary thrombosis in wild-type mice, with protection conferred by a deficiency in FXII, HK, or prekallikrein. Moreover, pretreatment of EVs with calf intestinal alkaline phosphatase inhibited their prothrombotic effect. These results indicate that polyphosphate mediates the binding of contact factors to EV and that EV-associated polyphosphate may contribute to the prothrombotic effects of EV in cancer.

Cancer-Associated Venous Thromboembolic Disease, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology.

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Cancer-Associated Venous Thromboembolic Disease focus on the prevention, diagnosis, and treatment of patients with cancer who have developed or who are at risk for developing venous thromboembolism (VTE). VTE is a significant concern among cancer patients, who are at heightened risks for developing as well as dying from the disease. The management of patients with cancer with VTE often requires multidisciplinary efforts at treating institutions. The NCCN panel comprises specialists from various fields: cardiology, hematology/hematologic oncology, internal medicine, interventional radiology, medical oncology, pharmacology/pharmacy, and surgery/surgical oncology. This article focuses on VTE prophylaxis for medical and surgical oncology inpatients and outpatients, and discusses risk factors for VTE development, risk assessment tools, as well as management methods, including pharmacological and mechanical prophylactics. Contraindications to therapeutic interventions and special dosing, when required, are also discussed.

Validation of the IMPEDE VTE score for prediction of venous thromboembolism in multiple myeloma: a retrospective cohort study.

The IMPEDE VTE score has recently emerged as a novel risk prediction tool for venous thromboembolism (VTE) in multiple myeloma (MM). We retrospectively reviewed 839 patients with newly diagnosed MM between 2010 and 2015 at Cleveland Clinic and included 575 patients in final analysis to validate this score. The c-statistic of the IMPEDE VTE score to predict VTE within 6 months of treatment start was 0·68 (95% CI: 0·61-0·75). The 6-month cumulative incidence of VTE was 5·0% (95% CI: 2·1-7·9) in the low risk group, compared to 12·6% (95% CI: 8·9-16·4%) and 24·1% (95% CI: 12·2-36·1) in the intermediate and high risk groups (P < 0·001 for both). In addition, a higher proportion of patients in the VTE cohort had ECOG performance status of ≥2 as compared to the no VTE cohort (33% vs. 16%, P = 0·001). Other MM characteristics such as stage, immunoglobulin subtype, and cytogenetics were not predictors of VTE. In summary, we have validated the IMPEDE VTE score in our patient cohort and our findings suggest that it can be utilized as a VTE risk stratification tool in prospective studies looking into investigating VTE prophylaxis strategies in MM patients.

Use of GMI-1271, an E-selectin antagonist, in healthy subjects and in 2 patients with calf vein thrombosis.

BACKGROUND: There is an unmet need for antithrombotic treatments for venous thromboembolic disease that do not increase bleeding risk. Selectins are cell adhesion molecules that augment thrombosis by activating immune cells to initiate the coagulation cascade. GMI-1271, a potent small-molecule E-selectin antagonist, has been shown in mouse models to decrease thrombus burden with a low risk of bleeding. METHODS: A first-in-human study of GMI-1271 was conducted to assess its safety, tolerability, and pharmacokinetic (PK) profile. As a secondary end point, biomarkers of coagulation, cell adhesion, and leukocyte/platelet activation were evaluated. Aims 1 and 2 were performed in healthy volunteers and evaluated single and multiple doses of the study drug, respectively. Aim 3 included 2 patients with isolated calf-level deep vein thrombosis (DVT). RESULTS: GMI-1271 showed consistent PK parameters for doses ranging from 2 to 40 mg/kg. Plasma levels increased in a linear manner with respect to dose, while clearance, volume of distribution, and half-life were not dose dependent. No accumulation was seen with multiple consecutive doses. No serious adverse events (grade 3 or 4) were reported. Biomarker analysis demonstrated a trend in reduction of soluble E-selectin (sEsel) levels with GMI-1271 exposure, while exposure did not impact laboratory testing of coagulation. Two patients with calf vein DVT were treated with GMI-1271 and demonstrated rapid improvement of symptoms after 48 hours, with repeat ultrasound showing signs of clot resolution. CONCLUSIONS: We demonstrate that GMI-1271 is safe in healthy volunteers and provide proof of concept that an E-selectin antagonist is a potential therapeutic approach to treat venous thrombosis.

Clinical outcomes of isolated distal deep vein thrombosis versus proximal venous thromboembolism in cancer patients: The Cleveland Clinic experience.

BACKGROUND: Previous studies suggest isolated distal deep vein thrombosis (IDDVT) has a self-limited clinical course. However, these studies excluded cancer patients, who remain a high-risk population. In addition, studies to evaluate the long-term clinical outcomes of IDDVT in cancer patients have been limited. Here, we report outcomes from our experience in treating cancer-associated IDDVT versus proximal venous thromboembolism (VTE). METHODS: We prospectively evaluated a cohort of patients referred to our cancer-associated thrombosis clinic from August 2014 through May 2018. We compared clinical characteristics, anticoagulation prescription, VTE recurrence, overall survival, major bleeding, and subsequent hospital admission between cancer patients with IDDVT and proximal VTE. A propensity score matching method was used to reduce bias from confounding variables. RESULTS: Of 1100 patients referred to the clinic, 124 IDDVT and 178 proximal VTE events were analyzed. After propensity score matching, 96 patients were included in each cohort. There was no difference in the rate of recurrent VTE between cancer patients with proximal VTE vs IDDVT, with or without matching (matched: hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.31-1.92; P = .58). There was no difference in overall survival between cancer patients with proximal VTE vs. IDDVT with or without matching (matched: HR, 1.18; 95% CI, 0.77-1.82; P = .45). Furthermore, subsequent hospital admissions and major bleeding events were similar between patients with proximal VTE events versus IDDVT. CONCLUSIONS: Cancer patients with IDDVT have similar outcomes as their proximal counterparts, including rate of recurrence and overall survival. These findings suggest treatment of cancer-associated IDDVT should mirror treatment of proximal events.

Implementation of an electronic medical record tool for early detection of deep vein thrombosis in the ambulatory oncology setting.

BACKGROUND: Venous thromboembolism (VTE) is a major cause of morbidity, mortality, and hospitalization in cancer patients. OBJECTIVES: To evaluate the feasibility of an electronic alert to identify and screen at-risk individuals and gather rates of early detection of deep vein thrombosis (DVT). PATIENTS/METHODS: An alert was built into the electronic medical record based on a validated risk tool (Khorana Score [KS]) and outcomes evaluated in an initial silent phase. The alert functioned in real time to warn physicians of high-risk patients (KS ≥ 3) and suggested lower extremity screening ultrasonography in a subsequent active phase. RESULTS: Of 194 consecutive patients identified as high risk in the silent phase, 14 (7.2%) developed subsequent DVT or pulmonary embolism (PE) over 90-day follow-up, with a median of 27 days. Mean 90-day emergency room (ER) visits, all-cause admissions, and length of stay (days) for patients with DVT were 1.2, 1.6, and 9.1 compared to 0.89, 0.93, and 5.1 for all patients, respectively. In the active phase, 197 consecutive alerts met inclusion criteria, and 40 patients (20.3%) received a screening ultrasound. Five (12.5%) had a DVT and were started on therapeutic anticoagulation. Of patients with alerts who had screening deferred, 13 (8.3%) were later diagnosed with DVT (median 50.5 days) and 7 (4.5%) with PE. CONCLUSION: An automated alert may have value in early detection of DVT in high-risk cancer patients leading to earlier intervention, and could potentially prevent VTE-related morbidity.

Bleeding incidence and risk factors among cancer patients treated with anticoagulation.

Compared to age-matched controls, cancer patients have increased risk of bleeding when treated with anticoagulation. However, there are little data regarding bleeding as it relates to anticoagulant choice and other risk factors. We evaluated the six-month incidence of bleeding among patients treated with anticoagulation who had bleeding risk factors. Data were obtained from Explorys (IBM Watson, Inc.), which pools data from multiple US healthcare organizations. Cohorts of patients were created to compare bleeding events between cancer and non-cancer patients treated with anticoagulation within six months of starting anticoagulation. Potential bleeding risk factors such as cancer type, metastatic disease, obesity, chronic kidney disease stage III or higher, and platelet count were evaluated. We compared ratios of numbers of patients in specific cohorts using chi-squared tests with continuity correction. The cohort comprised 3 283 140 cancer patients, of whom 435 140 (13.3%) received anticoagulation within six months of their cancer diagnosis. Bleeding incidence was higher in cancer vs non-cancer patients across all anticoagulants studied: warfarin 20.2% vs 12.6%, rivaroxaban 16.7% vs 12.1%, LMWH 13.2% vs 9.7%, and apixaban 14.5% vs 9.3%, P < .001 for all comparisons. Among all anticoagulants except warfarin, we found increased bleeding incidence in cancer patients with metastatic disease, gastrointestinal primary, CKD ≥ stage III, and platelets <100,000 × 109 /L. Bleeding incidence was higher in cancer patients regardless of the anticoagulant used. Patients with gastrointestinal malignancies had a higher incidence of bleeding compared to other tumors across all anticoagulants. Other factors associated with increased risk of bleeding included metastatic disease, chronic kidney disease, and thrombocytopenia.

NCCN Guidelines Insights: Cancer-Associated Venous Thromboembolic Disease, Version 2.2018.

Venous thromboembolism (VTE) is common in patients with cancer and increases morbidity and mortality. VTE prevention and treatment are more complex in patients with cancer. The NCCN Guidelines for Cancer-Associated Venous Thromboembolic Disease outline strategies for treatment and prevention of VTE in adult patients diagnosed with cancer or in whom cancer is clinically suspected. These NCCN Guidelines Insights explain recent changes in anticoagulants recommended for the treatment of cancer-associated VTE.

New Diagnosis of G6PD Deficiency Presenting as Severe Rhabdomyolysis.

A 24-year-old African-American man presented with malaise and low back pain and was found to have acute severe rhabdomyolysis followed by acute hemolysis. Glucose-6-phosphate dehydrogenase (G6PD) deficiency was suspected by the presence of blister cells on peripheral smear and was confirmed by a low enzyme activity assay. Our patient reported playing football, along with upper respiratory infection symptoms, prior to presentation. Extensive infectious and toxicology workup was negative; however, several inflammatory proteins were markedly elevated. We hypothesized the large inflammatory burden led to an increased reactive oxygen radical burden that overwhelmed muscle and erythrocyte reducing power. Severe rhabdomyolysis in G6PD deficiency is not a common presentation because skeletal muscles are more resistant to oxidative damage compared to red blood cells. Our case adds to the few existing reports of myolysis in the setting of G6PD deficiency.

Risk of Hematologic Malignancies After Radioiodine Treatment of Well-Differentiated Thyroid Cancer.

Purpose To investigate the risk and outcomes of second hematologic malignancies (SHMs) in a population-based cohort of patients with well-differentiated thyroid cancer (WDTC) treated or not with radioactive iodine (RAI). Methods Patients with WDTC were identified from SEER registries. Competing risk regression analysis was performed to calculate the risks of SHMs that occurred after WDTC treatment and outcomes after SHM development were assessed. Results Of 148,215 patients with WDTC, 53% received surgery alone and 47% received RAI. In total, 783 patients developed an SHM after a median interval of 6.5 years (interquartile range, 3.3 to 11.2 years) from WDTC diagnosis. In multivariable analysis, compared with those undergoing thyroidectomy alone, RAI treatment was associated with an increased early risk of developing acute myeloid leukemia (AML; hazard ratio, 1.79; 95% CI, 1.13 to 2.82; P = .01) and chronic myeloid leukemia (CML; hazard ratio, 3.44; 95% CI, 1.87 to 6.36; P < .001). This increased risk of AML and CML after RAI treatment was seen even in low-risk and intermediate-risk WDTC tumors. Occurrence of AML but not CML in patients with WDTC was associated with shorter median overall survival compared with matched controls (8.0 years v 31.0 years; P = .001). In addition, AML developing after RAI trended toward inferior survival compared with matched controls with de novo AML (median overall survival, 1.2 years v 2.9 years; P = .06). Conclusion Patients with WDTC treated with RAI had an increased early risk of developing AML and CML but no other hematologic malignancies. AML that arises after RAI treatment has a poor prognosis. RAI use in patients with WDTC should be limited to patients with high-risk disease features, and patients with WDTC treated with adjuvant RAI should be monitored for myeloid malignancies as part of cancer surveillance.

Risk Assessment Scores for Cancer-Associated Venous Thromboembolic Disease.

Current guidelines recommend that patients with cancer be assessed for venous thromboembolism (VTE) risk at the time of chemotherapy initiation and periodically thereafter. Rates of VTE vary substantially among cancer patients. Multiple clinical factors contribute to VTE risk, including the primary site of cancer, extent of disease, interventions including major surgery, hospitalization, and systemic therapy. However, risk of VTE cannot reliably be predicted based on a single risk factor or biomarker. Within the last decade, risk assessment scores have been developed in cancer patients to more reliably predict thromboembolic events. This review provides an overview of evidence supporting the use of such tools for both primary and recurrent cancer-associated VTE. Potential applications of risk assessment tools as well as current knowledge gaps are outlined.

Aging among persons with hemophilia: contemporary concerns.

The life expectancy of persons with hemophilia (PWH) has increased almost 10-fold over the past seven decades, largely due to access to safe factor replacement products. Concomitant with this success, however, comes the burden of aging. Older PWH are developing similar comorbidities as the general population, including increasing rates of hypertension, obesity, and diabetes, which predispose them to chronic diseases such as cardiovascular disease (CVD) and chronic kidney disease (CKD). How their coagulopathy affects the expression of these conditions remains unclear. In addition, the elderly hemophilia population must cope with chronic joint arthropathy, which provokes falls and fractures, and complications related to human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections, which greatly impact the incidence of cancer and liver disease. With a dearth of evidence-based guidelines to direct therapy, a new challenge has arisen for hematologists to optimally manage these complex age-related issues. This review will focus on common complications affecting the older hemophilia population, including joint disease, CVD, malignancy, renal insufficiency, and liver disease.