Stroke Risk in Blood or Marrow Transplant (BMT) Survivors - a Report from the BMT Survivor Study (BMTSS)

BACKGROUND: BMT recipients are vulnerable to accelerated atherosclerosis due to prior exposure to radiation with or without chemotherapy, and consequent long-term cardiovascular morbidity, such as stroke. A comprehensive evaluation of the risk of late-occurring stroke in adult BMT survivors and the associated risk factors has not been performed. We addressed this gap using the resources offered by the BMTSS. METHODS: BMTSS includes patients transplanted between 1974 and 2014 at 3 US sites who survived ≥2y after BMT, were alive and ≥18y at BMTSS survey completion. The survey asked participants to report if a healthcare provider had diagnosed specific chronic health conditions (including stroke), or relapse of primary cancer or development of new cancer, along with age at diagnosis. The participants provided information on sociodemographics, health behaviors and medication use. Medical record abstraction was used for information regarding primary cancer diagnosis, therapeutic exposures (pre-BMT chemotherapy/radiation, transplant preparative regimens), stem cell source (autologous, allogeneic), graft type (bone marrow, cord blood or peripheral blood stem cells), and history of chronic graft vs. host disease (GvHD). A cohort of 908 siblings also completed the BMTSS survey and served as a comparison group. Informed consent was obtained from all participants. RESULTS: The study included 3,479 BMT survivors; 50.3% had received an allogeneic BMT, 54.8% were males; 71.4% were non-Hispanic whites. Median age at study participation was 59y (range: 18-89y) for BMT survivors and 57y (range: 18-90y) for siblings. Patient characteristics are shown in Table 1. BMT survivors were followed for a median of 9y (range: 2-41 y) from BMT. Stroke was reported by 136 BMT survivors (67 allogeneic, 69 autologous); of these, 75 (55%) patients developed stroke ≥2y after BMT. Conditional on surviving ≥2y after BMT, the 10y cumulative incidence of stroke was 3.8% (Fig 1), and was comparable for allogeneic (3.4±0.5%) and autologous (4.2±0.6%) BMT recipients, p=0.3. Stroke in BMT recipients compared with siblings: Using logistic regression, and after adjusting for sociodemographics, physical activity and relevant comorbidities, we found that allogeneic BMT survivors were at a 2.1-fold higher odds of reporting stroke as compared to siblings (95%CI: 1.2-3.7, p=0.01), and autologous BMT recipients were at a 1.7-fold higher odds of reporting stroke compared to siblings (95%CI: 0.9-3.0, p=0.09). Stroke after Allogeneic BMT: History of hypertension (HR=2.2, 95%CI: 1.2-3.9, p=0.007), venous thromboembolism (HR=3.4, 95%CI: 1.6-7.1, p=0.002), diagnosis of acute lymphoblastic leukemia (HR=4.9, 95%CI: 1.6-15.0, p=0.006), acute myeloid leukemia/ myelodysplastic syndrome (HR=5.2, 95%CI: 1.4-19.0, p=0.013) (ref: non Hodgkin lymphoma), pre-BMT exposure to alkylating agents (HR=3.3, 95%CI: 1.3-8.5, p=0.01) and pre-BMT neck radiation (HR=5.4, 95%CI: 1.2-23.8, p=0.03) were associated with increased stroke risk. Exercise was associated with lower stroke risk (HR: 0.5, 95%CI: 0.3-0.9, p=0.01). Stroke after Autologous BMT: The risk factors for stroke in autologous BMT survivors included: increasing age at BMT (HR=1.02/y, 95%CI: 1.0-1.1, p=0.05), history of hypertension (HR=1.8, 95%CI: 1.1-3.2, p=0.03), coronary heart disease (HR=2.8, 95%CI: 1.3-6.4, p=0.01) and venous thromboembolism (HR=2.3, 95%CI: 1.1-4.7, p=0.02). Relapse of primary disease or development of new cancer were not associated with increased stroke risk in either autologous or allogeneic BMT recipients. CONCLUSION: In this large study, we found that the incidence of stroke was 4% among BMT survivors, and that they are at an increased risk of developing stroke when compared to an unaffected comparison group. The study also identified subgroups among BMT survivors at increased risk of stroke such as those who received neck radiation and those with cardiovascular comorbidity. These findings suggest a need for increased awareness of stroke as a late complication of BMT, such that aggressive management of cardiovascular risk factors can be instituted among those at highest risk. Disclosures Weisdorf: Incyte: Research Funding; Fate Therapeutics: Consultancy; Pharmacyclics: Consultancy.

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Venous Thromboembolism in Blood or Marrow Transplant (BMT) Survivors: A Report from BMT Survivor Study (BMTSS)

Blood ◽

10.1182/blood-2018-99-111179 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 823-823

Author(s):

Radhika Gangaraju ◽

Yanjun Chen ◽

Lindsey Hageman ◽

Jessica Wu ◽

Liton F. Francisco ◽

...

Keyword(s):

Venous Thromboembolism ◽

Myeloid Leukemia ◽

Prediction Models ◽

Comparison Group ◽

Chronic Gvhd ◽

Participation Rate ◽

Self Report ◽

Allogeneic Bmt ◽

Increased Risk ◽

History Of

Abstract BACKGROUND: Patients undergoing BMT are uniquely vulnerable to venous thromboembolism (VTE) due to high-intensity therapeutic exposures, prolonged hospitalizations (and attendant immobility), a high burden of comorbidities, and the pro-inflammatory state induced by graft-versus-host disease (GvHD) in allogeneic BMT recipients. An assessment of the long-term risk of VTE in BMT survivors and subsequent cause-specific late mortality remains unstudied. We used the BMTSS to address this gap. METHODS: In patients with hematologic malignancy treated with BMT at 3 sites in US, had survived ≥2y after BMT, were alive and ≥18yo at BMTSS survey completion, we examined: i) incidence/risk factors for VTE; ii) subsequent mortality by VTE status. The survey covered sociodemographics, tobacco use, diagnosis by a healthcare provider of specific chronic health conditions, including VTE, relapse, or development of new cancer and medication use. The outcome of interest (VTE) was defined as self-report of VTE diagnosed by a health care provider, supplemented by history of anticoagulant use. BMTSS survey was administered over two time periods: i) Survey completed between 2000 and 2004: 1,022 patients transplanted between 1974 and 1998 and survived ≥2y (original BMTSS cohort; participation rate: 63%). This cohort was followed for a median of 15.1y (range: 0.04-17.9) after survey completion, to determine the association between VTE and subsequent mortality using National Death Index; ii) Survey completed between 2014 and 2017: 1,711 patients transplanted between 1974 and 2010 and survived ≥2y (expanded BMTSS cohort; participation rate: 68%) - this cohort was used to determine demographic/clinical variables associated with VTE risk. A cohort of 644 siblings also completed the survey and served as a comparison group. Human Subjects Committee at participating sites approved the protocol. RESULTS: Risk of VTE: Of the 1,711 participants, 891 (52.1%) had received an allogeneic BMT; 53.5% were males and 78.8% were non-Hispanic whites; median age at BMT was 48y. The cohort was followed for a median of 10.9y (3.8-40.6). BMT survivors were at a 2.8-fold higher risk of VTE as compared to siblings (95%CI:1.7-4.5, p<0.0001), after adjusting for sociodemographics. Conditional on surviving ≥2y after BMT, the cumulative incidence of VTE was 6.9±0.9% at 10y (Fig 1), with similar rates in autologous (6.1±1.1%) and allogeneic BMT recipients (7.5±1.5%%, p=0.5). Risk of VTE in allogeneic BMT recipients: History of chronic GvHD (HR=3.6, 95%CI:2.2-6.0, p<0.0001), primary diagnosis of acute myeloid leukemia/myelodysplasia (HR=1.9, 95%CI:1.0-3.7, p=0.05) or non-Hodgkin lymphoma (NHL) (HR=2.3, 95%CI:1.1-4.8, p=0.02) (ref: chronic myeloid leukemia), male sex (HR=1.6, 95%CI:1.0-2.6, p=0.05), and older age at BMT (HR=1.03/y, 95%CI:1.0-1.1, p=0.002), were associated with increased VTE risk. Risk of VTE in autologous BMT recipients: Diagnosis of a plasma cell disorder (HR=2.4, 95%CI: 1.3-4.2, p=0.004) (ref: NHL) and annual house hold income <$50,000 (HR=2.0, 95%CI 1.2-3.6, p=0.02) (ref: income >$50,000) were associated with increased VTE risk. Of note, relapse of primary disease or development of new cancer were not associated with increased VTE risk in either autologous or allogeneic BMT patients. Subsequent mortality: In this cohort of 1,022 BMT survivors, median age at BMT was 34.9y; 55% had received allogeneic BMT. The overall survival among patients with and without VTE was 50.4% vs. 72.3%, respectively at 15y from survey completion, p<0.0001 (Fig 2), yielding a higher risk of subsequent mortality in VTE patients when compared to those without VTE (HR=1.6, 95%CI:1.1-2.3, p=0.02) after adjusting for relevant clinical/demographic predictors, relapse of primary cancer and development of new cancer. The VTE-associated mortality risk was primarily due to non-relapse mortality (NRM: HR=1.7, 95%CI:1.1-2.5, p=0.02) and not due to relapse (HR=0.7, 95%CI, 0.2-1.8, p=0.5). Leading causes of NRM among those with VTE included infection (15.5%), cardiac (8.5%) and subsequent neoplasms (7%). CONCLUSION: BMT survivors are at a 2.8-fold increased risk of developing VTE when compared with a non-BMT sibling comparison group. Those with VTE are at an increased risk of subsequent NRM. Development of risk prediction models to identify BMT survivors at highest risk would facilitate targeted thromboprophylaxis. Disclosures Weisdorf: Equillium: Consultancy; SL Behring: Consultancy; Seattle Genetics: Consultancy; FATE: Consultancy; Pharmacyclics: Consultancy. Forman:Mustang Therapeutics: Other: Licensing Agreement, Patents & Royalties, Research Funding.

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The Risk of Stroke Using CHA2 DS2 -VASc Score in Hemodialysis Patients at a Tertiary Hospital in Riyadh, Saudi Arabia

Journal of Clinical Review & Case Reports ◽

10.33140/jcrc.04.07.01 ◽

2019 ◽

Vol 4 (7) ◽

Keyword(s):

Risk Factors ◽

High Risk ◽

Stroke Risk ◽

Hemodialysis Patients ◽

Low Risk ◽

High Risk Patients ◽

Stroke Risk Factors ◽

Increased Risk ◽

Risk Patients ◽

History Of

Introduction: Patients undergoing hemodialysis are at increased risk of stroke. However, less known about the impact of some of the stroke risk factors, and the value of stroke risk scores in determining the risk in those patients. Our main goal. To assess the risk factors for stroke in hemodialysis patients and the use of the new CHA2DS2-VASc score for stroke assessment. Methods: Single center, retrospective cohort study of 336 patients undergoing hemodialysis from June 24, 2018, to September 6, 2018, was recruited. Baseline demographics, clinical, and laboratory data were collected. We calculated the CHA2 DS2 -VASc score for stroke assessment in all patients and categorized them into high, moderate and low risk patients according to CHA2 DS2 - VASc score and subcategorized them to two groups atrial fibrillation (AFib) and Non- Atrial fibrillation (Non AFib) patients. Results: 336 patients were included in our study; the majority of patients were at high risk with a CHA2 DS2 -VASc Score mean of 2.9± 1.5, although history of stroke was observed only in 15 patients (4.46%). According to CHA2 DS2 - VASc score, 280 patients were at high risk, 172 (51.19%) were high-risk patients on treatment (anticoagulant or antiplatelet) and 108(32.14%) patients were high risk patients not on treatment 48 were at moderate risk (14.28%) and 8 were at low risk (2.38 %). Patients were divided into subgroups as non-AFib and AFib. In non-AFib patients 320 (95.23%), high-risk patients 103 (32.18%) were not treated; high-risk patients with treatment are 162 (50.62%), moderate patients were 47 (14.68%), 8(2.5%) was in low risk. AFib patients were 16 with a mean CHA2 DS2 -VASc score of 4.4±1.1. Patients with AFib were all at high risk except 1 was at moderate risk (6.25%). There were 11 (68.75%) patients on treatment and 5 (31.25%) patients not on treatment. The risk factors for stroke that were statistically significant in increasing score risk for all patients were: age > 65 (95% CI, -2.04– -1.29; p = 0.000), being female (95% CI, -1.36– -0.68; p = 0.000) hypertension (95% CI, -2.59– -1.37; p = 0.000), diabetes (95% CI, -2.10– -1.50; p = 0.000), CVD (95% CI, -2.07– -1.24; p=0.000), history of stroke or TIA (95% CI, -3.70– -2.03; p = 0.000), CHF or LVEF (95% CI, -2.28– - 0.91; p = 0.000). Conclusions: The risk of stroke in hemodialysis patients is significant according to the use of CHA2 DS2 -VASc score in Non-AFib hemodialysis patients shows supportive evidence of increased risk of stroke in those patients, which suggest the importance of close monitoring of patients with stroke risk factors by the nephrologist and the stroke team which will lead to the initiation of early prophylaxis in those patients.

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Risk stratification and heparin prophylaxis to prevent venous thromboembolism in pregnant women

Thrombosis and Haemostasis ◽

10.1160/th07-05-0329 ◽

2007 ◽

Vol 98 (12) ◽

pp. 1237-1245 ◽

Cited By ~ 66

Author(s):

Joachim Dudenhausen ◽

Andree Faridi ◽

Thorsten Fischer ◽

Samson Fung ◽

Ulrich Geisen ◽

...

Keyword(s):

Risk Factors ◽

Venous Thromboembolism ◽

Pregnant Women ◽

Management Strategies ◽

Prospective Trial ◽

High Risk Group ◽

Group I ◽

Increased Risk ◽

History Of ◽

Heparin Prophylaxis

SummaryWomen with a history of venous thromboembolism (VTE), thrombophilia or both may be at increased risk of thrombosis during pregnancy, but the optimal management strategy is not well defined in clinical guidelines because of limited trial data. A strategy of risk assessment and heparin prophylaxis was evaluated in pregnant women at increased risk of VTE. In a prospective trial (Efficacy of Thromboprophylaxis as an Intervention during Gravidity [EThIG]), 810 pregnant women were assigned to one of three management strategies according to pre-defined risk factors related to history of VTE and thrombophilic profile. Low-risk women (group I), received 50–100 IU dalteparin/ kg body weight/ day for 14 days postpartum, or earlier when additional risk factors occurred. Women at high (group II) or very high risk (group III) received dalteparin from enrolment until six weeks postpartum (50–100 IU and 100–200 IU/ kg/ day, respectively). Objectively confirmed, symptomatic VTE occurred in 5/810 women (0.6%; 95% confidence interval [CI], 0.2 to 1.5%) (group I, 0 of 225; II, 3/469; III, 2/116). The rate of serious bleeding was 3.0% (95 % CI, 1.9 to 4.4%); 1.1% (95 % CI, 0.5 to 2.2%) was possibly dalteparin-related. There was no evidence of heparin- induced thrombocytopenia, one case of osteoporosis, and rates of miscarriage and stillbirth were similar to previous, retrospective studies. Risk-stratified heparin prophylaxis was associated with a low incidence of symptomatic VTE and few clinically important adverse events. Antepartum heparin prophylaxis is, therefore, warranted in pregnant women with idiopathic thrombosis or symptomatic thrombophilia.

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Coronary Heart Disease Risk in Blood or Marrow Transplant Survivors

Blood ◽

10.1182/blood-2020-137731 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 17-18

Author(s):

Radhika Gangaraju ◽

Yanjun Chen ◽

Lindsey Hageman ◽

Jessica Wu ◽

Liton F. Francisco ◽

...

Keyword(s):

Risk Factors ◽

Coronary Heart Disease ◽

Heart Disease ◽

Cumulative Incidence ◽

Research Funding ◽

Comparison Group ◽

Marrow Transplant ◽

Allogeneic Bmt ◽

History Of ◽

Male Sex

INTRODUCTION: Exposure to total body irradiation (TBI) increases the risk for cardiovascular risk factors (CVRFs) such as diabetes, hypertension and dyslipidemia in Blood or Marrow Transplant (BMT) survivors with the potential to increase the risk of post-BMT Coronary Heart Disease (CHD). Chest radiation is associated with accelerated atherosclerosis in conventionally treated patients. These factors, with or without additional factors such as smoking likely place BMT survivors at a high risk for CHD. Yet, a comprehensive evaluation of the risk of late-occurring CHD in BMT survivors is lacking. We addressed this gap using the resources offered by the BMT survivor study (BMTSS). METHODS: BMTSS includes patients transplanted between 1974 and 2014 at 3 US sites, and who had survived ≥2 years after BMT, and were alive and ≥18 years at BMTSS survey completion. The BMTSS survey asked participants to report chronic health conditions diagnosed by their healthcare provider (including CHD, diabetes, hypertension and dyslipidemia), along with age at diagnosis. The participants self-reported sociodemographics and health behaviors. Information regarding primary cancer diagnosis, therapeutic exposures, donor type, stem cell source, and history of chronic graft vs. host disease (GvHD; for allogeneic BMT recipients) was abstracted from medical records. A cohort of 1,131 siblings completed the BMTSS survey and served as a comparison group. We obtained informed consent from all participants. RESULTS: The study included 3,479 BMT survivors; 50.3% had received an allogeneic BMT, 54.8% were males, and 71.4% were non-Hispanic whites. Median age at study participation was 59 years (interquartile range [IQR]: 48-66 years) for BMT survivors and 57 years (IQR: 46-64 years) for siblings. BMT survivors were followed for a median of 9 years (range: 2-41 years) from BMT. CHD developed after BMT in 122 BMT survivors (52 allogeneic, 70 autologous). BMT recipients compared with siblings: After adjusting for sociodemographics and comorbidities, allogeneic BMT survivors were at a 7.2-fold higher odds (95%CI: 4.0-13.0, p<0.0001) and autologous BMT recipients at a 11.7-fold higher odds (95%CI: 6.8-20.2, p<0.0001) of reporting CHD as compared to siblings. Allogeneic BMT survivors: The 20 year cumulative incidence of CHD was 4.7% for allogeneic BMT recipients. Increasing age at BMT (HR=1.05/year, 95%CI: 1.02-1.07, p<0.0001), male sex (HR=2.09, 95%CI: 1.14-3.82, p=0.017), history of CVRFs (HR=3.6, 95%CI: 1.72-7.41, p=0.0006), and pre-BMT targeted chemotherapy such as tyrosine kinase inhibitors (HR=2.7, 95%CI: 1.10-6.77, p=0.030) were associated with increased CHD risk. The 20 year cumulative incidence of CHD among patients with CVRFs was 6.6% vs. 1.9% (p=0.005) among those who did not have CVRFs (Fig 1). Autologous BMT survivors: The 20 year cumulative incidence of CHD was 9.1% for autologous BMT recipients. The risk factors for CHD in autologous BMT survivors included: increasing age at BMT (HR=1.06/year, 95%CI: 1.03-1.09, p<0.0001), male sex (HR=2.3, 95%CI: 1.30-3.90, p=0.004), history of smoking (HR=1.66, 95%CI: 1.03-2.67, p=0.038), CVRFs (HR=1.77, 95%CI: 1.04-3.01, p=0.036), arrhythmia (HR=1.85, 95%CI: 1.01-3.42, p=0.048) and history of pre-BMT chest radiation (HR=4.56, 95%CI: 2.1-9.88, p=0.0001). For every 1 Gray increase in the dose of chest radiation, there was a 4% increase in the risk of CHD, p=0.0002. The 20 year cumulative incidence of CHD among patients with CVRFs was 10.2% vs. 7.4% among those who did not have CVRFs (p=0.04) (Fig 2). CONCLUSION: BMT survivors are at a 7-fold to 12-fold higher risk of CHD compared with a sibling comparison group. CVRFs are independent risk factors for CHD both among allogeneic and autologous BMT recipients. Pre-BMT chest radiation further increases this risk in autologous BMT recipients. These findings suggest a need for aggressive management of CVRFs in BMT recipients to prevent CHD-related morbidity. Disclosures Gangaraju: Sanofi Genzyme, Consultant for Cold Agglutinin Disease: Consultancy. Weisdorf:FATE Therapeutics: Consultancy; Incyte: Research Funding. Arora:Pharmacyclics: Research Funding; Kadmon: Research Funding; Syndax: Research Funding; Fate Therapeutics: Consultancy.

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Abstract P215: Sleep Medication and Incident Stroke: The REGARDS Study

Circulation ◽

10.1161/circ.129.suppl_1.p215 ◽

2014 ◽

Vol 129 (suppl_1) ◽

Author(s):

Megan E Petrov ◽

Virginia J Howard ◽

Dawn O Kleindorfer ◽

Michael Grandner ◽

Jennifer R Molano ◽

...

Keyword(s):

Risk Factors ◽

Racial Differences ◽

Stroke Risk ◽

Medication Use ◽

Older Individuals ◽

Vascular Events ◽

Over The Counter ◽

Sleep Medication ◽

Increased Risk ◽

History Of

Introduction: Preliminary evidence suggests sleep medications are associated with risk of vascular events; however, the long-term association with stroke risk is understudied. The aim of this study was to investigate the relation between sleep medication use and incident stroke. Methods: Within the REasons for Geographic And Racial Differences in Stroke study, 21,678 black and white participants (≥45 years) with no history of stroke were studied. Participants were recruited from 2003–2007. From 2008–2010, participants self-reported their prescription and over-the-counter sleep medication use over the past month. Suspected stroke events were identified on 6-month telephone contact, and associated medical records retrieved and physician adjudicated. Proportional hazards analysis was used to the estimate hazard ratios for incident stroke associated with sleeping medication use (0, 1–14, and 15+ days per month) controlling for sociodemographics, stroke risk factors, mental health symptoms, and sleep apnea risk. Results: At baseline, 9.6% of the sample used prescription sleep medication and 11.1% used over-the-counter sleep aids. Over an average follow-up of 3.3±1.0 years, 297 stroke events occurred. Over-the-counter sleeping medication use was associated (p = 0.014) with increased risk for incident stroke, with a 46% increased risk for use between 1 and 14 days a month (HR = 1.46; 95% CI: 0.99 - 2.15) and a 65% increased risk for use on 15 or more days (HR = 1.65; 95% CI: 0.96 - 2.85). There was no significant association with prescription sleep medications (p = 0.80). Discussion: Over-the-counter sleep medication use may independently increase the risk of stroke beyond other risk factors in middle-aged to older individuals with no history of stroke.

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The Development Of Venous Thromboembolism May Increase The Risk Of Osteonecrosis In Children With Acute Lymphoblastic Leukemia

Blood ◽

10.1182/blood.v122.21.3864.3864 ◽

2013 ◽

Vol 122 (21) ◽

pp. 3864-3864

Author(s):

Badhiwala H. Jetan ◽

Trishana Nayiager ◽

Uma H. Athale

Keyword(s):

Risk Factors ◽

Logistic Regression ◽

Venous Thromboembolism ◽

Acute Lymphoblastic Leukemia ◽

Lymphoblastic Leukemia ◽

Older Age ◽

Regression Analyses ◽

Female Ratio ◽

Increased Risk ◽

The Impact

Abstract Background Osteonecrosis (ON) is a severely disabling complication of anti-leukemic therapy, specifically long-term corticosteroid use. A hypercoagulable state is thought to underlie corticosteroid-related ON. Children with acute lymphoblastic leukemia (ALL) are also at increased risk of venous thromboembolism (VTE), indicating underlying hypercoagulability in this disease entity. Hence, we explored the relationship between ON and VTE, along with the association of ON with other variables, including age and asparaginase (ASP) therapy, in children with ALL. Methods Health records of children (< 18 yrs.) with de novo ALL treated at McMaster Children’s Hospital from 1992 to 2010 were reviewed. Patients were treated according to Dana-Farber Cancer Institute (DFCI) ALL Consortium Protocols. Data regarding demographics, leukemia diagnosis and therapy, development and characteristics of ON and VTE, and thrombophilia work-up, if any, were collected from computer records and chart review. Osteonecrosis was diagnosed by plain X-ray, computed tomography (CT), magnetic resonance (MR) imaging, and/or technetium-99m (99mTc) bone scan. We included ON diagnosed during therapy and/or at any point during post-treatment follow-up. Standard radiological measures, including venous Doppler ultrasound and/or venography (conventional, CT, MR), confirmed VTE. We included only clinically significant thromboembolic events, defined as symptomatic VTE, or asymptomatic VTE requiring anticoagulation, developing during ALL therapy. Logistic regression analyses were performed to identify possible predictors of ON. Odds ratios (ORs) with 95% confidence intervals (CIs) and corresponding p-values were determined. Results Mean age of the study cohort (n = 208) was 5.4 years and male/female ratio 1.2:1. Seventy-eight (37.5%) patients had high-risk (HR) ALL and 127 (61.1%) received dexamethasone (DEX) as post-induction steroid. One hundred and sixty-two (77.9%) patients received E. coli ASP, 19 (9.1%) Erwinia ASP, and 27 (13.0%) PEG ASP. Twenty-one (10.1%) children developed ON. Joints affected by ON included the ankle in 11 subjects, knee in 10, hip in 8, and heel in one. Fourteen of the 21 patients (66.7%) had involvement of more than one joint. All patients were diagnosed with ON during ALL treatment, with the average being 69.2 weeks following ALL diagnosis. Forty-two (20.2%) subjects had a VTE while receiving therapy at an average of 29.4 weeks after ALL diagnosis. Nine patients had cerebral sinovenous thrombosis, 7 deep vein thrombosis (DVT), and one pulmonary embolism (PE). Twenty-six patients developed a central venous line (CVL)-related VTE. Results of univariate logistic regression analyses for osteonecrosis are presented in Table 1. VTE strongly predicted development of ON – OR 8.85 (95% CI 3.37–23.25, p< 0.001). Thirteen (31.0%) patients with VTE developed ON compared to 8 (4.8%) of 166 subjects without VTE. In 10 of 13 (76.9%) patients who developed both VTE and ON, the diagnosis of VTE preceded that of ON. Given that older age is a known risk factor for both VTE and ON, we conducted a multivariate analysis, which confirmed that age, ASP type, and VTE were independent, significant risk factors for ON (Table 2). Conclusion In addition to the known impact of older age, we identified VTE and type of ASP as independent risk factors for ON in children with ALL. These observations suggest overlap in the etiopathogenesis of ON and VTE. We recommend larger, prospective studies to confirm the association of VTE and PEG ASP with ON and to assess the impact of hypercoagulability on the development of ON. This in turn may help develop preventive strategies (e.g., thromboprophylaxis) for ALL-associated ON. Disclosures: No relevant conflicts of interest to declare.

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Estimation of Acutely Ill Medical Patients at Venous Thromboembolism Risk Eligible for Extended Thromboprophylaxis Using APEX Criteria in US Hospitals

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029619880008 ◽

2019 ◽

Vol 25 ◽

pp. 107602961988000 ◽

Cited By ~ 1

Author(s):

Anne-Céline Martin ◽

Wei Huang ◽

Samuel Z. Goldhaber ◽

Russell D. Hull ◽

Adrian F. Hernandez ◽

...

Keyword(s):

Risk Factors ◽

At Risk ◽

Venous Thromboembolism ◽

The United States ◽

Care Hospital ◽

Medical Patients ◽

Hospital Discharges ◽

Increased Risk ◽

History Of ◽

History Of Cancer

Major medical illnesses place patients at risk of venous thromboembolism (VTE). Some risk factors including age ≥75 years or history of cancer place them at increased risk of VTE that extends for at least 5 to 6 weeks following hospital admission. Betrixaban thromboprophylaxis is now approved in the United States for this indication. We estimated the annual number of acutely ill medical patients at extended risk of VTE discharged from US hospital. Major medical illnesses (stroke, respiratory failure/chronic obstructive pulmonary disease, heart failure, pneumonia, other infections, and rheumatologic disorders) and 2 common risk factors for extended VTE risk, namely, age ≥75 years and history of cancer (active or past) were examined in 2014 US hospital discharges using the first 3 discharge diagnosis codes in the National Inpatient Sample (database of acute-care hospital discharges from the US Agency for Health Care Quality and Research). In 2014, there were 20.8 million discharges with potentially at risk of nonsurgical-related VTE. Overall, 7.2 million (35%) discharges corresponded to major medical illness that warranted thromboprophylaxis according to 2012 American College of Chest Physicians (ACCP) guideline. Among them, 2.79 million were aged ≥75 years and 1.36 million had a history of cancer (aged 40-74 years). Overall, 3.48 million discharges were at extended risk of VTE. Many medical inpatients at risk of VTE according to 2012 ACCP guideline might benefit from the awareness of continuing risk and some of these patients might benefit from extended thromboprophylaxis, depending on the risk of bleeding and comorbidities.

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Thromboembolic events in children with acute lymphoblastic leukemia (BFM protocols): prednisone versus dexamethasone administration

Blood ◽

10.1182/blood-2002-06-1901 ◽

2003 ◽

Vol 101 (7) ◽

pp. 2529-2533 ◽

Cited By ~ 90

Author(s):

Ulrike Nowak-Göttl ◽

Elvira Ahlke ◽

Gudrun Fleischhack ◽

Dirk Schwabe ◽

Rosmarie Schobess ◽

...

Keyword(s):

Risk Factors ◽

Venous Thromboembolism ◽

Acute Lymphoblastic Leukemia ◽

Induction Therapy ◽

Lymphoblastic Leukemia ◽

Treatment Modalities ◽

Thromboembolic Events ◽

Increased Risk ◽

Significant Difference ◽

Prothrombotic Risk Factors

Alterations in hemostasis leading to symptomatic thromboembolism have been observed in patients with acute lymphoblastic leukemia (ALL) receiving Escherichia coli asparaginase (CASP) combined with steroids. Moreover, hereditary prothrombotic risk factors are associated with an increased risk for venous thromboembolism in pediatric ALL patients treated according to the BFM 90/95 protocols (including CASP combined with prednisone during induction therapy). To assess whether the thromboembolic risk associated with established prothrombotic risk factors is modified by treatment modalities (prednisone or dexamethasone), the present analysis was performed. Three hundred thirty-six consecutively recruited leukemic children treated according to different BFM protocols (PRED group, n = 280, 60 mg/m2 prednisone; DEXA group, n = 56, 10 mg/m2 dexamethasone during induction therapy) were studied. Study end point was the onset of symptomatic vascular accidents during induction therapy. Cumulative thromboembolism-free survival was significantly reduced in children in the PRED group (thrombosis frequency, 10.4%) compared with children in the DEXA group (thrombosis frequency, 1.8%; P = .028). Although no significant difference was found in the overall prevalence of prothrombotic risk factors, 46.5% of patients in the PRED group who experienced thromboembolic events were carriers of a prothrombotic risk factor, whereas no carrier in the DEXA group had a thromboembolism. At the time of maximum CASP activity, fibrinogen and activities of antithrombin, plasminogen, and protein S were significantly reduced in the PRED group. No significant correlation could be found between CASP activity and levels of coagulation factors. In conclusion, the use of dexamethasone instead of prednisone, administered with CASP, significantly reduced the onset of venous thromboembolism.

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Clinical Characteristics Associated with Venous Thromboembolism in Patients with Non-APL Acute Myeloid Leukemia

Blood ◽

10.1182/blood-2021-151437 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 1220-1220

Author(s):

Adam Stepanovic ◽

Lauren Gabriele Banaszak ◽

Erica Reinig ◽

Jens Eickhoff ◽

Ryan J. Mattison

Keyword(s):

Risk Factors ◽

Dna Methylation ◽

Venous Thromboembolism ◽

Statistical Significance ◽

Previous History ◽

Small Sample ◽

Categorical Variables ◽

Coagulation Parameters ◽

Increased Risk ◽

History Of

Abstract INTRODUCTION: Venous thromboembolism (VTE) is an important complication of many cancers. Although more widely recognized in solid tumors, VTE is still an appreciable cause of morbidity and mortality among patients with hematologic malignancies. For example, acute promyelocytic leukemia (APL) is a well-recognized risk factor for disseminated intravascular coagulation (DIC), which can lead to thrombosis. Patients with non-APL AML are also at increased risk for VTE, though the exact mechanisms are currently unclear. Thus, we sought to explore how patient demographics, comorbidities, hematologic factors, coagulation parameters, and cytogenetic and molecular profiles impact the incidence of VTE in patients with non-APL AML. METHODS: This was a retrospective observational case-control study of 120 non-APL AML patients treated at the University of Wisconsin-Madison. The electronic health record was manually reviewed for extraction of the relevant clinical information. Coagulation parameters assessed included INR, PTT, fibrinogen, D-dimer, and fibrin monomer. Coagulation data were collected both at diagnosis and during the first 7 days of induction, if applicable. Cytogenetics was categorized based on the presence of a normal karyotype or not. Genomic data were subdivided into eight different functional categories of genes that are commonly mutated in AML. Other factors that could potentially increase the risk of thrombosis were also analyzed, including age, sex, BMI, baseline blood counts, baseline bone marrow blast percentage, previous history of VTE, use of antifibrinolytic agents, and whether blood products were transfused during the early treatment period. The variables of interest between VTE cases and non-VTE cases were compared using the nonparametric Wilcoxon rank sum test. RESULTS: Across the entire cohort (n=120), VTE developed in 25 patients (20.8%) and did not develop in 95 patients (79.2%). Table 1 and Table 2 show comparisons between VTE cases and patients without VTE for both quantitative and categorical variables. Median INR values at diagnosis and across the first 7 days of induction tended to be lower in patients with VTE and reached significance on days 3-5 (p=0.032 for INR-Day 3, p=0.046 for INR-Day 4, p=0.014 for INR-Day 5). Patients with VTE had a median BMI of 30, while patients without VTE had a median BMI of 28, which approached statistical significance (p=0.055). 8% of patients with VTE (2/25) had a history of VTE prior to the diagnosis of AML, while 3% without VTE (3/95) had a history of previous VTE (OR 2.7, p=0.281). Mutation in genes involved in DNA methylation also conferred an increased risk of VTE, with the association approaching statistical significance (p=0.083). There were no other variables that were significantly different between the two groups. CONCLUSIONS: In this cohort of patients with non-APL AML, there was a trend towards lower INR correlating with an increased incidence of VTE. Additionally, higher BMI, previous history of VTE, and mutation in DNA methylation genes were associated with increased incidence of VTE, though these trends did not reach statistical significance. The pathophysiology of VTE in this setting is likely complex and multifactorial. The shorter INR in those who developed VTE suggests a mechanism independent of the development of DIC, which is distinct from APL. The finding that obesity and personal history of VTE, both known risk factors for thrombosis, were associated with an increased incidence of VTE is also consistent with a non-DIC mechanism. Mutations in DNA methylation genes may have contributed to increased risk of VTE in this cohort; while this association is compelling, further studies with larger sample sizes are needed to confirm this finding. This study was limited by small sample size and missing data, especially regarding available data on coagulation tests. However, this analysis uncovers interesting associations that shed light on the pathophysiology of VTE in AML. More research is needed to further elucidate risk factors for VTE in order to provide optimal supportive care for this patient population. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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Incidence and Risk Factors of Venous Thromboembolism in Patients with Multiple Myeloma Receiving Immunomodulatory Agents

Blood ◽

10.1182/blood.v128.22.2624.2624 ◽

2016 ◽

Vol 128 (22) ◽

pp. 2624-2624 ◽

Cited By ~ 1

Author(s):

Miriam Kimpton ◽

Ryan Buyting ◽

Daniel J Corsi ◽

Natasha Rupani ◽

Marc Carrier ◽

...

Keyword(s):

Risk Factors ◽

Multiple Myeloma ◽

Venous Thromboembolism ◽

Previous History ◽

Patient Characteristics ◽

Hematologic Malignancies ◽

Personal History ◽

Immunomodulatory Agents ◽

Increased Risk ◽

History Of

Abstract Multiple myeloma (MM) is an incurable plasma cell disorder representing 10% of all hematologic malignancies. Cancer is a known risk factor for venous thromboembolism (VTE). Patients with MM are at a particularly high risk of developing VTE owing to patient characteristics (e.g. previous history of VTE), disease characteristics, and treatment characteristics including use of the immunomodulatory agents (IMIDs). Unfortunately, standard criteria to identify the patients most at risk for developing VTE in MM while receiving IMIDs are unknown. We sought to assess the incidence of VTE and its associated risk factors in MM patients receiving IMID therapy. A retrospective cohort study including 1680 consecutive patients with multiple myeloma treated at our centre between January 01, 1995 and January 26, 2016 was conducted. The annual incidence of VTE on immunomodulatory agents including thalidomide, lenalidomide, and pomalidomide was derived. Univariate incidence ratio analyses of VTE for different risk factors was performed including: previous history of VTE, concomitant use of dexamethasone, and ≥/< 6 months after IMID initiation. A total of 309 MM patients treated with an immunomodulatory agent were identified. Nineteen patients were excluded (incomplete data, lost to follow). Of the remaining 290 patients, the mean age was 67.9 and 42.4% were female. Twenty-seven VTE events were recorded. The overall risk ratio was 6.1 for the development of VTE. Patients with a personal history of VTE had an increased risk of suffering a VTE while on IMID therapy (IRR 5.4; CI, 1.9-13.6). The time from the initiation of the IMID therapy (less than 6 months) also increased the risk of developing a VTE (IRR 51.7; CI,19.4-160.1). The concomitant use of dexamethasone was not associated with a statistically significant increased risk (IRR 1.7; CI, 0.3-69.5). Incidence risk ratios for these risk factors are depicted in Table 1. Our results suggest that a personal history of VTE and the time from the initiation of the IMID (less than 6 months) are associated with an increased risk of VTE in MM patients receiving IMID therapy. This may be helpful in determining which multiple myeloma patients treated with an IMID agent warrant more aggressive thromboprophylaxis. Further prospective studies are needed to determine the optimal agent, intensity, and duration of thromboprophylaxis in patients with MM on IMID therapy. Disclosures McCurdy: Celgene: Honoraria.

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