Epidemiology of cancer-related venous thromboembolism Wun, Ted, MD, FACP, Professor of Medicine; White, Richard H., MD, FACP, Professor of Medicine
Best practice & research. Clinical haematology,
03/2009, Volume:
22, Issue:
1
Journal Article
Peer reviewed
Open access
Recent studies have better defined the epidemiology of venous thromboembolism (VTE) in cancer patients. The incidence is highest in patients who have metastatic disease at the time of presentation ...and who have fast growing, biologically aggressive cancers associated with a poor prognosis. The incidence is also high in patients with haematological cancers. Other specific risk factors that affect the incidence of VTE include undergoing invasive neurosurgery, the number of underlying chronic co-morbid conditions, and being of Asian/Pacific Islander decent (lower incidence). The incidence is highest in the first few months after diagnosis, which may reflect the biology of the cancer or medical interventions such as major surgery or start of chemotherapy. The development of VTE is clearly associated with decreased survival, and this effect is greater among patients initially diagnosed with local- or regional-stage cancer compared with patients with metastatic cancer, probably because VTE reflects the presence of a biologically aggressive cancer. Finally, a small percentage of patients with idiopathic VTE and no clinical or laboratory evidence of cancer may harbour an aggressive but ‘occult’ malignancy likely causally linked to the development of VTE.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Cancer-associated thrombosis (CAT) is an important cause of morbidity and mortality for patients with malignancy and varies by primary cancer type, stage, and therapy. We aimed to characterize the ...incidence, risk factors, temporal trends, and the effect on mortality of CAT. The California Cancer Registry was linked to the statewide hospitalization database to identify individuals with the 13 most common malignancies diagnosed between 2005 and 2017 and determine the 6- and 12-month cumulative incidence of CAT by venous thromboembolism (VTE) location, tumor type, and stage after adjusting for competing risk of death. Cox proportional hazard regression models were used to determine risk factors associated with CAT and the effect of CAT on all-cause mortality. 942 019 patients with cancer were identified; 62 003 (6.6%) had an incident diagnosis of CAT. Patients with pancreatic, brain, ovarian, and lung cancer had the highest, and patients with breast and prostate cancer had the lowest 12-month cumulative incidence of CAT. For most malignancies, men, those with metastatic disease and more comorbidities, and African Americans (vs non-Hispanic Whites) were at highest risk for CAT. Patients diagnosed with cancer between 2014 and 2017 had a higher risk of CAT compared with those diagnosed between 2005 and 2007. CAT was associated with increased overall mortality for all malignancies (HR ranges 1.89 to 4.79). The incidence of CAT increased over time and was driven by an increase in pulmonary embolism±deep vein thrombosis (PE±DVT). CAT incidence varies based on tumor type and stage and on individual risk factors including gender, race/ethnicity, and comorbidities. For all tumor types, CAT is associated with an increased mortality.
•Cancer-associated thrombosis (CAT) is increasing over time and is driven by an increase in PE±DVT.•CAT varies based on tumor type and stage and individual risk factors and is associated with increased risk of mortality.
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Recent studies suggest that sickle cell disease (SCD) is a hypercoagulable state contributing to vaso-occlusive events in the microcirculation, resulting in acute and chronic sickle cell-related ...organ damage. In this article, we review the existing evidence for contribution of hemostatic system perturbation to SCD pathophysiology. We also review the data showing increased risk of thromboembolic events, particularly newer information on the incidence of venous thromboembolism. Finally, the potential role of platelet inhibitors and anticoagulants in SCD is briefly reviewed.
BACKGROUND The extent to which vena cava filter (VCF) use varies between hospitals in the management of acute venous thromboembolism (VTE) is not clear. METHODS We conducted a retrospective ...observational study that compared the frequency of VCF use among California hospitals from January 1, 2006, through December 31, 2010. Using administrative hospital discharge data, we followed explicit criteria to identify nontrauma patients with acute VTE, and determined the frequency of VCF placement in each of the hospitals that admitted more than 55 VTE patients. Multivariable hierarchical regression models to predict VCF use included important clinical and demographic variables as fixed effects and hospital as a random effect. RESULTS Among the 263 hospitals included, 130 643 acute VTE hospitalizations occurred with the placement of 19 537 VCFs (14.95%). Variation in the percentage of acute VTE hospitalizations that included VCF placement was very high, from 0% to 38.96% (interquartile range, 6.23%-18.14%), with 18.49% of the observed variation due to differences among the hospitals that provided care. Significant clinical predictors of VCF use included acute bleeding at the time of admission (odds ratio, 3.4 95% CI, 3.2-3.6), a major operation after admission for VTE (3.4 3.3-3.5), presence of metastatic cancer (1.7 1.6-1.8), and extreme severity of illness (2.5 2.3-2.7 vs mild). Insertion of VCFs occurred more frequently than expected in 109 hospitals and less frequently in 59. Hospital characteristics associated with VCF use included a small number of beds (odds ratio, 0.2 95% CI, 0.2-0.4, <100 vs >400 beds), a rural location (0.4 0.2-0.5), and other private vs Kaiser hospitals (1.5 1.1-2.0). Use of VCFs varied widely even in geographically proximate areas. CONCLUSIONS The frequency of VCF use in patients with acute VTE varied widely and depended on which hospital provided the care, even after adjusting for clinical and socioeconomic factors. Further research is needed to determine whether this variation is associated with local cultural differences between hospitals or with differences in the availability of interventional radiologists or specialists, or whether it reflects the absence of high-quality evidence that VCFs are effective.
To describe the incidence and outcomes associated with venous thromboembolism (VTE) among patients with colorectal cancer.
This was a retrospective analysis of all colorectal cancer patients ...diagnosed in California between 1993 and 1995 and 1997 to 1999. Principal outcomes were incident symptomatic VTE events and death. Associations between specific risk factors and principal outcomes were analyzed using Cox proportional hazards models.
Among 68,142 colorectal cancer patients, 50% were women, mean age was 70 +/- 15 years, and approximately 70% underwent a major operation. The 2-year cumulative incidence of VTE was 2,100 patients (3.1%), with an incidence rate that decreased significantly over time from 5.0% (events/100 patient-years) in months 0 to 6 to 1.4% during months 7 to 12 to 0.6% during the second year. Significant predictors of VTE included metastatic stage (hazard ratio HR = 3.2; 95% CI, 2.8 to 3.8) and three or more comorbid conditions (HR = 2.0; 95% CI, 1.7 to 2.3). The risk of VTE was significantly reduced among Asians/Pacific Islanders (HR = 0.4; 95% CI, 0.3 to 0.5.) and patients who underwent an abdominal operation (HR = 0.4; 95% CI, 0.3 to 0.4). In risk-adjusted models, VTE was a significant predictor of death within 1 year of cancer diagnosis among patients with local- (HR = 1.8; 95% CI, 1.4 to 2.3) or regional-stage disease (HR = 1.5; 95% CI, 1.3 to 1.8) but not among patients with metastatic disease (HR = 1.1; 95% CI, 1.0 to 1.2).
The incidence of VTE among colorectal cancer patients was highest in the first 6 months after diagnosis and decreased rapidly thereafter. Metastatic disease and the number of medical comorbidities were the strongest predictors of VTE. Incident VTE reduced survival among patients with local or regional disease, suggesting that, in these patients, VTE may reflect the presence of a biologically more aggressive cancer.
Background
Stagnant outcomes for adolescents and young adults (AYAs) 15–39 years of age with cancer are partly attributed to poor enrollment onto clinical trials. Initiatives have focused on ...increasing accrual, but changes at the population‐level are unknown. We examined patterns of clinical trial participation over time in AYA patients with cancer.
Procedure
We utilized medical record data from AYAs in two population‐based National Cancer Institute Patterns of Care Studies identified through the Surveillance, Epidemiology and End Results Program. Among 3135 AYAs diagnosed with non‐Hodgkin lymphoma (NHL), Hodgkin lymphoma, acute lymphoblastic leukemia (ALL), and sarcoma, we used multivariate logistic regression to evaluate patient and provider characteristics associated with clinical trial enrollment. Interaction terms evaluated variation in clinical trial enrollment across patient and provider characteristics by year of diagnosis.
Results
From 2006 to 2012–2013, clinical trial participation increased from 14.8% to 17.9% (P < 0.01). Adjusting for patient and provider characteristics, we found lower clinical trial enrollment among those who were older at diagnosis, diagnosed with NHL vs ALL, treated by adult hematologist/oncologists only (vs pediatric hematologist/oncologists), and of non‐Hispanic Black race/ethnicity (vs non‐Hispanic White) (P < 0.05 for all). Interaction analyses indicate improved clinical trial enrollment from 2006 to 2012–2013 among young adults 25–29 years of age and the uninsured.
Conclusions
Although disparities in enrollment onto clinical trials remain for AYAs with cancer, our study identified increasing overall clinical trial participation over time. Further, we identify promising trends in enrollment uptake among AYAs 25–29 years of age and the uninsured.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Race and ethnicity are associated with risk of venous thromboembolism in population-based studies. Blacks/African Americans have a higher incidence, whereas Asians/Pacific Islanders and Hispanics ...have a lower incidence of venous thromboembolism compared with non-Hispanic Whites. The impact of race/ethnicity on the incidence of cancer-associated thrombosis (CAT), a common complication in patients with malignancy, has not been well defined. Using the California Cancer Registry linked to the California Patient Discharge Dataset and Emergency Department Utilization database, we studied a large, diverse cohort of patients (n = 942 109) from 2005 to 2017 with the 13 most common, first primary malignancies to determine the association between race/ethnicity and incidence of incident and recurrent CAT. Multivariable Cox proportional hazards regression models were performed to determine the effect of race/ethnicity on the risk of overall CAT, specific CAT by location, and recurrent CAT. Blacks/African Americans had a higher incidence of CAT for all tumor types except myeloma, whereas Asians/Pacific Islanders had a consistently lower incidence of CAT compared with non-Hispanic Whites, after adjusting for potential confounders. The main driver for the racial/ethnic differences was incidence of pulmonary embolism. We speculate the association of race/ethnicity with incidence of CAT may be partially because of underlying thrombotic predisposition that varies by ancestry, but we also must consider the impact of social determinants of health on our results.
•Blacks/African Americans have a higher incidence, whereas Asians/Pacific Islanders have a lower incidence, of CAT than White Americans.•The disparity is driven by the incidence of pulmonary embolism.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Sickle cell anemia is an inherited disorder of hemoglobin that leads to a variety of acute and chronic complications. Abnormal cellular adhesion, mediated in part by selectins, has been implicated in ...the pathophysiology of the vaso-occlusion seen in sickle cell anemia, and selectin inhibition was able to restore blood flow in a mouse model of sickle cell disease.
We performed a Phase 1 study of the selectin inhibitor GMI 1070 in patients with sickle cell anemia. Fifteen patients who were clinically stable received GMI 1070 in two infusions.
The drug was well tolerated without significant adverse events. There was a modest increase in total peripheral white blood cell count without clinical symptoms. Plasma concentrations were well-described by a two-compartment model with an elimination T1/2 of 7.7 hours and CLr of 19.6 mL/hour/kg. Computer-assisted intravital microscopy showed transient increases in red blood cell velocity in 3 of the 4 patients studied.
GMI 1070 was safe in stable patients with sickle cell anemia, and there was suggestion of increased blood flow in a subset of patients. At some time points between 4 and 48 hours after treatment with GMI 1070, there were significant decreases in biomarkers of endothelial activation (sE-selectin, sP-selectin, sICAM), leukocyte activation (MAC-1, LFA-1, PM aggregates) and the coagulation cascade (tissue factor, thrombin-antithrombin complexes). Development of GMI 1070 for the treatment of acute vaso-occlusive crisis is ongoing.
ClinicalTrials.gov NCT00911495.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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