Publications by authors named "Anjlee Mahajan"

14 Publications

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Incidence and Outcomes Associated with 6841 Isolated Distal Deep Vein Thromboses in Patients with 13 Common Cancers.

Thromb Haemost 2022 Jan 17. Epub 2022 Jan 17.

Hematology/Oncology, University of California Davis Health System, Sacramento, United States.

Introduction: The epidemiology of isolated distal deep venous thrombosis (iDDVT) among cancer patients is not well described, particularly the incidence of recurrent venous thromboembolism (rVTE) and effect on mortality by cancer type.

Methods: The cumulative incidence (CI) of iDDVT was determined for patients with 13 common cancers between 2005-2017 using the California Cancer Registry linked to the California Patient Discharge and Emergency Department Utilization datasets. The CI of rVTE was calculated and association of incident CAT location with rVTE was determined using Cox proportional hazards regression models. The association of incident cancer-associated venous thrombosis (CAT) location with overall and cancer-specific mortality was determined using Cox models, stratified by cancer site, and adjusted for individual characteristics.

Results: Among 942,109 cancer patients, CAT occurred in 62,003 (6.6%): of these, 6,841 (11.0%) were iDDVT. Compared to more proximal sites of CAT, iDDVT was associated with similar risk for rVTE. IDDVT was associated with increased mortality across all cancer types when compared to patients without CAT (HR 1.56-4.60). The effect of iDDVT on mortality was similar to that of proximal DVT (pDVT) for most cancers except lung, colorectal, bladder, uterine, brain, and myeloma, where iDDVT was associated with a lesser association with mortality.

Conclusion: iDDVT represented 11% of CAT. The risk of rVTE after iDDVT was similar to other sites of CAT and rVTE occurred in more proximal locations after an incident iDDVT. IDDVT was associated with increased mortality and this effect was similar to that of PE or pDVT for most cancer types.
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http://dx.doi.org/10.1055/a-1742-0177DOI Listing
January 2022

Direct oral anticoagulants or low-molecular-weight heparins for venous thromboembolism in patients with brain tumors.

Thromb Res 2021 Dec 29;208:148-155. Epub 2021 Oct 29.

Department of Clinical Pharmacy, University of California, San Francisco, 505 Parnassus Ave, San Francisco, CA 94143, United States of America; Department of Pharmacy Services, University of California, Davis Health, 2315 Stockton Blvd, Sacramento, CA 95817, United States of America.

Introduction: Patients with central nervous system malignancies have limited representation in studies evaluating DOACs for VTE treatment. This study evaluated the safety and efficacy of DOACs in comparison with LMWH for cancer-associated VTE in patients with primary brain tumors or secondary brain metastases.

Materials & Methods: In this multicenter, retrospective cohort study, adult patients with a diagnosis of primary brain tumor or secondary brain metastases who received either a DOAC or LMWH for treatment of cancer-associated VTE were evaluated. The primary outcome was the cumulative incidence of any intracranial hemorrhage within a 6-month period following the initiation of anticoagulation. Secondary outcomes included the cumulative incidence of any bleeding event, and recurrent VTE events.

Results: Between January 1, 2012 and October 9, 2019, one-hundred eleven patients met inclusion criteria. The 6-month cumulative incidence of intracranial hemorrhage was 4.3% (95% CI, 0.74-13.2%) in the DOAC group, compared to 5.9% (95% CI, 1.5-14.9%) in the LMWH group (p = 0.61). The 6-month cumulative incidence of bleeding events was 14.3% (95% CI, 6.2-25.8%) in the DOAC group, compared to 27.8% (95% CI, 15.5-41.6%) in the LMWH group (p = 0.10). The 6-month cumulative incidence of recurrent VTE events was 5.6% in the DOAC group (95% CI, 1.5-14.2%), compared to 6.6% in the LMWH group (95% CI, 1.7-16.5%) (p = 0.96). No differences were found with respect to other secondary outcomes.

Conclusion: There were no significant differences in bleeding or recurrent VTE events between DOACs and LMWH. These findings suggest DOACs may be safe and effective for VTE treatment in this patient population.
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http://dx.doi.org/10.1016/j.thromres.2021.10.023DOI Listing
December 2021

The incidence of cancer-associated thrombosis is increasing over time.

Blood Adv 2022 Jan;6(1):307-320

Center for Oncology Hematology Outcomes Research and Training (COHORT), Division of Hematology Oncology, University of California Davis School of Medicine, Sacramento, CA; and.

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.
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http://dx.doi.org/10.1182/bloodadvances.2021005590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8753193PMC
January 2022

In cancer-related VTE, DOACs reduce recurrent VTE compared with LMWH; groups do not differ for major bleeding.

Ann Intern Med 2020 12;173(12):JC62

University of California, Davis, Sacramento, California, USA (A.M., R.H.W.).

Source Citation: Haykal T, Zayed Y, Deliwala S, et al. Thromb Res. 2020;194:57-65. 32788122.
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http://dx.doi.org/10.7326/ACPJ202012150-062DOI Listing
December 2020

Incidence of Upper Extremity Deep Vein Thrombosis in Acute Leukemia and Effect on Mortality.

TH Open 2020 Oct 28;4(4):e309-e317. Epub 2020 Oct 28.

Center for Oncology Hematology Outcomes Research and Training (COHORT), Division of Hematology Oncology, University of California, Davis School of Medicine, Sacramento, California, United States.

The cumulative incidence, risk factors, rate of subsequent venous thromboembolism (VTE) and bleeding and impact on mortality of isolated upper extremity deep vein thrombosis (UE DVT) in acute leukemia are not well-described. The California Cancer Registry, used to identify treated patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) diagnosed between 2009 and 2014, was linked with the statewide hospitalization database to determine cumulative incidences of UE DVT and subsequent VTE and bleeding after UE DVT diagnosis. Cox proportional hazards regression models were used to assess the association of UE DVT on the risk of subsequent pulmonary embolism (PE) or lower extremity deep vein thrombosis (LE DVT) and subsequent bleeding, and the impact of UE DVT on mortality. There were 5,072 patients identified: 3,252 had AML and 1,820 had ALL. Three- and 12-month cumulative incidences of UE DVT were 4.8% (95% confidence interval [CI]: 4.1-5.6) and 6.6% (95% CI: 5.8-7.5) for AML and 4.1% (95% CI: 3.2-5.1) and 5.9% (95% CI: 4.9-7.1) for ALL, respectively. Twelve-month cumulative incidences of subsequent VTE after an incident UE DVT diagnosis were 5.3% for AML and 12.2% for ALL. Twelve-month cumulative incidences of subsequent bleeding after an incident UE DVT diagnosis were 15.4% for AML and 21.1% for ALL. UE DVT was associated with an increased risk of subsequent bleeding for both AML (hazard ratio [HR]: 2.07; 95% CI: 1.60-2.68) and ALL (HR: 1.62; 95% CI: 1.02-2.57) but was not an independent risk factor for subsequent PE or LE DVT for either leukemia subtype. Isolated incident UE DVT was associated with increased leukemia-specific mortality for AML (HR: 1.42; 95% CI: 1.16-1.73) and ALL (HR: 1.80; 95% CI: 1.31-2.47). UE DVT is a relatively common complication among patients with AML and ALL and has a significant impact on bleeding and mortality. Further research is needed to determine appropriate therapy for this high-risk population.
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http://dx.doi.org/10.1055/s-0040-1718883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593117PMC
October 2020

High incidence of venous thromboembolism and major bleeding in patients with primary CNS lymphoma.

Leuk Lymphoma 2020 11 23;61(11):2605-2613. Epub 2020 Jun 23.

Division of Hematology Oncology, Center for Oncology Hematology Outcomes Research and Training (COHORT), University of California Davis School of Medicine, Sacramento, CA, USA.

Venous thromboembolism (VTE) and major bleeding in primary central nervous system lymphoma (PCNSL) patients are not well described. We identified 992 PCNSL patients using the California Cancer Registry (2005-2014). The cumulative incidence of VTE and major bleeding was determined using California hospitalization data. The 12-month cumulative incidence of VTE was 13.6% (95% confidence interval (CI) 11.5-15.8%); chemotherapy and radiation therapy were associated with increased risk of VTE (hazard ratio (HR) 2.41, CI 1.31-4.46 and HR 1.56, CI 1.08-2.25, respectively). The 12-month cumulative incidence of major bleeding was 12.4% (CI 10.1-14.6%). Pulmonary embolism (PE) and proximal deep vein thrombosis were associated with increased risk of major bleeding, likely due to anticoagulation. PE (HR 1.61, CI 1.11-2.33, =.011) and major bleeding (HR 2.36, CI 1.82-3.06, <.0001) were associated with increased mortality. This study highlights the high incidence of both VTE and major bleeding and the significant impact on survival for PCNSL patients.
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http://dx.doi.org/10.1080/10428194.2020.1780584DOI Listing
November 2020

Bleeding in patients with sickle cell disease: a population-based study.

Blood Adv 2020 03;4(5):793-802

Center for Oncology Hematology Outcomes Research and Training, Division of Hematology Oncology, University of California, Davis School of Medicine, Davis, CA; and.

Bleeding is a known complication of sickle cell disease (SCD) and includes hemorrhagic stroke, hematuria, and vitreous hemorrhage. However, the incidence of bleeding events in patients with SCD has not been well described. We present a retrospective, population-based study examining the cumulative incidence of bleeding in 6423 patients with SCD from 1991 to 2014. We also studied risk factors associated with bleeding and the effects of bleeding on mortality, using Cox proportional hazards regression models. We used California emergency department and hospitalization databases to identify patients with SCD with intracranial hemorrhage, gastrointestinal (GI) bleeding, hemophthalmos, gross hematuria, epistaxis, menorrhagia, and other bleeding events. The cumulative incidence of any first bleeding event at age 40 years was 21% (95% confidence interval [CI], 19.8%-22.3%), increasing with age to 41% by age 60 years (95% CI, 38.8%-43.1%). The majority of bleeding events were GI (41.6%), particularly from the upper GI tract. A higher bleeding risk was associated with increased frequency of hospitalization (hazard ratio [HR], 2.16; 95% CI, 1.93-2.42), venous thromboembolism 180 days before bleeding event (HR, 4.24; 95% CI, 2.86-6.28), osteonecrosis of the femoral head (HR, 1.25; 95% CI, 1.08-1.46), and ischemic stroke (HR, 1.65; 95% CI, 1.20-2.26). Bleeding was also associated with a twofold increased risk for death (HR, 2.09; 95% CI, 1.82-2.41) adjusted for other SCD-related complications. Our novel finding of a high incidence of bleeding in patients with SCD, particularly from the upper GI tract, suggests that patients with SCD may be predisposed to bleeding, with possible etiologies including increased use of nonsteroidal anti-inflammatory drugs, mucosal infarction from vascular occlusion by sickled red blood cells, and increased stress ulceration from frequent hospitalization.
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http://dx.doi.org/10.1182/bloodadvances.2019000940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065478PMC
March 2020

Biomarkers of Cancer-Associated Thromboembolism.

Cancer Treat Res 2019 ;179:69-85

Division of Hematology and Oncology, UC Davis School of Medicine, UC Davis Cancer Center, 4501 X Street, Sacramento, CA, 95817, USA.

Venous thromboembolism is known to be associated with an increase in morbidity and mortality in patients with malignancy. Predictive laboratory biomarkers of venous thromboembolism (VTE) have long been sought after to improve outcomes and help guide clinical decision making. Previously studied biomarkers include C reactive protein (CRP), tissue factor expressing microparticles (TF MP), D-dimer, soluble P-selectin (sP-selectin), plasminogen activator inhibitor 1 (PAI-1), factor VIII, platelet count, and leukocyte counts. This chapter will focus on these possible biomarkers for cancer-associated thrombosis (CAT) with particular emphasis on the pathophysiology behind thrombosis formation as well as data from clinical studies in patients with malignancy. The incorporation of the above biomarkers into risk assessment tools to predict CAT will also be reviewed, as will risk factors for recurrent VTE in patients with malignancy. Further studies are ongoing to develop readily available biomarkers that can be incorporated into future risk assessment models with the goal of reducing morbidity and mortality due to cancer-associated thrombosis.
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http://dx.doi.org/10.1007/978-3-030-20315-3_5DOI Listing
September 2019

High incidence of venous thromboembolism recurrence in patients with sickle cell disease.

Am J Hematol 2019 08 12;94(8):862-870. Epub 2019 Jun 12.

Center for Oncology and Hematology Outcomes Research and Training (COHORT), Division of Hematology Oncology, UC Davis School of Medicine, Sacramento, California.

Previous reports show increased incidence of venous thromboembolism [VTE, deep-vein thrombosis (DVT) and pulmonary embolus (PE)] in sickle cell disease (SCD) patients. The incidence, time course, and risk factors for VTE recurrence have been less well described. We determined the cumulative incidence of first VTE recurrence and bleeding in a cohort of SCD patients with incident VTE. Risk factors for recurrence and bleeding were also determined using multivariable Cox regression models, adjusting for gender, race/ethnicity, era of incident VTE, location and hospitalization-associated status of incident VTE, and SCD-related complications. Results are presented as adjusted hazard ratios (HR) and 95% confidence intervals (CI). Among 877 SCD patients with an incident VTE, the 1-year and 5-year cumulative incidence of recurrence was 13.2% (95% CI 11.0%-15.5%) and 24.1% (95% CI 21.2%-27.1%). Risk factors for VTE recurrence included more severe SCD (HR = 2.41; CI: 1.67-3.47), lower extremity DVT as the incident event (HR = 1.64; CI: 1.17-2.30), and pneumonia/acute chest syndrome (HR = 1.68; CI: 1.15-2.45). The cumulative incidence of bleeding was 4.9% (CI 3.5%-6.4%) at 6 months and 7.9% (CI: 6.2%-9.8%) at 1 year. More severe SCD (HR = 1.61; CI: 1.11-2.35) was associated with bleeding. The high incidence of VTE recurrence in patients with SCD suggests that extended anticoagulation may be indicated; however, this must be weighed against a relatively high risk of bleeding. Prospective, randomized studies of anticoagulation in SCD patients with VTE are needed.
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http://dx.doi.org/10.1002/ajh.25508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6876692PMC
August 2019

The Epidemiology of Cancer-Associated Venous Thromboembolism: An Update.

Semin Thromb Hemost 2019 Jun 30;45(4):321-325. Epub 2019 Apr 30.

Division of Hematology and Oncology, UC Davis School of Medicine, Sacramento, California.

The incidence of venous thromboembolism (VTE) is known to be higher in patients with malignancy as compared with the general population. It is important to understand and review the epidemiology of VTE in cancer patients because it has implications regarding treatment and prognosis. Multiple studies have shown that cancer patients who develop VTE are at higher risk for mortality. This article will focus on an update regarding the epidemiology of cancer-associated thrombosis (CT). The authors will describe factors associated with CT risk including cancer type and stage at the time of diagnosis, race and ethnicity, and cancer-directed therapy. In addition, recurrent thrombosis and the effect of thromboembolism on survival in cancer patients will also be addressed.
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http://dx.doi.org/10.1055/s-0039-1688494DOI Listing
June 2019

Cancer specific survival in patients with sickle cell disease.

Br J Haematol 2019 04 22;185(1):128-132. Epub 2018 Nov 22.

Center for Oncology and Hematology Outcomes Research and Training (COHORT), Division of Hematology Oncology, UC Davis School of Medicine, Sacramento, CA, USA.

Sickle cell disease (SCD) patients have a higher incidence of certain cancers, but no studies have determined the impact of cancer on survival among SCD patients. SCD patients (n = 6423), identified from state-wide hospitalisation data, were linked to the California Cancer Registry (1988-2014). Multivariable Cox proportional hazards regression was used to examine survival. Among SCD patients, a cancer diagnosis was associated with a 3-fold increased hazard of death. Compared to matched cancer patients without SCD, SCD was associated with worse overall survival, but not cancer-specific survival, suggesting that SCD cancer patients should be treated with similar therapeutic intent.
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http://dx.doi.org/10.1111/bjh.15687DOI Listing
April 2019

Platelet response to direct thrombin inhibitor or fondaparinux treatment in patients with suspected heparin-induced thrombocytopenia.

J Thromb Thrombolysis 2018 May;45(4):536-542

University of California, Davis Medical Center, 2315 Stockton Blvd, Sacramento, CA, 95817, USA.

Making a definitive diagnosis of heparin-induced thrombocytopenia (HIT) can be problematic. A prompt platelet rise following treatment has been proposed as a "post-test" criterion for diagnosis. However, the platelet response following discontinuation of heparin and initiation of a recommended alternative anticoagulant remains largely undefined and unstudied. This study aimed to characterize platelet response to initial treatment in patients with a low, intermediate, or high likelihood of having HIT. This was a multicenter retrospective cohort study. Patients were over 18 years in age, underwent serologic testing for HIT, and received alternative anticoagulation treatment for HIT. Classification of each patient's likelihood of having HIT was based on an empiric, pre-hoc combination of the 4T score and serology results. The primary outcome for this study was a platelet count response after initiation of direct thrombin inhibitor (DTI) or fondaparinux therapy within 48 h. 124 patients were analyzed. The sensitivity and specificity of having an immediate platelet rise of at least 10,000/µL by day 2 after starting treatment among high-likelihood for HIT patients were 0.71 (95% CI 0.55-0.84) and 0.64 (95% CI 0.5-0.76), respectively. The negative predictive value of no platelet rise was 75.5% (95% CI 0.61-0.86). A prompt platelet count rise may be appropriate to consider along with other known criteria for the clinical diagnosis of HIT. The rise should be immediate following discontinuation of heparin and initiation of recommended treatment, with an upward rise within 48 h.
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http://dx.doi.org/10.1007/s11239-018-1646-xDOI Listing
May 2018

Increased risk of leukemia among sickle cell disease patients in California.

Blood 2017 09 22;130(13):1597-1599. Epub 2017 Aug 22.

Center for Oncology and Hematology Outcomes Research and Training (COHORT), Division of Hematology Oncology, School of Medicine.

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http://dx.doi.org/10.1182/blood-2017-05-783233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5620417PMC
September 2017

Lymphoma and venous thromboembolism: influence on mortality.

Thromb Res 2014 May;133 Suppl 2:S23-8

Division of General Internal Medicine, University of California, Davis. Electronic address:

Background: The population-based incidence of acute venous thromboembolism (VTE) in adult patients diagnosed with non-Hodgkin's lymphoma has not been established, and the effect of VTE on survival is not clear.

Aim: To determine the incidence of acute VTE in California residents diagnosed with lymphoma, and to determine the effect of acute VTE on survival.

Methods: We used the California Cancer Registry coupled with the California Patient Discharge database to identify incident cases with lymphoma, 1991-1997, and the incidence of first-time VTE in these patients. Multivariable models were constructed to evaluate risk of developing acute VTE within 2 years, and a proportional hazard model was used to predict death within 2 years, using acute VTE as a time-dependent covariate.

Results: There were 16,755 patients diagnosed with non-Hodgkin's lymphoma; 29% had low-grade, 66% intermediate/aggressive grade and 5.6% had high-grade lymphoma. Acute VTE developed in 3.6% of the patients by year 1 and 4.0% by the end of year 2. Significant predictors of acute VTE included advanced stage lymphoma, number of chronic comorbidities and advancing age. Significant predictors of death within 2 years included diagnosis of acute VTE, advanced stage disease, increasing number of co-morbidities, age over 75 years and intermediate or high grade histopathology. The effect of acute VTE on death increased as the time between lymphoma diagnosis and VTE diagnosis increased (HR=1.7 95%CI:1.5-1.9 for VTEs <6 months; HR=6.5 95%CI:4.7-8.9 VTEs 12-24 months).

Conclusions: Acute VTE developed frequently in patients with lymphoma, and VTE was a strong predictor of decreased survival.
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http://dx.doi.org/10.1016/S0049-3848(14)50004-7DOI Listing
May 2014
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