Incidence and Risk Factors of Venous Thromboembolic Events in Lymphoma

doi:10.1016/j.amjmed.2010.05.021

The American Journal of Medicine

Volume 123, Issue 10, October 2010, Pages 935-941

https://doi.org/10.1016/j.amjmed.2010.05.021 Get rights and content

Abstract

Background

Cancer patients are at increased risk of venous thromboembolism; however, the incidence and risk factors for venous thromboembolism in lymphoma patients are not well defined.

Methods

Medical records of 422 newly referred lymphoma patients at our institution were reviewed over 2-year follow-up for all venous thromboembolism events and potential risk factors. Multivariate logistic regression model was used to identify risk factors predictive of venous thromboembolism.

Results

Among 422 patients, 72 (17.1 %) had 80 new episodes of venous thromboembolism: 59 had deep vein thrombosis, 17 had pulmonary embolism, and 4 had combined deep vein thrombosis and pulmonary embolism. Only 18 of 422 patients (4.3%) were on thromboprophylaxis at baseline. Interestingly, 64% (51/80) of the episodes occurred by the third cycle of chemotherapy. By multivariate logistic regression, female sex (odds ratio [OR] 3.51, P = .001), high hemoglobin (OR 1.26, P = .020), high serum creatinine (OR 3.23, P = .009), and doxorubicin- or methotrexate-based chemotherapy (OR 3.47, P = 0.003) were important risk factors for new venous thromboembolism.

Conclusions

Lymphoma patients are at high risk for venous thromboembolism in the initial cycles of chemotherapy; the risk was higher for women, patients with elevated hemoglobin or creatinine, or those receiving doxorubicin or methotrexate. Future studies might focus on validation of these risk factors to identify the high-risk cohort and the potential role of thromboprophylaxis, particularly during initial cycles of chemotherapy.

Section snippets

Study Population

This study is a retrospective review of 422 consecutive patients newly referred to the lymphoma department in the MD Anderson Cancer Center from January 2003 to December 2003. All patients received at least 1 cycle of chemotherapy in our hospital. The medical records of these patients were reviewed for all venous thromboembolism events during a follow-up period of 2 years from the referral date. Approval for this retrospective medical record review study was obtained from the Institutional

Patients Characteristics

The study population included 422 eligible lymphoma patients who received at least 1 cycle of chemotherapy (total 2126 cycles) at our hospital in a period of 2 years follow-up from the referral date. The median age of the patients was 57 years (range, 17-87 years), with 58% males and 42% females (Table 1). Most patients (62%) were newly diagnosed, and had advanced stages of the disease (stage III 23.9%, stage IV 50.2%). Eighty-four percent (355/422) of the patients were non-Hodgkin's lymphoma,

Discussion

The purpose of our study was to define the incidence, the timing, and the risk factors predictive of venous thromboembolism in newly referred lymphoma patients at a comprehensive cancer center. Our study demonstrates that the incidence of venous thromboembolism is high in patients with lymphoma, with an overall incidence of 17.1%. Because this study did not prospectively screen for incidental venous thromboembolism, the actual risk may be underestimated in this population. The incidence was

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Venous thromboembolism (VTE) is a common complication occurring in 5% to 10% of patients with lymphoma. As the complexity of lymphoma management has increased with novel therapies, so too has the treatment of VTE. Therapeutic options for the treatment of cancer-associated VTE have expanded from only warfarin and low-molecular-weight heparins (LMWHs) to include the direct oral anticoagulants (DOACs) apixaban, edoxaban and rivaroxaban. There have been no head-to-head trials comparing different DOACs in this setting, and randomized trials comparing a DOAC with LMWH dalteparin differ in trial design and results. Drug–drug interactions, drug-specific side effects, and patient selection are important considerations when prescribing anticoagulant therapy. In all patients, the relative risks of thrombosis and bleeding, the availability of the anticoagulant, and the life expectancy of the patient are vital elements in selecting the most appropriate anticoagulant (which can vary over time) for the individual patient. We describe the intricacies and challenges of treating thrombotic complications in patients with lymphoma with an emphasis on evidence and guideline-based care.
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A total of 668 patients were analyzed. Thirty-three (4.94%) patients had at least one episode of VTE, and all of which were deep vein thrombosis alone. All VTEs occurred in patients who received chemotherapy, while no VTE occurred in patients who did not receive chemotherapy. By univariate analysis, central venous catheter (CVC) (odds ratio [OR] 6.63, confidence interval [CI] 2.24−19.57, P = 0.001), Eastern Cooperative Oncology Group (ECOG) performance status 2, 3, or 4 (OR: 62.15, CI: 15.42−250.48, P = 0.000), and stage III or IV (OR: 4.06, CI: 1.00−16.40, P = 0.049) were identified as risk factors for developing VTE. By multivariate analysis, CVC (OR: 3.23, CI: 1.49−7.23, P = 0.003) and stage III or IV (OR: 2.30, CI: 1.06−4.97, P = 0.035) were still significant risk factors for developing VTE.
The incidence of VTE in the present study population was comparable to that of lymphoma patients, other than T-cell lymphoma, and VTE was associated with CVC and advanced stage.
Venous thromboembolism incidence in hematologic malignancies
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Venous thromboembolism (VTE) remains a major cause of morbidity and mortality in patients with cancer. Although some very well validated scores delineate the risk of VTE by cancer subtype and other risk factors, hematologic malignancies are underrepresented in these models. This subgroup represents a unique entity that undergoes therapy that can be thrombogenic. The overall risk of VTE in patients with leukemia depends on the use of L-asparaginase treatment, older age, comorbidities and central venous catheters. Patients with acute promyelocytic leukemia are at particularly high risk of VTE but also have an increased risk of bleeding. Patients with aggressive lymphomas have a high incidence of VTE, roughly 10%. Patients with multiple myeloma at highest risk of VTE are those receiving immunomodulatory agents such as thalidomide or lenalidomide. Allogeneic stem cell transplantation carries a risk of thrombosis, particularly in patients developing graft versus host disease. This review summarizes the incidence of VTE in leukemia, lymphoma, myeloma and stem cell transplantation and provides practical guidance for preventing and managing VTE in patients with hematologic malignancies.
Venous thromboembolic events in lymphoma patients: Actual relationships between epidemiology, mechanisms, clinical profile and treatment
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Citation Excerpt :
It follows that more aggressive thromboprophylaxis in high-risk patients could reduce the mortality rate of lymphoma patients resulting from VTE. In lymphoma patients, the risk of VTE is associated with a variety of factors, which can be categorized as patient-related, lymphoma-related, and treatment-related (Table 1) [4,10–13,15–21,26–30,32–78]. Special consideration must be given to the presence of lupus anticoagulant (LA) in lymphoma patients.
Venous thromboembolic events (VTE) are an underestimated health problem in patients with lymphoma. Many factors contribute to the pathogenesis of thromboembolism and the interplay between various mechanisms that provoke VTE is still poorly understood. The identification of parameters that are associated with an increased risk of VTE in lymphoma patients led to the creation of several risk-assessment models. The models that evaluate potential VTE risk in lymphoma patients in particular are quite limited, and have to be validated in larger study populations. Furthermore, the VTE prophylaxis in lymphoma patients is largely underused, despite the incidence of VTE. The lack of adequate guidelines for the prophylaxis and treatment of VTE in lymphoma patients, together with a cautious approach due to an increased risk of bleeding, demands great efforts to ensure the implementation of current knowledge in order to reduce the incidence and complications of VTE in lymphoma patients.
Therapeutic implication of MicroRNA-320a antagonist in attenuating blood clots formed during venous thrombosis
2024, Journal of Thrombosis and Thrombolysis

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: Funding: Clinical research funding.

: Conflict of Interest: The authors indicated no potential conflicts of interest.

: Authorship: Saroj Vadhan-Raj, the principal investigator, was responsible for conception and design, execution of the study, analysis and interpretation of the data, and drafting of the article. Xiao Zhou, Shyam Teegala, and Auris Huen assisted with the writing of the protocol and manuscript, coordinated the collection and the statistical analysis of the data and critical review of the article. Yuan Ji was responsible for the statistical analysis and the interpretation of the results. Luis Fayad and Fredrick B. Hagemeister provided the study participants and critically reviewed the article, and Gregory Gladish provided radiologic expertise and critically reviewed the article.

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Clinical research studyIncidence and Risk Factors of Venous Thromboembolic Events in Lymphoma

Abstract

Background

Methods

Results

Conclusions

Section snippets

Study Population

Patients Characteristics

Discussion

Am J Med

Lancet Oncol

J Thromb Haemost

Chest

Hematol Oncol Clin North Am

J Thromb Haemost

J Thromb Haemost

Kidney Int

Clin Oncol (R Coll Radiol)

Int J Cardiol

Blood

Lancet

Blood

Venous thrombosis in cancer patients: insights from the frontline survey

Oncologist

The long-term clinical course of acute deep venous thrombosis

Ann Intern Med

Incidence of venous thromboembolism and its effect on survival among patients with common cancers

Arch Intern Med

Clinical research study
Incidence and Risk Factors of Venous Thromboembolic Events in Lymphoma