Background: Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in lymphoma patients. The 2021 American Society of Hematology (ASH) guidelines recommend low-molecular-weight heparin (LMWH) or direct oral anticoagulants (DOACs) for treatment of cancer-associated thrombosis, with DOACs preferred in low risk of bleeding. However, this is largely based on solid tumor studies and data specific to lymphoma is limited. Patients with lymphoma can have complicating factors, such as cytopenias, bulky disease, or central venous access. Balancing thrombosis and bleeding risk is difficult in primary CNS lymphoma, thrombocytopenia, or recurrent VTE. Our scoping review summarizes current approaches to VTE management in lymphoma, focusing on anticoagulation strategy, bleeding outcomes, thrombocytopenia, catheter associated events, and recurrence.

Methods: We conducted a scoping review of original studies published between 2010 and 2025 reporting VTE outcomes in adult lymphoma patients according to the PRISMA guidelines. Databases include PubMed, EMBASE, Scopus, Taylor and Francis, and Medline. Eligible studies reported on at least one of the following: VTE incidence, timing, anticoagulation strategy, bleeding, recurrence, or survival. We included retrospective and prospective cohorts, randomized trials, registries, and conference abstracts with original data. Data were extracted in duplicate and synthesized narratively. Due to heterogeneity in study design and definitions, quantitative meta-analysis was not performed. Risk of bias was assessed using the ROBINS-I tool.

Results: Of 1,059 records, 11 studies met inclusion criteria, encompassing 9,800 patients, including 8,766 with confirmed lymphoma. Most were retrospective and varied in design. VTE risk was highest within 3 to 6 months of treatment initiation, especially in aggressive subtypes like diffuse large B-cell lymphoma and primary CNS lymphoma (PCNSL). Consistent with ASH 2021 guidelines, most studies reported use of LMWH or DOACs, with increasing DOAC use in outpatient settings, without thrombocytopenia or high bleeding risk. Management during thrombocytopenia was variable. One study of patients with hematologic malignancy and platelets <50,000 found major bleeding in 27% in those on anticoagulation, versus 3% when held. Another found 13% major bleeding with full-dose anticoagulation compared to modified dosing. However, in lymphoma specific studies, DOACs had comparable or lower bleeding risk than LMWH in stable patients. Several studies described safe use of anticoagulation with platelet counts above 50,000, but bleeding risk remained high in those undergoing transplant or with aggressive disease. Catheter-associated VTE was a large contributor. One study in PCNSL patients found 74% of VTEs were catheter-associated upper extremity DVTs, mainly during the first two chemotherapy cycles. Most were symptomatic, with PICCs associated with higher thrombosis rates. PICC removal was often done at thrombosis diagnosis, despite ASH recommending to retain functional, non-infected catheters. Recurrent VTE was reported in 6 of 11 studies, with rates ranging from 6% to 25%. Some linked recurrent VTE to poorer survival outcomes. One found DOAC recurrence rates around 6%, similar to LMWH, though another reported higher bleeding with DOACs. Patients with PCNSL were a high-risk group with VTE incidence ranging from 25-31%. Despite concerns for intracranial hemorrhage, multiple studies reported low incidence of CNS bleeding with anticoagulation. One had major bleeding, including intracranial hemorrhage, in about 15% of patients, but these events were multifactorial and not clearly attributed to anticoagulation. Standard risk stratification tools, like Khorana scoring, had limited predictive value for VTE in lymphoma, with one study suggesting changing thresholds in PCNSL.

Conclusions: VTE is a common and serious complication in lymphoma, especially early in treatment. Anticoagulation approaches varied and the studies were predominantly retrospective with heterogenous design, limiting generalizability. However, several studies found that with careful patient selection and monitoring, DOACs may be a safe and effective option for anticoagulation, even in cases of CNS involvement and thrombocytopenia. Prospective lymphoma-specific trials are still needed to refine anticoagulation strategy.

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2025
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