Elevated Risk of Venous but Not Arterial Thrombosis in Waldenström's Macroglobulinemia and Lymphoplasmacytic Lymphoma
Authors: Hultcrantz Malin L , Pfeiffer Ruth M , Bjorkholm Magnus , Goldin Lynn , Turesson Ingemar , Schulman Sam , Landgren Ola , Kristinsson Sigurdur Y 
Published: October 2019

Abstract
Abstract 1603

Background
Most malignancies including plasma cell disorders are associated with an elevated risk of thromboembolism. Waldenström's macroglobulinemia (WM) is a disease with IgM paraprotein which can lead to hyperviscosity. However, there is limited information on the frequency of venous and arterial thrombosis in patients with WM. Patients with multiple myeloma (MM) and patients with IgG and IgA monoclonal gammopathy of unknown significance (MGUS) have been shown to have a higher risk of both venous and arterial thrombosis compared to the general population. IgM MGUS on the other hand has not been associated with an increased risk of thrombosis. The aim of this study was to assess the risk of venous and arterial thrombosis in patients with WM and lymphoplasmacytic lymphoma (LPL) in a population-based setting in Sweden.

Patients and Methods
Patients diagnosed with WM and LPL between 1986 and 2005 were identified through the Swedish Cancer Registry, the Swedish Patient Registry, and through our national network including all major hematology and oncology centers in Sweden. For each patient, four controls matched for age, gender, and county of residence were identified through the Swedish Register of Total Population. Venous thrombosis was defined as pulmonary embolism or deep vein thrombosis and arterial thrombosis was defined as myocardial infarction, angina pectoris, cerebral infarction, or transient ischemic attack. Information on occurrence of venous and arterial thrombosis after the diagnosis of WM/LPL was obtained through the centralized Swedish Patient Registry, which captures information on individual patient-based discharge diagnosis from inpatient and, since 2000, outpatient care. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results
A total of 1,747 patients with WM, 607 patients with LPL, and 8,908 controls were identified between 1986 and 2005. Median age at diagnosis was 74 years and 58% were men. Overall, patients with WM/LPL had an increased risk of venous thrombosis. The highest risk was seen during the first year after diagnosis, HR=3.88 (95% CI 2.41–6.24), and the risk was still elevated 5 years (HR=2.25; 1.70–2.98) and 10 years (HR=1.95; 1.53–2.48) after diagnosis. Patients with WM/LPL had no increased risk of arterial thrombosis during any period of follow-up time, reflected by HRs of 1.24 (0.99–1.55), 1.00 (0.88–1.14), and 0.96 (0.86–1.08) during the first 1, 5 and 10 years after diagnosis, respectively. There was no difference in risks when coronary and cerebral arterial thrombosis were analyzed separately. There was no difference in risk of overall thrombosis between patients with WM and LPL.

Summary and Conclusions
In this large population-based study, patients with WM/LPL had a two to four fold elevated risk of venous thrombosis compared to matched controls, possibly due to the hypercoagulable state, co-morbidities, immobilization, and treatment-related factors. Interestingly, in contrast to what has been observed in MM and IgG and IgA MGUS, there was no elevated risk of arterial thrombosis. This is consistent with our previous findings that patients with IgM MGUS do not have a higher risk of arterial thrombosis. The results of this study suggest that even though WM is associated with hyperviscosity due to the IgM pentamer, this does not increase the risk of arterial thrombosis. In addition, our results indicate that IgM-associated diseases do not share the same thrombotic mechanisms as the IgG/IgA plasma cell disorders. Future studies are needed to assess the role of thromboprophylaxis in WM/LPL, especially during the first year after diagnosis and in patients treated with novels agents that are known to be thrombogenic.

Disclosures:
No relevant conflicts of interest to declare.