title: Inflammation, TNFα and endothelial dysfunction link lenalidomide to venous thrombosis in chronic lymphocytic leukemia.
abstract: Patients receiving lenalidomide are at an increased risk for deep venous thrombosis (DVT). Here, we prospectively investigated the DVT risk in patients with relapsed chronic lymphocytic leukemia (CLL) treated with lenalidomide (n = 32). Five patients developed six incidents of DVT over 1 year for an annual incidence of 16%. Three of these were considered drug-related. Median time to DVT was 105 days (range 56-259 days). No pulmonary embolism was detected. Hypercoagulability screen before study entry was negative in all patients who subsequently developed DVTs. Compared to normal volunteers CLL patients had increased baseline levels of D-dimer, thrombin-antithrombin, soluble vascular endothelial adhesion molecule 1 (sVCAM-1), and thrombomodulin (p < 0.001). After 1 week on lenalidomide D-dimer, thrombomodulin, sVCAM-1, factor VIII, TNFα, and C-reactive protein were significantly increased while protein C was decreased (p < 0.001). In patients with lenalidomide-related DVTs, TNFα, and sVCAM-1 were more strongly upregulated than in all other patients (p < 0.05) and TNFα and sVCAM-1 levels were significantly correlated (r = 0.65, p < 0.001). These data link lenalidomide associated DVTs with TNFα upregulation and endothelial cell dysfunction and suggest that aspirin may have a role for DVT prophylaxis in these patients.
authors.affiliation: Hematology Branch, NHLBI, NIH, Bethesda, Maryland 20892-1202, USA.
authors.forename: Georg
authors.initials: G
authors.lastname: Aue
authors.forename: Jay
authors.initials: J
authors.lastname: Nelson Lozier
authors.forename: Xin
authors.initials: X
authors.lastname: Tian
authors.forename: Ann M
authors.initials: AM
authors.lastname: Cullinane
authors.forename: Susan
authors.initials: S
authors.lastname: Soto
authors.forename: Leigh
authors.initials: L
authors.lastname: Samsel
authors.forename: Philip
authors.initials: P
authors.lastname: McCoy
authors.forename: Adrian
authors.initials: A
authors.lastname: Wiestner
mesh_terms: D000328:Adult; D000368:Aged; D001777:Blood Coagulation; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000473:pathology; D000077269:Lenalidomide; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation; D020246:Venous Thrombosis / Q000097:blood / Q000139:chemically induced*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D013792:Thalidomide; D000077269:Lenalidomide