BackgroundCoagulation problems in amyloidosis are historically associated with bleeding tendencies (mostly Factor X abnormalities). Increased clotting was observed in isolated cases diagnosed with low-grade disseminated intravascular coagulation (DIC). Problem of venous thromboembolic disaease (VTD) in amyloidosis was not systematically investigated.MethodsWe evaluated frequency of VTD and risk factors for VTD in 56 consecutive amyloidosis patients with a documented disease evaluated and followed up at our Center from 1991–2001. Data was collected in 5 categories: (a) demographics, (b) disease and treatment, (c) thrombosis case information, (d) major risk factors for thrombosis and (e) baseline laboratory data. Univariable correlates of VTD were assessed using Kaplan-Meier analysis and Cox proportional hazards analysis.ResultsMean age of the patients was 67 (years range 21 – 83). Male/female percentage ratio was 70/30. 29 % of the patients had high creatinine level (> 1.4 mg/dl). Personal or family history of VTD was recorded in 2 and 0 % of patients, respectively. Known hypercoagulable state was present in 1 patient (2%). 8 % of patients were smokers. Of 56 patients, 6 developed VTD (11%). Median time from diagnosis of amyloidosis to VTD was 12.5 month (range 1–107). Treatment was given within a median of 1 month (range 0–4) from the development of thrombosis. Only sites of VTD were lower extremities. No cases were associated with I.V. line. 1 case (17 %) was identified postoperatively. We identified several univariable correlates of VTD in amyloid patients, including greater age at diagnosis (HR-2.99, P = .041), personal history of DVT (HR-47.7, P = .006) and immobility (HR-11.78, P = .006). Presence of circulating serum M-protein had protective role in our analysis (HR-.08, P = .031). There was no correlation with the type of treatment patients were receiving.ConclusionRisk for thromboembolic diseases in patients with amyloidosis is similar to one previously described for multiple myeloma. Additional studies with higher number of thromboembolic events could help to further elucidate risk factors for VTD in this population of patients.

The ubiquitin-proteasome pathway is the principal pathway for intracellular protein degradation1,2 (Fig 1). This pathway selectively degrades an extensive number of short-lived regulatory proteins involved in the control of normal cellular processes. In order to be degraded, proteins targeted by the ubiquitin-proteasome pathway are covalently tagged by polyubiquitination, via a three-step enzymatic process, which ultimately leads to their recognition and degradation, by the 26S proteasome in a highly specific and regulated manner. This process is accomplished by the sequential action of three enzymes: an ATP-dependent ubiquitin-activating enzyme (E1), an ubiquitin-conjugating enzyme (E2) and an ubiquitin-pro-tein ligase (E3).3 This cascade covalently links the C terminus of ubiquitin to a free amino group on the target protein, usually the e-amino of a lysine residue.