Risk for post-thrombotic syndrome after lower-limb deep vein thrombosis: location of the thrombus or residual thrombi? / Risk razvitiia posttromboflebiticheskogo sindroma posle tromboza glubokikh ven nizhnikh konechnostei: lokalizatsiia tromba ili rezidual'nyi tromboz?

BACKGROUND: Many works aimed to determine factors that influence the onset of postthrombotic syndrome after an acute episode of deep venous thrombosis. We aimed to compare the prognostic value of the most proximal extent of thrombus (proximal and distal DVT) versus the residual thrombosis as identified by venous ultrasonography performed during follow-up. METHOD: We conducted a retrospective study of prospectively collected 1183 consecutive cohort patients in the RIETE registry after a first episode of deep venous thrombosis and assessed for postthrombotic syndrome after 12 months. RESULTS: Multivariate analysis revealed that: residual thrombosis (OR 1.40; 95% CI 0,88-2,21), the presence of cancer (OR 1.38; 95% CI: 0,64-2,97), immobility (OR 1.31; 95% CI 0,70-2,43) and estrogen-containing drugs use (OR 2.08, 95% CI 0,63-6,83), all had a predictive value for the occurrence of PTS. CONCLUSION: Our study results revealed that ultrasound finding of residual thrombosis is more predictive than proximal location of thrombus for postthrombotic syndrome after episode of deep venous thrombosis. Real life data from a large group of patients from the RIETE registry substantiates that.

Myeloma and thrombotic complications.

Multiple myeloma (MM) is a hematological malignancy with high risk for thrombosis. While venous thromboembolism is more common, myeloma patients can also present with arterial thrombosis. Risk factors responsible for this complication can be patient-related, myeloma- and treatment-related. Thromboprophylaxis is indicated along with specific therapeutic regimens employed in myeloma patients. This review will cover potential risk factors for thrombosis in patients with multiple myeloma, prevention recommendations and treatment strategies in this clinical setting.

PO-46 - Influence of extracellular vesicles derived from AML patients on stem cells and their microenvironment.

INTRODUCTION: Acute myeloid leukemia (AML) is characterized by rapid growth of leukemic blast cells. Extracellular vesicles (EVs) are shed from normal and pathologic cells and express membrane proteins and antigens, reflecting their cellular origin. AIM: To explore whether bone marrow EVs of AML patients originate from blast cells and are capable of influencing hematopoietic stem cells (HSC) in a pseudo-natural microenvironment obtained by co-culture of HSC with mesenchymal stem cells (MSC). MATERIALS AND METHODS: Bone marrow (BM) samples were collected from healthy controls and patients with newly diagnosed AML at three time points: diagnosis, nadir and remission. EV concentration, cell origin and expression of coagulation proteins were characterized by FACS. Stem cells were obtained from Ficoll gradient of cord blood (CB) followed by CD34+ isolation. Cord blood stem cells with or without MSC were co-incubated with AML EVs. EV internalization was demonstrated by FACS-AMNIS and confocal microscopy. Mir-125b and -155 expressions in the cells were analyzed by RT-PCR. RESULTS: AML patients were enrolled in the study. The total BM-EVs number was higher in patients at first remission compared to controls, while blast EV counts (labeled with anti-CD34, CD33, CD117) were higher in patients at diagnosis compared to controls and to patients in remission. Internalization of CD117+/CD33+ BM-EVs to cord blood stem cells in the presence or absence of MSC was evaluated by FACS-AMNIS. Confocal microscopy of CD33+ stained EVs strengthens the findings and shows presence of EVs even in the cytoplasm and the nucleus. Quantitative analysis of mir-125b and mir-155 expression in cord blood stem cells incubated with AML EVs revealed a clear tendency of increased expression in case of cell exposure to AML EVs in comparison to healthy control EVs. This tendency was emphasized in the presence of MSC. CONCLUSIONS: EVs of AML patients are generated from blast cells. By internalization into naïve stem cells they can influence their differentiation. Moreover, the presence of mesenchymal stem cells is likely to be essential to the process.

Silent pulmonary embolism in patients with proximal deep vein thrombosis in the lower limbs.

BACKGROUND: One in every three patients with deep vein thrombosis (DVT) in the lower limbs may have silent pulmonary embolism (PE), but its clinical relevance has not been thoroughly studied. METHODS: We used the RIETE Registry data to study patients with proximal DVT and no PE symptoms, but with a systematic search for PE. We compared the outcome of DVT patients with silent PE and those with no PE. RESULTS: Of 2375 patients with DVT, 842 (35%) had silent PE and 1533 had no PE. During the first 15 days of anticoagulation, patients presenting with silent PE had a higher incidence of symptomatic PE events than those with no PE (0.95% vs. 0.13%; P = 0.015), with a similar incidence of major bleeding (0.95% vs. 1.63%; P = 0.09). In patients with silent PE, the incidence of PE events during the first 15 days was equal to the incidence of major bleeding (eight events each), but in those with no PE the incidence of PE events was eight times lower (3 vs. 25 bleeding events). Multivariate analysis confirmed that DVT patients with silent PE had a higher incidence of symptomatic PE events during the first 15 days than those with no PE (odds ratio, 4.80; 95% CI, 1.27-18.1), with no differences in bleeding. CONCLUSIONS: DVT patients with silent PE at baseline had an increased incidence of symptomatic PE events during the first 15 days of anticoagulant therapy. This effect disappeared after 3 months of anticoagulation.