PO-40 - Real-life use of non-vitamin k antagonist oral anticoagulants in patients with cancer associated venous thromboembolism: data from a prospective cohort.

INTRODUCTION: Cancer associated thrombosis (CAT) has an increased risk of recurrent venous thromboembolism (VTE). Type, stage of cancer and chemotherapy (CHT) influence thromboembolic risk. The use of novel oral anticoagulants (NOACs) is controversial in patients with CAT. AIM: The aim of this study is to assess mortality, recurrent VTE and bleeding complications in patients with CAT and in patients without cancer receiving NOACs. MATERIALS AND METHODS: Consecutive patients with acute objectively confirmed VTE receiving NOACs within 1 month from diagnosis are included from September 2013 in an ongoing prospective cohort study. Characteristics of patients and outcome are reported according to the presence of CAT. Chi-squared test and Student' t-test are used. RESULTS: As for November 10(th) 2015, 472 patients were included in the study: 78 with CAT (16.5%). Lung, breast, gastrointestinal and genitourinary cancer was observed in 16%, 24%, 20% and 24% of patients with CAT, respectively. 31 patients with CAT (40%) were on CHT or radiotherapy (RT). 10 patients with CAT (13%) had at least an additional risk factor for VTE (4 had a CVC related thrombosis) and 34 (43.5%) were inpatients. Baseline characteristics of patients with and without CAT are reported in the Table. Pulmonary embolism was index VTE in 152 patients: 24.4% of patients with CAT and in 33.8% of those without cancer (p=0.10). DVT only was present in 320 patients and 78 had both DVT and PE. Among NOACs patients, 312 (66%) received initial loading dose: 61% of those with CAT and 67% without. 53 (11%) received reduced maintenance doses (10% with CAT, 11% without). As for nowadays, 272 patients had at least 3 months of follow-up, the mean follow-up being 8.6 months. 20 patients died (7.3%): 17 were cancer related deaths. Non cancer related death occurred in 1 patient with CAT (2%) and in 2 patients without (0.9%). No fatal bleedings or fatal VTE recurrences occurred. Patients recruitment and follow-up is currently ongoing aimed at assessing mortality, recurrent VTE and bleeding complications. Updated results on clinical outcomes will be presented at the congress. CONCLUSIONS: Patients with CAT receiving NOACs are treated as patients without CAT in terms of use of loading doses and maintenance treatment. Upper arm thrombosis is more frequently involved in CAT patients and proximal lower vein in patients without CAT. Non cancer related mortality was higher in CAT patients but no fatal recurrences or fatal bleedings were observed so far.

Withdrawal of warfarin after deep vein thrombosis: effects of a low fixed dose on rebound thrombin generation.

The optimal procedure for withdrawal of warfarin in patients with deep vein thrombosis (DVT) is still not defined. Rebound thrombin generation, which occurs after the withdrawal of warfarin, has been said to be associated with early recurrence of DVT. The aim of this study was to compare two procedures for warfarin withdrawal after the first episode of DVT with respect to rebound thrombin generation. Forty-one consecutive patients were randomly assigned to abrupt withdrawal of warfarin (group A), or to an additional month of warfarin, at the fixed dose of 1.25 mg/day (group B). Plasma samples were withdrawn for the assay of prothrombin fragment F1+2 (F1+2), protein C, factor VII and International Normalized Ratio (INR), before any anticoagulant treatment (I), during initial heparin (II) and full dose warfarin (III), at the end of full dose warfarin (IV) and then 1 (V), 4 (VI), 5 (VII) and 9 (VIII) weeks after randomization. The mean duration of full-dose warfarin treatment, the mean warfarin dose and the mean INR during full-dose warfarin treatment were similar in the two groups. A decrease in F1+2 was observed during heparin and warfarin treatment (II, 1.7 nmol/ml; III, 1.0 nmol/ml; IV, 0.7 nmol/ml; versus I, 3.5 nmol/ml; P<0.01). After the withdrawal of warfarin, an increase in F1+2 was observed in both groups, but without significant statistical differences (group A: V, 1.2 nmol/ml; VI, 1.5 nmol/ml; VII, 1.6 nmol/ml; VIII, 1.1 nmol/ml; group B: V, 1.3 nmol/ml; IV, 1.5 nmol/ml; VII, 1.4 nmol/ml; VIII, 1.4 nmol/ml). No significant difference between the two groups was observed in the recovery of protein C and factor VII. Four patients experienced a recurrence of DVT, three in group B and one in group A. Our findings confirm that rebound thrombin generation occurs in patients with DVT after the withdrawal of warfarin. Rebound thrombin generation is not reduced by a low, fixed dose of warfarin.

Distribution and occlusiveness of thrombi in patients with surveillance detected deep vein thrombosis after hip surgery.

Venous thromboembolism is a leading cause of in-hospital postoperative morbidity and mortality. Postoperative deep vein thrombosis (DVT) is usually asymptomatic. A number of studies have consistently shown that the non invasive diagnostic methods are inaccurate in the screening of asymptomatic DVT. Failure of non invasive diagnostic methods to detect thrombi in asymptomatic patients has been suggested to be due to the features of thrombi in these patients. The aim of this study was to assess the distribution and the occlusiveness of thrombi in a series of 321 asymptomatic hip surgery patients with adequate bilateral venography of the lower limbs. Venography was performed 10 +/- 1 days after hip surgery. DVT was found in 180 limbs (28.0%). The distribution of thrombi was as follows: 26 (14.4%) isolated proximal thrombi, 55 (30.6%) proximal and distal thrombi, 99 (55.0%) isolated calf thrombi. We found that 14 of the 81 proximal trombi (17.3%) involved the superficial femoral vein either as exclusive location or in association with calf veins. An involvement of common femoral, superficial femoral and popliteal vein was observed in 37 (45.7%), 39 (48.1%) and 44 (54.3%) cases of the 91 proximal DVT. These thrombi were non occlusive in 25 (67.6%), 22 (56.4%) and 26 (59.1%) limbs, respectively. An involvement of at least one peroneal, anterior tibial and posterior tibial veins was observed in 118, 13 and 89 cases of the 220 distal thrombi. These thrombi were non occlusive in 61 (51.7%), 10 (76.9%) and 30 (33.7%) of the cases. We conclude that the majority of thrombi found in asymptomatic hip surgery patients are non occlusive. In view of this, non invasive diagnostic methods based upon venous flow measurement will be unlikely to improve the diagnosis of asymptomatic DVT. The high incidence of isolated superficial femoral vein thrombosis necessitates that real-time B-mode ultrasonography should be performed examining the entire proximal venous system.

Effects of low molecular weight heparins on fibrin polymerization and clot sensitivity to t-PA-induced lysis.

We have previously demonstrated that therapeutic concentrations of unfractionated heparin (UFH) impair fibrin polymerization leading to the formation of clots which are more sensitive to lysis induced by tissue plasminogen activator (t-PA). The aim of this study was to compare the effect of UFH with that of three different low molecular weight heparins (LMWHs) on clot sensitivity to t-PA-induced lysis. Labelled fibrin clots, prepared from plasma containing UFH, Fraxiparine, Reviparine, Enoxaparine or saline, were incubated in phosphate buffer containing t-PA (0.1 and 0.5 microgram/ml) and plasminogen (20 micrograms/ml). The extent of clot lysis was quantified by counting the residual radioactivity of the clots and by measuring D-dimer levels released into the medium. Fibrin polymerization and clot structure were evaluated by means of a turbidimetric assay and by electron microscopic scanning. Pre-incubation of plasma with 0.5 or 1.0 U/ml UFH resulted in a marked dose-dependent acceleration of lysis induced by 0.1 or 0.5 microgram/ml t-PA. In contrast, lysis rates induced by 0.5 microgram/ml t-PA were not modified by pre-incubation of plasma with LMWHs. When exposed to 0.1 microgram/ml t-PA clots formed from plasma containing 0.5-2 IU/ml of Fraxiparine, Reviparine and Enoxaparine showed only a minor increase in lysis rates compared to control clots. There was not a clear dose-response curve with LMWHs. Furthermore, lysis rates obtained with UFH-treated clots were always significantly higher than those seen with LMWHs-treated clots.(ABSTRACT TRUNCATED AT 250 WORDS)