Fondaparinux Reduces All Types of Symptomatic Thromboembolic Complications in Patients with Superficial-Vein Thrombosis in the Legs: Data From the CALISTO Study

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2310-2310
Author(s):  
Alain Leizorovicz ◽  
Paolo Prandoni ◽  
Hervé Décousus
Keyword(s):  
Board Of Directors ◽  
Anticoagulant Therapy ◽  
Research Funding ◽  
Superficial Vein ◽  
Composite Outcome ◽  
Thromboembolic Complications ◽  
Advisory Committees ◽  
Vein Thrombosis ◽  
Efficacy Outcome ◽  
Superficial Vein Thrombosis

Abstract Abstract 2310 on behalf of the Steering Committee of the CALISTO Study. Background The CALISTO trial demonstrated the clinical benefit of anticoagulant therapy in patients with spontaneous isolated superficial-vein thrombosis (SVT) in the legs (n=3002).1 Compared with placebo, a 45-day once-daily subcutaneous treatment with fondaparinux 2.5 mg was associated with a 85% relative reduction in the risk of the composite of all-cause death and adjudicated symptomatic thromboembolic complications at day 47, a benefit that was maintained at 30-day follow-up (day 77) and was not associated with an increased bleeding risk. The benefit of fondaparinux was observed with the same magnitude on each thromboembolic component of the primary efficacy outcome, including symptomatic extension of SVT to the sapheno-femoral junction (SFJ). However, although all symptomatic extensions of the index SVT were reported and reviewed, only those within 3 cm of the SFJ were counted for the primary outcome. To better characterize the efficacy of fondaparinux we used a new composite efficacy outcome, including all symptomatic extensions of SVT, regardless of their distance from the SFJ. Methods The composite thromboembolic outcome of the original primary endpoint of the CALISTO trial included symptomatic pulmonary embolism (PE), symptomatic deep-vein thrombosis (DVT), symptomatic extension of the index SVT to ≤3 cm (EXT ≤3 cm) from the SFJ, and symptomatic recurrence of SVT (composite outcome CO-1). In a post-hoc analysis, we additionally included in the composite outcome (CO-2) all symptomatic extensions of the index SVT regardless of their final distance from the SFJ (EXT >3 cm). All symptomatic thromboembolic events were confirmed by appropriate objective tests and reviewed by an independent, central, blinded adjudication committee. Results Overall, symptomatic EXT ≤3 cm and EXT >3 cm of index SVT at day 77 were reported in 59 (2.0%) and 68 patients (2.3%), respectively. Compared with placebo, fondaparinux significantly reduced at day 77 both the rate of CO-1, from 6.2% (93/1500) to 1.1% (17/1502; RR, 0.18, 95% confidence interval [CI], 0.11 to 0.31, p<0.001) and the rate of CO-2, from 9.4% (141/1500) to 1.9% (29/1502; RR, 0.21, 95% CI, 0.14 to 0.30, p<0.001). 1 Fondaparinux significantly lowered the rate of symptomatic EXT >3 cm from 3.7% (56/1500) to 0.8% (12/1501; RR, 0.21, 95% CI, 0.12 to 0.40, p<0.001), a reduction similar in magnitude to the reduction of EXT ≤3 cm. In the placebo group, 5/54 (9.3%) patients with a symptomatic EXT ≤3 cm and 5/56 (8.9%) of those with a symptomatic EXT >3 cm also experienced symptomatic PE or DVT during the course of the trial. In the fondaparinux group, none of the patients with SVT extension, reaching ≤3 cm or >3 cm from the SFJ, experienced symptomatic PE or DVT. Fondaparinux was associated with less use of medical resources, particularly in terms of surgery to treat SVT or need for anticoagulant therapy (Table). Conclusion Extension of the index SVT is a clinically relevant complication of the disease, regardless of the distance of the extension from the SFJ, and is associated with additional use of medical resources. Compared with placebo, fondaparinux reduced the rate of symptomatic thromboembolic complications in patients with spontaneous isolated SVT in the legs. 1 Decousus H, et al; CALISTO Study Group. N Engl J Med 2010;363:1222-32. Disclosures: Leizorovicz: BMS: Research Funding; Sanofi Aventis: Honoraria; Bayer: Consultancy, Honoraria; GSK: Consultancy, Honoraria, Research Funding; Boehringer Ingelheim: Consultancy, Honoraria. Off Label Use: Fondaparinux for the treatment of Superficial Vein Thrombosis, labelled in Europe. Prandoni:GSK: Membership on an entity's Board of Directors or advisory committees. Décousus:GSK: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Research Funding; Boehringer Ingelheim: Research Funding; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees.

Anatomical Predictors of Venous Thromboembolism Recurrence after Isolated Superficial Vein Thrombosis

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 651-651
Author(s):  
Jean-Philippe Galanaud ◽  
Marie-Antoinette Sevestre ◽  
Céline Genty ◽  
Susan R Kahn ◽  
Gilles Pernod ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Board Of Directors ◽  
Research Funding ◽  
Superficial Vein ◽  
Advisory Committees ◽  
Vein Thrombosis ◽  
Superficial Vein Thrombosis ◽  
The Impact

Abstract Background: Isolated superficial vein thrombosis (iSVT) (i.e. without concurrent deep-vein thrombosis or pulmonary embolism) is a frequent event. Its clinical significance and management are controversial. Data on long-term follow-up are scarce and the impact of anatomical characteristics of iSVT on the risk of venous thromboembolism (VTE) (DVT and/or PE) recurrence has not been assessed. Objective: To determine the impact of anatomical characteristics of iSVT on the long-term risk of VTE recurrence. Methods: Using data from the The OPTIMEV (OPTimisation de l'Interrogatoire dans l'_evaluation du risque throMbo-Embolique Veineux) study, a prospective, observational, multicenter study, we assessed at 3 years in patients recruited for an objectively confirmed iSVT i) cumulative rates of DVT, PE and SVT recurrences using the Kaplan-Meier method; and ii) anatomical predictors of VTE recurrence (SVT involving the sapheno-femoral junction (i.e. ≤3 cm), SVT of the trunk of the great saphenous vein, bilateral SVT, SVT occurring in a varicose vein (i.e. C≥2 according to CEAP classification) using a Cox multivariable model adjusted for age, sex, cancer and personal history of VTE. At baseline, all patients with SVT underwent a complete bilateral swhole leg ultrasound to exclude concurrent DVT and during follow-up, all suspected VTE recurrences were confirmed/ruled out with objective tests. All recurrences were centrally adjudicated by the study's expert committee. Results: Among the 479 recruited patients with iSVT, 12.5% (n=60) had a thrombotic recurrence during the 3 years of follow-up. Cumulative rates of recurrence as a PE, DVT and iSVT were 1.9%, 4.8% and 5.8%, respectively. In multivariate analysis, a thrombus involving the sapheno-femoral junction at baseline independently increased the risk of VTE recurrence (HR=3.34 [1.5-7.2]). Presence of varicose veins also increased the risk but this result did not reach statistical significance (HR=1.8 [0.9 - 3.9], p=0.11). Conclusion: In an unselected population of patients with iSVT, long-term risk of VTE recurrence is substantial. Involvement of the sapheno-femoral junction is a strong independent predictor of VTE during the subsequent 3 years. Our results suggest the need for more aggressive management and follow-up of patients with iSVT exhibiting this anatomical characteristic. Disclosures Galanaud: Daichi: Membership on an entity's Board of Directors or advisory committees, Research Funding; bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding. Sevestre:bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Daichi: Membership on an entity's Board of Directors or advisory committees, Research Funding. Pernod:pfizer: Consultancy; leo: Consultancy; bristol meyers: Consultancy; Daichi: Consultancy; bayer: Consultancy. Brisot:bayer: Membership on an entity's Board of Directors or advisory committees; daichi: Membership on an entity's Board of Directors or advisory committees. Quéré:3-M: Research Funding; thuasne: Research Funding; aspen: Research Funding; daichi: Membership on an entity's Board of Directors or advisory committees; bayer: Membership on an entity's Board of Directors or advisory committees; leo: Membership on an entity's Board of Directors or advisory committees.

Reevaluation of the Incidence of Thromboembolic Complications in Congenital Factor XII Deficiency

1999 ◽  
Vol 82 (10) ◽  
pp. 1240-1246 ◽  
Author(s):  
S. Zeerleder ◽  
M. Schloesser ◽  
M. Redondo ◽  
W. A. Wuillemin ◽  
W. Engel ◽  
...  
Keyword(s):  
Life Time ◽  
Factor Xii ◽  
Superficial Vein ◽  
Thromboembolic Complications ◽  
Vein Thrombosis ◽  
Kaplan Meier ◽  
Superficial Vein Thrombosis ◽  
Thrombophilic Condition ◽  
Cerebrovascular Stroke

SummaryTo further elucidate the debated role of hereditary FXII deficiency as a thrombophilic risk factor this follow-up study on 65 subjects out of 12 Swiss families was undertaken (follow-up: 6 yrs). Fifteen severely FXII deficient subjects (FXII:C < 1%), 35 partially FXII deficient subjects (FXII:C ≥ 1-59%), 10 with normal FXII values (FXII:C ≥ 70%), and 5 non-classifiable subjects (FXII:C ≥ 60-69%) were reevaluated. Eight subjects (4 severely and 3 partially FXII deficient, 1 non-classifiable) were newly enrolled. Four instances of deep vein thrombosis, one superficial vein thrombosis and one myocardial infarction were noted in 2 out of 19 severely FXII deficient subjects during a total life-time period of 866.6 patient-years. In 38 partially FXII deficient subjects (1862.8 patient-years) one ischemic cerebrovascular stroke and one superficial vein thrombosis were recorded in 2 individuals. The 10 subjects with normal FXII values (498.2 patient-years) remained thrombosis-free. One superficial vein thrombosis occurred in an unclassifiable woman. None of the 3 different FXII gene defects revealed in our patients was specifically associated with thromboembolic complications. Kaplan-Meier analysis of thrombosis-free survival suggests that hereditary partial (and probably severe) FXII deficiency does not constitute a thrombophilic condition.

The EINSTEIN DVT Study: Does Localization of the Initial DVT Affect the Occurrence of Recurrent VTE While Patients Are on Anticoagulation?

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 207-207
Author(s):  
Martin H Prins ◽  
Paolo Prandoni ◽  
Anthonie WA Lensing ◽  
Bonno van Bellen ◽  
Akos F Pap ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Recurrent Events ◽  
Femoral Vein ◽  
Popliteal Vein ◽  
Advisory Committees ◽  
Common Femoral Vein ◽  
Vein Thrombosis ◽  
Venous Thromboembolic Events ◽  
Recurrent Vte

Abstract Abstract 207 Background: The extent of deep vein thrombosis (DVT) is, for many physicians, an important variable that is considered in decisions on the type and duration of anticoagulant treatment. Although it has been consistently demonstrated that localization of the initial DVT is a powerful and independent predictor of recurrent venous thromboembolism (VTE) after discontinuation of anticoagulation (Baglin T et al. J Thromb Haemost 2010;8:2436–2442), it remains unknown to what extent localization of the initial DVT affects the occurrence of recurrent VTE while patients are on anticoagulation. Data from the EINSTEIN DVT study, which randomized 3,449 patients with proximal DVT, offers an opportunity to investigate this question. Aim: To investigate whether localization of the initial DVT was predictive of the rate of recurrent venous thromboembolic events in the whole cohort of patients in the EINSTEIN DVT study, in those who received rivaroxaban, or in those who received conventional anticoagulation with enoxaparin plus vitamin K antagonists (VKA) followed by VKA alone. Methods: Patients were randomized to rivaroxaban or enoxaparin plus VKA followed by VKA only for intended treatment durations of 3, 6, or 12 months. Patients were grouped into four categories according to the extent of the proximal vein thrombosis that was recorded at baseline: 1) popliteal vein alone; 2) popliteal and superficial femoral vein; 3) popliteal, superficial femoral, and common femoral vein; and 4) all combinations of DVT without popliteal vein involvement. Patients were followed for recurrent events. All baseline and recurrent events were assessed by a central independent adjudication committee that was unaware of treatment allocation. The effect of thrombus location on the incidence of recurrent VTE was assessed using a Cox proportional hazard model. Results: Recurrent VTE occurred in 21/1,040 (2.0%) patients with popliteal vein thrombosis only; in 28/1,002 (2.8%) patients with thrombosis located in the popliteal and superficial femoral vein; in 26/935 (2.8%) patients with thrombosis in the popliteal, superficial femoral, and common femoral vein (± iliac vein); and in 11/370 (3.0%) patients without popliteal vein involvement. None of these differences was statistically significant (p=0.87). The relative effect of rivaroxaban versus enoxaparin/VKA was similar in these subgroups (Table). Conclusions: At baseline, most patients in the EINSTEIN DVT study had thrombosis that involved more than one proximal vein. While patients were on treatment, the extent of the DVT at baseline was not predictive for recurrent VTE irrespective of type of treatment. Patients with extensive thrombosis (i.e. popliteal, superficial femoral, and common femoral vein involvement) had a recurrence rate below 3%, which was similar to the rate of recurrence in patients with thrombosis in only one vein at baseline. In summary, this analysis suggests that the localization and extent of the initial DVT was not predictive of the rate of recurrent venous thromboembolic events in the EINSTEIN DVT patient population while patients were on anticoagulation. Character count: 2670/3800 (spaces excluded) (2983 including table) Disclosures: Prins: Bayer HealthCare: Consultancy, Honoraria. Prandoni:GSK: Membership on an entity's Board of Directors or advisory committees. Lensing:Bayer HealthCare AG: Employment. van Bellen:Bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding. Pap:Bayer HealthCare AG: Employment. Raskob:Bayer: Consultancy, Honoraria; Johnson & Johnson: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Daiichi Sankyo: Consultancy, Honoraria; Boehringer-Ingelhiem: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; GSK: Consultancy, Honoraria; Sanofi-Aventis: Consultancy, Honoraria. Büller:Sanofi-aventis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer HealthCare: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Meyers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Daiichi-Sankyo: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GlaxoSmithKline: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Two Years Versus Six Months of Oral Anticoagulation after a First Episode of Unprovoked Pulmonary Embolism: The Padis PE Multicenter, Double-Blind, Randomized Trial

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. LBA-3-LBA-3
Author(s):  
Francis Couturaud ◽  
Olivier Sanchez ◽  
Gilles Pernod ◽  
Patrick Mismetti ◽  
Patrick Jego ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Placebo Group ◽  
Board Of Directors ◽  
Major Bleeding ◽  
Research Funding ◽  
Composite Outcome ◽  
Advisory Committees ◽  
Entire Study ◽  
Warfarin Group ◽  
Recurrent Vte

Abstract Background: Patients with a first episode of unprovoked pulmonary embolism have a high risk of recurrent venous thromboembolism (VTE) after anticoagulation is discontinued. Prolongation of anticoagulant therapy beyond the initial period of 3 to 6 months is associated with a significant reduction of recurrent VTE, but an excess of bleeding events. In addition, most studies assessing prolonged treatment did not follow the patients after treatment had been stopped. Thus, the optimal duration of anticoagulation in patients with a first unprovoked pulmonary embolism remains uncertain. Method: In a multicenter, randomized, double-blind, controlled trial, we compared an additional 18 months of warfarin (target International Normalized Ratio, 2 to 3) with placebo in patients with a first episode of unprovoked pulmonary embolism that had been initially treated with a vitamin K antagonist for 6 uninterrupted months. In both groups, all patients were followed up for an additional median period of 2 years after treatment had been stopped. Primary outcome was the composite of recurrent VTE or major bleeding during the 18-month treatment period. Secondary outcomes included the composite outcome during the entire study period (i.e. 18 months plus a median follow-up of 2 years), deaths not caused by pulmonary embolism or major bleeding and the components of the composite outcome during the treatment period and during the entire study period. All outcomes were centrally adjudicated. Results: A total of 371 patients were included in the study and analyzed on an intention-to-treat basis. During the treatment period, the composite outcome occurred in 6 of 184 patients (3.3%) in the warfarin group and in 25 of 187 patients (13.5%) in the placebo group (hazard ratio [HR], 0.23; 95% confidence interval [CI], 0.09-0.55; p=0.0004). Recurrent VTE occurred in 3 (1.7%) patients in the warfarin group and in 25 (13.5%) in the placebo group (HR, 0.11; 95%CI, 0.03-0.37); major bleeding occurred in 4 (2.2%) patients in the warfarin group and in 1 (0.5%) in the placebo group (HR, 4.07; 95%CI, 0.45-36.38). Two deaths not related to the study outcome occurred in each group. During the entire median study period of 41 months, the composite outcome occurred in 33 (20.8%) patients in the warfarin group and in 41 (23.5%) in the placebo group (HR, 0.76; 95%CI, 0.48-1.20; p=0.24) (Figure 1). Recurrent VTE occurred in 28 (17.9%) patients in the warfarin group and in 39 (22.1%) in the placebo group (HR, 0.67; 95%CI, 0.41-1.08); major bleeding occurred in 6 (3.5%) patients in the warfarin group and in 4 (2.5%) in the placebo group (HR, 1.57; 95%CI, 0.44-5.55). Thirteen (11.9%) patients died in the warfarin group, four deaths being related to recurrent VTE and one to major bleeding; six (3.6%) patients died in the placebo group from a cause unrelated to recurrent VTE or bleeding (p=0.08). Of the 67 episodes of recurrent VTE, 52 (77.6%) were pulmonary embolism and 58 (86.6%) were unprovoked. Conclusion: After 6 months of anticoagulation for a first episode of unprovoked pulmonary embolism, extending anticoagulation for an additional 18 months was associated with a major reduction in the risk of recurrent VTE or major bleeding during the treatment period. However, this benefit was not maintained after discontinuation of anticoagulation. (ClinicalTrials.gov number NCT00740883). Figure 1. Cumulative risk of the composite outcome (recurrent VTE or major bleeding) over the entire study period Figure 1. Cumulative risk of the composite outcome (recurrent VTE or major bleeding) over the entire study period Disclosures Couturaud: Astra Zeneka: Co-investigator in clinical trial, Co-investigator in clinical trial Other, Membership on an entity's Board of Directors or advisory committees; Bayer: Co-investigator in clinical trial Other, Membership on an entity's Board of Directors or advisory committees. Sanchez:Bayer: Membership on an entity's Board of Directors or advisory committees. Mismetti:Bayer: Membership on an entity's Board of Directors or advisory committees; pfizer: Membership on an entity's Board of Directors or advisory committees; boerhinger ingelheim: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees. Jego:Bayer: Membership on an entity's Board of Directors or advisory committees; actelion: Research Funding; GlaxoSmithKline: Research Funding. Parent:Bayer: Membership on an entity's Board of Directors or advisory committees. Lorillon:Astra Zeneka: Membership on an entity's Board of Directors or advisory committees, symposium invitation Other; Sanofi: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Boehringer Ingelheim: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees. Girard:Leo Pharma: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees. Lacut:Bayer-Healthcare: Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding; Boehringer Ingelheim: Research Funding. Leroyer:Novartis: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Investigator in COPD clinical trials, Investigator in COPD clinical trials Other, Membership on an entity's Board of Directors or advisory committees; Astra Zeneka: Investigator in asthma clinical trials Other, Membership on an entity's Board of Directors or advisory committees. Decousus:Daiichi-Sankyo: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees. Meyer:Sanofi-Aventis: Research Funding; LEO Pharma: Research Funding; Bayer: Research Funding; Boehringer Ingelheim: Research Funding. Mottier:Pfizer: Membership on an entity's Board of Directors or advisory committees; bayer: Membership on an entity's Board of Directors or advisory committees; Boehringer Ingelheim: Membership on an entity's Board of Directors or advisory committees; Sanofi: Research Funding.

Long Term Follow up of a Phase 2 Study of Ruxolitinib in Patients with Splanchnic Vein Thrombosis Associated with Myeloproliferative Neoplasm

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2803-2803 ◽  
Author(s):  
Lisa Pieri ◽  
Chiara Paoli ◽  
Umberto Arena ◽  
Fabio Marra ◽  
Fabio Mori ◽  
...  
Keyword(s):  
Platelet Count ◽  
Weight Gain ◽  
Board Of Directors ◽  
Phase Ii ◽  
Esophageal Varices ◽  
Research Funding ◽  
Advisory Committees ◽  
Splanchnic Vein Thrombosis ◽  
Vein Thrombosis

Abstract Background: Philadelphia-negative Myeloproliferative Neoplasms (MPN) include Polycythemia Vera (PV), Essential Thrombocythemia (ET) and Myelofibrosis, both Primary (PMF) and secondary to PV or ET (PPV-MF and PET-MF). A MPN is frequently the underlying cause of splanchnic vein thrombosis (SVT). Ruxolitinib, a JAK1/2 inhibitor, efficiently reduced spleen volume and improved symptoms in patients (pts) with MF and PV in the COMFORT-I/II and RESPONSE phase III trials, and in ET pts in a phase II study. We reported (Blood 2014 124:3192) that ruxolitinib was safe in pts with MPN associated to SVT and effective in reducing spleen size at the planned primary endpoint analysis at 24 weeks (w) in a phase II clinical trial. Herein we present follow up data with cut off at 1 year after core period (a total of 72 w of treatment). Methods: Main enrolment criteria included diagnosis of PV, ET, PMF or PPV-/PET-MF associated with SVT, splenomegaly >5 cm below costal margin (bcm), active anticoagulant or antiaggregant thrombosis prophylaxis, platelet count (plt) >100 x109/L, neutrophils count >1x109/L, normal hepatic and renal function, absence of esophageal varices >grade 2. Pts who completed the 24 w of study treatment and tolerated well the drug and had evidence of clinically-significant improvement were allowed to enter an extension phase aimed at collecting and reviewing safety and efficacy data. The drug was provided free of charge by Novartis, that had no role in trial design nor in data analysis. Results: Diagnosis of MPN were: PMF 8 (38.1%), PV 5 (23.8%), ET 4 (19.1%), PPV-MF 3 (14.3%), PET-MF 1 (4.8%). Nineteen pts had spleno-porto-mesenteric thrombosis and 3 Budd-Chiari syndrome (BCS); one pt had both sites involved. Initial dose of ruxolitinib was 10 mg BID for PV, 25 mg BID for ET, 15 mg BID for MF pts with baseline (bl) platelet count of 100 to 200x109/L and 20 mg BID for platelet count >200x109/L. Currently 17/21 pts are on active treatment, 14 completed w72; final data for all 17 pts will be available at meeting. One pt with MF discontinued from the study being shifted to commercial ruxolitinib at w60, one ET and one MF pt discontinued for inefficacy at w24 and one MF pt for an unrelated adverse event after w72. Efficacy: 13/21 (61.9%) pts obtained a ≥50% spleen length (sl) reduction by palpation at w24, that was maintained at w72 in 8/14 pts (57.1%). Median sl reduction at w72 was 63% (range 0-100). No significant differences in resistive or pulsatility index of splanchnic artery were noted, nor in esophageal varices status evaluated at w72. 10/11 evaluated pts with echocardiography at w72 showed a median reduction of the cardiac output of 20.1% (range 2.3-42.2) mainly due to a reduction of heart rate and of cardiac index (-21.9%, range 8.8-44.3) due to increase in body surface area. The first effect could be attributed to decrease of proinflammatory cytokines, the second to weight gain associated with ruxolitinib. Symptomatology was evaluated by MPN-SAF up to w24, showing a median total symptom score reduction from 65 to 42. Safety: regardless of drug relationship, the most common adverse events (AE) (% any grade, % grade ≥3) were thrombocythopenia (57.1%; 14.3%) and anemia (33.3%, 19%) that were the main reasons for dose adjustments. Other AE included AST or ALT increase (42.9%, 0%), diarrhea (28.6%, 0%), abdominal pain (23.8%, 0%), ascites (19%, 0%), fever (23.8%, 0%), neutropenia, (9.5%, 9.5%), upper airways infection (19%, 0%), weight gain (14.3%, 4.8%), muscle cramps (14.3%, 0%). Three serious AE occurred: one case of hepatocarcinoma in a pts with BCS, one grade 2 pneumonia and one grade 2 haematemesis not related to esophageal varices. Median ruxolitinib total daily dose at w72, after dose adjustments, was 19.1 mg for MF, 16 mg for PV and 28.3 mg for ET. Median hemoglobin reduced from 12.9 gr/dL (range 9.4-16.7) at bl to 10.7 (8.4-14.4) at w16 and recovered at w72 (12.1, range 10.8-14.7). No pts received transfusions. Median platelet count was 212 x109/L (100-389) at bl, reached to the lowest level at w4 (139, range 48-252) and improved to 160 (69-285) at w72. Median leukocyte count decreased from 7.3 x109/L (1.8-16.4) at bl to 4.08 (1.2-21.7) at w 24, and remained substantially stable through w 72 (4.96; range 2.45-17.3). Median reduction of JAK2 allele burden at w72 was 9% (range 0-38). Conclusions: At w 72 follow up, ruxolitinib continues to be safe in pts with MPN associated to SVT and maintains efficacy against splenomegaly in 57% of the pts. Disclosures De Stefano: Roche: Research Funding; GlaxoSmithKline: Speakers Bureau; Bruno Farmaceutici: Research Funding; Novartis: Research Funding, Speakers Bureau; Janssen Cilag: Research Funding; Celgene: Speakers Bureau; Shire: Speakers Bureau; Amgen: Speakers Bureau. Barbui:Novartis: Speakers Bureau. Vannucchi:Novartis: Other: Research Funding paid to institution (University of Florence), Research Funding; Shire: Speakers Bureau; Baxalta: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

scholarly journals Meta-Analysis of Long-Term Risk of Recurrent Venous Thromboembolism after Stopping Anticoagulation in Men and Women with First Unprovoked Venous Thromboembolism

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2527-2527 ◽  
Author(s):  
Faizan Khan ◽  
Alvi Rahman ◽  
Marc Carrier ◽  
Clive Kearon ◽  
Jeffrey I. Weitz ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Anticoagulant Therapy ◽  
Research Funding ◽  
Meta Analysis ◽  
First Year ◽  
Advisory Committees ◽  
Men And Women ◽  
Second Year ◽  
Recurrent Vte

Abstract Background: The optimal duration of anticoagulation after a first unprovoked venous thromboembolism (VTE) is uncertain. Anticoagulant therapy is highly effective at reducing the risk of recurrent VTE, but this clinical benefit is not maintained once anticoagulation is stopped. Current guidelines suggest considering indefinite anticoagulation in all patients with unprovoked who have a non-high bleeding risk. However, this is a weak recommendation based on limited evidence. Deciding whether patients with a first unprovoked VTE should be considered for indefinite anticoagulant therapy requires estimation of the long-term risk of recurrent VTE after stopping anticoagulation. This risk however, is poorly established, hindering decision making. Methods: We performed a systematic review and meta-analysis of randomized clinical trials and prospective observational studies to determine the rate of recurrent VTE in the first year, in the second year, between years 2 and 5, and years 5 and 10; and the cumulative incidence for recurrent VTE at 2, 5 and 10 years after stopping anticoagulation in men and women with first unprovoked VTE, who had completed at least 3 months of initial treatment. Studies were identified through a comprehensive literature search using MEDLINE, EMBASE and the Cochrane CENTRAL databases. Data clarifications were requested from authors of eligible studies. Rates of recurrent VTE were calculated for each study from the total number of recurrent VTE events divided by the person-years of follow-up, and then pooled using random-effects meta-analysis. Results: Fourteen studies involving 6, 446 patients were included in the analysis. Among men with a first unprovoked VTE, the pooled rate of recurrent VTE per 100 person-years after stopping anticoagulation was 11.2 events (95% CI, 9.0-13.6) in the first year; 7.4 events (95% CI, 5.5-9.5) in the second year; 4.4 events/year (95% CI, 3.2-5.7) between years 2 and 5, and 3.8 events/year (95% CI, 1.6-6.9) between years 5 and 10 [Table 1]. Among women with a first unprovoked VTE, the pooled rate of recurrent VTE per 100 person-years after stopping anticoagulation was 8.6 events (95% CI, 6.5-11.0) within the first year; 5.2 events (95% CI, 3.5-7.2) in the second year; 3.0 events/year (95% CI, 1.6-4.7) between years 2 and 5, and 2.0 events/year (95% CI, 1.3-2.9) between years 5 and 10 [Table 1]. In men and women respectively, the cumulative incidence for recurrent VTE was 17.8% (95% CI, 14.0%-21.9%) and 13.4% (95% CI, 9.8%-17.4%) at 2 years, 28.2% (95% CI, 22.0%-34.4%) and 20.9% (95% CI, 14.0%-28.5%) at 5 years, and 40.8% (95% CI, 28.0%-53.9%) and 28.5% (95% CI, 19.5%-38.3%) at 10 years after stopping anticoagulant therapy [Table 2]. Conclusions: Among patients with a first unprovoked VTE who have completed at least 3 months of initial treatment, men have a higher long-term risk of recurrent VTE after stopping anticoagulation, and may be given greater consideration for indefinite anticoagulant therapy. Our findings affirm the importance of considering patient's sex in deciding the optimal duration of anticoagulation, and as such, emphasize the need for individualized, patient-centered approach for the long-term management of unprovoked VTE. Disclosures Carrier: BMS: Honoraria, Research Funding; Leo Pharma: Research Funding; Pfizer: Honoraria; Bayer: Honoraria. Weitz:Bristol-Myers Squibb: Honoraria; Daiichi-Sankyo: Honoraria; Ionis: Consultancy, Honoraria; Janssen: Honoraria; Servier: Honoraria; Novartis: Honoraria; Bayer: Honoraria; Boehringer Ingelheim: Honoraria, Research Funding. Schulman:Boehringer-Ingelheim: Honoraria, Research Funding; Daiichi-Sankyo: Honoraria; Sanofi: Honoraria; Bayer: Honoraria. Couturaud:Pfizer: Research Funding; Bayer: Honoraria, Other: Travel Support; AstraZeneca: Honoraria; Actelion: Other: Travel Support; Intermune: Other: Travel Support; Leo Pharma: Other: Travel Support; Daiichi Sankyo: Other: Travel Support. Becattini:Bayer HealthCare: Other: Lecture Fees; Boehringer Ingelheim: Other: Lecture Fees; Bristol Meyer Squibb: Other: Lecture Fees. Agnelli:Daiichi Sankyo: Other: Personal Fees; Boehringer Ingelheim: Other: Personal Fees; Bayer Healthcare: Other: Personal Fees; Pfizer: Other: Personal Fees; Bristol-Myers-Squibb: Other: Personal Fees. Brighton:Glaxo Smith Klein: Other: Personal Fees; Novo Nordisk: Other: Personal Fees; Bayer: Other: Personal Fees. Lensing:Bayer: Employment. Prins:Pfizer: Consultancy; Daiichi Sankyo: Consultancy. Hutton:Cornerstone Research Group: Honoraria. Palareti:Roche: Membership on an entity's Board of Directors or advisory committees; Werfen: Speakers Bureau; Alfa-Wassermann: Membership on an entity's Board of Directors or advisory committees; Daiichi-Sankyo: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees. Prandoni:Pfizer: Consultancy; Daiichi-Sankyo: Consultancy; Sanofi: Consultancy; Bayer: Consultancy. Büller:Pfizer: Consultancy, Research Funding; Daiichi-Sankyo: Consultancy, Research Funding; Roche: Consultancy, Research Funding; Sanofi-Aventis: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Bayer: Consultancy, Research Funding; Boehringer Ingelheim: Consultancy, Research Funding; Thrombogenics: Consultancy, Research Funding; Isis: Consultancy, Research Funding; GlaxoSmithKline: Consultancy, Research Funding. Rodger:Biomerieux: Research Funding.

Dalteparin Thromboprophylaxis in Cancer Patients at High Risk for Venous Thromboembolism: A Randomized Trial

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 427-427 ◽  
Author(s):  
Alok A. Khorana ◽  
Charles W. Francis ◽  
Nicole Kuderer ◽  
Marc Carrier ◽  
Thomas L. Ortel ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
High Risk ◽  
Board Of Directors ◽  
Cancer Patients ◽  
Research Funding ◽  
Primary Efficacy ◽  
Advisory Committees ◽  
Intention To Treat ◽  
Efficacy Outcome ◽  
Risk Patients

Abstract Background: Ambulatory cancer patients at high-risk for venous thromboembolism (VTE) can be identified using a validated risk score. We evaluated the benefit of outpatient thromboprophylaxis with dalteparin in such high-risk patients in a multicenter randomized controlled trial. Methods: Cancer patients at high risk for VTE (Khorana score ≥3) and initiating a new systemic chemotherapy regimen were screened for VTE and, if negative, randomized to either dalteparin 5000 units daily subcutaneously or no prophylactic anticoagulation for 12 weeks. Subjects in both arms were screened with lower extremity ultrasounds every 4 weeks on study. Primary efficacy endpoint was any VTE over 12 weeks and primary safety endpoint was clinically relevant bleeding events over 13 weeks. The study was terminated due to poor accrual. Results: Of 117 enrolled patients, 19 were not randomized due to the presence of VTE on initial screening (N=10, 8.5%) or for other reasons (N=9). The mean age was 59 years with 46% female and 54% male, similar in both arms. The most common primary sites of cancer were pancreas, gastro-esophageal junction, lung and lymphoma. Over three-fourths of patients in each arm had an ECOG performance status of 0 or 1.Of 98 patients randomized, VTE occurred in 12% (N=6/50) of patients on the dalteparin arm and 21% (N=10/48) on the control arm (hazard ratio, HR 0.69, 95% CI 0.23-1.89) (absolute risk reduction 9%, relative risk reduction 42%, number needed to treat = 12). Major bleeding was similar (N=1) in each arm but clinically relevant bleeding was higher in the dalteparin arm (N=7 versus 1 in the control arm) (HR = 7.0, 95% CI 1.2-131.6). There was no difference in overall survival. Conclusions: Thromboprophylaxis is associated with a non-significant reduced risk of VTE with no effect on major bleeding or survival but increased risk of clinically relevant bleeding in this underpowered study population. The Khorana score successfully identifies patients with high incidence of VTE both at baseline and during study. The high incidence of baseline VTE suggests that consideration should be given to screening high-risk patients in clinical practice prior to starting systemic therapy. Future studies should continue to focus on risk-adapted approaches to reduce the burden of VTE in cancer. (Funded by NIH/NHLBI R01HL095109; clinicaltrials.gov identifier: NCT00876915). Table 1. Baseline Characteristics of Patients Enrolled in the PHACS trial Dalteparin Observation Total Enrolled (n) Baseline VTE, n (%) DVT PE Other reasons for not randomizing Randomized (n) Age, mean (SD), y --- --- --- --- --- 50 60 (10) --- --- --- --- --- 48 58 (12) 117 10 (9%) 6* (5%) 4 (3%) 9 98 59 (11) Gender, n (%) Female 21 (42%) 24 (50%) 45 (46%) Male 29 (58%) 24 (50%) 53 (54%) Primary Tumor Site, No. (%) Gynecologic 4 (8%) 4 (8%) 8 (8%) Colorectal 1 (2%) 3 (6%) 4 (4%) GE junction 8 (16%) 4 (8%) 12 (25%) Lung 6 (12%) 7(15%) 13 (27%) Genitourinary 2 (4%) 0 (0%) 2 (2%) Lymphoma 5 (10%) 2 (4%) 7 (15%) Breast 1 (2%) 1 (2%) 2 (2%) Pancreatic 19 (38%) 17 (35%) 36 (37%) Gastric 4 (8%) 6 (13%) 10 (10%) Other 0 (0%) 4 (8%) 4 (4%) Previous history of VTE, n (%) 4 (8%) 2 (4%) 6 (6%) *NOTE: 1 subject had both DVT and PE at baseline screening Abbreviations: DVT, deep vein thrombosis; PE pulmonary embolism; VTE, venous thromboembolism; ECOG: Eastern Cooperative Oncology Group Figure 1. Cumulative Incidence Curves for the Primary Efficacy Outcome in the Intention-to-Treat Population, According to Study Arm. Figure 1. Cumulative Incidence Curves for the Primary Efficacy Outcome in the Intention-to-Treat Population, According to Study Arm. Disclosures Khorana: Leo Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Boehringer-Ingelheim: Consultancy, Honoraria; Daiichi Sankyo: Consultancy, Honoraria; sanofi: Consultancy, Honoraria. Off Label Use: Randomized trial of dalteparin as prophylaxis. The drug is approved for treatment of cancer-associated thrombosis but not for prophylaxis.. Francis:Eisai: Consultancy, Research Funding; Portola: Consultancy, Honoraria; NHLBI: Consultancy; Lilly: Consultancy. Kuderer:Hospira: Consultancy; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Daiichi Sankyo: Consultancy. Carrier:Leo Pharma: Consultancy, Research Funding; BMS: Research Funding; Bayer: Consultancy, Honoraria; Pfizer: Consultancy. Ortel:Instrumentation Laboratory: Consultancy; Instrumentation Laboratory: Research Funding; Eisai: Research Funding; Daiichi Sankyo: Consultancy. Wun:Janssen: Consultancy. Iyer:Ipsen Pharmaceuticals: Consultancy; Genentec: Research Funding; Bristol Myers Squibb: Honoraria. Lyman:Amgen: Research Funding.

scholarly journals Outcomes of Abdominal Thrombosis in Patients with Myeloproliferative Neoplasms in a Single Center Experience

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4307-4307
Author(s):  
Douglas Tremblay ◽  
Alexander Vogel ◽  
Erin Moshier ◽  
Ronald Hoffman ◽  
Marina Kremyanskaya ◽  
...  
Keyword(s):  
Overall Survival ◽  
Hepatic Encephalopathy ◽  
Board Of Directors ◽  
Research Funding ◽  
Myeloproliferative Neoplasms ◽  
Single Center ◽  
Advisory Committees ◽  
Vein Thrombosis ◽  
Single Center Experience ◽  
Significant Difference

Abstract Background Abdominal thrombosis (AT) is a concerning complication of myeloproliferative neoplasms (MPNs), leading to significant morbidity and mortality. While the epidemiology of AT in MPNs has previously been described, outcomes based on timing of AT relative to MPN diagnosis are unknown. Additionally, it is unclear how the treatment of the MPN affects outcomes including esophageal variceal bleeding (EVB), development of ascites, and additional thrombosis. Methods We conducted a retrospective review of patients at a single tertiary care institution. Inclusion criteria included: 18 years or older, a diagnosis of an MPN, including polycythemia vera (PV), myelofibrosis (MF), essential thrombocythemia (ET), and AT, including portal vein thrombosis (PVT), Budd Chiari Syndrome (BCS), or other splanchnic vein thrombosis. Primary outcome measures included EVB, additional thrombosis, development of ascites, hepatic encephalopathy, and death due to any cause. Years to outcome events were calculated by Kaplan Meier analysis. Results Baseline disease characteristics are summarized in Table 1. Sixty-four eligible patients were identified, 46 (72%) were female. The median age at time of AT was 45 years (range, 18-89). PV was the most common MPN, followed by ET then MF. Sixty patients (95%) harbored a mutation in JAK2. Characteristics of the AT are summarized in Table 2. Twenty-nine patients (45%) were diagnosed with AT after the MPN, with a median of 44 months (1-288) between diagnoses. Nineteen patients (30%) were diagnosed with AT before MPN, a median of 4 months (1-90). Sixteen patients (25%) were diagnosed concurrently (within 1 month). There was no difference in age at diagnosis of MPN among the three groups, however, patients diagnosed with AT before MPN were significantly younger (37 [18-89]) than those diagnosed with an AT after MPN (52 [31-85]) or concurrently (48 [20-70]) (p=0.0045). There was no significant difference among these three groups with respect to other AT characteristics. The median overall survival (OS) of the cohort was not reached. Five-year OS probability was 98%. No significant difference in overall survival (OS) was observed among those diagnosed with an AT before, concurrent, or after being diagnosed with an MPN. Treatment of the AT was primarily with warfarin (39%), although 19% of patients were treated with a direct oral anticoagulant. Additionally, 20% of patients received a transjugular intrahepatic portosystemic shunt (TIPS). Seven patients (11%) received no treatment for their AT. Of the entire cohort, 16 patients (25%) experienced an EVB. For patients who were on MPN directed therapy at time of AT, the hazard ratio (HR) for years to bleeding event was 1.24 (0.28-5.57) as compared to those who were not treated (p=0.7798). Ten patients (15.6%) experienced a non-abdominal thrombosis, predominantly deep vein thrombosis or pulmonary embolism. Thirty patients went on to develop ascites. HR for years to ascites from thrombosis was 1.94 (0.17-21.64) in the MPN treated patients (p=0.5823). Six patients (9%) developed hepatic encephalopathy. There was no difference between the MPN treated patients and non-MPN treated patients in a composite outcome of EV bleed, additional AT, ascites, or hepatic encephalopathy. Conclusions In this single center experience, a significant portion of patients were diagnosed with an AT before their MPN diagnosis. Treatment of the MPN at time of AT diagnosis did not appear to affect outcomes including EVB, additional thrombosis, development of ascites, or hepatic encephalopathy. These results suggest that once developed, treatment of the underlying MPN may not decrease complication rates of an AT. Further analyses are underway to clarify whether this finding is true in each AT subtype. Disclosures Hoffman: Merus: Research Funding; Summer Road: Research Funding; Formation Biologics: Research Funding; Janssen: Research Funding; Incyte: Research Funding. Kremyanskaya:Incyte: Research Funding. Mascarenhas:Merck: Research Funding; Promedior: Research Funding; Novartis: Research Funding; CTI Biopharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding.

scholarly journals High Incidence of Bleeding Found with Direct Oral Anticoagulant Use in Myeloproliferative Neoplasm Patients

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3632-3632
Author(s):  
Chi-Joan How ◽  
Charlotte McIlwaine Story ◽  
Siyang Ren ◽  
Donna S. Neuberg ◽  
Rachel P. Rosovsky ◽  
...  
Keyword(s):  
Risk Factors ◽  
Board Of Directors ◽  
Median Duration ◽  
Cumulative Incidence ◽  
Research Funding ◽  
Practice Patterns ◽  
Recurrent Thrombosis ◽  
Advisory Committees ◽  
Bleeding Rate ◽  
Vein Thrombosis

Abstract BACKGROUND: Patients with myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF) are at increased risk of arterial (ATE) and venous thromboembolism (VTE). There are no clear guidelines regarding selection of anticoagulation (AC) in MPN patients. Direct oral anticoagulants (DOACs) are increasingly used in the general population to treat a variety of conditions including VTE, ATE, and atrial fibrillation (AF). Data on the safety and efficacy of DOACs in MPNs limited. We conducted a multi-center, retrospective analysis of DOAC use in MPN patients to characterize real-world practice patterns and evaluate thrombosis and bleeding risks. METHODS: We retrospectively analyzed 133 MPN patients prescribed DOACs across the Massachusetts General Brigham / Dana Farber Harvard Cancer Center system from 1995 to 2020. Patients were identified using ICD-9 and 10 codes in the electronic medical record. Patient and treatment characteristics were described with summary statistics. We calculated cumulative incidence functions of VTE and ATE, and major and clinically relevant non-major bleeding (CRNMB) by ISTH criteria, using death on DOAC as a competing risk. A Gray's test was used to compare cumulative incidence between groups. Analysis of risk factors associated with bleeding/thrombosis was carried out by univariate and multivariable Fine-Gray models. RESULTS: Baseline characteristics are displayed in Table 1. Seventy-five (56.4%) MPN patients were prescribed DOAC for VTE, 46 (34.6%) for AF, 7 (5.3%) for stroke, and 5 for other ATE (3.8%). The median age at DOAC initiation was 71; the AF population was significantly older than patients with VTE (75 vs 59, p&lt;0.001). Fifty-seven percent of patients (N = 76) had a diagnosis of PV, with 89% (N = 118) of patients carrying a JAK2 driver mutation. Apixaban was the most commonly prescribed DOAC (N = 83, 62.4%). Nearly half (N = 59, 45%) of patients had a prior VTE/ATE at DOAC initiation, and 23% (N = 31) of patients were switched from warfarin. Among the VTE-treated patients, 43% of events were deep vein thrombosis (N = 39), 31% (N = 28) were pulmonary embolism, 21% (N = 19) were splanchnic vein thrombosis (SVT), and 4.4% (N=4) were other VTE. Table 2 displays practice patterns of DOAC use in MPN patients. The median duration of AC was 37.0 months for all patients, with no difference (p=0.01) between patients treated for AF (42.3 months) and VTE (37.0 months). Twenty-one percent of VTE-treated patients completed a finite course of AC of 6 months median duration. Fifteen percent (N = 11) of VTE-treated and 4.3% (N = 2) of AF patients had reduction to prophylactic dosing. Fifty percent (N = 66) of patients took aspirin and AC concurrently; 83% (N = 110) of patients took cytoreduction with AC. After a median follow-up of 37 months, we found 12 thrombotic (7 arterial, 3 venous, 2 TIPS occlusions) and 28 bleeding (6 major with 4 contributing to patient death, 2 CRNMB) events on DOAC. The estimated 1-year cumulative incidence of thrombosis and bleeding on DOAC was 5.5% (1.5%-9.5%) and 12.3% (6.4%-18.2%), respectively (Figure 1). Thrombosis and bleeding rates were not significantly different between patients treated for VTE versus AF. Prior history of thrombosis and use of dabigatran or edoxaban were significantly associated with increased thrombosis on both univariate and multivariable analysis (p&lt;0.05). Age ≤ 65 also emerged as a risk factor for recurrent thrombosis in multivariate analysis (p=0.04). Use of dabigatran or edoxaban trended toward increased bleeding, but otherwise we found no significant risk factors for bleeding at α=0.05 level, including concomitant aspirin use. DISCUSSION: DOACs are increasingly prescribed in MPN patients for a wide range of indications, with heterogeneity in practice patterns. In our cohort, 1-year thrombosis and bleeding incidence rates on DOAC were 5.5% and 12.3%, respectively. While our 5.5% thrombosis rate is similar to recurrent thrombosis rates reported in MPN patients on DOACs and VKA, our 12.3% bleeding rate appears much higher. This may be related to the complexity of patients seen at our tertiary referral center. The higher-than-expected bleeding rate found in our study indicates the continued need for rigorous evaluation of DOACs in this population, with the gold standard being randomized controlled trials comparing DOAC with warfarin. Figure 1 Figure 1. Disclosures Neuberg: Madrigal Pharmaceuticals: Other: Stock ownership; Pharmacyclics: Research Funding. Rosovsky: Janssen: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Inari: Consultancy, Membership on an entity's Board of Directors or advisory committees; Dova: Consultancy, Membership on an entity's Board of Directors or advisory committees. Hobbs: Bayer: Research Funding; Merck: Research Funding; AbbVie.: Consultancy; Celgene/Bristol Myers Squibb: Consultancy; Novartis: Consultancy; Incyte Corporation: Research Funding; Constellation Pharmaceuticals: Consultancy, Research Funding. Connors: Abbott: Consultancy; Bristol-Myers Squibb: Honoraria; takeda: Honoraria; Alnylam: Consultancy; Pfizer: Honoraria; CSL Behring: Research Funding.

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