Non-OO blood type influences the risk of recurrent venous thromboembolism

SummaryThe role of ABO blood type as a risk factor for recurrent venous thromboembolism (VTE) in patients with a first unprovoked VTE who complete oral anticoagulation therapy is unknown. The aim of this study was to determine if non-OO blood type is a risk factor for recurrent VTE in patients with a first unprovoked VTE who completed 5–7 months of anticoagulant therapy. In an ongoing cohort study of patients with unprovoked VTE who discontinued oral anticoagulation after 5–7 months of therapy, six single nucleotide polymorphisms sites were tested to determine ABO blood type using banked DNA. The main outcome was objectively proven recurrent VTE. Mean follow-up for the cohort was 4.19 years (SD 2.16). During 1,553 patient-years of follow-up, 101 events occurred in 380 non-OO patients (6.5 events per 100 patient years; 95% CI 5.3–7.7) compared to 14 events during 560 patient years of follow-up in 129 OO patients (2.5 per 100 patient years; 95% CI 1.2–3.7), the adjusted hazard ratio was 1.98 (1.2–3.8). In conclusion, non-OO blood type is associated with a statistically significant and clinically relevant increased risk of recurrent VTE following discontinuation of anticoagulant therapy for a first episode of unprovoked VTE.

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D-Dimer Levels and Risk of Recurrence Following Provoked Venous Thromboembolism: Findings from the Riete Registry

Blood ◽

10.1182/blood-2018-99-111190 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 3810-3810

Author(s):

Martin Ellis ◽

Martin Mar ◽

Monreal Manuel ◽

Orly Hamburger-Avnery ◽

Alessandra Bura-Riviere ◽

...

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Venous Thromboembolism ◽

Anticoagulant Therapy ◽

Conflicts Of Interest ◽

Hazard Ratio ◽

Increased Risk ◽

Risk Patients ◽

Recurrent Vte ◽

D Dimer

Abstract Background. Patients with venous thromboembolism (VTE) secondary to transient risk factors or cancer may develop VTE recurrences after discontinuing anticoagulant therapy. Identifying at-risk patients could help to guide the ideal duration of anticoagulant therapy in these patients. Methods. We used the RIETE database to assess the prognostic value of d-dimer testing after discontinuing anticoagulation to identify patients at increased risk for recurrences. The proportion of patients with raised d-dimer levels was determined and the hazard ratio (HR) for VTE recurrences compared to those with normal levels was calculated. Univariate and multivariate analyses of factors associated with VTE recurrence were performed. Results. 3 606 patients were identified in the database in April 2018: 2 590 had VTE after a transient risk factor and 1016 had a cancer. D-dimer levels were measured after discontinuing anticoagulation in 1 732 (67%) patients with transient risk factors and 732 (72%) patients with cancer-associated VTE and these patients formed the cohort in which recurrent VTE rate was calculated. D-dimers and were elevated in 551 (31.8%) of patients with a transient risk factor and were normal in 1181 (68.2%). In the cancer-associated group, d-dimers were elevated in 398 (54.3%) and normal in 334 (45.7%) patients. The adjusted hazard ratio for recurrent VTE was: 2.32 (95%CI: 1.55-3.49) in patients with transient risk factors and 2.23 (95%CI: 1.50-3.39) in those with cancer. Conclusions. Patients with raised d-dimer levels after discontinuing anticoagulant therapy for provoked or cancer-associated VTE are at increased risk for recurrent VTE and death. Future studies could target these patients for extended anticoagulation. Disclosures No relevant conflicts of interest to declare.

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The Incidence, Risk Factors, and Prognosis of Recurrent Venous Thromboembolism (VTE) in Patients with Advanced Solid Cancers Receiving Anticoagulation Therapy After the Diagnosis of Index Vte; A Korean Venous Thromboembolism Registry Study.

Blood ◽

10.1182/blood.v120.21.2247.2247 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2247-2247

Author(s):

Ho-Young Yhim ◽

Moon Ju Jang ◽

Won-Il Choi ◽

Yong Cheol Lee ◽

Jeong-Ok Lee ◽

...

Keyword(s):

Risk Factors ◽

Venous Thromboembolism ◽

Anticoagulation Therapy ◽

Tumor Site ◽

Primary Tumor Site ◽

Increased Risk ◽

Recurrent Venous Thromboembolism ◽

Independent Risk Factors ◽

Recurrent Vte

Abstract Abstract 2247 Introduction Patients (pts) with cancer have been associated with increased risk of recurrent venous thromboembolism (VTE). However, few data are available regarding the recurrent VTE in Asian pts with advanced solid cancers. Thus, the aim of the study is to investigate the incidence and risk factors for recurrent VTE in pts with advanced solid cancers receiving anticoagulation therapy after index VTE. And, we also evaluate the prognostic impact of recurrent VTE on overall survival (OS) in this population. Methods This study was conducted using data from the web-based registry of the Korean Thrombosis Working Party (http://kdvt.chamc.co.kr), which is an ongoing, multicenter database for recruiting consecutive pts presenting with VTE. Pts were included in the study cohort if they had been diagnosed with recurrent/metastatic solid cancers between May 2004 and Dec 2011 and initiated anticoagulation therapy. Pts were excluded if they had received a diagnosis of hematologic malignancies, if solid cancers were not recurrent or metastatic disease, if index VTE was intra-abdominal venous thrombosis or vascular access-induced thrombosis, or if anticoagulation therapy was not instituted. Pts were also excluded if they were lost to follow-up within 1 week after initiating anticoagulation therapy. Maximal duration of anticoagulation therapy was 12 months and pts in whom anticoagulation therapy was stopped within 12 months were censored at the time of discontinuation. Results A total of 456 pts were included in this analysis. The median age was 65 (range, 27–91) years and 249 pts (55%) were male. Eastern Cooperative Oncology Group (ECOG) performance status (PS) was 0 or 1 in 185 pts (41%). The primary sites of tumor were breast in 22 (5%), genito-urinary tracts in 38 (8%), esophago-gastric in 76 (17%), colo-rectum in 81 (18%), hepato-biliary tracts in 37 (8%), pancreas in 66 (15%), and lung in 136 (30%). Palliative chemotherapy was administered in 328 pts (72%). The location of index VTE was isolated pulmonary embolism (PE) in 196 (43%), isolated lower-extremity deep venous thrombosis (DVT) in 169 (37%), and concomitant PE and DVT in 91 (20%). For initial anticoagulation therapy, low molecular weight heparin was administered in 362 pts (79%), and for long-term therapy, 306 pts (75%) received warfarin. The median duration of anticoagulation therapy after index VTE was 2.4 (range, 0.1–58.3) months. The 6-months and 12-month cumulative incidences of recurrent VTE were 22.4% (95% CI, 19.4–25.4) and 28.7% (95% CI, 24.0–33.4), respectively. In the multivariate analysis for identifying the risk factors associated with the development of recurrent VTE, pancreas (HR, 6.12; 95% CI, 2.00–18.73) and lung (HR, 2.98; 95% CI, 1.03–8.58) as the primary tumor site, poor ECOG PS (HR, 1.74; 95% CI, 1.14–2.67) and VTE initially presented with PE (HR, 2.29; 95% CI, 1.17–4.47) were independent risk factors for increased risk of recurrent VTE. With a median follow-up of 29.1 (range, 1.0–91.2) months, median OS was 11.9 (95% CI, 10.2–13.6) months. Pts with recurrent VTE had a significantly shorter OS than those without recurrent VTE (median, 8.4 vs. 13.0 months, P<0.001). In the multivariate model, occurrence of recurrent VTE was independently associated with the increased risk of death (HR, 1.39; 95% CI, 1.03–1.88). Conclusion Although Asian populations are thought to have lower risk for developing recurrent VTE, our study demonstrates that the incidence of recurrent VTE in pts with advanced solid cancers is comparable to that of Western populations. Lung or pancreas as a primary tumor site, poor PS, and initial presentation with PE are independent risk factors for recurrent VTE. Additionally, survival is adversely affected by recurrent VTE. Further studies are needed to validate the results of our study and to optimize the treatment strategies for improving treatment outcomes in advanced cancer pts. Disclosures: No relevant conflicts of interest to declare.

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Long-term Clinical Follow-up in 265 Patients with Deep Venous Thrombosis Initially Treated with either Unfractionated Heparin or Dalteparin: A Retrospective Analysis

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614364 ◽

1999 ◽

Vol 82 (10) ◽

pp. 1222-1226 ◽

Cited By ~ 16

Author(s):

W. Åberg ◽

D. Lockner ◽

C. Paul ◽

M. Holmström

Keyword(s):

Risk Factor ◽

Venous Thromboembolism ◽

Venous Thrombosis ◽

Deep Venous Thrombosis ◽

Unfractionated Heparin ◽

Malignant Disease ◽

Duration Of Treatment ◽

Post Thrombotic Syndrome ◽

Recurrent Vte

SummaryThe primary objective of this retrospective study was to describe the frequency of a post-thrombotic syndrome in 265 patients previously treated for deep venous thrombosis (DVT). The secondary objectives were to document the frequency of recurrent venous thromboembolism (VTE) and mortality, especially from malignant disease. The patients were evaluated 5-14 years after inclusion in three randomized trials comparing continuous intravenous (i. v.) infusion of unfractionated heparin (UFH) (n = 85) with a low molecular weight heparin (LMWH), dalteparin (n = 180). The median post-thrombotic score at follow-up was 2 (range 0-8). In a multiple step-wise regression analysis the post-thrombotic score was significantly higher among patients with initial proximal DVT (p = 0,0001) as compared with those who had distal DVT. A recurrent venous thromboembolic event was diagnosed in 29,4% of the patients treated with dalteparin and in 23,5% of the patients treated with UFH (ns). A secondary risk factor for venous thromboembolism and a longer duration of treatment with oral anticoagulants (OAC) were significantly associated with a lower risk for recurrent VTE, whereas malignant disease diagnosed during follow-up was associated with a higher risk. During follow-up a total of 40,7% of patients had died. No difference in total mortality or mortality from malignant disease was demonstrated between the two drugs. In conclusion, a severe post-thrombotic syndrome occured relatively infrequent. considering the long observation period. Proximal DVT was significantly associated with a more severe post-thrombotic syndrome. After 14 years follow-up, no significant differences were observed in overall mortality, mortality from malignant disease or recurrent VTE between UFH- and dalteparin-treated patients. Malignant disease was a risk factor for recurrent VTE, the presence of a secondary risk factor and a longer duration of treatment with OAC decreased the risk for recurrent VTE.

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Impact of ABO Blood Group Type on Risk of Venous Thromboembolism in Patients with Cancer

Blood ◽

10.1182/blood-2021-145713 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 2119-2119

Author(s):

Cornelia Englisch ◽

Florian Moik ◽

Stephan Nopp ◽

Markus Raderer ◽

Ingrid Pabinger ◽

...

Keyword(s):

Risk Factor ◽

Blood Type ◽

Thrombotic Risk ◽

Patients With Cancer ◽

Abo Blood Type ◽

Tumor Types ◽

Risk Of Cancer ◽

Very High ◽

Study Inclusion

Abstract Introduction: Venous thromboembolism (VTE) is common in patients with cancer. Non-O blood type is associated with higher levels of factor FVIII activity and von Willebrand factor compared to blood type O, and has been identified as a risk factor for VTE in the general population. However, the impact of ABO blood type on risk of cancer-associated VTE has not been clarified. Methods: To determine the influence of non-O blood type on risk of cancer-associated VTE, we utilized the dataset of the Vienna Cancer and Thrombosis Study (CATS), which is a single center, prospective observational cohort study including patients with newly diagnosed or recurrent cancer. Patients were followed for objectively diagnosed, independently adjudicated VTE for a maximum of 2 years. VTE was quantified in competing risk analysis, accounting for all-cause mortality as competing outcome event. A proportional sub-hazard regression model according to Fine & Gray was used for between-group comparisons. Based on the violation of the proportional sub-hazard assumption, we explored potential time-dependent effects of non-O blood type on VTE risk in a restricted cubic spline analysis, modeling differences in risk estimates over follow-up time. Further, time-restricted subdistribution hazard ratios (SHR) were obtained specifically for the <3 months and ≥3 months follow-up intervals. In a subgroup analysis, differences in VTE risk according to ABO-blood type were analyzed for patients with very high thrombotic risk tumor types (pancreatic, gastric, glioblastoma), compared to the remainder of patients. Results: In total, 1,708 patients were included in our analysis (46% female, median age: 61 years [interquartile range, IQR: 52-68]). The most common tumor types were lung (19%), breast (16%), and brain (14%) cancer, with 32% of solid tumor patients having metastatic disease at study inclusion. Over a median follow-up of 24 months (IQR: 10-24), 151 patients were diagnosed with VTE (cumulative 2-year incidence: 9.2%, 95% confidence interval [CI]: 7.9-10.7) and 649 patients died (2-year mortality: 38%). Overall, blood type O was present in 38% of patients, A in 40%, B in 15%, and AB in 7%. The cumulative incidence of VTE at 3-, 6-, 12-, and 24-months for patients with blood type O was 3.8% (95% CI: 2.5-5.5), 5.7% (95% CI: 4.1-7.7), 7.0% (95% CI: 5.1-9.1), and 7.6% (95% CI: 5.7-9.9), compared to 3.4% (95% CI: 2.4-4.7), 6.5% (95% CI: 5.1-8.1), 8.4% (95% CI:6.8-10.2), and 10.2% (95% CI: 8.4-12.2) in patients with non-O blood type (Gray´s test: p=0.103, Figure 1). Upon visual inspection of cumulative incidence functions, a violation of the proportional sub-hazard assumption was suspected. In restricted cubic spline analysis, estimating hazard ratio (HR) for VTE of patients with non-O compared to O blood type, a time-varying effect of non-O blood type towards an increased VTE risk was observed (Figure 2). Based on that, time-restricted competing risk regression models were performed. During the first 3 months of follow-up, no differences in VTE risk were found (SHR for non-O vs. O blood type: 1.00, 95% CI: 0.60-1.67, p=0.992). Beyond the first 3-month follow-up, patients with non-O blood type had an increased VTE risk compared to patients with blood type O (SHR 1.79, 95%CI: 1.12-2.85, p=0.015). In a subgroup analysis, no association with VTE risk was found in patients with very high thrombotic risk tumor types (SHR 0.94, 95% CI: 0.55-1.61, p=0.824). In contrast, in patients with low/intermediate risk cancer, non-O blood type was associated with increased risk of VTE (SHR 1.73, 95% CI: 1.09-2.73, p=0.019). Conclusion: Non-O blood type was identified as a time dependent risk factor for cancer-associated VTE. In the first 3 months after study inclusion, characterized as the highest VTE risk period in our cancer cohort, no differences in VTE risk between blood types were found. Afterwards, beyond the first 3 months of follow-up, an increased VTE-risk in non-O blood types was observed, comparably in magnitude to the risk difference in the general non-cancer population. Further, an association of non-O blood type with VTE risk in patients with low/intermediate thrombotic risk cancers was observed, whereas no effect was present in those with very high-risk tumors. These findings indicate non-O blood type as a putative risk factor for VTE in patients with cancer in comparably low thrombotic risk scenarios. Figure 1 Figure 1. Disclosures Pabinger: Pfizer: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Alexion: Consultancy, Honoraria; Daiichi Sanchyo: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Bayer: Consultancy, Honoraria; NovoNordisk: Consultancy, Research Funding; CSL Behring: Consultancy, Honoraria, Research Funding.

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P3850Impact of sex and risk factors for venous thromboembolism on the clinical course of first acute venous thromboembolism. Insights from the PREFER in VTE

European Heart Journal ◽

10.1093/eurheartj/ehz745.0690 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

M Giustozzi ◽

S Barco ◽

L Valerio ◽

F A Klok ◽

M C Vedovati ◽

...

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Venous Thromboembolism ◽

Baseline Risk ◽

Major Surgery ◽

First Episode ◽

Risk Of Recurrence ◽

Recurrent Vte ◽

The Impact

Abstract Introduction The interaction between sex and specific provoking risk factors for venous thromboembolism (VTE) may influence initial presentation and prognosis. Purpose We investigated the impact of sex on the risk of recurrence across subgroups of patients with first VTE classified according to baseline risk factors. Methods PREFER in VTE was an international, non-interventional registry (2013–2015) including patients with a first episode of acute symptomatic objectively diagnosed VTE. We studied the risk of recurrence in patients classified according to baseline provoking risk factors for VTE consisted of i) major transient (major surgery/trauma, >5 days in bed), ii) minor transient (pregnancy or puerperium, estroprogestinic therapy, prolonged immobilization, current infection or bone fracture/soft tissue trauma); iii) unprovoked events, iv) active cancer-associated VTE. Results A total of 3,455 patients diagnosed with first acute VTE were identified, of whom 1,623 (47%) were women. The percentage of patients with a major transient risk factor was 22.2% among women and 19.7% among men. Minor transient risk factors were present in 21.3% and 12.4%, unprovoked VTE in 51.6% and 61.6%, cancer-associated VTE in 4.9% of women and 6.3% of men, respectively. The proportions of cases treated with Vitamin-K antagonists (VKAs) and direct oral anticoagulants (DOACs) were similar between sexes. Median length of treatment of VKAs was 181.5 and 182.0 days and of DOACs was 113.0 and 155.0 days in women and men, respectively. At 12-months of follow-up, VTE recurrence was reported in 74 (4.8%) women and 80 (4.5%) men. Table 1 shows the sex-specific proportion of recurrences by VTE risk factor categories. Table 1 Major Transient (n=722) Minor transient (n=573) Cancer-associated (n=195) Unprovoked (1965) Women (361) Men (361) OR (95% CI) Women (346) Men (227) OR (95% CI) Women (79) Men (116) OR (95% CI) Women (837) Men (1128) OR (95% CI) One-year follow-up, n (N%) Recurrent VTE, 21 (6.2) 10 (2.9) 0.46 (0.2; 0.9) 9 (2.7) 12 (5.4) 2.09 (0.9; 5.0) 6 (8.0) 5 (4.5) 0.54 (0.2; 1.9) 38 (4.7) 53 (4.7) 1.03 (0.7; 1.6) Major bleeding, 6 (1.8) 5 (1.5) 0.83 (0.3; 2.7) 5 (1.5) 1 (0.5) 0.30 (0.1; 2.6) 1 (1.3) 3 (2.7) 2.07 (0.2; 20) 10 (1.2) 15 (1.4) 1.11 (0.6; 2.4) All-cause death, 37 (10.2) 31 (8.5) 0.82 (0.5; 1.4) 10 (2.9) 14 (6.2) 2.21 (0.9; 5.1) 26 (32.9) 49 (42.2) 1.49 (0.8; 2.7) 33 (3.9) 30 (2.7) 0.66 (0.4; 1.1) Conclusions The proportion of patients with recurrent VTE events after first acute symptomatic VTE provoked by transient risk factors was not negligible during the first year of follow-up during in both women and men. These results may have implications on the decision whether to consider extended anticoagulant therapy in selected patients with provoked events. Acknowledgement/Funding This study was funded by Daiichi Sankyo.

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Two doses of rivaroxaban versus aspirin for prevention of recurrent venous thromboembolism

Thrombosis and Haemostasis ◽

10.1160/th15-02-0131 ◽

2015 ◽

Vol 114 (09) ◽

pp. 645-650 ◽

Cited By ~ 31

Author(s):

Rupert Bauersachs ◽

Jan Beyer-Westendorf ◽

Henri Bounameaux ◽

Timothy Brighton ◽

Alexander Cohen ◽

...

Keyword(s):

Venous Thromboembolism ◽

Anticoagulant Therapy ◽

Low Dose ◽

Double Blind ◽

Once Daily ◽

Safety Outcome ◽

Dose Aspirin ◽

Recurrent Venous Thromboembolism ◽

Low Dose Aspirin ◽

Recurrent Vte

SummaryPatients with unprovoked venous thromboembolism (VTE) are at high risk for recurrence. Although rivaroxaban is effective for extended VTE treatment at a dose of 20 mg once daily, use of the 10 mg dose may further improve its benefit-to-risk ratio. Low-dose aspirin also reduces rates of recurrent VTE, but has not been compared with anticoagulant therapy. The EINSTEIN CHOICE study is a multicentre, randomised, double-blind, active-controlled, event-driven study comparing the efficacy and safety of two once daily doses of rivaroxaban (20 and 10 mg) with aspirin (100 mg daily) for the prevention of recurrent VTE in patients who completed 6–12 months of anticoagulant therapy for their index acute VTE event. All treatments will be given for 12 months. The primary efficacy objective is to determine whether both doses of rivaroxaban are superior to aspirin for the prevention of symptomatic recurrent VTE, while the principal safety outcome is the incidence of major bleeding. The trial is anticipated to enrol 2,850 patients from 230 sites in 31 countries over a period of 27 months. In conclusion, the EINSTEIN CHOICE study will provide new insights into the optimal antithrombotic strategy for extended VTE treatment by comparing two doses of rivaroxaban with aspirin (clinicaltrials.gov NCT02064439).

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Influence Of Antithrombin Deficiency On Symptomatic Recurrent Venous Thromboembolism (VTE) In Children: A Multicenter Cohort Study

Blood ◽

10.1182/blood.v122.21.3619.3619 ◽

2013 ◽

Vol 122 (21) ◽

pp. 3619-3619

Author(s):

Gili Kenet ◽

Verena Limperger ◽

Neil A Goldenberg ◽

Christine Heller ◽

Susanne Holzhauer ◽

...

Keyword(s):

Multivariate Analysis ◽

Venous Thromboembolism ◽

Pediatric Patients ◽

Cox Regression ◽

Conflicts Of Interest ◽

Antithrombin Deficiency ◽

Increased Risk ◽

Recurrent Venous Thromboembolism ◽

At Deficiency ◽

Recurrent Vte

Abstract Objective To determine the importance of antithrombin [AT] deficiency as risk factor or predictor for fatal/non-fatal recurrent venous thromboembolism (VTE) in children. Methods In the present cohort of 874 consecutively enrolled pediatric patients with VTE aged newborn to <18 years the rate of VTE recurrence and the time to recurrence in relation to AT-deficiency [confirmed by underlying gene mutations; type 1 deficiency n=17; type 2 deficiency n=3], age and sex was determined. Twenty of 874 patients [2.4%] suffered from AT-deficiency. From the same cohort 150 VTE children carrying the heterozygous F5 G1691A mutation [F5: 17.7%] served as controls. Patients were prospectively followed for a median of 84 months. Data were pooled across participating sites to increase power and to enhance the generalisability of the data. Incidence rates were given as events per 1000 person-years. Results Of the 170 children enrolled 26 [AT n=9; F5 n=17] had recurrent VTE at a median of 15 months [95%CI: 12-36] following VTE onset: two of nine [AT] and two of 17 [F5] children suffered recurrent VTE while on anticoagulation with warfarin. The overall incidence rate of recurrence was 61.5 in patients with AT-deficiency compared to 23.5 for pediatric F5 carriers [p=0.02]. The recurrent-free survival probability is shown in the figure [logrank p-value: p=0.001]. When comparing AT patients and F5 children multivariate analysis [Cox regression] adjusted for age, sex and duration of anticoagulation treatment showed that AT deficiency [HR/95%CI: 4.1/1.8-9.4] significantly influenced the hazard for recurrent VTE. Conclusions Based on multivariate analysis, the presence of AT deficiency was associated with an increased risk of VTE recurrence. AT-deficiency in pediatric patients should be identified at VTE onset and the possible influence of intensified treatment protocols on recurrence should be studied in future prospective international studies. Condensed abstract To determine the relative importance of antithrombin deficiency or factor V (FV) mutations as risk factors for fatal/non-fatal recurrence in pediatric thromboembolism (VTE). Antithrombin deficiency influenced the hazard for recurrent VTE. Disclosures: No relevant conflicts of interest to declare.

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Risk of recurrent venous thromboembolism after a first oestrogen-associated episode

Thrombosis and Haemostasis ◽

10.1160/th09-10-0685 ◽

2010 ◽

Vol 104 (09) ◽

pp. 498-503 ◽

Cited By ~ 41

Author(s):

Grégoire Le Gal ◽

Michael Kovacs ◽

Marc Carrier ◽

Kimberley Do ◽

Susan Kahn ◽

...

Keyword(s):

Venous Thromboembolism ◽

Oral Contraceptives ◽

Hormone Replacement ◽

Anticoagulant Treatment ◽

Exogenous Oestrogen ◽

Recurrent Venous Thromboembolism ◽

Recurrent Vte ◽

Post Menopausal ◽

Age Range

SummaryThe use of exogenous oestrogen in women with otherwise unprovoked venous thromboembolism (VTE) could be considered sufficient explanation to classify VTE as provoked if the risk of recurrent VTE after 3–6 months of anticoagulant treatment is similar to the risk of recurrent VTE observed after a surgery or prolonged immobilisation. Our objective was to assess the risk of recurrent VTE in women after a first unprovoked episode on oestrogen. The REVERSE study is a cohort study of patients with a first unprovoked VTE treated with anticoagulant treatment for 5–7 months. The risk of recurrent VTE during follow-up was compared between women users and non users of oestrogen at the time of index VTE. Among the 646 patients included, 314 were women, of them 67 were current users of oestrogen at the time of their VTE: 49 were on oral contraceptives and 18 on post-menopausal hormone replacement therapy (HRT). No significant association was found between oestrogen exposure, either oral contraceptives or HRT, and a lower risk of recurrent VTE after adjustment for age, or analysis restricted to women in the same age range as oestrogen contraceptives and HRT users, respectively. The risk of recurrent VTE is low in women after a first otherwise unprovoked oestrogen-associated VTE. However, this risk is not significantly lower than in women whose VTE was not related to oestrogen use.

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Post-Anticoagulation Cessation D-Dimer Testing and VTE Recurrence in Real-World Australian Audit

Blood ◽

10.1182/blood-2018-99-118661 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 1227-1227

Author(s):

Julie Wang ◽

Rowena Brook ◽

Alison Slocombe ◽

Lisa Hong ◽

Prahlad Ho

Keyword(s):

Risk Factor ◽

Significant Risk ◽

Significant Risk Factor ◽

Risk Of Recurrence ◽

Increased Risk ◽

Recurrent Vte ◽

Residual Thrombus ◽

Repeat Imaging ◽

D Dimer

Abstract Aim Elevated D-dimer post-anticoagulation cessation is a recognised risk factor for recurrent venous thromboembolic events (VTE). In particular, raised D-dimer post cessation has been associated with increased risk of recurrence in unprovoked major VTE. Currently in Australia, D-dimer has not been widely used in practice to stratify the risk of VTE recurrence. This study aims to retrospectively analyse the effect of routine D-dimer testing and it's association with VTE recurrence. Methods A retrospective evaluation was performed on 1024 patients with a diagnosis of VTE at a tertiary hospital in Australia between January 2013 and December 2016. Data collected included demographics, results and timing of D-dimer testing and serial imaging results. Results 1024 patients were reviewed with a total median follow up of 12 months (range 0-59 months). D-dimer was tested in 189 patients (18.5%) within 90 days after cessation of anticoagulation. Of these patients, median age was 58 (18-92) and 55.3% (n=105) were female. 33.3% (n=63) had isolated distal deep vein thrombosis (IDDVT), 66.3% (n=126) had above knee DVT (AKDVT)/pulmonary embolus (PE), 54.5% (n=103) of VTE were provoked. Abnormal post cessation D-dimer (>500) was found in 72 patients (37.9%). Of these, 25 patients were restarted on anticoagulation; one had recurrent VTE whilst on low dose apixaban 2.5mg BD and one had recurrence after cessation of anticoagulation at a later date. Patients with elevated D-dimer post cessation had a higher rate of recurrence with the highest risk in patients with D-dimer >1000 (RR 7.38, p=<0.01) outlined in Table 1. Of the 164 patients with post cessation D-dimer testing who remained off anticoagulation there were a total of 24 (12.6%) episodes of recurrent VTE. Elevated D-dimer post anticoagulation cessation was a significant risk factor for recurrence in both provoked VTE (RR 4.21, p=0.01) and unprovoked VTE cohorts (RR 4.55, p=0.008) outlined in Table 2. When provoked VTE were sub-categorised, raised D-dimer demonstrated the most statistical significance in VTE provoked by travel (RR 13.5 p=0.06). Of the patients with post anticoagulation cessation D-dimer testing 170 patients (89.9%) had repeat imaging to assess for residual thrombus. In the subgroup of patients with no residual thrombus, elevated D-dimer was a significant risk factor for VTE recurrence (RR 6.4, p=<0.01). Patients with normal D-dimer and no residual thrombus had the lowest rate of recurrence 5.4% (n=4) see Table 3. When stratified by type of VTE, elevated D-dimer post anticoagulation cessation was significantly related to risk for recurrence in the overall IDDVT sub-cohort (RR 4.09, p=0.007). This was not significant for the AKDVT/PE sub cohort (RR 3.24, p=0.079). However, for patients with unprovoked AKDVT or PE, having D-dimer tested post anticoagulation, regardless of result, was associated with lower rates of VTE recurrence RR 0.30 (p=0.02) compared to those who had no D-dimer testing as part of follow-up. Conclusion Post treatment D-dimer testing may have a clinical role in stratifying the risk of VTE recurrence along with repeat imaging to detect residual thrombus. Elevated D-dimer post anticoagulation cessation is associated with increased risk of VTE recurrence for both provoked and unprovoked VTE with highest risk in patients with D-dimer >1000. Patients with no residual thrombus and a negative D-dimer post anticoagulation cessation had the lowest rate of recurrence. In the subgroup of patients with provoked VTE and IDDVT a positive D-dimer post cessation was associated with 4.21 and 4.09 relative risk of recurrence respectively, suggesting that the role of D-dimer testing can be extended to these subpopulations. Interestingly, in patients with unprovoked AKDVT or PE, having post-cessation D-dimer testing performed, regardless of result, was associated with a significantly lower rate of VTE recurrence compared to patients without D-dimer testing, which may be related to specialist review and recommencement of anticoagulation in high-risk patients. Disclosures No relevant conflicts of interest to declare.

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Risk of Recurrent Venous Thromboembolism and Bleeding in Patients with Cancer Associated Thrombosis

Blood ◽

10.1182/blood-2020-142805 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 18-18

Author(s):

Doaa Attia ◽

Xuefei Jia ◽

Mailey L Wilks ◽

Barbara Tripp ◽

Christopher D'Andrea ◽

...

Keyword(s):

Venous Thromboembolism ◽

Cancer Patients ◽

Major Bleeding ◽

Research Funding ◽

Cleveland Clinic ◽

Treatment Groups ◽

Recurrent Venous Thromboembolism ◽

Recurrent Vte ◽

Cancer Associated Thrombosis

Background: The treatment paradigm for cancer associated thrombosis (CAT) has evolved over recent years from using low molecular weight heparin (LMWH) to direct oral anticoagulants (DOACs). Some randomized trials suggest decreased rates of recurrent venous thromboembolism (VTE) in CAT patients treated with DOACs compared to LMWH but also reported increased rates of bleeding. The Cleveland Clinic Taussig Cancer Center has been treating cancer thrombosis in a centralized CAT clinic since 2014. Here we report our rates of bleeding and recurrent VTE in cancer patients treated with anticoagulation. Methods: We prospectively followed cancer patients referred to our clinic from 8/2014-10/2019. A total of 1548 patients were referred to the clinic, of whom 462 were diagnosed with an acute VTE. VTE events, including deep venous thrombosis, pulmonary embolism, and visceral thrombosis, were noted. The comparison of bleeding rates (defined using ISTH criteria for major and clinically relevant non major bleeding, CRNMB) among treatment groups (LMWH vs DOACs) was examined using chi-square test. Rate of recurrent VTE was analyzed using a competing model in which death was treated as a competing risk. Results: The study population comprised 462 patients with acute VTE with a mean age of 62.67±12.23 and 51.8 % males. Of these, 234 (52.9%) received LMWH, 161(36.4%) received DOACs, and 47 (10.6%) received other agents including warfarin for initial anticoagulation. Overall, the 6-month, 1 year, and 2-year VTE recurrence rate was 5.9%, 6.6%, 7.9%, respectively. Recurrent VTE rates were similar for LMWHs, DOACs and other agents (P>0.05). Of 368 patients for whom follow-up data was available, 74 (16.7%) had bleeding event , of which 25 (33.8%) had major bleeding and 49 (66.4%) had CRNMB at 6 month follow-up with no difference across three treatment groups (p=0.56). Conclusion: In this real-world practice setting, rates of recurrent VTE and bleeding were similar for DOACs and LMWH suggesting that with careful patient selection the concern for higher bleeding with DOACs in cancer patients can be safely overcome. Disclosures McCrae: Momenta Pharmaceuticals: Consultancy; Novartis: Honoraria; Rigel: Consultancy; Dova: Consultancy. Khorana:Merck: Research Funding; Medscape: Honoraria; Leo Pharma: Honoraria; Seattle Genetics: Honoraria; Pharmacyte: Honoraria; Pharmacyclics: Honoraria; Array: Other: Research funding (to institution); Janssen: Honoraria; Bayer: Honoraria; Pfizer: Honoraria; Sanofi: Honoraria; BMS: Honoraria, Research Funding; Leap: Research Funding.

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