In Children with Provoked Venous Thromboembolism, Increasing Plasma Coagulability during the First 3 Months Postdiagnosis is Prognostic of Recurrence

AbstractPrognostic factors for venous thromboembolism (VTE) recurrence following provoked VTE are largely unknown. Using the Clot Formation and Lysis (CloFAL) assay, single institutional research has shown overall improvement in acute hypercoagulability during the first 3 months postpediatric VTE, yet a rise in plasma coagulability in a subgroup of patients. We sought to define the incidence of rise in coagulability during the first 3 months post-provoked VTE, to investigate its relationship with elevated D-dimer, and to test the hypothesis that a marked rise in coagulability is independently prognostic of VTE recurrence. CloFAL and D-dimer assays were performed on plasma at 4 to 6 weeks and 3 months post-VTE in the Johns Hopkins pediatric VTE cohort and National Institutes of Health-sponsored Kids-DOTT trial. Associations of VTE recurrence with D-dimer and CloFAL assay measures were evaluated via logistic regression. Eighty-seven patients were included. Median follow-up was 1 year. Complete veno-occlusion was determined in 12% at 6 weeks. During the first 3 months post-VTE, a marked rise in coagulability was observed by CloFAL assay in 17% of patients, while D-dimer was elevated in 21%. Recurrent VTE occurred in 10% of patients. CloFAL assay, but not D-dimer, was associated with recurrence (odds ratio [OR] 5.87, 95% confidence interval [95% CI], 1.34–25.8]). After adjustment for veno-occlusion, patients with a marked rise in coagulability by CloFAL assay had a 10-fold increased risk of recurrent VTE (OR 10.33 [95% CI, 1.83–58.19]). Future work should seek to elucidate the mechanisms underlying a rise in plasma coagulability following provoked VTE and to substantiate its prognostic utility for recurrent VTE.

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

Thrombosis and Haemostasis ◽

10.1160/th13-06-0488 ◽

2013 ◽

Vol 110 (12) ◽

pp. 1172-1179 ◽

Cited By ~ 33

Author(s):

Esteban Gándara ◽

Michael J. Kovacs ◽

Susan R. Kahn ◽

Philip S. Wells ◽

David A. Anderson ◽

...

Keyword(s):

Risk Factor ◽

Venous Thromboembolism ◽

Anticoagulant Therapy ◽

Oral Anticoagulation ◽

Blood Type ◽

Increased Risk ◽

Recurrent Venous Thromboembolism ◽

Abo Blood Type ◽

Recurrent Vte

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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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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Venous Thromboembolism in Patients with Liver Cirrhosis: Findings from the RIETE (Registro Informatizado de la Enfermedad TromboEmbolica) Registry

Seminars in Thrombosis and Hemostasis ◽

10.1055/s-0039-1697682 ◽

2019 ◽

Vol 45 (08) ◽

pp. 793-801 ◽

Cited By ~ 5

Author(s):

Behnood Bikdeli ◽

David Jiménez ◽

Guadalupe Garcia-Tsao ◽

Raquel Barba ◽

Carme Font ◽

...

Keyword(s):

Venous Thromboembolism ◽

Hazard Ratio ◽

Risk Of Bleeding ◽

Fatal Bleeding ◽

Increased Risk ◽

All Cause Mortality ◽

Recurrent Vte ◽

One Year ◽

Related Mortality

AbstractPatients with cirrhosis are not only at an increased risk of bleeding but also at risk of venous thromboembolism (VTE). We sought to determine the clinical characteristics, management, and outcomes after VTE in patients with cirrhosis. We used the data from RIETE (Registro Informatizado de la Enfermedad TromboEmbolica), an international registry of patients with VTE, to compare the outcomes in patients with and without cirrhosis. Main outcomes included all-cause mortality, pulmonary embolism (PE)-related mortality, recurrent VTE, and bleeding. Among 43,611 patients with acute VTE, 187 (0.4%) had cirrhosis. Of these, 184 (98.4%) received anticoagulation for a median of 109 days (interquartile range [IQR]: 43–201 days), most commonly with enoxaparin (median dose: 1.77 [IQR: 1.38–2.00] mg/kg/day). Compared with patients without cirrhosis, those with cirrhosis had a higher rate of all-cause mortality (10.7 vs. 3.4%; odds ratio [OR]: 3.41; 95% confidence interval [CI]: 2.03–5.46) and fatal bleeding (2.1 vs. 0.2%; OR: 13.94; 95% CI: 3.65–37.90) but similar rates of fatal PE (0.5 vs. 0.5%; OR: 1.17; 95% CI: 0.03–6.70). Patients with cirrhosis had a higher rate of all-cause mortality per 100 patient-years of follow-up (58.9 vs. 16.0; hazard ratio [HR]: 3.70; 95% CI: 2.69–4.91). One-year hazard ratio of clinically relevant bleeding (HR: 2.86; 95% CI: 1.91–4.27), fatal bleeding (HR: 8.51; 95% CI: 3.5–20.7), or recurrent VTE (HR: 2.08; 95% CI: 1.00–4.36) was higher in patients with cirrhosis. Cirrhosis is a challenging comorbidity in patients with VTE. Most patients were treated with anticoagulation and had an elevated risk of recurrence, similar risk of fatal PE, and a very high risk of bleeding including fatal bleeds.

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Venous thromboembolism and bleeding in a community setting

Thrombosis and Haemostasis ◽

10.1160/th08-06-0352 ◽

2009 ◽

Vol 101 (05) ◽

pp. 878-885 ◽

Cited By ~ 17

Author(s):

Joel Gore ◽

George Reed ◽

Darleen Lessard ◽

Luigi Pacifico ◽

Cathy Emery ◽

...

Keyword(s):

Venous Thromboembolism ◽

Total Mortality ◽

Community Setting ◽

Patient Characteristics ◽

Recurrence Rates ◽

Increased Risk ◽

History Of ◽

Recurrent Vte ◽

The Impact

SummaryBleeding is the most frequent complication of antithrombotic therapy for venous thromboembolism (VTE). However, little attention has been paid to the impact of bleeding after VTE in the community setting. The purpose of this investigation was to describe the incidence rate of bleeding after VTE, to characterize patients most at risk for bleeding, and to assess the impact of bleeding on rates of recurrent VTE and all-cause mortality. The medical records of residents of the Worcester (MA, USA) metropolitan area diagnosed with ICD-9 codes consistent with potential VTE during 1999, 2001, and 2003 were individually validated and reviewed by trained data abstracters. Clinical characteristics, acute treatment, and outcomes (including VTE recurrence rates, bleeding rates, and mortality) over follow-up (up to 3 years maximum) were evaluated. Bleeding occurred in 228 (12%) of 1,897 patients with VTE during our follow-up. Of these, 115 (58.8%) had evidence of early bleeding occurring within 30 days of VTE diagnosis. Patient characteristics associated with bleeding included impaired renal function and recent trauma. Other than a history of prior VTE, the occurrence of bleeding was the strongest predictor of recurrent VTE (hazard ratio [HR] 2.18; 95% confidence interval [CI] 1.54–3.09) and was also a predictor of total mortality (HR 1.97; 95%CI 1.57–2.47). The occur-rence of bleeding following VTE is associated with an increased risk of recurrent VTE and mortality. Future study of antithrombotic strategies for VTE should be informed by this finding. Advances that result in decreased bleeding rates may paradoxically decrease the risk of VTE recurrence.

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Preliminary Investigations Showing Venous Thromboembolism Recurrence in Patients with Residual Venous Obstruction in Singaporean Population

International Journal of Angiology ◽

10.1055/s-0037-1603906 ◽

2017 ◽

Vol 26 (04) ◽

pp. 223-227

Author(s):

Chaozer Er ◽

Claudia Chong ◽

Han Chin ◽

Tay Chin ◽

Ashish Sule

Keyword(s):

Venous Thromboembolism ◽

Femoral Vein ◽

Asian Population ◽

Common Iliac Vein ◽

Venous Obstruction ◽

Diagnostic Laboratory ◽

Superficial Femoral Vein ◽

Increased Risk ◽

Recurrent Vte

AbstractThis study aims to determine the association of residual venous obstruction (RVO) with recurrent venous thromboembolism (VTE). A retrospective cohort study was conducted determining if RVO on ultrasonography is associated with recurrent VTE in a Singaporean population. The subjects were identified from the Vascular Diagnostic Laboratory patients' record of Tan Tock Seng Hospital (TTSH), Singapore between 2008 and 2013. All the patients included had RVO after 3 months of anticoagulation. Data such as age, gender, race, thrombus location, etiology, history of malignancy, thrombophilia screen, treatment duration, and follow-up were recorded for analysis. Statistical analysis was performed using Stata/SE 13.1 (StataCorp LLC). The study was approved by the National Healthcare Group Domain Specific Review Board (DSRB), Singapore. Out of the 34 patients who had RVO, 6 (17.6%) developed VTE recurrence. Patients were treated with anticoagulation for a mean time of 24.5 months. The mean follow-up time for VTE recurrence was 25.4 months. Out of the six patients who had VTE recurrence, one had common iliac vein involvement, four had superficial femoral vein and common femoral vein involvement, zero had popliteal vein involvement, and one had calf veins involvement. There was a significant association between thrombophilia (p = 0.0195) and malignancy (p = 0.020) at inclusion with the risk of recurrent VTE. The presence of RVO after 3 months of anticoagulation is likely to increase the risk of VTE recurrence. Larger studies with RVO are needed to evaluate if there is an increased risk of VTE recurrence in the Asian population.

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Prevalence and Characteristics of Occult Cancer in Patients with Venous Thromboembolism.

Blood ◽

10.1182/blood.v106.11.1623.1623 ◽

2005 ◽

Vol 106 (11) ◽

pp. 1623-1623

Author(s):

Marielle M.J. Beckers ◽

Roger E.G. Schutgens ◽

Martin H. Prins ◽

Douwe H. Biesma

Keyword(s):

Venous Thromboembolism ◽

Incidence Rates ◽

Screening Programs ◽

Occult Cancer ◽

Netherlands Cancer Registry ◽

Increased Risk ◽

High Prevalence ◽

Prevalence Of Cancer ◽

D Dimer

Abstract Background: Venous thromboembolism (VTE) can be the first sign of occult cancer. It is still a matter of debate if screening programs for cancer should be encouraged. No one would advocate extensive screening in an at random VTE-population. It is, however, possible that a subgroup of VTE-patients has a relatively high risk for developing cancer. Objective: To identify a group of patients with a high prevalence of cancer during follow-up (occult cancer). Results: We retrospectively reviewed the prevalence and type of cancer in 610 consecutive VTE-patients (267 men and 343 women). Mean age of the patients was 51.9 years and the mean follow-up was 50 months. There were 73 cancer cases (overall prevalence 12%): 32 patients were known with active cancer and 14 patients were diagnosed with cancer at presentation with VTE. A total of 27 patients (4.8%; 27/564) had cancer during follow-up. Among patients with VTE secondary to immobilisation, increased estrogens levels or thrombophilia (n=382) the prevalence of cancer was significantly lower compared to the 228 patients with idiopathic VTE (1.5% versus 10%; p<0.001). In the idiopathic VTE group, patients older than 60 years had a relatively high prevalence of occult cancer (OR=2.7; 95% CI 1.0–7.3; as compared to patients < 60). Gender, location of VTE (PE or DVT) and recurrent VTE were not associated with an increased risk for occult cancer. Laboratory tests of erythrocyte sedimentation rate, blood count, liver and renal function did not predict the occurrence of occult cancer. In 142 patients with idiopathic VTE, the D-dimer concentration was measured at presentation using the Tinaquant® quantitative assay (the DD-group). Eleven patients in the DD-group developed cancer within 24 months of follow-up; 9 (82%) had high D-dimer concentration (>4000 μg/L FEU) at VTE-presentation. The two patients younger than 60 years and occult cancer within 24 months both had a D-dimer concentration >4000 μg/L FEU. In patients older than 60 years and cancer within 24 months after idiopathic VTE, 77.8% (7/9) had initial high D-dimer concentration compared to 22.2% (2/9) with low D-dimer concentration (<4000 μg/L FEU). Five patients diagnosed with cancer after 36 months had all low D-dimer concentrations (<4000 μg/L FEU). The relative risk (RR) of cancer during follow-up was determined by calculating the expected number of cancer using the age and sex specific incidence rates of cancer among the general Dutch population (Netherlands Cancer Registry). At 6 months the RR of being diagnosed with cancer was 5.9 (95% CI= 1.6–15.1), at 12 months the RR was 9.1 (95% CI= 3.34–19.8), at 24 months the RR was 3.3 (95% CI= 0.9–8.3) and at 36 months the RR was 1 (95 % CI= 0.03–5.7). Conclusion: Screening for cancer in patients with VTE may be limited to patients older than 60 years with idiopathic VTE and to patients with high D-dimer concentration (>4000 μg/L FEU). Within 2 years of follow-up patients with idiopathic VTE have the highest risk for being diagnosed with cancer when compared to the general population.

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Serial D-Dimer Measurements Are Useful in Predicting the Recurrence of Venous Thromboembolism after Discontinuation of Anticoagulation

Blood ◽

10.1182/blood.v112.11.525.525 ◽

2008 ◽

Vol 112 (11) ◽

pp. 525-525

Author(s):

Montserrat Briz ◽

Helen Marr ◽

Kate Talks ◽

John Hanley ◽

Patrick Kesteven

Keyword(s):

Risk Factors ◽

Venous Thromboembolism ◽

Accurate Method ◽

Recurrent Event ◽

Minor Trauma ◽

Normal Range ◽

Chi Square ◽

Increased Risk ◽

Recurrent Vte ◽

D Dimer

Abstract The optimal duration of anticoagulation following a venous thromboembolism (VTE) is influenced by the site of the event and the presence of risk factors. After anticoagulation is discontinued, approximately 10% of patients will have a recurrent event. At present, there is no accurate method of identifying this group of patients, in whom the benefits of reanticoagulation may outweigh the bleeding risks. In 2006, Palaretti et al reported the use of a single qualitative d-dimer measurement, 4 weeks after stopping anticoagulation for a spontaneous VTE, to identify patients at increased risk of a recurrent VTE. Our observational study investigates whether serial quantitative d-dimer measurements, after the discontinuation of anticoagulation for VTE, are of use in identifying patients at higher risk of VTE recurrence. We followed an unselected group of patients attending a hospital based Thrombosis Clinic in whom anticoagulation for VTE was stopped. Over a 2 year period from July 2005 to July 2007, anticoagulation was discontinued in 216 patients (112 females, 104 males) after a median period of 6 months’ treatment (range 2–324 months). The patients ranged in age from 16–88 years, with a mean age of 54 years. Of the group, 146 had been anticoagulated for a deep vein thrombosis (DVT), 59 for pulmonary embolism (PE) +/− DVT, and 11 had been anticoagulated for VTE at other sites. Major risk factors for VTE (recent surgical procedure, malignancy, pregnancy) were present at diagnosis in 80 patients. Minor risk factors (minor trauma, prolonged travel or immobility, hormone therapy) were present in 61 patients, while no risk factors were identified in 69 patients. Presence of risk factors was unknown in the remaining 6 patients. After discontinuation of their anticoagulation, patients were followed up in the Thrombosis Clinic for a median of 14.5 months (range 0–41 months). D-dimer measurements were recorded at the point of stopping anticoagulation, 4 weeks later, and then on subsequent clinic visits. Quantitative d-dimer results were obtained using an automated latex immunoassay (Instrumentation Laboratories, d-dimers HS) on an ACL TOP CTS analyser. Recurrence of VTE occurred in 23 of the 216 (10.7%) patients. D-dimer results off anticoagulation were available in 207 patients. Forty six patients had repeatedly high d-dimer measurements (> 300ng/ml) off anticoagulation. D-dimers remained within the normal range in 112 patients. In 33 patients, d-dimers were initially normal, but subsequently became high, while the opposite was true in 16 patients, where initially high d-dimers later fell into the normal range. Of the recurrences, 8 occurred in the group who had repeatedly high d-dimers after anticoagulation was stopped (17.4%), whilst only 3 recurrences occurred in patients whose d-dimers were consistently normal (2.7%). In the group whose d-dimers were initially normal, but subsequently became high during follow up, there were 6 recurrences (18.2%). There was 1 recurrence in the group whose d-dimers were initially high, but then became normal. In the 9 patients in whom serial d-dimer results were not available, 5 recurrent VTE were observed: 4 of these occurred within 4 weeks of the patient stopping anticoagulation. After statistical analysis of the data, taking into account the nature of the original event, age, gender and d-dimer measurements, a high d-dimer off anticoagulation was the only significant independent variable predicting for recurrence of VTE (Chi-square 13.1 p<0.00001). This data supports a role for monitoring d-dimer measurements in identifying patients at increased risk of VTE recurrence. Further investigation is needed to establish the benefits of reanticoagulation in these patients.

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Clinical Predictors of Confirmed Venous Thromboembolism in Patients with a Suspected Recurrent Venous Thromboembolism: A Retrospective Study of the Reverse I Cohort

Blood ◽

10.1182/blood.v120.21.1153.1153 ◽

2012 ◽

Vol 120 (21) ◽

pp. 1153-1153 ◽

Cited By ~ 1

Author(s):

Karine Gauthier ◽

Melanie Tan ◽

Gregoire Le Gal ◽

Marc A. Rodger

Keyword(s):

Venous Thromboembolism ◽

Shortness Of Breath ◽

Clinical Predictors ◽

Vein Thrombosis ◽

History Of ◽

Recurrent Vte ◽

Deep Vein ◽

Test Probability ◽

D Dimer

Abstract Abstract 1153 Background: Many clinical decision rules (CDR), such as the Wells models for deep vein thrombosis of the legs (DVT) and pulmonary embolism (PE), have been established for patients with suspected first venous thromboembolism (VTE). However these rules may have limitations for patients with suspected recurrent VTE. First, patients with suspected PE and a history of VTE have their diagnosis more likely confirmed than patients with a suspected PE without a history of VTE (40.3 vs. 20.6%) (Le Gal G et al. Arch Intern Med, 2006), suggesting a different pre-test probability. Furthermore, patients who had a previous pulmonary embolism often have complaints of chronic dyspnea (Klok FA et al. Eur J Intern Med, 2008), which could complicate the risk estimation of recurrent PE. A similar scenario arises for patients who suffered a DVT, as 30–50% of patients will show signs and symptoms of post-thrombotic syndrome (PTS) following a deep vein thrombosis (Kahn SR. Curr Opin Pulm Med, 2006). In addition, the value of D-dimer testing is still uncertain in patients with suspected recurrent VTE. Finally, imaging has limitations, as residual thrombosis may be present and may be misdiagnosed as an acute recurrent event. Hence, because pre-test probability, laboratory testing and diagnostic imaging performances differ in patients with a suspected recurrent VTE, a different approach may be needed for effective management of these patients. Our objective was to study clinical predictors for the diagnosis of recurrent VTE in patients with a history of VTE. Methods: The REVERSE I study enrolled patients with a first unprovoked, objectively proven VTE (Rodger M et al. CMAJ, 2008). Each patient in the REVERSE I cohort that had a suspected recurrent VTE during follow-up was screened for eligibility. Only first adjudicated suspected recurrent events were studied. All these events were blindly adjudicated by an independent committee. Potential clinical predictors of recurrent VTE consisted of clinical predictors collected at the baseline visit (5–7 months after the unprovoked event), and of information collected in physicians' clinical notes, laboratory or imaging results at the time of the suspected recurrent VTE. The predictive value of each predictor was determined by the Chi-square test for nominal data and the unpaired 2-tailed T-test for continuous data. Results: In the REVERSE I cohort, out of the 646 patients who were followed, 402 patients had a suspected recurrent VTE within a mean of 20.2 months (range: 0 – 97 months) of follow-up. After screening, 376 patients were enrolled in our study: 52.7 % of patients were males, and the mean age was 53.1 years (± 17.5). Among all suspected recurrent VTE events, male gender and a positive d-dimer result at the time of suspected recurrent VTE (p < 0.01), as well as symptoms occurring for 10 days or less at the time of presentation (p < 0.05) were in favor of a recurrent VTE diagnosis. In addition, mean age was higher in patients with a confirmed recurrent VTE (p < 0.05). In patients with suspected DVT, the presence of leg swelling was in favor of a confirmed diagnosis (p < 0.01), while leg pain was not associated with a higher rate of confirmed DVT. A suspected DVT in the same leg as the previous event seemed less likely to have a confirmed diagnosis of recurrent DVT. However this trend was not statistically significant. In patients with suspected PE, mean oxygen saturation was lower among patients with a new PE diagnosis (p < 0.05). Chest pain and shortness of breath were not important predictors. Finally, in the case of a suspected DVT and PE event, shortness of breath was a significant predictor (p < 0.05) for the diagnosis of recurrent VTE. Conclusion: This is the first study to show that predictors for the diagnosis of a recurrent VTE may be different than predictors for the diagnosis of a first VTE. For instance, our results show that male gender is not only a risk factor for recurrent VTE (McRae S et al. Lancet, 2006), but is also an important predictor for confirmed VTE among patients with suspected recurrent VTE, while none of the existing CDRs take this in consideration. A CDR specific to patients with a history of VTE may be needed for better management of these patients. Disclosures: Le Gal: Bayer, bioMérieux, GSK, Leo Pharma, Sanofi Aventis: Honoraria.

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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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