Circulating P-selectin and the risk of recurrent venous thromboembolism

2007 ◽  
Vol 97 (06) ◽  
pp. 880-883 ◽  
Author(s):  
Gregor Hron ◽  
Sabine Eichinger ◽  
Oswald Wagner ◽  
Paul Kyrle

SummaryThe clinical relevance of high P-selectin levels in venous thrombosis is unknown. We prospectively followed 544 patients with first unprovoked venous thromboembolism (VTE) after cessation of anticoagulation and evaluated P-selectin as a risk factor of recurrent VTE. VTE recurred in 63 (12%) patients. Patients with recurrence had significantly higher P-selectin levels than those without (45.8 mg/dl ± 16.4 vs. 40.1 mg/dl ± 13.3; p = 0.006). After four years, the probability of recurrence was 20.6% (95% confidence interval [CI] 12.6–28.5) among patients with P-selectin values above the 75th percentile of the patient population and was 10.8% (95% CI 7.2–14.3) among patients with lower values (p = 0.046). Compared to patients with low P-selectin, adjusted risk of recurrence was 1.7-fold (95% CI 1.0–2.9, p = 0.045) increased among patients with P-selectin levels exceeding the 75th percentile. We conclude that high circulating P-selectin is a risk factor of recurrent VTE.

1999 ◽  
Vol 82 (10) ◽  
pp. 1222-1226 ◽  
Author(s):  
W. Åberg ◽  
D. Lockner ◽  
C. Paul ◽  
M. Holmström

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.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Giustozzi ◽  
S Barco ◽  
L Valerio ◽  
F A Klok ◽  
M C Vedovati ◽  
...  

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.


2013 ◽  
Vol 110 (12) ◽  
pp. 1172-1179 ◽  
Author(s):  
Esteban Gándara ◽  
Michael J. Kovacs ◽  
Susan R. Kahn ◽  
Philip S. Wells ◽  
David A. Anderson ◽  
...  

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.


2007 ◽  
Vol 98 (12) ◽  
pp. 1232-1236 ◽  
Author(s):  
Gregor Hron ◽  
Mirko Hirschl ◽  
Christine Bialonczyk ◽  
Erich Minar ◽  
Marietta Kollars ◽  
...  

SummaryIn patients with venous thromboembolism (VTE) a laboratory assay that globally measures the overall thrombophilic tendency is not available. We hypothesized that determination of ProC® Global, a plasma assay which tests the global function of the protein C pathway, could be used to stratify patients according to their risk of recurrent VTE. We prospectively followed 774 patients with first spontaneous VTE for a mean time of 52 months. ProC Global normalized ratio (NR) was measured in plasma by use of a commercially available assay based on activated partial thromboplastin time. Ninety-eight of the 774 patients had recurrent VTE. Patients with ProC Global NR ≥ 0.75 had a relative risk of recurrence of 0.59 (95% CI 0.40–0.87) as compared with those with lower ratio. After four years, cumulative probability of recurrence was 8.6% in patients with ProC Global NR ≥ 0.75 and 17.4% in patients with a lower ratio (p=0.006). Patients with a high ProC Global NR have a low risk of recurrent VTE. ProC Global NR can be used to stratify patients with a first unprovoked VTE according to their risk of recurrence.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 271-271 ◽  
Author(s):  
Sabine Eichinger ◽  
Natalie M. Pecheniuk ◽  
Gregor Hron ◽  
Hiroshi Deguchi ◽  
Paul A. Kyrle ◽  
...  

Abstract Venous thrombosis is clinically distinct from arterial thrombosis, with notable differences in thrombus appearance, pathogenic mechanisms, and therapeutic approaches. High-density lipoprotein (HDL) protects against arterial atherothrombosis, but it is not known if HDL protects against recurrent venous thromboembolism. We hypothesized that HDL protects against recurrent venous thrombosis because of its multiple antithrombotic and anti-inflammatory actions. These protective activities include down-regulation of thrombin generation by acting as an anticoagulant cofactor for activated protein C/protein S, enhancement of protective endothelial nitric oxide synthase activity, reduction of leukocyte adhesion to endothelium, and anti-apoptotic effects on endothelium. To test our hypothesis, we prospectively studied 772 patients who had a first episode of spontaneous venous thromboembolism. During an average follow-up observation period of 48 months we recorded the end point of objectively documented, symptomatic recurrent venous thromboembolism. Patients with a genetic deficiency of a plasma coagulation inhibitor deficiency, with a lupus anticoagulant, or with cancer as well as those who required long-term antithrombotic treatment or were on statin therapy were excluded. The relationship between plasma lipoprotein parameters and recurrence of venous thrombosis was evaluated. Plasma apolipoproteins AI and B were measured by immunoassays for all subjects. Using NMR, we determined the levels of ten major lipoprotein subclasses in plasma for 99 patients with venous thrombosis recurrence and for 297 matched patients without recurrence. Recurrent venous thromboembolism developed in 100 of the 772 patients (12.8%). Patients with recurrence compared to those without recurrence had lower mean (±SD) plasma levels of apolipoprotein AI (1.12±0.22 vs. 1.23±0.27 mg/ml, P<0.001) but similar apolipoprotein B levels. The relative risk of recurrence was 0.87 (95% CI, 0.80 to 0.94) for each increase of 0.1 mg/ml in plasma apolipoprotein AI. For patients with apolipoprotein AI above the 67th percentile of the study population values compared with those with lower levels, the relative risk of recurrence was 0.51 (95% CI 0.32–0.83). Comparisons of plasma lipoprotein particle levels from subjects with recurrence versus those without recurrence gave similar results showing that HDL particle concentrations were lower in subjects with recurrence. Patients with high levels of apolipoprotein AI, HDL-cholesterol, and large HDL particles had decreased risk of recurrent venous thromboembolism. In summary, these novel findings that HDL appears to protect against recurrent venous thrombosis may have implications for testing HDL parameters to predict risk and may imply that lipid-altering drugs that increase HDL might reduce the risk for first or recurrent venous thrombotic events.


2018 ◽  
Vol 2 (7) ◽  
pp. 788-796 ◽  
Author(s):  
Martin H. Prins ◽  
Anthonie W. A. Lensing ◽  
Paolo Prandoni ◽  
Philip S. Wells ◽  
Peter Verhamme ◽  
...  

Key Points The risk of recurrence in patients with VTE provoked by minor transient or persistent risk factors is uncertain. The risk of recurrence with VTE provoked by minor transient or persistent risk factors is similar to that with unprovoked VTE.


Author(s):  
Jeffrey A. Kline ◽  
David H. Adler ◽  
Naomi Alanis ◽  
Joseph R. Bledsoe ◽  
Daniel M. Courtney ◽  
...  

BACKGROUND: The objective was to test if low-risk emergency department patients with vitamin K antagonist (venous thromboembolism [VTE]; including venous thrombosis and pulmonary embolism [PE]) can be safely and effectively treated at home with direct acting oral (monotherapy) anticoagulation in a large-scale, real-world pragmatic effectiveness trial. METHODS: This was a single-arm trial, conducted from 2016 to 2019 in accordance with the Standards for Reporting Implementation Studies guideline in 33 emergency departments in the United States. Participants had newly diagnosed VTE with low risk of death based upon either the modified Hestia criteria, or physician judgment plus the simplified PE severity index score of zero, together with nonhigh bleeding risk were eligible. Patients had to be discharged within 24 hours of triage and treated with either apixaban or rivaroxaban. Effectiveness was defined by the primary efficacy and safety outcomes, image-proven recurrent VTE and bleeding requiring hospitalization >24 hours, respectively, with an upper limit of the 95% CI for the 30-day frequency of VTE recurrence below 2.0% for both outcomes. RESULTS: We enrolled 1421 patients with complete outcomes data, including 903 with venous thrombosis and 518 with PE. The recurrent VTE requiring hospitalization occurred in 14/1421 (1.0% [95% CI, 0.5%–1.7%]), and bleeding requiring hospitalization occurred in 12/1421 (0.8% [0.4%–1.5%). The rate of severe bleeding using International Society for Thrombosis and Haemostasis criteria was 2/1421 (0.1% [0%–0.5%]). No patient died, and serious adverse events occurred in 2.5% of venous thrombosis patients and 2.3% of patients with PE. Medication nonadherence was reported by patients in 8.0% (6.6%–9.5%) and was associated with a risk ratio of 6.0 (2.3–15.2) for VTE recurrence. Among all patients diagnosed with VTE in the emergency department during the period of study, 18% of venous thrombosis patients and 10% of patients with PE were enrolled. CONCLUSIONS: Monotherapy treatment of low-risk patients with venous thrombosis or PE in the emergency department setting produced a low rate of bleeding and VTE recurrence, but may be underused. Patients with venous thrombosis and PE should undergo risk-stratification before home treatment. Improved patient adherence may reduce rate of recurrent VTE. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03404635


2020 ◽  
Vol 9 (5) ◽  
pp. 1582 ◽  
Author(s):  
Hannah Stevens ◽  
Karlheinz Peter ◽  
Huyen Tran ◽  
James McFadyen

Acute venous thromboembolism (VTE) is a commonly diagnosed condition and requires treatment with anticoagulation to reduce the risk of embolisation as well as recurrent venous thrombotic events. In many cases, cessation of anticoagulation is associated with an unacceptably high risk of recurrent VTE, precipitating the use of indefinite anticoagulation. In contrast, however, continuing anticoagulation is associated with increased major bleeding events. As a consequence, it is essential to accurately predict the subgroup of patients who have the highest probability of experiencing recurrent VTE, so that treatment can be appropriately tailored to each individual. To this end, the development of clinical prediction models has aided in calculating the risk of recurrent thrombotic events; however, there are several limitations with regards to routine use for all patients with acute VTE. More recently, focus has shifted towards the utility of novel biomarkers in the understanding of disease pathogenesis as well as their application in predicting recurrent VTE. Below, we review the current strategies used to predict the development of recurrent VTE, with emphasis on the application of several promising novel biomarkers in this field.


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