High Concentrations of Soluble P-Selectin Are Associated with Risk of Venous Thromboembolism and the P-Selectin Thr715 Variant

Ay, Cihan; Jungbauer, Lea V.; Sailer, Thomas; Tengler, Theres; Koder, Silvia; Kaider, Alexandra; Panzer, Simon; Quehenberger, Peter; Pabinger, Ingrid; Mannhalter, Christine

doi:10.1373/clinchem.2006.085068

Cited by 118 publications

(127 citation statements)

References 41 publications

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“…26,30,31 Recent data suggest that sP-selectin is associated with primary and recurrent thrombosis in noncancer patients. [32][33][34] sP-selectin can be easily and accurately measured by ELISA, which has been demonstrated previously by our group. 17,32 We have also validated the predictive power of elevated sP-selectin and elevated D-Dimer for occurrence of VTE in cancer patients in a new and independent cohort of 305 cancer patients (see supplemental material for detailed results).…”

Section: Discussionmentioning

confidence: 66%

“…[32][33][34] sP-selectin can be easily and accurately measured by ELISA, which has been demonstrated previously by our group. 17,32 We have also validated the predictive power of elevated sP-selectin and elevated D-Dimer for occurrence of VTE in cancer patients in a new and independent cohort of 305 cancer patients (see supplemental material for detailed results). D-Dimer and sP-selectin are both continuous parameters and the assignment of a point of "1" at the predefined cutoff level in our study is based on our previous data and clinical experience.…”

Section: Discussionmentioning

confidence: 66%

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Prediction of venous thromboembolism in cancer patients

Ay¹,

Dunkler²,

Marosi³

et al. 2010

Blood

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The risk of venous thromboembolism (VTE) is increased in cancer patients. To improve prediction of VTE in cancer patients, we performed a prospective and observational cohort study of patients with newly diagnosed cancer or progression of disease after remission. A previously developed risk scoring model for prediction of VTE that included clinical (tumor entity and body mass index) and laboratory (hemoglobin level and thrombocyte and leukocyte count) parameters was expanded by incorporating 2 biomarkers, soluble P-selectin, and D-Dimer. Of 819 patients 61 (7.4%) experienced VTE during a median follow-up of 656 days. The cumulative VTE probability in the original risk model after 6 months was 17.7% in patients with the highest risk score (> 3, n ‫؍‬ 93), 9.6% in those with score 2 (n ‫؍‬ 221), 3.8% in those with score 1 (n ‫؍‬ 229), and 1.5% in those with score 0 (n ‫؍‬ 276). In the expanded risk model, the cumulative VTE probability after 6 months in patients with the highest

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Section: Discussionmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 66%

Prediction of venous thromboembolism in cancer patients

Ay¹,

Dunkler²,

Marosi³

et al. 2010

Blood

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688

600

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“…Our group reported the association of elevated sP-selectin (Ͼ95 th percentile for healthy controls) with VTE to be even stronger in a casecontrol study of 116 patients with objectively confirmed recurrent VTE and 129 age-and sex-matched healthy individuals with an OR of 10.6 (95% CI: 3.7 to 23.3), adjusted for established VTE risk factors. 28 These results were subsequently supported by a large prospective cohort study that investigated circulating sP-selectin as a predictive biomarker for recurrence of VTE in patients with a first episode of unprovoked VTE, in the absence of cancer or other known risk factors. 29 sP-selectin levels were also found to be elevated in lupus anticoagulant patients with a previous event of VTE, 30 and preliminary results indicate that sP-selectin plasma levels are partially modulated by genotype status.…”

Section: Soluble P-selectinmentioning

confidence: 78%

Biomarkers and Venous Thromboembolism

Pabinger

2009

ATVB

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Abstract-Venous thromboembolism (VTE) represents a significant health concern because of its high morbidity and mortality and is moreover characterized by high rates of recurrence. It would be useful to know biomarkers that enable early identification of patients at high or low risk of primary and recurrent VTE. enous thromboembolism is a frequent disease with an age-adjusted incidence of 1 to 2 events per 1000 of the general population and constitutes a major health care problem because of its high morbidity and mortality. 1 About one-third of patients suffering from a first episode of deep venous thrombosis (DVT) or pulmonary embolism (PE) develops a recurrence of VTE within 10 years. 2 From a clinical perspective, it would be extremely helpful to have biomarkers that enable early identification of patients at high or low risk of primary and recurrent VTE and allow prompt diagnosis and therapy assessment.In this brief overview only some selected biomarkers associated with a first or recurrent event of VTE are highlighted that are either well-investigated (D-Dimer and coagulation factor VIII), novel and promising (P-selectin and endogenous thrombin potential), or controversially discussed (inflammatory cytokines). D-DimerD-Dimer is a degradation product of cross-linked fibrin that is formed immediately after thrombin-generated fibrin clots are degraded by plasmin and reflects a global activation of blood coagulation and fibrinolysis. As D-Dimer levels rise during an acute event of VTE, testing for D-Dimer was explored as a tool for the diagnosis of VTE and has been integrated into diagnostic algorithms in the management of patients with suspected VTE. [3][4][5] Being the best-recognized biomarker for the initial assessment of suspected VTE, a negative value of D-Dimer may safely rule out both DVT and PE with a high sensitivity of up to 95% and a negative predictive value of nearly 100%, using the various commercially available D-Dimer assays. However, because of its poor specificity to prove VTE, D-Dimer testing has to be included in comprehensive sequential diagnostic strategies that incorporate clinical probability assessment and imaging techniques.Elevated D-Dimer levels may also indicate the presence of hypercoagulability. In a case-control study high D-Dimer levels (Ͼ70 th percentile of levels in healthy controls) measured at least 6 months after a first event of DVT in 474 patients and 474 age-and sex-matched control individuals have been shown to be associated with a 2.2-fold increase in the risk of thrombosis. 6 In a population-based cohort study D-Dimer was investigated as a risk factor for the occurrence of a future first event of VTE and was associated with a 3-fold increased risk. 7 Moreover, D-Dimer levels are a wellinvestigated biomarker for the prediction of the risk of VTE recurrence after discontinuing oral anticoagulant therapy in prospective cohort studies. 8 Palareti et al measured D-Dimer levels 1 month after withdrawal of oral anticoagulation in subjects with previous unprovoked VTE and de...

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“…The activation of blood platelets causes the conformation changes to GMP-140 molecule (CD 62P, P-selectin, PADGEM) stored in alpha granules and its integration into blood platelets cell membranes where it functions as a CD62P receptor. P-selectin is recognized as a typical marker of blood platelets activation, as well as the reaction of release of cell granules [17]. P-selectin occurs also in plasma as soluble P-selectin (sP-selectin).…”

Section: Introductionmentioning

confidence: 99%

“…P-selectin takes part in the migration of white blood cells during the inflammatory process causing their adhesion and 'rolling' of the white blood cell on the endothelial cells in blood vessels [1]. An increased concentration of sP-selectin has been found in the course of inflammatory and cancerous processes [16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Assessment of the influence of the inflammatory process on the activation of blood platelets and morphological parameters in patients with ulcerative colitis (<i>colitis ulcerosa</i>)

Polińska¹,

Matowicka-Karna²,

Kemona³

2011

Folia Histochem Cytobiol.

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Ulcerative colitis (colitis ulcerosa) is a non-specific inflammatory bowel disease of unknown etiology. The symptoms which are observed in the course of ulcerative colitis are: an increase in the number of leukocytes and blood platelets, an increase in the concentration of IL-6 and anemia. Blood platelets are the key element, linking the processes of hemostasis, inflammation and the repair of damaged tissues. Activation of blood platelets is connected with changes in their shape and the occurrence of the reaction of release. P-selectin appears on the surfaces of activated blood platelets and the concentration level of soluble P-selectin increases in the blood plasma. The aim of this study was to define whether the increased number of blood platelets in patients with ulcerative colitis accompanies changes in their activation and morphology. A total of 16 subjects with ulcerative colitis and 32 healthy subjects were studied. Mean platelet count, morphological parameters of platelets and MPC were measured using an ADVIA 120 hematology analyzer. Concentrations of sP-selectin and IL-6 in serum were marked by immunoassay (ELISA). MPC, concentration of sP-selectin and IL-6 were significantly higher in subjects with ulcerative colitis compared to those in the healthy group. There was a decrease of MPV in patients with ulcerative colitis, which is statistically significant. Chronic inflammation in patients with ulcerative colitis causes an increase in the number of blood platelets, a change in their morphology and activation. Decreased MPV value reflects activation and the role blood platelets play in the inflammatory process of the mucous membrane of the colon. A high concentration of sP-selectin, which is a marker of blood platelet activation, demonstrates their part in the inflammatory process. The increase in the concentration of sP-selectin correlated positively with the increase in concentration of IL-6. This is why it may be a useful marker of the activity of colitis ulcerosa.

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High Concentrations of Soluble P-Selectin Are Associated with Risk of Venous Thromboembolism and the P-Selectin Thr715 Variant

Cited by 118 publications

References 41 publications

Prediction of venous thromboembolism in cancer patients

Prediction of venous thromboembolism in cancer patients

Biomarkers and Venous Thromboembolism

Assessment of the influence of the inflammatory process on the activation of blood platelets and morphological parameters in patients with ulcerative colitis (<i>colitis ulcerosa</i>)

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