Microparticle-linked tissue factor activity and increased thrombin activity play a potential role in fibrinolysis failure in ST-segment elevation myocardial infarction

2009 ◽  
Vol 101 (04) ◽  
pp. 734-740 ◽  
Author(s):  
Nadine Ajzenberg ◽  
Laurent Feldman ◽  
Marie-Claude Guillin ◽  
Philippe Gabriel Steg ◽  
Marie-Geneviève Huisse
Keyword(s):  
Tissue Factor ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Platelet Glycoprotein ◽  
Factor Activity ◽  
St Segment Elevation ◽  
Tissue Factor Activity ◽  
St Segment ◽  
Significant Difference ◽  
Pai 1

SummaryFibrinolysis for acute ST-segment elevation MI achieves early recanalisation of the infarct artery in approximately 60% of cases. The aim of the study was to determine whether failure to achieve recanalisation was associated with differences in haemostasis biomarkers compared to patients with successful fibrinolysis. Fourty-three patients were prospectively enrolled in a case-control study. All patients had received tenecteplase (TNKtPA) together with aspirin (500 mg) and heparin (5,000 IU). Emergency angiography within 90 minutes of bolus TNK-tPA identified 13 TIMI 0–2 patients (cases) and 30 TIMI 3 patients (controls). Blood samples were collected before angiography to determine tissue factor activity associated with microparticles (TF-MP); soluble platelet glycoprotein V (sGPV) and thrombinantithrombin complexes (TAT) as markers of thrombin generation; tissue plasminogen activator (endogenous tPA+ TNKtPA), plasminogen activator inhibitor (PAI-1) and plasmin-anti-plasmin complexes (PAP) as markers of plasmin generation. The baseline characteristics of the two patients’ groups were similar with respect to sex, age, and risks factors. Cases differed from controls by higher TF-MP levels (1.9 [1–13] vs. 1 [0.6–1.3] pM), sGPV (67 [51–126] vs. (48 [39–72] ng/ml), p=0.039 and TAT (10 [4–37.5] vs. 4 [2.9–7.2] ng/ml), p=0.035. TAT correlated with TF-MP (r=0.51, p=0.0064) and sGPV (r=0.51, p=0.0018). No significant difference was observed in tPA or PAI-1 levels. PAP were lower in cases (18.83 [14.83–40.43] μg/ml) than in controls (35.83 [27.9–43.94] μg/ml), p=0.045. In conclusion, fibrinolysis failure in AMI is characterised by a higher procoagulant state associated with TF-MP and a lower plasmin generation.

scholarly journals Prothrombotic markers and early spontaneous recanalization in ST-segment elevation myocardial infarction

2007 ◽  
Vol 98 (08) ◽  
pp. 420-426 ◽  
Author(s):  
Emilie Lanoy ◽  
Didier Tcheche ◽  
Laurent Feldman ◽  
Annie Bezeaud ◽  
Eduardo Anglès-Cano ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Plasminogen Activator ◽  
Platelet Activation ◽  
Plasminogen Activator Inhibitor ◽  
Platelet Glycoprotein ◽  
Activation Markers ◽  
St Segment Elevation ◽  
St Segment ◽  
Circulating Microparticles ◽  
The Difference

SummaryWe tested the hypothesis that selected prothrombotic biomarkers might be associated with early spontaneous coronary recanalization in patients with ST-segment elevation acute myocardial infarction (STEMI). We prospectively enrolled 123 patients with STEMI including 53 patients with spontaneous coronary recanalization (cases) and 70 patients with persistent occlusion (controls) at the time of emergent coronary angiography and before angioplasty. All had received aspirin and heparin. Blood samples were collected immediately before angioplasty to measure soluble P-selectin, circulating microparticles originating from platelets (PMPs), granulocytes (GMPs), endothelial cells (EMPs); tissue factor-associated MP (TF-MP); soluble platelet glycoprotein V (sGPV) and prothrombin F1+2; tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI-1) and plasmin-antiplasmin (PAP). A sub-group of 70 patients (35 cases, 35 controls) was available for flow cytometry analysis of platelet P-selectin and activated GPIIb-IIIa. Baseline clinical characteristics did not differ between groups except for more frequent hypertension and dyslipidemia in controls. Platelet activation markers and PMP did not differ between the two groups. Controls had higher numbers of EMPs and GMPs compared to cases, but the difference was no longer significant when corrected for risk factors. Controls differed from cases by higher plasma levels of sGPV [64 (47–84) ng/ml vs. 53 (44–63) ng/ml] and PAP [114(65–225) ng/ml vs. 88 (51–147) ng/ml].The difference persisted after adjustment for risks factors (p=0.031 and 0.037, respectively). Persistent occlusion of the infarct related artery is associated with some markers related to higher thrombin (sGPV) and plasmin (PAP) production but is not associated with markers of platelet activation.

A Specific Immunologic Assay for Functional Plasminogen Activator Inhibitor 1 in Plasma – Standardized Measurements of the Inhibitor and Related Parameters in Patients with Venous Thromboembolic Disease

1992 ◽  
Vol 68 (05) ◽  
pp. 486-494 ◽  
Author(s):  
Malou Philips ◽  
Anne-Grethe Juul ◽  
Johan Selmer ◽  
Bent Lind ◽  
Sixtus Thorsen
Keyword(s):  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Normal Subjects ◽  
Tissue Type ◽  
Blood Collection ◽  
Plasminogen Activator Inhibitor 1 ◽  
Type Plasminogen Activator ◽  
Significant Difference ◽  
Activator Inhibitor ◽  
Pai 1

SummaryA new assay for functional plasminogen activator inhibitor 1 (PAI-1) in plasma was developed. The assay is based on the quantitative conversion of PAI-1 to urokinase-type plasminogen activator (u-PA)-PAI-l complex the concentration of which is then determined by an ELISA employing monoclonal anti-PAI-1 as catching antibody and monoclonal anti-u-PA as detecting antibody. The assay exhibits high sensitivity, specificity, accuracy, and precision. The level of functional PAI-1, tissue-type plasminogen activator (t-PA) activity and t-PA-PAI-1 complex was measured in normal subjects and in patients with venous thromboembolism in a silent phase. Blood collection procedures and calibration of the respective assays were rigorously standardized. It was found that the patients had a decreased fibrinolytic capacity. This could be ascribed to high plasma levels of PAI-1. The release of t-PA during venous occlusion of an arm for 10 min expressed as the increase in t-PA + t-PA-PAI-1 complex exhibited great variation and no significant difference could be demonstrated between the patients with a thrombotic tendency and the normal subjects.

Abstract 267: A Single Dose of Reconstituted High Density Lipoprotein Reduces Expression of Tissue-Factor In Human Carotid Atherosclerotic Plaques

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Hosaam H Nasr ◽  
Ian M Loftus ◽  
Saiqa Sayed ◽  
Alun Jones ◽  
Evelyn Torsney ◽  
...  
Keyword(s):  
Single Dose ◽  
Tissue Factor ◽  
Plasminogen Activator ◽  
Clinical Event ◽  
Tissue Type ◽  
Transcriptional Level ◽  
Rt Pcr ◽  
Significant Difference ◽  
Plaque Stabilisation ◽  
Pai 1

Background: Multiple infusions of HDLs have been shown to mediate approximately 4% reduction in plaque volume. This may relate to removal of intra-plaque lipid, but the precise mechanism is unknown. To test the hypothesis that HDLs may influence plaque stabilisation through modulating transcription, we examined the effects of a single dose of rHDL on expression of thrombomodulatory genes in carotid plaques. Materials and Methods: Forty patients undergoing carotid endarterectomy (CEA) were stratified to three groups: early symptomatics ( n =12, stroke/transient ischemic attack (TIA) 1month before CEA)late symptomatics ( n =14, stroke/TIA > 1month before CEA); and asymptomatics ( n =12). RNA was isolated from plaques following CEA, and expression of the thrombomodulatory genes, tissue factor (TF); tissue factor pathway inhibitor (TFPI); thrombomodulin (TM); tissue type plasminogen activator (tPA); urokinase plasminogen activator (uPA); plasminogen activator inhibitor-1 (PAI-1), measured using QRT-RT-PCR. Nine patients with early symptomatic carotid disease, undergoing CEA, were then randomised to infusion of reconstituted HDL (rHDL) 80mg/kg Apo A-I ( n =4) or a similar volume of phosphate buffered saline ( n =5). Plaque specimens were collected 24 hrs later and RNA isolated for QRT-RT- PCR measurement of thrombomodulatory gene expression. Results: A significant difference in TF, TM, tPA and PAI-1 genes were observed in the 3 patient groups (see Table 1 ). In the rHDL group, a single dose of rHDL reduced the expression of TF (0.71 (0.65–0.75) vs 0.98 (0.81–1.14), P=0.05). No significant difference was observed in other thrombomodulatory factors between the 2 groups. Conclusions: Plaque stabilisation, which occurs within one month of a clinical event may be facilitated, at the transcriptional level, following rHDL infusion. We hope to report a larger double blind placebo controlled trial which will determine the full effects of rHDLs on plaque stability. Table 1

Sex Differences in the Determinants of Fibrinolytic Activity

1998 ◽  
Vol 79 (03) ◽  
pp. 587-590 ◽  
Author(s):  
J. A. Cooper ◽  
D. J. Howarth ◽  
T. W. Meade ◽  
G. J. Miller ◽  
P. K. MacCallum
Keyword(s):  
Plasminogen Activator ◽  
Whole Blood ◽  
Fibrinolytic Activity ◽  
Plasminogen Activator Inhibitor ◽  
Tissue Type ◽  
Clot Lysis ◽  
Significant Difference ◽  
Main Determinants ◽  
Activator Inhibitor Type ◽  
Pai 1

SummaryImpaired whole blood fibrinolytic activity (FA), measured by the dilute clot lysis time (DCLT), is associated with first episodes of ischaemic heart disease (IHD) in the Northwick Park Heart Study in men, especially under 55 years, and in women. In a community-based study to investigate possible determinants of the DCLT, and therefore to assess which fibrinolytic components might be predictors of first IHD events, we measured fibrinolytic variables in a sub-sample of 150 healthy adults (73 males, 77 females) randomly selected from a single general practice.Most of the variance in DCLT (68% in men, 63% in women) was explained by tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type-1 (PAI-1) activities. In multiple regression analysis there was a significant difference in the strength of the association of t-PA activity with DCLT in men compared to women (test for interaction p = 0.05), the association of t-PA activity with DCLT being significant in males but not in females. Plasma PAI-1 activity was strongly associated with DCLT in both sexes. There was no independent association of DCLT with plasma fibrinogen, t-PA antigen, other fibrinolytic inhibitors, body mass index, serum lipids or C-reactive protein.Plasma PAI-1 activity in females and both t-PA and PAI-1 activities in males are the main determinants of whole blood FA measured by DCLT. It is therefore likely that these modulators of the plasma fibrinolytic system are associated with the onset of first clinical episodes of IHD. Elevated levels of t-PA antigen were positively associated with DCLT after adjustment for age and sex and therefore indicate impaired rather than enhanced FA. Further studies of the association of FA with risk of IHD should include not only “global” measures but also assessment of t-PA and PAI-1 activities, particularly as our results suggest that their associations with IHD may differ in men and women.

scholarly journals Is There a Tendency for Thrombosis in Gestational Diabetes Mellitus?

2016 ◽  
Vol 8 (02) ◽  
pp. 101-105 ◽  
Author(s):  
Suheyla Gorar ◽  
Bulent Alioglu ◽  
Esranur Ademoglu ◽  
Seyit Uyar ◽  
Handan Bekdemir ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Study Groups ◽  
Tissue Type ◽  
Coagulation System ◽  
Significant Difference ◽  
Pai 1

ABSTRACT Context: Impact of gestational diabetes mellitus (GDM) on the coagulation system, dynamics involved at a pathophysiological level and the exact mechanism remain unclear. Aims: To evaluate the association between diabetes-related parameters and hemostatic factors to search for a tendency of thrombosis in GDM. Settings and Design: Nineteen pregnant women who had GDM, 16 healthy pregnant and 13 healthy nonpregnant controls admitted to the Endocrinology outpatient clinics were enrolled in the study. Subjects and Methods: Fasting and postprandial glucose, hemoglobin A1c and insulin levels, and insulin resistance; fructosamine, thrombin activatable fibrinolysis inhibitor (TAFI), tissue factor pathway inhibitor (TFPI), plasminogen activator inhibitor Type-1 (PAI-1), tissue-type plasminogen activator (t-PA), fibrinogen, plasminogen and hemoglobin levels, platelet counts, prothrombin time (PT), and activated partial thromboplastin time (aPTT) were studied. Statistical Analysis Used: One-way analysis of variance, Kruskal–Wallis, and post hoc Tukey honestly significant difference or Conover’s nonparametric multiple comparison tests for comparison of the study groups. Results: PT and aPTT were significantly lower in GDM patients compared to controls (P < 0.05), whereas fibrinogen and plasminogen levels were significantly higher in this group compared to both nonpregnant and healthy pregnant controls (P < 0.05 for each). TAFI, TFPI, PAI-1, and tissue t-PA levels were not significantly different among groups. Conclusions: Our findings indicate tendency to develop thrombosis in GDM similar to diabetes mellitus; but more comprehensive studies with larger sample size are needed to determine the relationship between GDM and hemostasis.

scholarly journals Insulin Inhibits the Pro-Inflammatory Transcription Factor Early Growth Response Gene-1 (Egr)-1 Expression in Mononuclear Cells (MNC) and Reduces Plasma Tissue Factor (TF) and Plasminogen Activator Inhibitor-1 (PAI-1) Concentrations

2002 ◽  
Vol 87 (3) ◽  
pp. 1419-1422 ◽  
Author(s):  
Ahmad Aljada ◽  
Husam Ghanim ◽  
Priya Mohanty ◽  
Neeti Kapur ◽  
Paresh Dandona
Keyword(s):  
Transcription Factor ◽  
Tissue Factor ◽  
Plasminogen Activator ◽  
Growth Response ◽  
Plasminogen Activator Inhibitor ◽  
Early Growth ◽  
Plasminogen Activator Inhibitor 1 ◽  
Early Growth Response ◽  
Activator Inhibitor ◽  
Pai 1

We have recently demonstrated that an infusion of a low dose of insulin reduces the intranuclear NF-κB (a pro-inflammatory transcription factor) content in MNC while also reducing the p;asma concentration of NF-κB dependent pro-inflammatory cytokines and adhesion molecules. We have now tested the effect of insulin on the pro-inflammatory transcription factor, early growth response-1 (Egr-1) and plasma concentration of tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1), two major proteins whose expression is modulated by Egr-1. Insulin was infused at the rate of 2 IU/h in 5% dextrose (100 mL/h) and KCI (8 mmol/h) for 4 h in the fasting state in ten obese subjects. Blood samples were obtained at 0, 2, 4 and 6 h. MNC were isolated and their total homogenates and nuclear fractions were prepared and Egr-1 was measured by electrophoretic mobility shift assay (EMSA). Plasma TF and PAI-1 were assayed by ELISA. There was a significant fall in Egr-1 at 2 (66 ± 14% of basal level) and 4 h (47± 17% of the basal level; P&lt;0.01). PAI-1 levels (basal = 100%) decreased significantly after insulin infusion at 2 h (57 ± 6.7% of the basal level) and at 4 h (58 ± 8.3% of the basal level; P&lt;0.001). Plasma TF levels (basal = 100%) decreased to 76 ± 7.7% of the basal level at 2 h and to 85 ± 10.4% of the basal level at 4 h (P&lt;0.05). Thus, insulin reduces intranuclear Egr-1 and the expression of TF and PAI-1. These data provide further evidence that insulin has an anti-inflammatory effect including the inhibition of TF and PAI-1 expression. These effects suggest a potential beneficial effect of insulin in thrombin formation and fibrinolysis in atherothrombosis.

Abnormal Expression of Type 1 Plasminogen Activator Inhibitor and Tissue Factor in Severe Preeclampsia

1998 ◽  
Vol 79 (03) ◽  
pp. 500-508 ◽  
Author(s):  
Juan Gilabert ◽  
Salvador Grancha ◽  
Koji Yamamoto ◽  
Terri Thinnes ◽  
Francisco España ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Tissue Factor ◽  
Plasminogen Activator ◽  
Present Report ◽  
Interleukin 1 ◽  
Plasminogen Activator Inhibitor ◽  
Unknown Etiology ◽  
Activator Inhibitor ◽  
Pai 1

SummaryPreeclampsia is a multisystemic obstetric disease of unknown etiology that is commonly associated with fibrin deposition, occlusive lesions in placental vasculature, and intrauterine fetal growth retardation. We previously reported that type 1 plasminogen activator inhibitor (PAI-1) levels are significantly increased in plasma and placenta from pregnant women with preeclampsia compared to normal pregnant women. In the present report we localize the expression of placental PAI-1 in greater detail and compare it with that of tissue factor (TF), a procoagulant molecule, and vitronectin (Vn), a PAI-1 cofactor. We also examine the expression of two cytokines, tumor necrosis factor α (TNFα) and interleukin-1 (IL-1), in order to begin to define the underlying mechanisms responsible for the elevated levels of PAI-1 and fibrin deposits observed in placenta from preeclampsia. We demonstrate a significant increase in PAI-1, TF and TNFα antigen and PAI-1 and TF mRNA in placentas from preeclamptic patients. PAI-1 mRNA was increased not only in syncytiotrophoblast and infarction areas, but also in fibroblasts and in some endothelial cells of fetal vessels in placentas from preeclamptic patients. However, there was no colocalization between PAI-1, TF, Vn and TNFα in placental villi. The elevated TNFα in the placenta may induce PAI-1 and TF, and thus promote the thrombotic alterations associated with preeclampsia.

Angiotensin II Increases Plasminogen Activator Inhibitor-1 and Tissue Factor mRNA Expression without Changing that of Tissue Type Plasminogen Activator or Tissue Factor Pathway Inhibitor in Cultured Rat Aortic Endothelial Cells

1997 ◽  
Vol 77 (06) ◽  
pp. 1189-1195 ◽  
Author(s):  
Hiromi Nishimura ◽  
Hajime Tsuji ◽  
Haruchika Masuda ◽  
Katsumi Nakagawa ◽  
Yoshihumi Nakahara ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tissue Factor ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Tissue Type ◽  
Ang Ii ◽  
Plasminogen Activator Inhibitor 1 ◽  
Aortic Endothelial Cells ◽  
Type Plasminogen Activator ◽  
Pai 1

SummaryAngiotensin converting enzyme inhibitors (ACE-I) have been reported to prevent the recurrence of cardiovascular events. The mechanism of this decrease, however, can not be completely explained by anti-hypertensive and anti-hypertrophic effects of ACE-I. To investigate the mechanism of this decrease, we studied the regulation of plasminogen activator inhibitor-1 (PAI-1), tissue type plasminogen activator (TPA), tissue factor (TF), and tissue factor pathway inhibitor (TFPI) by angiotensin II (Ang II) in cultured rat aortic endothelial cells. Ang II increased PAI-1 and TF mRNA expression without affecting that of TPA or TFPI. These inductions were accompanied by increases in PAI-1 and TF activities and were inhibited by a type 1 Ang II receptor antagonist. The results suggest that Ang II decreases the antithrombotic properties of endothelial cells which increases the chance of thrombosis. Thus, inhibition of the renin-angiotensin system may be beneficial to prevent thrombus formation in treatment of ischemic heart disease.

Abstract 113: Monocytes Embedded in Plasma Clots Synthesize Coagulation Factors: Balancing Procoagulant and Anticoagulant Signals

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Robert A Campbell ◽  
Adriana Vieira de Abreu ◽  
Andrew S Weyrich
Keyword(s):  
Tissue Factor ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Fold Increase ◽  
Clot Formation ◽  
Dependent Manner ◽  
Vascular Cells ◽  
Plasminogen Activator Inhibitor 1 ◽  
Plasma Clot ◽  
Pai 1

Objective: Previous studies have demonstrated that vascular cells acutely regulate fibrin clot structure and stability. However, the mechanisms by which fibrin clots push vascular cells, in particular leukocytes, to synthesize pro-and anti-coagulant proteins is unknown. Here, we characterize monocyte-derived pro-and anti-coagulant activity in clots. Methods: Human monocytes were isolated from whole blood using CD14 microbeads. In parallel, cell-free plasma was isolated and clot formation induced in the presence of monocytes by the addition of tissue factor and calcium. RNA was isolated using RNAzol. Cell surface tissue factor (TF), tissue factor pathway inhibitor (TFPI), urokinase plasminogen activator (uPA) and its receptor (uPAR) as well as plasminogen activator inhibitor-1 (PAI-1) was measured by ELISA. TF activity was measured using a chromogenic factor Xa assay. Results: Monocytes embedded within plasma clots transcribed mRNA for uPAR (2.3-fold), uPA (9.5-fold), TF (9.2-fold), TFPI, and PAI-1 (6.2-fold) in a time-dependent manner. Consistent with this transcriptional response, increased levels of TF, TFPI, and uPAR protein were visually detected on the monocyte surface 18-hours after plasma clot formation. Accumulation of TF, TFPI and uPAR protein was blocked by actinomycin D and cycloheximide, indicating protein synthesis was dependent on transcription of new mRNA. TF-activity was similarly increased (8.9-fold) on the surface monocytes (i.e., increase in plasma-clot versus suspension monocytes). Lastly, active PAI-1 (11.1-fold increase), but not uPA, increased in the culture supernatant over time. Conclusions: Plasma clot formation induced robust increases in coagulation-related mRNAs and their corresponding proteins. The balance between the transcription of pro- and anti-coagulant mRNAs and their subsequent translation into bioactive protein likely plays key roles in clot development, stability and resolution.

Hemostatic Biomarkers and Venous Thromboembolism Are Associated With Mortality and Response to Chemotherapy in Patients With Pancreatic Cancer

2021 ◽  
Author(s):  
Florian Moik ◽  
Gerald Prager ◽  
Johannes Thaler ◽  
Florian Posch ◽  
Sarah Wiedemann ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tissue Factor ◽  
Palliative Chemotherapy ◽  
Cox Regression ◽  
Extracellular Vesicle ◽  
Hazard Ratio ◽  
Factor Activity ◽  
Tissue Factor Activity ◽  
Pai 1 ◽  
D Dimer

Objective: Pancreatic cancer activates coagulation and increases risk of venous thromboembolism (VTE). We aimed at characterizing the association of hemostatic biomarkers and VTE with mortality and chemotherapy response. Approach and Results: Pancreatic cancer patients (n=145) were included in a prospective, observational cohort study (CATS [Vienna Cancer and Thrombosis Study]). Hemostatic biomarkers (D-dimer, extracellular vesicle–tissue factor activity, prothrombin fragment 1+2, fibrinogen, factor VIII, PAI-1 [plasminogen activator inhibitor 1], sP-selectin [soluble P-selectin], thrombin generation assay) were measured at inclusion. The impact of VTE on overall survival/progression-free survival (OS/PFS) was evaluated by multistate modeling. The association of biomarkers with OS was analyzed by Cox-regression and with PFS and disease control rate in patients initiating palliative chemotherapy (n=95) by Cox-regression and logistic regression. Multivariable analysis included stage, grade, sex, age, performance status, VTE (time-dependent), vascular infiltration/compression, and tumor marker levels (carbohydrate-antigen 19-9, carcinoembryonic antigen). VTE occurrence was associated with shorter OS (transition hazard ratio, 3.40 [95% CI, 2.05–5.64]) and shorter PFS (transition hazard ratio, 2.10 [1.16–3.79]). Median post-VTE OS/PFS in months was 5.5 [2.2–6.5] and 3.0 [1.5–3.9], compared with 13.4 [9.7–16.6] and 7.5 [5.9–9.8] in patients without VTE (both P <0.001). D-dimer, extracellular vesicle–tissue factor activity, PAI-1, and sP-selectin were associated with increased mortality (hazard ratio per doubling, 1.27 [1.00–1.61]; 1.63 [1.14–2.36]; 1.25 [1.06–1.47]; 1.52 [1.05–2.20]). In patients initiating palliative chemotherapy, higher D-dimer predicted shorter PFS (hazard ratio per doubling, 1.27 [1.01–1.60]) and lower disease control rate (odds ratio per doubling, 0.59 [0.36–0.98]). Conclusions: VTE diagnosis is associated with shorter OS and PFS. Higher baseline levels of D-dimer, extracellular vesicle–tissue factor activity, PAI-1, and sP-selectin were independently prognostic for increased mortality, and D-dimer predicted response to palliative chemotherapy.

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