The Identification of Hypercoagulable Markers in Patients with Malignant Gliomas and Venous Thromboembolism.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4097-4097
Author(s):  
Rachel P. Rosovsky ◽  
Patrick Wen ◽  
Santosh Kesari ◽  
Elizabeth M. Van Cott ◽  
David J. Kuter
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Malignant Gliomas ◽  
Tumor Grade ◽  
Residual Tumor ◽  
Time To Death ◽  
Increased Risk ◽  
Batch Testing ◽  
Initiation Of Therapy ◽  
D Dimer

Abstract Introduction: Patients with malignant gliomas have a high incidence of thrombotic events. There is no definitive data on what specific factors induce or predict for this hypercoagulable state. Aim: The purpose of this prospective study was to identify specific risk factors for venous thromboembolism (VTE) in patients with malignant gliomas by examining suspected procoagulant markers in their plasma. Patients and Methods: Adult patients who presented for outpatient consultation to the neuro-oncology clinic at the Dana-Farber Cancer Institute from 9/4/2003 to 6/9/2005 with a pathologically documented diagnosis of malignant glioma were evaluated for study. Patients with a prior diagnosis of VTE or on current chemotherapy or anticoagulant therapy were excluded. Upon study entry and prior to the initiation of radiation therapy or chemotherapy, a single peripheral blood sample was collected. Citrated plasma was stored at −80°C until batch testing occurred. Tests for D-dimer, von Willebrand factor antigen, fibrinogen, factor VIII, plasminogen, lupus anticoagulant, thrombin-antithrombin, and prothrombin fragment 1+2 were performed at reference laboratories. All patients were prospectively followed for development of symptomatic VTE (confirmed by radiological testing). Of the twenty-nine patients on study, twenty-five died and four are still alive. Time to death, number of recurrences, and number of hospitalizations were collected to determine if there was an association between these events and presence of VTE. Results: Twenty-nine patients who met criteria and had analyzable blood samples were included in study. The rate of symptomatic VTE was 24% and VTE occurred 1–13 months after entry onto the study. Development of VTE was associated with elevated levels of D-dimer [defined as greater than 500 mg/dL (p=0.0230)] and elevated levels of fibrinogen [defined as greater than 400% (p=0.0164)]. The median levels of D-dimer and fibrinogen were significantly greater in the patients who developed VTE compared to those who did not develop VTE (953 mg/dL v 481 mg/dL, p=0.0249 and 425% v 290%, p=0.0312, respectively). The number of hospitalizations was also significantly associated with the presence of VTE (p=0.0130). There was no association between the number of tumor recurrences/progressions or time to death and presence of VTE. All patients underwent surgery prior to study enrollment. There was no difference between the patients who developed VTE and those who did not in terms of timing of the surgery, presence of residual tumor, grade or type of tumor, or steroid use. Conclusion: The incidence of symptomatic VTE in patients with malignant gliomas was 24%. Elevated levels of D-dimer and fibrinogen at initiation of therapy were associated with the development of VTE. These risk factors may help determine which patients are at increased risk of VTE and might benefit from prophylactic anticoagulation. These suggestive results need to be confirmed in a larger trial.

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

Blood ◽  
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.

scholarly journals Risk Factors of Survival in Dedifferentiated Liposarcoma

2021 ◽  
pp. 1-7
Author(s):  
Kevin Nguyen ◽  
Kevin Nguyen ◽  
Jonathan Gootee ◽  
Sarah Aurit ◽  
Sara Albagoush ◽  
...  
Keyword(s):  
Risk Factors ◽  
Therapeutic Option ◽  
Multivariable Analysis ◽  
Tumor Grade ◽  
Residual Tumor ◽  
Older Age ◽  
Surgical Margins ◽  
Dedifferentiated Liposarcoma ◽  
Anatomic Site ◽  
Increased Risk

Background: Liposarcoma is the most common malignant soft tissue sarcoma for which surgical resection is the most utilized therapeutic option. In this study, we aimed to explore the associations of surgical margins among other risk factors on survival in patients with dedifferentiated liposarcoma. Patients and Methods: The National Cancer Database (NCDB) was used to select patients with dedifferentiated liposarcoma to determine if surgical margins were associated with worse overall survival after controlling for age, gender, race, Charlson-Deyo score, anatomic site, treatment approach, tumor size, tumor grade, and presence of metastases through multivariable analysis. Results: Multivariable analyses showed that mortality risk increased for dedifferentiated liposarcoma patients with the following: older age, male, metastasis, high tumor grade, macroscopic residual tumor compared to no residual tumor. Conclusion: Older age, male sex, presence of metastasis, retroperitoneal/abdomen primary site, high grade tumors, and macroscopic residual tumor present after surgery led to an increased risk of mortality.

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

Blood ◽  
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.

Abstract 47: Atrial Fibrillation is Associated With Increased Risk of Incident Venous Thromboembolism: The Atherosclerosis Risk in Communities Study

Circulation ◽  
2017 ◽  
Vol 135 (suppl_1) ◽  
Author(s):  
Pamela L Lutsey ◽  
Faye L Norby ◽  
Alvaro Alonso ◽  
Mary Cushman ◽  
Lin Y Chen ◽  
...  
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
Venous Thromboembolism ◽  
Incidence Rate ◽  
Case Reports ◽  
Time Dependent ◽  
Atherosclerosis Risk In Communities ◽  
Increased Risk ◽  
Atherosclerosis Risk ◽  
Shared Risk

Background: It is well-established that atrial fibrillation (AF) is associated with thrombus formation in the left atrium, which can lead to ischemic stroke. Case reports, autopsies, and transesophageal echo data have indicated that clot formation also occurs in the right atrium (i.e. right-side intracardiac thrombosis) of AF patients, which could lead to pulmonary embolism (PE). However, it is unclear whether this occurrence is common. Objective: Test the hypotheses that individuals with incident AF are at elevated risk of developing venous thromboembolism (VTE), and that the association will be stronger for those presenting with PE alone versus PE and deep vein thrombosis (DVT) or DVT alone. Methods: A total of 15,205 Atherosclerosis Risk in Communities (ARIC) study participants, aged 45-64 years, were followed from baseline (1987-1989) to 2011 for incidence of AF and VTE (median follow-up 19.8 years). Incident AF and VTE events were identified via active surveillance and defined by relevant hospital discharge ICD codes. VTE events were validated by medical record review. Multivariable-adjusted Cox proportional hazards regression models were used, with AF modeled as a time-dependent covariate. We also evaluated separately risk of PE without evidence of DVT, DVT without PE, and events presenting with both PE and DVT. Results: At baseline participants were on average 54 years old, 55% female and 26% black. In the absence of AF there were 678 VTE events, for an incidence rate of 2.6 per 1000 person-years. After an AF diagnosis there were 77 events, with an incidence rate of 7.1 per 1000 person-years. In multivariable-adjusted models, having AF (versus no AF) was associated with a greater risk of incident VTE; the HR (95% CI) was 2.10 (1.65-2.68) after adjustment for demographics, 1.82 (1.42-2.32) additionally accounting for numerous AF and VTE risk factors, and 1.97 (1.53-2.53) after further adjusting for time-dependent anticoagulant use. When we restricted to PE events without evidence of DVT there were 188 events in total, of which 19 occurred following a diagnosis of AF. The HR for AF (versus no AF) was 1.53 (0.92-2.56) in fully adjusted models. For DVT alone there were 384 events in total, of which 48 occurred after AF diagnosis; the HR for AF was 2.43 (1.77-3.33). Among the 116 events presenting with both DVT and PE, 10 occurred after AF diagnosis, and the HR for AF was 1.36 (0.67-2.75). Conclusions: Diagnosis with AF was associated with a nearly 2-fold increased risk of incident VTE. The association was not stronger when isolated to those with PE without DVT, suggesting that higher risk of VTE among AF patients may be due to either the coagulation abnormalities that accompany AF, or shared risk factors that were not fully accounted for in this analysis.

Venous Thromboembolism

2020 ◽  
Author(s):  
Samuel Z. Goldhaber
Keyword(s):  
Risk Factors ◽  
Pulmonary Embolism ◽  
Venous Thromboembolism ◽  
Venous Thrombosis ◽  
Antithrombotic Agents ◽  
Vein Thrombosis ◽  
Recurrent Venous Thrombosis ◽  
Deep Vein ◽  
D Dimer ◽  
In Pregnancy

Venous thromboembolism, which involves venous thrombosis and pulmonary embolism, is a leading cause of morbidity and mortality in hospitalized patients and is being seen with increasing frequency in outpatients. This chapter discusses the risk factors, etiology, classification, pathophysiology, natural history, prognosis, diagnosis (including venous thrombosis, recurrent venous thrombosis, and pulmonary embolism), prophylaxis, and treatment of venous thromboembolism (including the pharmacology of antithrombotic agents), as well as venous thromboembolism in pregnancy and miscellaneous thromboembolic disorders (including thrombosis of unusual sites).  This review contains 8 figures, 16 tables, and 79 references. Keywords: Venous thromboembolism, pulmonary embolism, deep vein thrombosis, embolectomy, thrombolysis, hypercoagulability, duplex ultrasonography, D-dimer, anticoagulation

Risk factors for venous thromboembolism in patients with diabetes undergoing joint arthroplasty

2020 ◽  
Author(s):  
Wei Deng ◽  
Lili Huo ◽  
Qiang Yuan ◽  
Deyong Huang ◽  
Quan Li ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Protective Role ◽  
Pulmonary Angiography ◽  
Joint Arthroplasty ◽  
Multivariate Logistic Regression Model ◽  
Mechanical Prophylaxis ◽  
Patients With Diabetes ◽  
High Level ◽  
D Dimer

Abstract Background: Venous thromboembolism (VTE) is a significant complication after joint arthroplasty. Diabetes is related to a few changes in coagulation and fibrinolysis that may lead to thrombophilia. We aim to investigate the incidence of and risk factors for VTEs in patients with diabetes undergoing total hip (THA) or total knee anthroplasty (TKA) in a single centre in China. Methods: Patients with diabetes who underwent THA or TKA from January 2016 to December 2018 (n=400) at Beijing Jishuitan Hospital were recruited in this study. Lower limb venous Doppler ultrasound was performed before and after surgery to confirm deep venous thrombosis (DVT). Computer tomography pulmonary angiography was done to confirm pulmonary embolism (PE) for those with new postoperative DVT and typical symptoms of PE. A multivariate logistic regression model was conducted to examine factors associated with the development of postoperative VTE. Results: The overall incidence of postoperative VTE in patients with diabetes after THA or TKA was 46.8% (187 of 400). Female patients and patients undergoing TKA had higher incidence of postoperative VTE. Patients who developed postoperative VTE were older, and had higher levels of preoperative D-Dimer level and Caprini score. Increased VTE risks were associated with high level of preoperative D-Dimer (OR=2.11, 95%CI=1.35-3.30) and TKA (OR=2.29, 95%CI=1.29-4.01). Postoperative initiation of concomitant mechanical prophylaxis and low molecular weight heparin (LMWH) was protective for postoperative DVT (OR=0.56, 95%CI=0.37-0.86). Conclusions: VTE is common in patients with diabetes undergoing joint arthroplasty. Patients undergoing TKA or with a high level of preoperative D-Dimer are at a considerable risk of developing postoperative VTE. There may be a protective role of postoperative initiation of concomitant mechanical prophylaxis and LMWH for VTE.

Factor V Leiden (G1691A) and Prothrombin Gene G20210A Mutations as Potential Risk Factors for Venous Thromboembolism after Total Hip or Total Knee Replacement Surgery

2002 ◽  
Vol 87 (04) ◽  
pp. 580-585 ◽  
Author(s):  
G. Larson ◽  
T. L. Lindahl ◽  
C. Andersson ◽  
L. Frison ◽  
D. Gustafsson ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Factor V Leiden ◽  
Composite Endpoint ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
G20210a Mutation ◽  
Symptomatic Pulmonary Embolism ◽  
Increased Risk ◽  
Prothrombin Gene

SummaryPatients (n = 1600) from 12 European countries, scheduled for elective orthopaedic hip or knee surgery, were screened for Factor V Leiden and prothrombin gene G20210A mutations, found in 5.5% and 2.9% of the populations, respectively. All patients underwent prophylactic treatment with one of four doses of melagatran and ximelagatran or dalteparin, starting pre-operatively. Bilateral ascending venography was performed on study day 8-11. The patients were subsequently treated according to local routines and followed for 4-6 weeks postoperatively. The composite endpoint of screened deep vein thrombosis (DVT) and symptomatic pulmonary embolism (PE) during prophylaxis did not differ significantly between patients with or without these mutations. Symptomatic venous thromboembolism (VTE) during prophylaxis and follow-up (1.9%) was significantly over-represented among patients with the prothrombin gene G20210A mutation (p = 0.0002). A tendency towards increased risk of VTE was found with the Factor V Leiden mutation (p = 0.09). PE were few, but significantly over-represented in both the Factor V Leiden and prothrombin gene G20210A mutated patients (p = 0.03 and p = 0.05, respectively). However, since 90% of the patients with these genetic risk factors will not suffer a VTE event, a general pre-operative genotyping is, in our opinion, of questionable value.

scholarly journals Modified IMPROVE VTE Risk Score and Elevated D-Dimer Identify a High Venous Thromboembolism Risk in Acutely Ill Medical Population for Extended Thromboprophylaxis

TH Open ◽  
2020 ◽  
Vol 04 (01) ◽  
pp. e59-e65 ◽  
Author(s):  
Alex C. Spyropoulos ◽  
Concetta Lipardi ◽  
Jianfeng Xu ◽  
Colleen Peluso ◽  
Theodore E. Spiro ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
High Risk ◽  
Risk Score ◽  
Lower Risk ◽  
Risk Group ◽  
High Risk Group ◽  
Cutoff Score ◽  
Risk Of Bleeding ◽  
Increased Risk ◽  
D Dimer

AbstractAn individualized approach to identify acutely ill medical patients at increased risk of venous thromboembolism (VTE) and a low risk of bleeding to optimize the benefit and risk of extended thromboprophylaxis (ET) is needed. The International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) VTE risk score has undergone extensive external validation in medically ill patients for in-hospital use and a modified model was used in the MARINER trial of ET also incorporating an elevated D-dimer. The MAGELLAN study demonstrated efficacy with rivaroxaban but had excess bleeding. This retrospective analysis investigated whether the modified IMPROVE VTE model with an elevated D-dimer could identify a high VTE risk subgroup of patients for ET from a subpopulation of the MAGELLAN study, which was previously identified as having a lower risk of bleeding. We incorporated the modified IMPROVE VTE score using a cutoff score of 4 or more or 2 and 3 with an elevated D-dimer (>2 times the upper limit of normal) to the MAGELLAN subpopulation. In total, 56% of the patients met the high-risk criteria. In the placebo group, the total VTE event rate at Day 35 was 7.94% in the high-risk group and 2.83% for patients in the lower-risk group. A reduction in VTE was observed with rivaroxaban in the high-risk group (relative risk [RR]: 0.68, 95% confidence interval [CI]: 0.51–0.91, p = 0.008) and in the lower-risk group (RR: 0.69, 95% CI: 0.40 -1.20, p = 0.187). The modified IMPROVE VTE score with an elevated D-dimer identified a nearly threefold higher VTE risk subpopulation of patients where a significant benefit exists for ET using rivaroxaban.

Prospective Evaluation of Hemostatic System Activation and Thrombin Potential in Healthy Pregnant Women with and without Factor V Leiden

1999 ◽  
Vol 82 (10) ◽  
pp. 1232-1236 ◽  
Author(s):  
Ansgar Weltermann ◽  
Karl Philipp ◽  
Erich Hafner ◽  
Alexandra Kaider ◽  
Eva-Maria Kittl ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Pregnant Women ◽  
Factor V Leiden ◽  
Fibrinolytic System ◽  
Factor V ◽  
Uncomplicated Pregnancy ◽  
Hemostatic System ◽  
Increased Risk ◽  
System Activation ◽  
D Dimer

SummaryNormal pregnancy is associated with alterations of the hemostatic system towards a hypercoagulable state and an increased risk of venous thromboembolism. The risk of venous thrombosis is higher in pregnant women with factor V Leiden (FVL) than in those with wildtype factor V. Routine laboratory assays are not useful to detect hypercoagulable conditions. A prospective and systematic evaluation of hemostatic system activation in women with and without FVL during an uncomplicated pregnancy employing more sensitive markers of hypercoagulability, such as prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT), D-Dimer, or the endogenous thrombin potential (ETP), an indicator of the plasma’s potential to generate thrombin, has not been performed. We prospectively followed 113 pregnant women with (n = 11) and without (n = 102) FVL and measured F1+2, TAT, D-Dimer and the ETP at the 12th, 22nd and 34th gestational week as well as 3 months after delivery (baseline) in each subject. None of the women developed clinical signs of venous thromboembolism during pregnancy or postpartum. Pregnant women with and without FVL exhibited substantial activation of the coagulation and fibrinolytic system as indicated by a gradual increase of F1+2, TAT and D-Dimer throughout uncomplicated pregnancy up to levels similar to those found in acute thromboembolic events (p < 0.0001 by analysis of variance for each parameters). Levels of F1+2 and TAT were comparable between women with and without FVL, but levels of D-Dimer were significantly higher in women with FVL than in those without the mutation (p = 0.0005). The ETP remained unchanged in both women with and without FVL at all timepoints. Our data demonstrate a substantial coagulation and fibrinolytic system activation in healthy women with and without FVL during uncomplicated pregnancy. An elevated F1+2, TAT or D-Dimer level during pregnancy is not necessarily indicative for an acute thromboembolic event. The normal ETP in both women with and without FVL suggests that the capacity of the plasma to generate thrombin after in vitro activation of the clotting system is not affected by pregnancy. Higher levels of D-Dimer in women with FVL than in women with wildtype factor V at baseline as well as during pregnancy indicate increased fibrinolytic system activation in carriers of the mutation.

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