Poor performance of D-dimer in excluding venous thromboembolism among patients with lymphoma and leukemia.
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ABSTRACT:
SUBMITTER: Qdaisat A
PROVIDER: S-EPMC6545857 | biostudies-literature | 2019 Jun
REPOSITORIES: biostudies-literature
Publications
Poor performance of D-dimer in excluding venous thromboembolism among patients with lymphoma and leukemia.
Qdaisat Aiham A Soud Rawan Al RA Wu Carol C CC Rojas Hernandez Cristhiam M CM Li Jieli J Meng Qing H QH Abdel-Razeq Hikmat H Yeung Sai-Ching Jim SJ
Haematologica 20190110 6
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Project description:BackgroundCoagulopathy and associated bleeding and venous thromboembolism (VTE) are major causes of morbidity and mortality in patients with acute leukemia. The underlying mechanisms of these complications have not been fully elucidated.ObjectivesTo evaluate the associations between biomarker levels and bleeding and VTE in acute leukemia patients.Patients/methodWe examined plasma levels of activators, inhibitors and biomarkers of the coagulation and fibrinolytic pathways in patients ≥18 years with newly diagnosed acute leukemia compared to healthy controls. Multivariable regression models were used to examine the association of biomarkers with bleeding and VTE in acute leukemia patients. The study included 358 patients with acute leukemia (29 acute promyelocytic leukemia [APL], 253 non-APL acute myeloid leukemia [AML] and 76 acute lymphoblastic leukemia [ALL]), and 30 healthy controls.ResultsPatients with acute leukemia had higher levels of extracellular vesicle (EV) tissue factor (TF) activity, phosphatidylserine-positive EVs, plasminogen activator inhibitor-1 (PAI-1), plasmin-antiplasmin complexes, cell-free DNA and lower levels of citrullinated histone H3-DNA complexes compared to healthy controls. APL patients had the highest levels of EVTF activity and the lowest levels of tissue plasminogen activator among the acute leukemia patients. There were 41 bleeding and 37 VTE events in acute leukemia patients. High EVTF activity was associated with increased risk of bleeding (sHR 2.30, 95%CI 0.99-5.31) whereas high PAI-1 was associated with increased risk of VTE (sHR 3.79, 95%CI 1.40-10.28) in these patients.ConclusionsOur study shows alterations in several biomarkers in acute leukemia and identifies biomarkers associated with risk of bleeding and VTE.
| S-EPMC10615001 | biostudies-literature
Project description:BackgroundLymphomas are characterized by elevated synthesis of inflammatory soluble mediators that could trigger the development of venous thromboembolism (VTE). However, data on the relationship between specific immune dysregulation and VTE occurrence in patients with lymphoma are scarce. Therefore, this study aimed to assess the association between inflammatory markers and the risk of VTE development in patients with lymphoma.MethodsThe erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lactate dehydrogenase (LDH), total protein (TP), and albumin were assessed in 706 patients with newly diagnosed or relapsed lymphoma. Data were collected for all VTE events, while the diagnosis of VTE was established objectively based on radiographic studies. ROC (receiver operating characteristic) curve analysis was performed to define the optimal cutoff values for predicting VTE.ResultsThe majority of patients was diagnosed with aggressive non-Hodgkin lymphoma (58.8%) and had advanced stage disease (59.9%). Sixty-nine patients (9.8%) developed VTE. The NLR, PLR, ESR, CRP, and LDH were significantly higher in the patients with lymphoma with VTE, whereas the TP and albumin were significantly lower in those patients. Using the univariate regression analysis, the NLR, PLR, TP, albumin, LDH, and CRP were prognostic factors for VTE development. In the multivariate regression model, the NLR and CRP were independent prognostic factors for VTE development. ROC curve analysis demonstrated acceptable specificity and sensitivity of the parameters: NLR, PLR, and CRP for predicting VTE.ConclusionInflammatory dysregulation plays an important role in VTE development in patients with lymphoma. Widely accessible, simple inflammatory parameters can classify patients with lymphoma at risk of VTE development.
| S-EPMC9016935 | biostudies-literature
Project description:Background Hospitalized patients with COVID-19 and raised D-dimer levels have high rates of venous thromboembolism (VTE). Methods We used data from hospitalized patients with COVID-19 that were tested for pulmonary embolism (PE) or deep vein thrombosis (DVT) because of raised D-dimer levels. We aimed to identify patients at increased risk for VTE. Results From March 25 to July 5th, 2020, 1,306 hospitalized patients with COVID-19 and raised D-dimer levels underwent testing for VTE in 12 centers. In all, 171 of 714 (24%) had PE, and 161 of 810 (20%) had DVT. The median time elapsed from admission to VTE testing was 12 days, and the median time from D-dimer measurement to testing 2 days. Most patients with VTE were men (62%), mean age was 62 ± 15 years, 45% were in an intensive care unit. Overall, 681 patients (52%) received VTE prophylaxis with standard doses, 241 (18%) with intermediate doses and 100 (7.7%) with therapeutic doses of anticoagulants. On multivariable analysis, patients with D-dimer levels >20 times the upper normal range (19% of the whole cohort) were at increased risk for VTE (odds ratio [OR]: 3.24; 95%CI: 2.18–4.83), as were those with a platelet count <100,000/μL (OR: 4.17; 95%CI: 1.72–10.0). Conclusions Hospitalized patients with COVID-19 and D-dimer levels >20 times the upper normal range were at an increased risk for VTE. This may help to identify what patients could likely benefit from the use of higher than recommended doses of anticoagulants for VTE prophylaxis.
| S-EPMC7832524 | biostudies-literature
Project description:BackgroundUnprovoked venous thromboembolism (VTE) is related to a higher incidence of occult cancer. D-dimer is clinically used for screening VTE, and has often been shown to be present in patients with malignancy. We explored the predictive value of D-dimer for detecting occult cancer in patients with unprovoked VTE.MethodsWe retrospectively examined data from 824 patients diagnosed with deep vein thrombosis or pulmonary thromboembolism. Of these, 169 (20.5%) patients diagnosed with unprovoked VTE were selected to participate in this study. D-dimer was categorized into three groups as: <2,000, 2,000-4,000, and >4,000 ng/ml. Cox regression analysis was employed to estimate the odds of occult cancer and metastatic state of cancer according to D-dimer categories.ResultsDuring a median 5.3 (interquartile range: 3.4-6.7) years of follow-up, 24 (14%) patients with unprovoked VTE were diagnosed with cancer. Of these patients, 16 (67%) were identified as having been diagnosed with metastatic cancer. Log transformed D-dimer levels were significantly higher in those with occult cancer as compared with patients without diagnosis of occult cancer (3.5±0.5 vs. 3.2±0.5, P-value = 0.009, respectively). D-dimer levels >4,000 ng/ml was independently associated with occult cancer (HR: 4.12, 95% CI: 1.54-11.04, P-value = 0.005) when compared with D-dimer levels <2,000 ng/ml, even after adjusting for age, gender, and type of VTE (e.g., deep vein thrombosis or pulmonary thromboembolism). D-dimer levels >4000 ng/ml were also associated with a higher likelihood of metastatic cancer (HR: 9.55, 95% CI: 2.46-37.17, P-value <0.001).ConclusionElevated D-dimer concentrations >4000 ng/ml are independently associated with the likelihood of occult cancer among patients with unprovoked VTE.
| S-EPMC4830616 | biostudies-literature
Project description:Patients with lymphoma are at high risk of developing venous thromboembolism (VTE). The purpose of the present study was to identify the target gene associated with VTE for patients with lymphoma. Microarray data was downloaded from the gene expression omnibus database (GSE17078), which comprised the control group, 27 normal blood outgrowth endothelial cell (BOEC) samples, and the case group, 3 BOEC samples of venous thrombosis with protein C deficiency. Differentially expressed genes (DEGs) were identified by the Limma package of R. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses were performed via the database for annotation, visualization and integrated discovery. Differentially coexpressed pairs were identified by the DCGL package of R. The subsequent protein-protein interaction (PPI) networks and gene coexpression networks were constructed by the Search Tool for the Retrieval of Interacting Genes/Proteins database, and were visualized by Cytoscape software. A total of 110 DEGs were obtained, including 73 upregulated and 37 downregulated genes. GO and KEGG pathway enrichment analyses identified 132 significant GO terms and 9 significant KEGG pathways. In total, 97 PPI pairs for PPI network and 309 differential coexpression pairs for the gene coexpression network were obtained. Additionally, the connective tissue growth factor (CTGF) gene was closely connected with other genes in the two networks. A total of 2 KEGG pathways were associated with VTE and CTGF may be the target gene of VTE in patients with lymphoma. The present study may identify the molecular mechanism of VTE, but additional clinical study is required to validate the results.
| S-EPMC5588007 | biostudies-literature
Project description: Not available
| S-EPMC7495176 | biostudies-literature
Project description:BackgroundClinical risk assessment scores, such as IMPEDE VTE, can identify patients with multiple myeloma (MM) at high-risk of venous thromboembolism (VTE). Refinement of these scores, by including 1 or more biomarkers, could improve risk assessment.ObjectivesWe sought to determine the association between soluble P-selectin (sP-selectin) and D-dimer with VTE in MM.MethodsWe identified 545 patients with newly diagnosed MM. Using a nested case-control design, we identified 38 cases of VTE within 6-months of MM treatment and 137 randomly selected controls. Using logistic regression, we examined the association between D-dimer and sP-selectin with VTE. We also analyzed the association after adjusting for IMPEDE VTE.ResultsEach 1-point increase in IMPEDE VTE score was associated with a 27% increase in odds of VTE (odds ratio 1.27; 95% CI 1.08-1.51; c-statistic 0.61; 95% CI 0.51-0.71). There was no association between sP-selectin and VTE. Each one increase in natural log of D-dimer was associated with a 44% increase in odds of VTE, so we assigned points (ranging from -2 to +2) to D-dimer values and incorporated them into IMPEDE VTE, forming IMPEDED VTE. There was a 30% increase in odds of VTE per each 1-point increase in IMPEDED VTE (OR 1.30; 95% CI 1.12-1.52; c-statistic 0.65; 95% CI 0.55-0.75).ConclusionAmong patients with newly diagnosed MM starting chemotherapy, D-dimer was associated with increased odds of developing VTE within the subsequent 6-months. The addition of D-dimer to IMPEDE VTE-IMPEDED VTE-could improve prediction of VTE among patients with MM.
| S-EPMC10772878 | biostudies-literature
Project description:BackgroundPatients with non-Hodgkin lymphoma (NHL) have an increased risk of venous thromboembolism (VTE), particularly when they are receiving treatment. Blood or marrow transplantation (BMT) is recommended for relapsed/refractory NHL, and the risk of VTE after these patients undergo BMT is uncertain.MethodsPatients with NHL who survived 2 years or longer after BMT were surveyed for long-term health outcomes, including VTE. The median follow-up was 8.1 years (interquartile range, 5.6-12.9 years). The risk of VTE in 734 patients with NHL versus 897 siblings without a history of cancer and the risk factors associated with VTE were analyzed.ResultsBMT survivors of NHL were at increased risk for VTE in comparison with siblings (odds ratio for allogeneic BMT survivors, 4.61; P < .0001; odds ratio for autologous BMT survivors, 1.75; P = .035). The cumulative incidence of VTE was 6.3% ± 0.9% at 5 years after BMT and 8.1% ± 1.1% at 10 years after BMT. In allogeneic BMT recipients, an increased body mass index (BMI; hazard ratio [HR] for BMI of 25-30 kg/m2 , 3.52; 95% confidence interval [CI], 1.43-8.64; P = .006; HR for BMI > 30 kg/m2 , 3.44; 95% CI, 1.15-10.23; P = .027) and a history of chronic graft-versus-host disease (HR, 3.33; 95% CI, 1.59-6.97; P = .001) were associated with an increased risk of VTE. Among autologous BMT recipients, a diagnosis of coronary artery disease (HR, 5.94; 95% CI, 1.7-20.71; P = .005) and prior treatment with carmustine (HR, 4.91; 95% CI, 1.66-14.51; P = .004) were associated with increased VTE risk.ConclusionsPatients with NHL who survive BMT are at risk for developing late occurring VTE, and ongoing vigilance for this complication is required. Future studies assessing the role of thromboprophylaxis in high-risk patients with NHL are needed.
| S-EPMC6891120 | biostudies-literature
Project description:Background: To date, there are no large-scale data on the association between D-dimer levels at admission and the occurrence of venous thromboembolism (VTE) in Japanese patients with coronavirus disease 2019 (COVID-19). Methods and Results: The CLOT-COVID study was a retrospective, multicenter cohort study enrolling consecutive hospitalized patients with COVID-19 across 16 centers in Japan from April 2021 to September 2021. Among 2,894 enrolled patients, 2,771 (96%) had D-dimer levels measured at admission. Patients were divided into 3 groups based on tertiles of D-dimer levels at admission (1st tertile, D-dimer ≤0.5 μg/mL, n=949; 2nd tertile, D-dimer 0.51-1.09 μg/mL, n=894; 3rd tertile, D-dimer ≥1.1 μg/mL, n=928). The higher the tertile group, the more severe the COVID-19 status at admission. The incidence of VTE during hospitalization was highest in the 3rd tertile group (1st tertile, 0.3%; 2nd tertile, 0.3%; 3rd tertile, 3.6%; P<0.001). Even after adjusting for confounders in the multivariable logistic regression model, the higher D-dimer levels in the 3rd tertile (≥1.1 μg/mL) were independently associated with a higher risk of VTE during hospitalization (adjusted odds ratio 4.83 [95% confidence interval 1.93-12.11; P<0.001]; reference=1st tertile). Conclusions: Higher D-dimer levels at admission were associated with a higher risk of VTE events during hospitalization in Japanese patients with COVID-19. This could be helpful in determining patient-specific anticoagulation management strategies for COVID-19 in Japan.
| S-EPMC9072098 | biostudies-literature
Project description:BackgroundD-dimer is a biomarker of fibrin production and degradation, and changes in D-dimer concentration suggest fibrin clot formation, which is associated with thromboembolism and hypercoagulable states. Thus, an elevated D-dimer concentration could be a useful prognostic predictor for patients with venous thromboembolism (VTE).Methods and resultsIn this subanalysis of the J'xactly study, a prospective multicenter study conducted in Japan, we examined the clinical outcomes of 949 patients with VTE stratified by baseline D-dimer concentration. The median D-dimer concentration was 7.6 μg/ml (low D-dimer group: <7.6 μg/ml [n = 473, 49.8%]; high D-dimer group: ≥7.6 μg/ml [n = 476, 50.2%]). The mean age of the patients was 68 years, and 386 patients (40.7%) were male. Compared with the low D-dimer group, the high D-dimer group had more frequent pulmonary embolism with or without deep vein thrombosis (DVT), proximal DVT, atrial fibrillation, or diabetes mellitus, and underwent intensive treatment with 30 mg/day rivaroxaban. The incidence of composite clinically relevant events (recurrence or exacerbation of symptomatic VTE, acute coronary syndrome [ACS], ischemic stroke, death from any cause, or major bleeding) was higher in the high D-dimer group than in the low D-dimer group (11.1% vs. 7.5% per patient-year; hazard ratio, 1.46; 95% confidence interval, 1.05-2.04; p = 0.025). There was no significant difference between the high and low D-dimer groups in the incidence of VTE (2.8% vs. 2.5% per patient-year, respectively; p = 0.788), ACS (0.4% per patient-year vs. not observed, respectively; p = 0.078), or major bleeding (4.0% vs. 2.1% per patient-year, respectively; p = 0.087), but there was a significant difference in the incidence of ischemic stroke (1.0% per patient-year vs. not observed, respectively; p = 0.004).ConclusionElevated D-dimer concentration may be an important prognostic predictor in Japanese patients with VTE.Clinical Trial Registration: UMIN CTR, UMIN000025072 (https://www.umin.ac.jp/ctr/index.htm).
| S-EPMC9949378 | biostudies-literature