Cancer Thromboembolism Research Articles

Update in venous thromboembolism in cancer: Lessons from multi-centre registries

Cancer-associated thrombosis is a common problem in cancer patients and one of the leading causes of death in this population. Randomised clinical trials have shown that both low-molecular-weight heparins and direct oral anticoagulants are the treatments of choice for cancer-associated thrombosis. Despite this, small sample sizes, poor representation of some patient subgroups and lack of information about real-world clinical situations are some of the limitations of randomised trials. To overcome these problems, registries have been established to collect real-world data from patients with cancer-associated thrombosis, offering new evidence and information to supplement the findings of randomised clinical trials. However, few registries have focused exclusively on cancer patients, and some have excluded various subgroups of patients. Additionally, data collection and processing are another major challenge in analysing registry results, where the emergence of artificial intelligence will play a fundamental role.

Inherited Thrombophilia Gene Mutations and Risk of Venous Thromboembolism in Cancer: A Systematic Review and Meta-Analysis

Inherited thrombophilia and cancer are both recognized risk factors for venous thromboembolism (VTE). In the general population, the risk of thrombosis is increased in patients with inherited thrombophilia, but the role of inherited thrombophilia on the risk of cancer-associated VTE remains controversial. The objective of this study was to summarize and determine whether cancer patients with inherited thrombophilia gene mutations have an increased risk of developing VTE. We conducted a systematic literature search in Medline, EMBASE and Cochrane Central databases, as well as references of included studies from inception until September 26 th 2022. We included observational (cohort or case-control) and interventional studies comprising of human adult cancer patients who were tested for any inherited thrombophilia gene mutation. The outcome was objectively confirmed symptomatic or asymptomatic first VTE (upper or lower limbs deep vein thrombosis, pulmonary embolism, and/or splanchnic or cerebral vein thrombosis) occurring after a cancer diagnosis. Two reviewers independently screened the titles/abstracts and full texts of all potentially eligible articles. Pooled odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using Mantel-Haenszel random-effects models. We used the Quality in Prognostic Studies (QUIPS) risk of bias tool to assess study risk of bias. A total of 4274 studies were screened for eligibility. Thirty-six studies involving different cancer types and treatments were included in the systematic review, of which 28 studies were included in the meta-analysis (Figure 1). Among studies included in the meta-analysis, 9 studies included various cancer types while the remaining 19 studies were in selected cancer types (3 lung, 3 myeloma, 2 brain, 2 bladder, 2 breast, 2 gynecologic, 1 testicular, 1 lung or gastrointestinal, 1 pancreas, 1 colorectal and 1 breast or gastrointestinal). There were 18 cohort (11 prospective and 7 retrospective) and 10 case-control studies. The following seven inherited thrombophilia gene mutations were meta-analyzed: ABO blood type, Factor V Leiden (FVL), Methylenetrahydrofolate Reductase (MTHFR) C677T, Plasminogen-Activator Inhibitor-1 (PAI-1) 4G/5G, Prothrombin Factor II G20210A, Vascular Endothelial Growth Factor (VEGF) C634G and VEGF C2578A. In cancer patients with non-O blood types, FVL and Prothrombin Factor II G20210A mutations, the risk of VTE was significantly increased with ORs of 1.56 (95% CI: 1.28-1.90), 2.28 (95% CI: 1.51-3.48) and 2.14 (95% CI: 1.14-4.03), respectively, compared to patients with O blood and wild types (Table 1). In addition, heterozygous and homozygous MTHFR C677T were associated with ORs of 1.50 (95% CI: 1.00-2.24) and 1.38 (95% CI: 0.87-2.22), respectively (Table 1). Among those with heterozygous and homozygous PAI-1 4G/5G, VEGF C634G and VEGF C2578A, no significant increase in the odds of VTE and moderate to considerable heterogeneity were observed (Table 1). Few studies had low risk of bias, except for studies of ABO blood group, which predominantly had low risk of bias. In conclusion, this meta-analysis provides evidence that non-O blood type, FVL, Prothrombin Factor II G20210A and heterozygous MTHFR C677T significantly increase the risk of VTE in cancer patients. However, there is moderate to high risk of bias in the currently available data, further well-designed studies are needed.

Low-Dose Rivaroxaban to Prevent Recurrences of Venous Thromboembolism in Cancer: A Real-Life Experience with a Focus on Female Patients.

The way in which to prevent recurrent venous thromboembolism (VTE) is an unmet clinical need in cancer patients. International guidelines only provide conditional recommendations and do not specify which anticoagulant and dose should be used. In the last 2 years, we have been using low-dose rivaroxaban to prevent VTE recurrences in cancer patients. The results of this real-life experience are presented in this study. All patients had cancer and had previously completed a cycle of at least six months of full-dose anticoagulation for the treatment of a VTE index event, before receiving a prescription of low-dose rivaroxaban (10 mg once daily) for secondary prevention of VTE. Effectiveness and safety of this therapeutic regimen were evaluated in terms of VTE recurrences, major bleedings (MB), and clinically relevant non-major bleedings (CRNMB). The analysis included 106 cancer patients. Their median age was 60 years (IQR 50-69). Metastatic cancer was present in 87 patients (82.1%). Six patients (5.7%) had brain metastases. Over a median follow-up time of 333 days (IQR 156-484), the incidence of VTE recurrences was 3.8% (95%CI 1.0-9.4), with a recurrence rate of 4.0 per 100 person-years (95%CI 1.1-10.2). We observed no MB (0.0%) and three CRNMB (2.8%) (95%CI 0.6-8.1). Low-dose rivaroxaban is potentially effective and safe in cancer patients that require prevention of recurrent VTE. Large-scale studies are needed to confirm these findings.

774P Immune checkpoint inhibitor monotherapy and the risk of venous thromboembolism in cancer: A systematic review and meta-analysis

Immune checkpoint inhibitor (ICI) therapy, an emerging class of cancer treatment, is being actively investigated in multiple trials. However, the risk of venous thromboembolism (VTE) with ICI drugs remains unexplored.

Risk Factor Analysis of Venous Thromboembolism in Cancer: A National Inpatient Sample Study

ObjectiveIn this study, we aimed to explore the association of demographic characteristics and comorbidities with the risk of venous thromboembolism (VTE) in cancer inpatients, as well as to delineate the mortality risk in cancer inpatients with VTE.MethodsWe conducted a retrospective cohort analysis based on the National Inpatient Sample (NIS) 2012-2014, involving 339,395 inpatients with a primary diagnosis of cancer subdivided into cohorts without VTE (n=331,695) and with VTE (n=7,700). We used a binomial logistic regression model to evaluate the odds ratio (OR) of demographics, comorbidities, and in-hospital mortality rate with respect to cancer inpatients with VTE.ResultsA higher proportion of cancer inpatients with VTE were 36-50 years in age (83.1%), male (50%), and of black (19.3%) and Hispanic ethnicity (17.2%) compared to the non-VTE cohort. The prevalence of comorbidities was higher in the VTE cohort, including HIV/AIDS, congestive heart failure (CHF), chronic pulmonary disease, diabetes, hypertension, and obesity. CHF demonstrated the highest risk of association with VTE (OR: 2.68, 95% CI: 2.30-3.12), followed by hypertension (OR: 1.23, 95% CI: 1.16-1.29), diabetes (OR: 1.16, 95% CI: 1.07-1.26), and chronic pulmonary disease (OR: 1.13, 95% CI: 1.05-1.22). Conversely, valvular diseases, obesity, and drug abuse were not significantly associated with VTE in cancer inpatients. The in-hospital mortality rate was higher in cancer inpatients with VTE (12% vs. 2.1%), thereby increasing the in-hospital mortality risk (OR: 3.87, 95% CI: 3.58-4.18).ConclusionVTE risk was significantly higher in cancer patients with comorbid CHF, hypertension, diabetes, and chronic pulmonary disease. The risk of all-cause in-hospital mortality was increased by four times in cancer inpatients with VTE.

In Hospital Burden of Venous Thromboembolism in Cancer: A 13 Year Analysis

Introduction:Patients with malignancies tend to develop a hypercoagulable state which predisposes them to thromboembolic events such as deep vein thrombosis (DVT) and pulmonary emboli (PE). Cancer increases the risk of venous thrombosis several fold with varying degree of relative risks (range 4-7). Various factors including tumor type, location, stage and time since diagnosis influence such incidence. The hospital burden of venous thromboembolism (VTE) associated with cancer has yet to be determined, as well as it's impact on cost, length of stay and mortality. The purpose of this study was to identify the annual trend in incidence, cost, and length of stay of VTE among patients with a diagnosis of cancer as well as determine the associated in-hospital mortality based on cancer origin.Methods:Data on inpatient hospitalizations was collected using the National Inpatient Sample (NIS) for years 2002 to 2014. VTE was identified using the clinical classification software code in conjunction with ICD 9 codes for acute pulmonary embolus. Annual trends for incidence, length of stay, and cost of admission were assessed with a linear regression analysis. Associated cancer type and mortality due to PE was evaluated using univariate logistic regression analysis.Results:During the years between 2002 and 2014 a weighted estimate of total admissions for VTE among cancer patients is 903,610. This represents 23% of all admissions for VTE. A trending increase in annual admissions is seen from 61,614 in 2002 to 69,585 in 2014. This increase is primarily driven by a primary diagnosis of acute pulmonary embolus, as these admissions increased from an annual 23,042 to 38,780, while admissions with a primary diagnosis of DVT decreased from 38,571 to 30,805. The total cost of admission increased from $19,380 to $40,105 (p<0.001) while the total length of stay decreased from 6.15 to 4.81 (p<0.001). Mortality among patients with PEs with and without cancer are 2.9% vs 5.6% respectively (p<.0001). Notably, patients with a history of esophageal, gastric, liver, pancreatic and lung cancers all had a more than two-fold increase in the likelihood of mortality.Conclusion:Among patients admitted between 2002 and 2014, VTE remains a source of mortality and morbidity, VTE associated with cancer significantly more so. Admissions for VTE are increasing, and this is primarily driven by an increase in acute pulmonary emboli. On the other hand admissions for acute DVT is decreasing which could imply that these are being managed more frequently in the outpatient setting. The mortality from pulmonary emboli doubles with a history of cancer. More specifically mortality in this population is most associated with esophageal, gastric, liver, pancreatic, and lung cancers. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

The comparative effectiveness of direct oral anti-coagulants and low molecular weight heparins for prevention of recurrent venous thromboembolism in cancer: The CANVAS pragmatic randomized trial.

12020 Background: Previous randomized trials in cancer patients suggest that DOACs are non-inferior to LMWH for preventing recurrent VTE but have higher risk of bleeding. However, the balance of benefits and burdens remains uncertain. Objective: The CANVAS pragmatic trial compared recurrent VTE, bleeding and death in cancer patients following an initial VTE treated with either DOAC or LMWH therapy. Methods: CANVAS was an unblinded hybrid comparative effectiveness non-inferiority trial, with randomized and preference cohorts. Between 12/16 and 4/20, 671 participants were randomized and followed for 6-months. Between 12/16 and 12/17, 140 participants declined randomization, chose their preferred anticoagulant and were followed for 6-months. The preference cohort was closed when predetermined stopping criteria were met. Final follow-up was 11/30/20. Randomized patients were assigned 1:1 to receive either a DOAC or a LMWH. If assigned to LMWH, transitions to warfarin were allowed. Physicians and patients could choose among any DOAC or LMWH. Doses were suggested based on FDA-approved labeling but not mandated. Patients from 67 practices in the US with any invasive solid tumor, lymphoma, multiple myeloma or CLL and a diagnosis of symptomatic or radiographically detected VTE within 30 days of enrollment were eligible. The 1° analysis was conducted in the randomized modified-into to treat popululation, (all subjects who received study drug). The 1° outcome was recurrent VTE. The aim was to establish noninferiority of anticoagulation with a DOAC as defined by the upper limit of the 2-sided 90% CI for the difference in the event rate at 6 months of &lt; 3%. Secondary outcomes included death and bleeding. Hypothesis testing included only the randomized cohort but propensity score adjusted results for the preference and combined cohorts are also shown. Results: The non-inferiority criteria for recurrent VTE was met. Conclusions: Among adult cancer patients with VTE, the use of a DOAC compared with a LMWH resulted in a noninferior risk of recurrent VTE with no differences in rates of bleeding or death in randomized patients. Clinical trial information: NCT02744092. [Table: see text]

Treatment of venous thromboembolism in cancer patients: a systematic review and meta-analysis on the efficacy and safety of different direct oral anticoagulants (DOACs).

BackgroundTo evaluate the efficacy and safety of different direct oral anticoagulants (DOACs) compared with low molecular weight heparins (LMWHs) in the treatment of venous thromboembolism (VTE) in cancer patients.MethodsLiterature was searched in databases including Cochrane Library, EMBASE (Ovid), and MEDLINE (PubMed). Eligible studies were included, and data were collected independently by 2 reviewers. We conducted a systematic review of the efficacy and safety of DOACs in the treatment of VTE in cancer patients. The odds ratios (ORs) of different DOACs compared with LMWHs for VTE, deep vein thrombosis (DVT), pulmonary embolism (PE) recurrence, major bleeding, and clinically relevant non-major bleeding (CRNMB), were calculated in meta-analyses and subgroup analyses.ResultsA total of 18 articles were eligible for analyses, including 4 randomized controlled trials (RCTs) and 14 retrospective studies. Both RCTs and retrospective studies confirmed that DOACs decreased the risk of VTE recurrence [RCTs: OR, 0.60; 95% confidence interval (CI), 0.45–0.80; retrospective studies: OR, 0.73; 95% CI, 0.59–0.90] and DVT recurrence (RCTs: OR, 0.54; 95% CI, 0.36–0.80; retrospective studies: OR, 0.20; 95% CI, 0.06–0.63), but not PE recurrence or fatal PE in cancer patients. Subgroup analyses revealed an important role of rivaroxaban in decreasing recurrent VTE. Meanwhile, major bleeding events were not increased in the DOAC group, but the risks of CRNMBs were significantly elevated. Subgroup analyses confirmed the role of rivaroxaban in increasing the risk of major bleeding events and CRNMBs.ConclusionsCompared with LMWHs, DOACs (especially rivaroxaban) significantly reduce the risk of VTE and DVT, but not PE recurrence, in patients with cancer. Although DOACs did not increase the major bleeding events in pooled analysis, rivaroxaban showed an elevated risk of this adverse effect in subgroup analysis. In addition, the risk of CRNMB events was increased after the application of DOACs including rivaroxaban.

Long-term effects of non-retrieved inferior vena cava filters on recurrences of venous thromboembolism in cancer and non-cancer patients: From the COMMAND VTE registry

There is a paucity of data comparing the long-term outcomes after inferior vena cava (IVC) filters placement for patients with acute venous thromboembolism (VTE) between those with and without active cancer. In the COMMAND VTE Registry, we evaluated the effects of IVC filter use on the long-term clinical outcomes stratified by the presence and absence of active cancer. Among 2,626 patients with acute symptomatic VTE, there were 604 patients with active cancer, and 2022 patients without active cancer. IVC filters were placed and not retrieved in 455 patients (17%) in the entire cohort, in 150 patients (24.8%) in the active cancer stratum, and in 305 patients (15.1%) in the non-cancer stratum. In the entire cohort, non-retrieved IVC filter placement was not associated with a lower adjusted risk for PE recurrence (HR 0.59, 95% CI 0.30-1.15, P=0.122), but with an increased adjusted risk for DVT recurrence (HR 2.27, 95% CI 1.43-3.60, P<0.001). In the non-cancer stratum, the non-retrieved IVC filter placement was associated with a decreased risk for PE (HR 0.29, 95% CI 0.09-0.93, P=0.037), but not with an increased risk for DVT (HR 1.73, 95% CI 0.89-3.38, P=0.108), while in the active cancer stratum, it was associated with an increased risk for DVT (HR 2.47, 95% CI 1.24-4.91, P=0.010), but not with a decreased risk for PE (HR 0.82, 95% CI 0.34--1.96, P=0.650). There were some differences in the risk-benefit balance between VTE patients with and without active cancer.

Dynamic prediction modeling for cancer‐associated venous thromboembolism

Dynamic prediction modeling for cancer‐associated venous thromboembolism

Cancer-associated prothrombotic pathways: leucocytosis, but not thrombocytosis, correlates with venous thromboembolism in women with ovarian cancer.

Risk factors for venous thromboembolism in cancer vary between tumours. Leucocytosis, thrombocytosis, tumour histology and vascular compression may drive thrombosis in ovarian cancer. Thrombosis developed in 13.4% of our patients. Higher median leucocyte, neutrophil and monocyte counts were related to thrombosis. Thrombocytosis >350 × 109 /L was frequent (63.8%), but not predictive of thrombosis. Identification of prothrombotic biomarkers may help personalise preventive treatments.

Direct oral anticoagulants more effective than low-molecular-weight heparin for venous thrombo-embolism in cancer: an updated meta-analysis of randomized trials.

In the recent past, low-molecular-weight heparin (LMWH) was the first choice in the treatment of cancer related venous thrombo-embolism (VTE). Evidence supporting the preferential use of direct anticoagulants (DOACs) in patients with cancer, instead, is less robust so far. We therefore aimed to assess in an updated meta-analysis of randomized controlled trials whether the use of DOACs may be associated with a more favorable profile when compared to LMWH. We performed a meta-analysis of RCTs enrolling patients with VTE and cancer. We assessed Mantel-Haenszel pooled estimates of risk ratios (RRs) and 95% CIs for recurrence of VTE, major bleeding, and mortality comparing subjects treated with DOACs with those with LMWH. After study selection, three RCTs (HOKUSAI-Cancer, SELECT-D and ADAM-VTE) were included for the analysis with an overall population of 1739 patients. DOACs patients had a lower incidence of 6-month recurrent VTE when compared to LMWHs (RR 0.56, 95% CI 0.40-0.79; p < 0.001). Incidence of major bleeding was not significantly different between DOACs and LMWH treated patients (RR 1.56, 95% CI 0.95-2.47, p = n.s.), and mortality rates were comparable (RR 1.03, 95% CI 0.91-2.47, p = n.s.). In a meta-analysis of RCTs therapy with DOACs was superior to LMWH in terms of efficacy and lower recurrence of VTE with a comparable safety profile in terms of bleeding events and complications.

Molecular Dynamics Simulation Estrogen Receptor Alpha againts Andrographolide as Anti Breast Cancer

Breast cancer is the most common cancer suffered by women with 1.67 million new cases in the world by 2012 with a mortality rate of 12.9%. Tamoxifen is a standard therapy for breast cancer but can cause endometrial and thromboembolic cancer. Andrografolid is an active compound from Andrographis paniculata which has antiproliferation activity of MCF-7 breast cancer cells with IC50 was 61.11 μM. The purpose of this study was to design andrographolide modification structures as human estrogen receptor alpha (hER-α) antagonists. Molecular docking simulation results showed that the andrographolide and AND5 (best andrographolide derivative) have free binding energy (ΔG) values were -9.65 kcal/mol and -12.43 kcal/mol, respectively, and hydrogen bonds were formed with Gly521, Asp351, and Met343. The ΔG value of ANDS was lower than tamoxifen (-11.40 kcal/mol). Pharmacophore modeling results showed that andrographolide and AND5 had a high pharmacophore-fit value of 46.39% and 63.47%, respectively. Molecular dynamics simulation using MM-PBSA calculation method, showed that the hERα-AND5 system has a value of ΔGTOTAL = -50.52 kcal/mol compared to the hERα-estradiol system as an agonist with a value of ∆GTOTAL = -40.86 kcal/mol . These results suggested that AND5 has better affinity for hERα compared to estradiol so that AND5 is a very promising anti breast cancer agent.Keywords: Andrographolide, molecular dynamics, breast cancer, molecular docking, estrogen receptor alpha

Treatment of Venous Thromboembolism in Cancer. Historical Perspective and Evolving Role of the Direct Oral Anticoagulants.

The management of cancer-associated thrombosis (CAT) is complex, and treatment strategies have been evolving over the past 15years. It is well recognized that oral vitamin K antagonists are difficult to use in cancer patients, with higher rates of treatment failure and bleeding complications than in non-cancer patients. Low-molecular-weight-heparin (LMWH) became the widely accepted standard of care for treatment of cancer-associated thrombosis, following the CLOT study comparing dalteparin with warfarin in 2003. LMWH remains widely used for the treatment of CAT. However, in the past twoyears, several studies have served to validate direct oral anticoagulants as a safe and effective alternative to LMWH. Two randomized clinical trials comparing edoxaban and rivaroxaban with dalteparin, and several retrospective studies have shown the efficacy of edoxaban and rivaroxaban for the treatment of CAT. However, there is an evidence of increased bleeding with the DOACs, particularly gastrointestinal or urinary tract bleeding in patients with lesions within the gastrointestinal or urinary tracts. This chapter discusses the ongoing development of optimal treatment strategies for cancer-associated thrombosis.

Targeting Protein Disulfide Isomerase with the Oral Flavonoid Isoquercetin Prevents Venous Thromboembolism in Advanced Cancer: Results of a Multi-Dose, Multi-Center, Phase II Clinical Trial (CATIQ Study)

▪BackgroundProtein disulfide isomerase (PDI) is a thiol isomerase secreted by platelets and endothelial cells and is required for thrombus formation. We previously showed that quercetin flavonoids inhibit PDI and block thrombus formation following vascular injury in a mouse model. Quercetins are present in a wide range of fruits and vegetables and epidemiologic data suggest an antithrombotic effect. Initial human studies demonstrated that the oral administration of isoquercetin reduces PDI activity in plasma. To evaluate the antithrombotic strategy of inhibiting PDI, we performed a phase II trial to evaluate the efficacy of isoquercetin to reduce the hypercoagulability of cancer patients at high risk for venous thromboembolism (VTE). In high-risk cancer cohorts with protocol-mandated screening for VTE, the reported incidence of VTE often exceeds 20% within months of initiation of chemotherapy. The risk of major hemorrhage is also higher in patients with advanced cancer which complicates the decision to recommend thromboprophylaxis.MethodsWe performed a phase II study at 11 sites to assess the safety and efficacy of isoquercetin in cancer patients at high risk for VTE. Cohort A received isoquercetin 500 mg daily and Cohort B received 1000 mg isoquercetin daily for 56 days with laboratory assays performed at the beginning and at completion of study. Eligible patients had locally advanced or metastatic pancreatic, non-small cell lung, or colorectal cancer and enrolled within 4 weeks of initiating first or second line chemotherapy. The primary endpoint of the study was a reduction in D-dimer at day 56. Patients were monitored for the development of venous thromboembolism including a protocol-required bilateral lower extremity ultrasound performed at day 56. The primary VTE endpoint was defined as any symptomatic proximal or distal lower extremity DVT, symptomatic pulmonary embolism or fatal PE, or asymptomatic proximal DVT diagnosed by screening compression ultrasound. Radiology images for all suspected VTE were centrally reviewed and adjudicated by an independent committee.ResultsThere were no primary VTE endpoints observed in either cohort. Paired plasma samples were analyzed in 25 patients who received isoquercetin 500 mg daily (Cohort A) and 21 patients who received the isoquercetin 1000 mg daily (Cohort B). For the primary D-dimer endpoint, the administration of isoquercetin 1000 mg decreased D-dimer plasma concentrations by a median of 20% equating to a median decrease of 206 ng/ml fibrinogen equivalent units (P<0.001). The administration of isoquercetin 500 mg did not affect plasma D-dimer levels at 56 days (median change +9.90%, P=0.93). In both cohorts we measured an increase in PDI inhibition in plasma at day 56 (cohort A median increase 46%, P<0.001; cohort B median increase 78%, P<0.001). Corroborating the antithrombotic efficacy of the 1000 mg dose, we also observed a significant decrease in circulating soluble P-selectin (median decrease 58%, P<0.001) and platelet-dependent thrombin generation (median decrease 55%, P=0.006) as shown in the Figure. Isoquercetin did not prolong the PT or PTT. There were two grade 1 hemorrhoidal bleeds and no major hemorrhages observed.ConclusionsThe oral flavonoid, isoquercetin, prevented venous thromboembolism in cancer without an observed increase in hemorrhage. These results represent the first evidence in humans that targeting extracellular PDI has antithrombotic efficacy in a high VTE-risk population and implicate PDI-targeted therapies as a new class of antithrombotic therapeutics. (Clinicaltrials.gov #NCT02195232). DisclosuresZwicker:Daiichi: Honoraria; Quercegen: Research Funding; Parexel: Consultancy; Incyte: Research Funding.

Индивидуальный подход к послеоперационной профилактике тромбозов в онкологии

Цель исследования: повысить эффективность профилактики венозных тромбоэмболических осложнений (ВТЭО) у онкологических больных на хирургическом этапе лечения. Материалы и методы. Проанализированы результаты антикоагулянтной профилактики ВТЭО в послеоперационном периоде у 216 больных с высоким риском тромбоза, обусловленным злокачественными новообразованиями (ЗНО) желудочно-кишечного тракта. В динамике сравнивали результаты показателей коагулограммы, нового глобального теста оценки гемостаза и ультразвукового исследования триплексного сканирования венозной системы нижних конечностей в течение 1 месяца. Результаты. Наибольшее количество ВТЭО зарегистрировано в группе без использования медикаментозной профилактики (26,9%) после оперативного вмешательства. Наименьшая частота ВТЭО отмечена в группе с индивидуальным подбором дозы антикоагулянта (4,9%) на основании глобального теста оценки гемостаза. Заключение. Полагаем, что в послеоперационном периоде у больных со ЗНО желудочно-кишечного тракта необходима комплексная оценка состояния свертывающей системы с коррекцией режима антикоагулянтной профилактики на основании динамики показателей гемостаза, что позволяет снизить частоту ВТЭО. Aim: to increase prophylaxis eff ectiveness of venous thromboembolic complications (VTE) in cancer patients under surgery. Materials and methods. We analyzed the results of anticoagulant postoperative VTE prophylaxis in 216 patients with high risk of thrombosis due to malignant neoplasms of gastrointestinal tract. In dynamics we compared coagulogram parameters, the results of new global hemostatic assessment test, and ultrasound triplex scan of lower limbs venous system during 1 month. Results. Most VTE cases were registered in patients without medicamentous prophylaxis (26.9%) after surgery. The lowest VTE frequency was observed in patients with individual anticoagulant dose selection (4.9%) based on the global hemostatic assessment test. Conclusion. We consider that in postoperative period in patients with malignant neoplasms of gastrointestinal tract integrated assessment of coagulation system and correction of anticoagulant prophylaxis regimen based on the dynamics of hemostasis parameters are required that allows to reduce VTE frequency.

Effect of rosuvastatin on risk markers for venous thromboembolism in cancer

Background Statin therapy is associated with lower risk of venous thromboembolism (VTE) but has not been prospectively evaluated in patients with advanced cancer. Objectives We determined if statin administration in this high-risk population reduces the risk of VTE, based on established and emerging biomarkers. Patients/Methods This double-blind, crossover, randomized controlled trial among patients with advanced cancer receiving systemic therapy allocated participants to rosuvastatin 20mg daily or placebo for 3-4weeks prior to crossover to the alternative therapy, with a 3-5-week washout. D-dimer, C-reactive protein (CRP), soluble (s)P-selectin, factor VIII (FVIII), thrombin generation and exploratory biomarkers focusing on endogenous thrombin potential, including tissue factor (TF), activated factor IX (FIXa) and activated factor XI (FXIa), were measured at the start and end of both treatment periods. The primary outcome was change in D-dimer with rosuvastatin compared with placebo. Results Of 38 enrolled participants, 24 (63%) completed the study. Rosuvastatin did not cause statistically significant changes in D-dimer levels or any other biomarker. CRP levels decreased by 40%; 4.3mgL-1 (95% confidence interval, -11.0 to +2.5mgL-1 ) compared with placebo. In post-hoc analysis, participants who received rosuvastatin initially during their first line of treatment had a 13% decrease in D-dimer. Circulating TF, FIXa and FXIa were detected in 26%, 68% and 71% of cancer patients despite not being found in healthy individuals. Conclusions Rosuvastatin did not cause favorable changes in biomarkers of VTE risk in advanced cancer patients receiving chemotherapy. The role of statin therapy as thromboprophylaxis in the cancer population remains uncertain.

Long-Term Incidence of Venous Thromboembolism in Cancer: The Scandinavian Thrombosis and Cancer Cohort.

The risk of venous thromboembolism (VTE) in patients who survive the first years after a cancer diagnosis after the acute effects of disease and treatment in comparison to a similar background population has been sparsely investigated. The aim of the study was to investigate if incidence rates (IRs) of VTE differed in patients who were alive at least 2 years after a cancer diagnosis without VTE compared with cancer-free references in a population-based cohort study. The study entry was 2 years after a first cancer diagnosis. For each cancer-exposed subject, five reference subjects were identified within the cohort. The IRs were calculated as number of VTEs per 1,000 person years (×10 −3 p-y) in total and in distinct cancer types and corresponding reference subjects. Incidence rate ratios (IRRs) were calculated by Poisson's regression. During a mean follow-up of 5.3 years, 110 VTEs occurred among the 7,288 cancer-exposed subjects and 321 VTEs occurred among the 36,297 identified reference subjects. The IR of VTE was higher for cancer-exposed subjects compared with reference subjects, IRs 3.7 × 10 −3 p-y, 95% CI: 3.1 to 4.5 and 1.9 × 10 −3 p-y, 95% CI: 1.7 to 2.2, respectively. IRs of VTE in most solid cancer types declined to almost the same level as in the reference subjects 2 years after cancer diagnosis, but remained higher in hematological cancers, IRR 4.0, 95% CI: 2.0 to 7.8.

Joint effects of GP6 rs1613662 and pre-cancer platelet count on the risk of venous thromboembolism in cancer

Joint effects of GP6 rs1613662 and pre-cancer platelet count on the risk of venous thromboembolism in cancer

Prothrombotic genotypes and risk of venous thromboembolism in cancer

Venous thromboembolism (VTE) is a common and potentially life-threatening complication in cancer. Patients with cancer are at a higher risk of VTE-related complications such as major bleeding during anticoagulant treatment, recurrence and mortality. Therefore, it is important to identify cancer patients with high risk of VTE in order to implement targeted prevention to those with a favorable benefit-to-harm ratio for thromboprophylaxis. VTE is strongly heritable, and during the last decades, several prothrombotic genotypes associated with VTE-risk have been identified. However, most of these studies were conducted in non-cancer patients, and the role of prothrombotic genotypes in cancer-related VTE is scarcely studied. In this review, we summarize current knowledge on the role of prothrombotic genotypes in cancer-related VTE, with particular focus on factor V Leiden, the prothrombin G20210A mutation and polymorphisms in the ABO gene. In general, many of the studies were small and performed in selected cancer populations, and they showed somewhat diverging results. Results from recent, larger, studies indicated that there is an association between these prothrombotic genotypes and cancer-related VTE. However, their predictive capability has not been assessed and the clinical implications are yet unclear. Future research should be conducted in larger cancer patient populations, and should be extended to include recently identified prothrombotic genotypes and assess the predictive value of genetic risk scores.