Benefit Of Thromboprophylaxis Research Articles

Thromboprophylaxis during neoadjuvant chemotherapy for bladder cancer reduces thromboembolism and bleeding.

To assess the risk of venous thromboembolic events (VTEs) and bleeding with or without thromboprophylaxis during neoadjuvant chemotherapy in bladder cancer patients scheduled for radical cystectomy. We conducted a retrospective cohort study in 4886 patients with non-metastatic bladder cancer undergoing cystectomy across 28 centres in 13 countries between 1990 and 2021. Inverse probability weighting analyses were performed to estimate the effect of thromboprophylaxis on VTE and bleeding. In 147 patients (3%) VTEs were recorded within the first year. These occurred a median (interquartile range [IQR]) of 127 (82-198) days after bladder cancer diagnosis. Bleeding events occurred in 131 patients (3%) within the first year. These occurred a median (IQR) of 101 (83-171) days after cancer diagnosis. In inverse probability weighting analyses, compared to patients without thromboprophylaxis during chemotherapy, patients with thromboprophylaxis had not only a lower risk of VTE (hazard ratio [HR] 0.32, 95% confidence interval [CI] 0.12-0.81; P = 0.016) but also a lower bleeding risk (HR 0.03, 95% CI 0.09-0.12; P <0.0001). The retrospective nature of the study was its main limitation. In this retrospective analysis, the benefit of thromboprophylaxis during neoadjuvant chemotherapy before cystectomy is in line with data from randomised trials in other malignancies. Our data suggest thromboprophylaxis is protective against VTEs and should be the standard of care during neoadjuvant chemotherapy.

High-risk subgroups were not identified to benefit from thromboprophylaxis after hospitalization for COVID-19

BackgroundThe Accelerating COVID-19 Therapeutic Interventions and Vaccines-4c (ACTIV-4c) trial investigated prophylactic apixaban for 30 days following hospitalization for COVID-19. The overall incidence of early postdischarge death or thromboembolism was low, and the trial was closed early. ObjectivesTo identify a high-risk patient population who might benefit from postdischarge thromboprophylaxis through subgroup analyses stratified by age, race/ethnicity, obesity, D-dimer elevation, World Health Organization score, and modified International Medical Prevention Registry on Venous Thromboembolism score on 30-day composite outcome of all-cause death, arterial thromboembolism (ATE), and venous thromboembolism (VTE). MethodsCumulative incidences of all-cause death, ATE, and VTE within 30 days were described for each subgroup. Time to death, ATE, or VTE by 30 days was analyzed using Cox proportional hazard models with interaction testing for each subgroup. ResultsAmong 1217 patients randomized to apixaban or placebo group, 32% were >60 years old. Modified International Medical Prevention Registry on Venous Thromboembolism score was ≥4 in 2% and 2 or 3 with an elevated D-dimer in an additional 9% of participants. The overall incidence of the primary endpoint was 2.13% in the apixaban group and 2.31% in the placebo group. At day 30, similar rates of the primary endpoint occurred within subgroups, except for participants aged >60 years. No benefit of thromboprophylaxis was seen in any subgroup. ConclusionThe combined incidence of 30-day death, ATE, and VTE was low in patients who survived COVID-19 hospitalization, except in patients over age 60 years. Due to the limited number of events, the findings remain inconclusive; nonetheless, the study did not identify a high-risk subgroup that would derive benefits from extended thromboprophylaxis.

Predictive accuracy of boosted regression model in estimating risk of venous thromboembolism following minimally invasive radical surgery in pharmacological prophylaxis-naïve men with prostate cancer.

Venous thromboembolism (VTE) is a potentially life-threatening but preventable complication after urological surgery. Physicians are faced with the challenges of weighing the risks and benefits of thromboprophylaxis given scanty evidence for or against and practice variation worldwide. The primary objective of the study was to explore the possibility of a risk-stratified approach for thromboembolism prophylaxis following radical prostatectomy. A prospective database was accessed to cross-link venous thromboembolism events in 522 men who underwent minimally invasive prostatectomy between February 2010 and October 2021. A deterministic data linkage method was used to record events through electronic systems. Community Health Index (CHI) numbers were used to identify patients via electronic health records. Patient demographics and clinical characteristics such as age, comorbidities, Gleason staging, and readmission details accrued. VTE within 90days and development of a risk-stratified scoring system. All statistical analysis was performed using R-Statistical Software and the risk of VTE within 90days of surgery was estimated via gradient-boosting decision trees (BRT) model. 1.1% (6/522) of patients developed deep vein thrombosis or pulmonary embolism within 3months post-minimally invasive prostatectomy. Statistical analysis demonstrated a significant difference in the body mass index (p = 0.016), duration of hospital stay (p < 0.001), and number of readmissions (p = 0.036) between patients who developed VTE versus patients who did not develop VTE. BRT analysis found 8 variables that demonstrated relative importance in predicting VTE. The receiver operating curves (ROC) were constructed to assess the discrimination power of a new model. The model showed an AUC of 0.97 (95% confidence intervals [CI]: 0.945,0.999). For predicting VTE, a single-center study is a limitation. The incidence of VTE post-minimally invasive prostatectomy in men who did not receive prophylaxis with low molecular weight heparin is low (1.1%). The proposed risk-scoring system may aid in the identification of higher-risk patients for thromboprophylaxis. In this report, we looked at the outcomes of venous thromboembolism following minimally invasive radical prostatectomy for prostate cancer in consecutive men. We developed a new scoring system using advanced statistical analysis. We conclude that the VTE risk is very low and our model, if applied, can risk stratify men for the development of VTE following radical surgery for prostate cancer.

Role of thromboprophylaxis during neoadjuvant chemotherapy before radical cystectomy in patients with bladder cancer: Results of a multicenter retrospective cohort study.

598 Background: Patients undergoing radical cystectomy are at risk of developing venous thromboembolic events (VTE), with most VTEs occurring during neoadjuvant chemotherapy. The ASCO Clinical Practice Guideline Update recommends thromboprophylaxis in cancer patients with a high risk of VTE and a low risk of bleeding. However, the risks of VTE and bleeding with or without thromboprophylaxis in bladder cancer patients scheduled for radical cystectomy have not been well evaluated. Methods: We conducted a retrospective cohort study of patients with non-metastatic bladder cancer undergoing cystectomy across 28 centers in 13 countries between 1990 and 2021. Inverse probability weighting analyses were performed to estimate the effect of thromboprophylaxis during neoadjuvant chemotherapy on VTE and bleeding. Results: Of 4886 patients, 4631 (95%) received neither thromboprophylaxis nor anticoagulation during chemotherapy. Thromboprophylaxis during neoadjuvant chemotherapy was prescribed in 151 (3%) patients mainly being enoxaparin (80%) with a median duration of 94 (range 38 to 104) days. In inverse probability weighting analyses, patients with thromboprophylaxis compared to patients without thromboprophylaxis during chemotherapy had not only a lower VTE (HR 0.32 [95% CI, 0.12 to 0.81], p-value = 0.016) but also a lower bleeding risk (HR 0.03 [95% CI, 0.09 to 0.12], p-value: &lt;0.0001). Conclusions: In this retrospective analysis, the benefit of thromboprophylaxis during neoadjuvant chemotherapy before cystectomy is in line with data from randomized trials in other malignancies. Our data suggests thromboprophylaxis seems protective against VTEs during neoadjuvant chemotherapy in bladder cancer patients planned for cystectomy. The ASCO guidelines recommending thromboprophylaxis during chemotherapy should therefore also be regarded as a standard of care in patients treated with neoadjuvant chemotherapy before cystectomy.

Prevention of Hospital Associated Venous Thromboembolism in Psychiatric Inpatients- a Survey of Current Practice Within Mental Health Trusts in England

AimsGeneral hospital inpatients are routinely risk assessed for hospital associated venous thromboembolism (HAT) and given appropriate thromboprophylaxis if indicated. However, mental health trusts have not taken a similar approach in psychiatric inpatients, despite known risk factors, including some unique to psychiatric inpatients. We explored current practice of HAT prevention in English psychiatric inpatients.MethodsA Freedom of Information Act (FOI) request was sent to all 71 English mental health trusts, asking whether there was a Venous Thromboembolism (VTE) policy, whether a VTE risk assessment tool was being used, what is looked like, and the incidence of HAT in their psychiatric inpatients i.e., VTE during admission or occurring up to 90 days post discharge.ResultsWe received 54 unique responses (76%) to the FOI. Of these, 36 (86%) shared their VTE policy, 26 (72%) of which had been adapted for this population; 38 (90%) shared their VTE risk assessment tool, of which 17 (45%) were adapted from the Department of Health VTE risk assessment tool.Only five trusts out of 42 (12%) monitored VTE events up to 90 days post-discharge and 4 of these shared their monitoring policy. Only 18 (43%) were able to provide data on the number of psychiatric patients diagnosed with a VTE during their stay and up to 90 days post discharge between February 2016–2021, 6 (14%) said they would incur costs to collect this data and 9 (21%) were unable to access this data. Where information was provided, the number of HAT events ranged from 0–224 within each trust. Of the 18 trusts who provided data, a total of 514 events were recorded between Feb 2016-Feb 2021, but none of the trusts were able to confirm if this included VTE events up to 90 days post discharge.ConclusionOur FOI survey suggest a high incidence of VTE in psychiatric patients and indicate wide variation in HAT prevention in English hospitalised psychiatric patients. Most had a VTE Trusts had a policy in place, with 45% having a VTE risk assessment tool that listed risk factors unique to psychiatric patients, adapting VTE risk assessment tools in this way may lead to a greater use of thromboprophylaxis. The lack of access to data on HAT by mental health trusts is concerning. Further research is required to understand the rates of VTE, validate a VTE risk assessment tool and conduct trials looking at the benefit of thromboprophylaxis in psychiatric inpatients.

Clozapine-Related Thromboembolic Events.

Clozapine is an atypical antipsychotic used for treatment-resistant schizophrenia. Venous thromboembolism (VTE) is a rare side effect of clozapine which can be fatal. This article summarizes current evidence regarding the risk of VTE associated with the use of clozapine. We performed a PubMed (MeSH) and Google Scholar search for the last two decades. Studies or case reports performed in humans were included in the review, of which 42 case reports of patients taking clozapine at VTE onset were included in the analysis of this review. According to the articles reviewed, the mean age was 42.9 years, with more males (71.43%) than females (28.57%). The average clozapine dose was 285.62 mg/day. VTE onset occurred within the first six months in 71.8% of the cases. Overall, 70.37% of the patients had comorbidities, and 87.5% had risk factors for VTE. In total, 68.57% were prescribed other medications at VTE onset, and 60% were being treated with another antipsychotic concomitantly. Finally, 32.5% of the patients died, while 67.5% survived. In 60% of the cases, clozapine was discontinued after VTE. In our literature review, we observed that among clozapine users, VTE occurred at a wide dose range, and most of the events occurred within the first six months. As many patients who are prescribed clozapine have risk factors for VTE, the risk should be considered at the time of prescribing. Further research should be conducted to elucidate the risk of VTE in clozapine users and the benefits of thromboprophylaxis.

Safety and effectiveness of thromboprophylaxis use in hospitalized elderly medical patients at a Saudi tertiary care center

IntroductionAppropriate prescribing of thromboprophylaxis according to guidelines’ recommendations can heighten over- or underutilization risk. The study intended to evaluate the safety and effectiveness of appropriate/inappropriate thromboprophylaxis use among hospitalized elderly medical patients. MethodsA retrospective observational cohort study was conducted, including patients who were ≥60 years old, hospitalized for an acute medical illness that required hospitalization in a medical ward for >48 h, and received thromboprophylaxis. Against the American College of Chest Physicians guidelines, the thromboprophylaxis use appropriateness was assessed. ResultsA total of 370 patients met the inclusion criteria, in 71.9% of whom thromboprophylaxis use was appropriate. The mean age of the included patients was 75 years (±9.1), and 72.4% of them were at high risk of venous thromboembolism (VTE), and almost all these patients received appropriate thromboprophylaxis. The occurrence of bleeding was significantly higher in the appropriate use group during hospitalization than the inappropriate use group (11.7% vs. 2.9%, p = 0.009); the majority of these bleeding events were classified as major. There were no differences in VTE events during hospitalization or 90 days all-cause mortality between the two groups. ConclusionThe study demonstrates high prescribers’ compliance with recommendations in high-risk patients. In patients at low risk for VTE, the overutilization of thromboprophylaxis did not increase their bleeding risk. This study suggests that the benefits of thromboprophylaxis in elderly patients, regardless of their VTE risk, may outweigh the risk of bleeding.

Incidence and Risk Factors for Venous Thromboembolism Following 2462 Major Abdomino-Pelvic Surgeries in Tertiary Hospital.

PurposeTo determine the incidence and risk factor of postoperative venous thromboembolism (VTE) in Thai populations and to evaluate morbidity, mortality, bleeding complications and the benefit of thromboprophylaxis in real-world practice.Patients and MethodsWe performed a retrospective, single-center, cohort study of patients from all age groups who underwent elective open or laparoscopic major abdomino-pelvic surgery between January 2008 and December 2018 at Chulabhorn Hospital, Bangkok, Thailand. We collected general medical information and specific data based on items from the Caprini risk scoring system.ResultsA total of 2462 major abdomino-pelvic surgeries were included. The study population consisted of 742 males (30.1%) and 1720 females (69.9%) aged 54.59 ± 13.27 years. The incidence of VTE in Thai patients that underwent major abdominal surgery was 0.48%. The most frequent influencing factor for VTE was a history of pulmonary embolism, which increased the risk of VTE 98.28-fold, whereas a history of deep vein thrombosis increased the risk of VTE by 12.34-fold. Other factors influencing VTE development were obesity, anticoagulant use, postoperative chemotherapy, preoperative chemotherapy, endometrium cancer, tumor-node-metastasis (TNM) stage 4 and American College of Chest Physicians (ACCP) class 4. Protective factors included no history of VTE, laparoscopic surgery, TNM stage 0 and benign disease and BMI<30. VTE significantly increased mortality whereas following ACCP guideline reduced mortality.ConclusionPost-operative VTE incidence in Thai patients undergoing major abdomino-pelvic surgery was lower compared with Western patients. Factors influencing for VTE were history of VTE, anticoagulant use, postoperative chemotherapy, preoperative chemotherapy, endometrium cancer, TNM stage 4 and ACCP class 4. Following ACCP guideline reduced the incidence of mortality.

Venous thromboembolism prophylaxis for women at risk during pregnancy and the early postnatal period.

Venous thromboembolism prophylaxis for women at risk during pregnancy and the early postnatal period.

Venous thromboembolism (VTE) in melanoma patients (pts) on immunotherapy (IO).

94 Background: VTE in cancer significantly contributes to morbidity and a worse overall prognosis. Little is known about the incidence of VTE in melanoma pts receiving IO. This study aims to assess the incidence of VTE in melanoma pts on IO, interrogate potential association with specific therapies, and ascertain its prognostic utility. Methods: We conducted a retrospective cohort study of melanoma pts who received any IO including ipilimumab (ipi), nivolumab (nivo) or pembrolizumab (pembro) from July 2015 to December 2017 at the Cleveland Clinic. VTE including deep venous thrombosis and pulmonary embolism were identified by chart review. VTE-free survival and overall survival (OS) were estimated by Kaplan-Meier and Cox proportional hazard models; association between VTE and IO was examined using the Pearson’s chi-squared test. Results: This cohort comprised 219 pts with median age of 65 years (range 24-92) and 66.7% male. Pembro was most common (36.5%), followed by ipi/nivo (26.9%), ipi (21.9%), and nivo (14.6%). Most had distant metastatic disease (79.9%), and 16.4% had brain metastases. VTE occurred in 14.2% (n = 31) of pts on therapy. Of those with VTE, 12 (38.7%) were receiving ipi/nivo and 19 (61.3%) single agent IO. Median VTE-free time was 4.9 months on ipi/nivo compared to 9.2 months on single agent IO (p = 0.05). The 6-month VTE-free survival was 18.5% for ipi/nivo and 71.8% for single agent IO. Among pts with distant metastatic disease, ipi/nivo was significantly associated with earlier time to VTE when adjusted for age, gender, and presence of brain metastases, (median VTE-free time 4.9 months vs. 9.3; p = 0.024; HR 2.96 [95% CI, 1.15-7.59]). Among pts without brain metastases, VTE was associated with worse OS (median OS 1.3 years vs. NR; p&lt;0.001; HR 3.47 [95% CI, 1.66-7.24]). Conclusions: VTE risk may be elevated for melanoma pts on IO, specifically those receiving ipi/nivo. Further studies are needed to identify pathophysiology, risk factors, and benefit of thromboprophylaxis in this setting. [Table: see text]

Venous thromboembolism in breast cancer patients receiving cyclin-dependent kinase inhibitors.

e18184 Background: Venous thromboembolism (VTE) complicates several anti-cancer regimens including chemotherapy and anti-angiogenic agents. Cyclin-dependent kinase 4/6 inhibitors (CDKIs) are a new approach for hormone receptor positive (HR+) metastatic breast cancer (mBC). Reported VTE rates in randomized trials range from 0.6% for ribociclib (MONALEESA-2) to 2% for palbociclib (PALOMA-3) and 5% for abemaciclib (MONARCH-3) but these may underestimate actual rates compared to patients in clinical practice who are generally older and have greater comorbidities. Little is known about real world incidence or prevalence of VTE with CDKIs in mBC. The aim of this study was to evaluate rates of VTE in clinical practice and association with outcomes in mBC patients on CDKIs. Methods: We conducted a retrospective cohort study at Cleveland Clinic Taussig Cancer Institute, approved by the institutional review board. We identified consecutive mBC patients who received any of three FDA-approved CDKIs (palbociclib, ribociclib, abemaciclib) from 1/2015 through 12/2017. VTE including deep venous thrombosis (DVT) and pulmonary embolism (PE) were identified by electronic medical record review. Overall survival (OS), progression free survival (PFS) and time to VTE were estimated by the Kaplan-Meier method and evaluated for association with VTE using Cox proportional hazard regression. Results: The study population included 424 patients, with a median age at diagnosis of 54.76 yrs, (range 27 -85). Palbociclib was the most commonly used CDKI (n = 390, 91.8%); 27 patients (6.3%) received more than one drug. VTE during CDKI therapy occurred in 9% of patients (n = 38), including DVT in 52.6% (n = 20), PE in 18.5% (n = 7) and visceral vein thrombosis (VVT) in 15.8% (n = 6). Median time to VTE was 314 days, and 6-months rate was 4.1%. VTE was associated with numerically worse PFS and OS, but this was not statistically significant (PFS [HR 1.25, 95% CI 0.73 – 2.14, p = 0.42], OS [HR 1.60, 95% CI 0.89 – 2.87, p = 0.12]). Conclusions: VTE affected nearly 10% of breast cancer patients receiving CDKIs, 2- to 5-fold greater than reported in registration trials. Further work is necessary to identify pathophysiology, risk factors and benefit of thromboprophylaxis.

Rivaroxaban for Thromboprophylaxis in High-Risk Ambulatory Patients with Cancer

BackgroundAmbulatory patients receiving systemic cancer therapy are at varying risk for venous thromboembolism. However, the benefit of thromboprophylaxis in these patients is uncertain.MethodsIn this double-blind, randomized trial involving high-risk ambulatory patients with cancer (Khorana score of ≥2, on a scale from 0 to 6, with higher scores indicating a higher risk of venous thromboembolism), we randomly assigned patients without deep-vein thrombosis at screening to receive rivaroxaban (at a dose of 10 mg) or placebo daily for up to 180 days, with screening every 8 weeks. The primary efficacy end point was a composite of objectively confirmed proximal deep-vein thrombosis in a lower limb, pulmonary embolism, symptomatic deep-vein thrombosis in an upper limb or distal deep-vein thrombosis in a lower limb, and death from venous thromboembolism and was assessed up to day 180. In a prespecified supportive analysis involving the same population, the same end point was assessed during the intervention period (first receipt of trial agent to last dose plus 2 days). The primary safety end point was major bleeding.ResultsOf 1080 enrolled patients, 49 (4.5%) had thrombosis at screening and did not undergo randomization. Of the 841 patients who underwent randomization, the primary end point occurred in 25 of 420 patients (6.0%) in the rivaroxaban group and in 37 of 421 (8.8%) in the placebo group (hazard ratio, 0.66; 95% confidence interval [CI], 0.40 to 1.09; P=0.10) in the period up to day 180. In the prespecified intervention-period analysis, the primary end point occurred in 11 patients (2.6%) in the rivaroxaban group and in 27 (6.4%) in the placebo group (hazard ratio, 0.40; 95% CI, 0.20 to 0.80). Major bleeding occurred in 8 of 405 patients (2.0%) in the rivaroxaban group and in 4 of 404 (1.0%) in the placebo group (hazard ratio, 1.96; 95% CI, 0.59 to 6.49).ConclusionsIn high-risk ambulatory patients with cancer, treatment with rivaroxaban did not result in a significantly lower incidence of venous thromboembolism or death due to venous thromboembolism in the 180-day trial period. During the intervention period, rivaroxaban led to a substantially lower incidence of such events, with a low incidence of major bleeding. (Funded by Janssen and others; CASSINI ClinicalTrials.gov number, NCT02555878.)

Venous Thromboembolism in Cancer Patients Receiving Immunotherapy

BackgroundVenous thromboembolism (VTE) is known to complicate several classes of anti-cancer therapies including chemotherapy and anti-angiogenic agents. Immunotherapy is a novel and growing approach to systemic treatment of cancer, but little is known about incidence or prevalence of VTE in cancer patients on immunotherapy. The objective of this study was to describe rates of VTE in cancer patients on various immunotherapy regimens.MethodsWe conducted a single institution, retrospective cohort study at Taussig Cancer Center of the Cleveland Clinic. The study was approved by the institutional review board. The study cohort was created using our center's pharmacy database of patients who received any of the six FDA approved immunotherapy agents (ipilimumab, nivolumab, pembrolizumab, atezolizumab, avelumab or durvalumab) between July 2015 and December 2017. VTE events including deep venous thrombosis (DVT) and pulmonary embolism (PE) were identified by chart review. Overall survival (OS) was estimated by the Kaplan-Meier method and evaluated for association with VTE following immunotherapy using Cox proportional hazard regression with two-sided Wald test and adjustment for age at diagnosis and presence/absence of metastases. Patients receiving combination therapies were matched 1:3 to patients receiving monotherapy based on demographic and clinical attributes including: gender, race, ethnicity, primary cancer site, age at diagnosis, and stage. The incidence of VTE following immunotherapy was compared between single and combination therapy cohorts using the Pearson chi-squared test.ResultsThe study population comprised 522 patients, of whom a small majority (n=307, 58.8%) were males with a median age at cancer diagnosis of 64 years (range 10 to 91 years). The vast majority of patients (n=463, 88.7%) had metastatic disease. Lung (n= 259, 49.6%) was the most common primary site of cancer. Nivolumab was the most commonly used single drug immunotherapy (n=273, 52.3%) and nivolumab + ipilimumab was the most common multidrug regimen (n=34, 6.5%). VTE occurred in 30.3% of patients (n=158), including DVT in 34.8% (n=55), PE in 34.2% (n=54), DVT+PE in 18.4% (n=29), visceral vein thrombosis in 8.9% (n=14), DVT +PE+ visceral vein in 2.5% (n=4). Using the matched subset of patients receiving single (n=129) and combination (n=43) immunotherapies, the rate of VTE in single vs. combination immunotherapy was 36% vs. 28% (p value = 0.45). VTE in patients on immunotherapy was associated with worse survival, but this association was not statistically significant when adjusting for age and metastases [HR = 1.215, (95%CI 0.94 to 1.55) p value = 0.121].ConclusionsVTE is common in cancer patients receiving immunotherapy either as single-agent or combination regimens, affecting nearly one-third of all patients and may potentially be associated with worsened survival. Further work is necessary to identify pathophysiology, risk factors and benefit of thromboprophylaxis in this setting. [Display omitted] DisclosuresKhorana:Janssen: Consultancy; Bayer: Consultancy; Pfizer: Consultancy; Sanofi: Consultancy.

Perioperative thromboprophylaxis in liver transplant patients.

Improvements in surgical and anesthetic procedures have increased patient survival after liver transplantation (LT). However, the perioperative period of LT can still be affected by several complications. Among these, thromboembolic complications (intracardiac thrombosis, pulmonary embolism, hepatic artery and portal vein thrombosis) are relatively common causes of increased morbidity and mortality. The benefit of thromboprophylaxis in general surgical patients has already been established, but it is not the standard of care in LT recipients. LT is associated with a high bleeding risk, as it is performed in a setting of already unstable hemostasis. For this reason, the role of routine perioperative prophylactic anticoagulation is usually restricted. However, recent data have shown that the bleeding tendency of cirrhotic patients is not an expression of an acquired bleeding disorder but rather of coexisting factors (portal hypertension, hypervolemia and infections). Furthermore, in cirrhotic patients, the new paradigm of ‘‘rebalanced hemostasis’’ can easily tip towards hypercoagulability because of the recently described enhanced thrombin generation, procoagulant changes in fibrin structure and platelet hyperreactivity. This new coagulation balance, along with improvements in surgical techniques and critical support, has led to a dramatic reduction in transfusion requirements, and the intraoperative thromboembolic-favoring factors (venous stasis, vessels clamping, surgical injury) have increased the awareness of thrombotic complications and led clinicians to reconsider the limited use of anticoagulants or antiplatelets in the postoperative period of LT.

Heparin for the prevention of venous thromboembolism in acutely ill medical patients (excluding stroke and myocardial infarction).

Venous thromboembolic disease has been extensively studied in surgical patients. The benefit of thromboprophylaxis is now generally accepted, but it is medical patients who make up the greater proportion of the hospital population. Medical patients differ from surgical patients with regard to their health and the pathogenesis of thromboembolism and the impact that preventative measures can have. The extensive experience from thromboprophylaxis studies in surgical patients is therefore not necessarily applicable to non-surgical patients. This is an update of a review first published in 2009. To determine the effectiveness and safety of heparin (unfractionated heparin or low molecular weight heparin) thromboprophylaxis in acutely ill medical patients admitted to hospital, excluding those admitted to hospital with an acute myocardial infarction or stroke (ischaemic or haemorrhagic) or those requiring admission to an intensive care unit. For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched November 2013) and CENTRAL (2013, Issue 10). Randomised controlled trials comparing unfractionated heparin (UFH) or low molecular weight heparin (LMWH) with placebo or no treatment, or comparing UFH with LMWH. One review author identified possible trials and a second review author confirmed their eligibility for inclusion in the review. Two review authors extracted the data. Disagreements were resolved by discussion. We performed the meta-analysis using a fixed-effect model with the results expressed as odds ratios (ORs) with 95% confidence intervals (CIs). Sixteen studies with a combined total of 34,369 participants with an acute medical illness were included in this review. We identified 10 studies comparing heparin with placebo or no treatment and six studies comparing LMWH to UFH. Just under half of the studies had an open-label design, putting them at a risk of performance bias. Descriptions of random sequence generation and allocation concealment were missing in most of the studies. Heparin reduced the odds of deep vein thrombosis (DVT) (OR 0.38; 95% CI 0.29 to 0.51; P < 0.00001). The estimated reductions in symptomatic non-fatal pulmonary embolism (PE) (OR 0.46; 95% CI 0.19 to 1.10; P = 0.08), fatal PE (OR 0.71; 95% CI 0.43 to 1.15; P = 0.16) and in combined non-fatal PE and fatal PE (OR 0.65; 95% CI 0.42 to 1.00; P = 0.05) associated with heparin were imprecise. Heparin resulted in an increase in major haemorrhage (OR 1.81; 95% CI 1.10 to 2.98; P = 0.02). There was no clear evidence that heparin had an effect on all-cause mortality and thrombocytopaenia. Compared with UFH, LMWH reduced the risk of DVT (OR 0.77; 95% CI 0.62 to 0.96; P = 0.02) and major bleeding (OR 0.43; 95% CI 0.22 to 0.83; P = 0.01). There was no clear evidence that the effects of LMWH and UFH differed for the PE outcomes, all-cause mortality and thrombocytopaenia. The data from this review describe a reduction in the risk of DVT in patients presenting with an acute medical illness who receive heparin thromboprophylaxis. This needs to be balanced against an increase in the risk of bleeding associated with thromboprophylaxis. The analysis favoured LMWH compared with UFH, with a reduced risk of both DVT and bleeding.

New strategies of VTE prevention in cancer patients

Venous thromboembolism (VTE) is a common complication in patients with cancer. VTE is a main cause of morbidity and mortality in patients with cancer and has a significant impact on their quality of life. Preventing VTE in cancer patients reduces both morbidity and mortality. The level of evidence for antithrombotic prophylaxis of VTE in patients with cancer varies for hospitalized and ambulatory patients. Hospitalized patients with active cancer (for both medical or surgical indication) and reduced mobility should receive thromboprophylaxis throughout hospital stay. Prophylaxis of VTE is not routinely recommended for outpatients with cancer on chemotherapy. For these patients, current guidelines suggest that clinicians should consider antithrombotic prophylaxis on a case-by-case basis in highly selected outpatients. Different strategies for identification of high-risk outpatients with cancer who could benefit of thromboprophylaxis are under consideration. The new oral anticoagulants could have a role for VTE prevention in ambulatory patients with cancer who are on chemotherapy, as they are administered at a fixed dose without routine laboratory monitoring and may have fewer drug interactions with anticancer agents.

Prophylaxis for venous thromboembolic disease in pregnancy and the early postnatal period

Venous thromboembolic disease (TED), although rare, is a major cause of maternal mortality and morbidity, hence methods of prophylaxis are often used for women at risk. This may include women delivered by caesarean section, those with a personal or family history of TED and women with inherited or acquired thrombophilias (conditions that predispose people to thrombosis). Many methods of prophylaxis carry a risk of side effects, and as the risk of TED is low, it is possible that the benefits of thromboprophylaxis may be outweighed by harm. Current guidelines for clinical practice are based on expert opinion only, rather than high quality evidence from randomised trials.To determine the effects of thromboprophylaxis in women who are pregnant or have recently delivered and are at increased risk of TED on the incidence of venous TED and side effects of treatment.We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (May 2009).Randomised trials comparing one method of thromboprophylaxis with placebo or no treatment, and randomised trials comparing two (or more) methods of thromboprophylaxis.Two review authors extracted data independently and resolved any discrepancies by discussion.Sixteen trials met the inclusion criteria but only 13 trials, involving 1774 women, examining a range of methods of thromboprophylaxis, contributed data for the outcomes of interest. Four of them compared methods of antenatal prophylaxis: low molecular weight heparin (LMWH) versus unfractionated heparin (UFH) (two studies), and heparin versus no treatment (two studies). Eight studies assessed postnatal prophylaxis after caesarean section; one compared hydroxyethyl starch with unfractionated heparin; four compared heparin with placebo; and the other three compared UFH with LMWH. One study examined prophylaxis in the postnatal period.The small number of statistically significant findings in this review are largely derived from trials which are not of high methodological quality. It was not possible to assess the effects of any of these interventions on most outcomes, and especially on rare outcomes such as death, TED and osteoporosis, because of small sample sizes and the small number of trials making the same comparisons.There was some evidence of side effects associated with thromboprophylaxis.There is insufficient evidence on which to base recommendations for thromboprophylaxis during pregnancy and the early postnatal period. Large scale randomised trials of currently-used interventions should be conducted.

Thromboembolism during neoadjuvant therapy for rectal cancer: a systematic review

Thromboembolism (TE) is a common, costly and morbid complication that is also associated with decreased survival in cancer patients. However, the risk of cancer-associated TE varies because of the multitude of patient-, cancer- and treatment-related influences. Thromboprophylaxis (TP) is currently not widely adopted in the ambulant population. A review of the literature was undertaken to determine the rate of TE and the benefit of TP in patients with rectal cancer during neoadjuvant therapy (nT). A systematic literature search of electronic databases, including PubMed and Embase, was performed (1995-2012) for all studies assessing nT in rectal cancer. Data were extracted and used to assess study design, patient demographic and clinical characteristics, treatment protocols and TE incidence. A systematic review was conducted to identify the rates of TE. The search strategy included text terms and MeSH headings for TP, rectal cancer and nT. Twelve of 86 studies met quality criteria for reporting TE complications and described 10 pulmonary emboli and three deep-vein thromboses in 3375 patients (overall TE rate = 0.38%). Ninety per cent of pulmonary emboli reported were fatal, suggesting significant under-reporting of TE events, even in high-quality studies. The risk of fatal pulmonary embolism in studies examining nT in rectal cancer that reported complications systematically was one in 375 (0.27%; 95% CI: 0.09-0.44%). The overall TE rate, as well as the effectiveness of TP during nT, remains unknown. TE events should be systematically reported using common terminology frameworks in cancer studies.

Actitud ante el riesgo tromboembólico en pacientes con cáncer

Venous thromboembolism is a frequent complication in cancer patients and affects their morbidity and mortality. The risk of this event differs according to the characteristics of the tumor, the patient's circumstances, and the treatments provided. Although the benefits of thromboprophylaxis in certain subgroups of patients with cancer have been demonstrated, currently generic prescription is not recommended unless other risk factors are present, or the patient has multiple myeloma and has been treated with thalidomide or lenalidomide. The insertion of a central venous catheter in these patients does not imply prescription of thromboprophylaxis, although the risk factors for catheter thrombosis are known. Finally, a risk scoring model for the prediction of venous thromboembolism has been defined in outpatients with cancer starting chemotherapy, which has been externally validated and supplemented with the addition of two biomarkers.

Chemotherapy-associated thromboembolic risk in cancer outpatients and effect of nadroparin thromboprophylaxis: results of a retrospective analysis of the PROTECHT study

BackgroundCancer patients receiving chemotherapy are at increased risk of thrombosis. Nadroparin has been demonstrated to reduce the incidence of venous and arterial thrombotic events (TEs) by about 50% in cancer outpatients receiving chemotherapy. The aims of this retrospective analysis were to evaluate the thromboembolic risk and the benefit of thromboprophylaxis according to type of chemotherapy.MethodsCancer outpatients were randomly assigned to receive subcutaneous injections of nadroparin or placebo. The incidence of symptomatic TEs was assessed according to the type of chemotherapy. Results were reported as risk ratios with associated 95% CI and two-tailed probability values.Results769 and 381 patients have been evaluated in the nadroparin and placebo group, respectively. In the absence of thromboprophylaxis, the highest rate of TEs was found in patients receiving gemcitabine- (8.1%) or cisplatin-based chemotherapy (7.0%). The combination of gemcitabine and cisplatin or carboplatin increased the risk to 10.2%. Thromboprophylaxis reduced TE risk by 68% in patients receiving gemcitabine; with a further decrease to 78% in those receiving a combination of gemcitabine and platinum.ConclusionsThis retrospective analysis confirms that patients undergoing chemotherapy including gemcitabine, platinum analogues or their combination are at higher risk of TEs. Our results also suggest that outpatients receiving chemotherapy regimens including these agents might achieve an increased benefit from thromboprophylaxis with nadroparin. Clinical Trial registration number: NCT 00951574