Efficacy Of Thromboprophylaxis Research Articles

External Validation of the Saved Score for Venous Thromboembolism Risk Stratification in Patients with Multiple Myeloma Receiving Immunomodulatory Drugs

Background: High thrombogenicity is a well-established phenomenon in multiple myeloma (MM) and can lead to high morbidity and mortality. The risk of venous thromboembolism (VTE) is particularly elevated in the subset of MM patients treated with immunomodulatory drug (IMiD) containing regimens. The National Comprehensive Cancer Network (NCCN) and International Myeloma Working Group (IMWG) have implemented VTE risk assessment models, and recommend prophylactic anticoagulation based on individual patient, disease, or treatment-related factors specifically for MM patients receiving IMiD. With the recent incorporation of the SAVED (PMID 31319391) scoring system in the NCCN guidelines for VTE risk stratification, we sought to externally validate this risk assessment model and evaluate its predictive ability in our MM patient cohort. Methods: We retrospectively evaluated 501 adult patients with either newly diagnosed or relapsed/refractory MM who were newly initiated on an IMiD-based regimen between 2010 and 2019. Patients already on therapeutic or prophylactic anticoagulation were excluded from the study (aspirin was allowed). The SAVED score was calculated at IMiD initiation according to the following five parameters: surgery within last 90 days (+2), Asian race (-3), prior VTE history (+3), age ≥80 years (+1), dexamethasone use (+2 for high dose [>160 mg/30-day], or +1 for standard dose [120-160 mg/30-day]). Patients with SAVED scores of <2 and ≥2 were considered of low and high risk, respectively, for developing VTE after IMiD initiation. Time to VTE was estimated by Kaplan-Meier failure method. Logistic regression model was used to test components of the SAVED score with 1-year VTE status. Model discrimination was assessed via c statistic by calculating the area under the receiver operating characteristic curve (AUC) with bootstrapped 95% confidence interval (CI). Results: The median age of our cohort at the IMiD initiation was 64 years (range 34-89); 264 (53%) patients were male and 378 (75%) were white. IgG and IgA heavy chain subtypes were present in 280 (56%), and 105 (21%) patients respectively, whereas 110 (22%) patients had light chain disease only. The International Staging System (ISS) was I, II, III, and unknown for 161 (32%), 149 (30%), 136 (27%), and 55 (11%) of patients, respectively. Most patients (94%) received lenalidomide, whereas 14 (3%) and 15 (3%) patients were treated with thalidomide and pomalidomide, respectively. The distribution of SAVED covariates is shown in Table 1. The cumulative incidence of VTE at 12-month after IMiD initiation for the entire cohort was 16% (95% CI: 13-20%). Among the 84 patients who developed new VTE after IMiD initiation, 60 (71%) had lower extremity deep venous thrombosis (DVT), 10 (12%) had pulmonary embolism, 9 (11%) had both DVT and PE, and 5 (6%) had upper extremity DVT. The SAVED score stratified 112 patients (22%) as high-risk and 389 patients (78%) as low-risk (similar proportion as the original derivation study). Cumulative incidence of VTE at 6 and 12 months was 31% and 41% in the high-risk group, versus 6% and 9% in the low-risk group, respectively (Figure 1). Each point of SAVED score increase was associated with significantly higher chance of VTE within 1-year post IMiD initiation with excellent discrimination (odds ratio = 2.10 [95% CI 1.71-2.56], c statistic (AUC) = 0.76 [95% CI 0.70-0.81]). Conclusion: Our results successfully externally validated the SAVED model to predict IMiD-associated VTE in a real-life cohort of patients with MM. Patients with SAVED score of ≥2 had significantly higher incidence for VTE. This indicates that more aggressive pharmacologic thromboprophylaxis is needed in this specific patient population. The SAVED score outperformed several other similar VTE prediction models that were also validated in the current cohort (c statistic=0.68 for IMPEDE [PMID: 33997961] and 0.62 for PRISM [PMID: 35772005]). In contrast to other risk models that focused on all patients with MM, the SAVED score was derived and now validated specifically for patients starting IMiD as this it is the only cancer population with a strong guideline recommendation for ambulatory thromboprophylaxis. Future prospective validation would be useful to determine the predictive nature of SAVED while evaluating safety and efficacy of thromboprophylaxis with direct oral anticoagulant in high-risk patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Risk and benefit trade-off of thromboprophylaxis in patients with Fontan circulation: insights from the National Database of Health Insurance Claims of Japan

Abstract Background Patients with Fontan circulation are at an increased risk of developing thromboembolic events in the first 3–12 months after surgery [1,2]. Thromboembolic events can lead to significant mortality [3]. The current guidelines recommend the use of antithrombotic therapy, either aspirin or warfarin, as a primary thromboprophylaxis [4,5]. On the other hand, the main adverse effect of thromboprophylaxis is bleeding, which may increase the risk of death. However, there are limited data to assess the outcomes of the thromboembolic and bleeding complications of thromboprophylaxis. Therefore, this retrospective cohort study aimed to evaluate the safety and efficacy of thromboprophylaxis after Fontan surgery. Methods We identified 1903 patients who underwent Fontan surgery between June 2011 and September 2019 from the National Database of Health Insurance Claims and Specific Health Checkups of Japan. The patients were followed-up from 2 months to 1 year after Fontan surgery to assess the primary outcomes of thromboembolic and bleeding events. Moreover, we identified the factors associated with primary outcomes in this population using multivariate logistic regression analysis. Results A total of 1903 patients (56.1% male) underwent Fontan surgery at a median age of 3 years (1–22); 1815 patients (95.4%) had an extracardiac conduit. No thromboprophylaxis was prescribed to 65 patients (3.4%), whereas 228 patients (12.0%) received aspirin alone, 346 patients (18.2%) received warfarin alone, and 1264 patients (66.4%) received a combination therapy of aspirin and warfarin. In the first post-operative year, thromboembolic events occurred in 234 patients (12.3%) and bleeding events occurred in 202 patients (10.6%). Older age (odds ratio, 1.08; 95% confidence interval, 1.06–1.11) and aspirin use (odds ratio, 0.34; 95% confidence interval, 0.15–0.78) were independently associated with thromboembolic events. In particular, up to 5 months after surgery, the incidence rate of thromboembolism was significantly lower in patients who received aspirin alone (0.9%) than in those who received other thromboprophylaxis regimens (no thromboprophylaxis, 13.8%; warfarin, 7.5%; combination therapy, 7.4%; p&amp;lt;0.05). No significant difference in incidence of bleeding events was observed among the four thromboprophylaxis regimens. A history of postoperative hemorrhage (odds ratio, 1.49; 95% confidence interval, 1.01–2.21) and the use of a potassium channel blocker (odds ratio, 2.12; 95% confidence interval, 1.10–4.05) was associated with a higher risk of bleeding events. Conclusions In this study, patients who received aspirin alone showed a significantly lower incidence of thromboembolic events. Aspirin may be useful for preventing thromboembolism a year after Fontan surgery. After Fontan surgery, it is important to select a safe and effective thromboprophylaxis regimen and evaluate the risk factors for thromboembolic and bleeding events in a timely manner. Funding Acknowledgement Type of funding sources: None.

Thromboprophylaxis after knee arthroscopy does not decrease the risk of deep vein thrombosis: a network meta-analysis.

The primary aim of this network meta-analysis (NMA) is to compare the incidence of venous thromboembolisms (VTE) and bleeding risk following the use of pharmacological and non-pharmacological thromboprophylaxis for arthroscopic knee surgery (AKS). This study assumed the null hypothesis which was that there will be no difference in the incidence of VTE and bleeding risk when comparing no treatment, pharmacological treatment, and non-pharmacological treatment for preventing VTE events following AKS. A systematic electronic search of CENTRAL, Medline, Embase, and ClinicalTrials.gov was carried out. All English language prospective randomized clinical trials published from date of database inception to November 21, 2021 were eligible for inclusion. All papers addressing arthroscopic knee surgery were eligible for inclusion regardless of timing of surgery, operation, surgical technique, or rehabilitation. Multiple random effects NMAs were conducted to compare all treatments for each outcome. The primary outcome was the incidence of pulmonary embolism (PE) and secondary outcomes consisted of overall deep vein thrombosis (DVT), symptomatic DVT, asymptomatic DVT, and all-cause mortality. Adverse outcomes consisted of major and minor bleeding, as well as adverse events. A total of nine studies with 4526 patients were included for analysis. There were 1054 patients in the no treatment/placebo group (NT/Placebo), 1646 patients in the graduated compression stockings, 810 patients in the extended-duration (> 10days) low molecular weight heparin (Ext-LMWH) group, 650 patients in the short-duration (< 10days) LMWH group (Short-LMWH), and 356 patients in the rivaroxaban group. GCS, Ext-LMWH, Short-LMWH and rivaroxaban all demonstrated low risks of PE, symptomatic DVT, asymptomatic DVT, combined DVT and all-cause mortality. Similarly, all interventions demonstrated a low risk of major bleeding. There is no significant difference in the risk reduction of PEs, symptomatic DVTs, major/minor bleeding, and/or all-cause mortality when using LWMH (including short or extended regimens), rivaroxaban, graduated compression stockings or no treatment following arthroscopic knee surgery. Future primary research on the efficacy of thromboprophylaxis following arthroscopic knee surgery should stratify outcomes based on key patient (i.e., age, sex, comorbidities) and surgical (i.e., major vs. minor surgery) characteristics and should include acetylsalicylic acid as an intervention. I, network meta-analysis of Level I studies.

Optimizing Thromboembolism Prophylaxis for the Contemporary Age of Multiple Myeloma.

Venous thromboembolism (VTE) is a major complication in all patients with cancer. Compared with the general population, patients with multiple myeloma (MM) have a 9-fold increase in VTE risk, likely because of their malignancy, its treatments, and other additional patient-related factors. In MM, thromboembolism events tend to occur within 6 months of treatment initiation, regardless of treatment regimen; however, the use of immunomodulatory agents such as thalidomide or lenalidomide, especially in combination with dexamethasone or multiagent chemotherapy, is known to create a significant risk for VTE. Currently, official recommendations for VTE prophylaxis in MM outlined in various national guidelines or multidisciplinary society panels are based on expert opinion, because data from randomized controlled trials are scarce. Large studies which have mainly focused on the efficacy of thromboprophylaxis in patients with cancer at higher risk for VTE either had a very low representation of patients with MM, or excluded them all together, limiting our ability to draw evidence-based conclusions on how to effectively protect MM population from VTE. In this brief perspective, we highlight some of the greatest challenges that have hampered the field concerning the availability of high-quality clinical trial data for the formulation of best VTE prophylaxis strategies in patients with newly diagnosed MM, as well as the rationale for the latest updates in the NCCN Guidelines on this topic.

A known unknown? Pharmacological prevention of venous thromboembolism in nursing home residents.

A known unknown? Pharmacological prevention of venous thromboembolism in nursing home residents.

Thromboembolic Events During Treatment with Cisplatin-based Chemotherapy in Metastatic Testicular Germ-cell Cancer 2000–2014: A Population-based Cohort Study

BackgroundCisplatin-based chemotherapy (CBCT) in testicular cancer (TC) is associated with elevated venous thromboembolism (VTE) risk, but trials evaluating the safety and efficacy of thromboprophylaxis are lacking. ObjectiveTo evaluate the arterial thromboembolism (ATE) and VTE incidence and risk factors during first-line CBCT for metastatic TC, and the effect of thromboprophylaxis on VTE and bleeding. Design, setting, and participantsIn a population-based study, 506 men administered first-line CBCT during 2000–2014 at three university hospitals in Norway were included. Clinical variables were retrieved from medical records. Outcome measurements and statistical analysisPatients with ATE and VTE diagnosed at initiation of or during CBCT until 3 mo after completion were registered. Age-adjusted logistic regression was performed to identify possible VTE risk factors. Results and limitationsOverall, 69 men (13.6%) were diagnosed with 70 thromboembolic events. Twelve men (2.4%) experienced ATE. Overall, 58 men (11.5%) experienced VTE, of whom 13 (2.6%) were prevalent at CBCT initiation, while 45 (8.9%) were diagnosed with incident VTE. Age-adjusted logistic regression identified retroperitoneal lymph node metastasis >5 cm (odds ratio [OR] 1.99, 95% confidence interval [CI] 1.01–3.91), central venous access (OR 2.84, 95% CI 1.46–5.50), and elevated C-reactive protein (>5 mg/l; OR 2.38, 95% CI 1.12–5.07) as incident VTE risk factors. Thromboprophylaxis (n = 84) did not influence the risk of VTE (VTE incidence with or without prophylaxis 13% vs 8%, p = 0.16). The incidence of bleeding events was significantly higher among those who received thromboprophylaxis than among those without thromboprophylaxis (14.5% vs 1.1%, p < 0.001). ConclusionsWe found a high rate of thromboembolism incidence of 13.6%. Thromboprophylaxis did not decrease the risk of VTE but was associated with an increased risk of bleeding. Patient summaryWe found a high rate of thromboembolism (13.6%) during cisplatin-based chemotherapy for metastatic testicular cancer. Prophylactic treatment against thromboses did not reduce the thrombosis frequency, but it resulted in a high incidence of bleeding events.

Prolonged thromboprophylaxis with low molecular weight heparin for abdominal or pelvic surgery.

This an update of the review first published in 2009.Major abdominal and pelvic surgery carries a high risk of venous thromboembolism (VTE). The efficacy of thromboprophylaxis with low molecular weight heparin (LMWH) administered during the in-hospital period is well-documented, but the optimal duration of prophylaxis after surgery remains controversial. Some studies suggest that patients undergoing major abdominopelvic surgery benefit from prolongation of the prophylaxis up to 28 days after surgery. To evaluate the efficacy and safety of prolonged thromboprophylaxis with LMWH for at least 14 days after abdominal or pelvic surgery compared with thromboprophylaxis administered during the in-hospital period only in preventing late onset VTE. We performed electronic searches on 28 October 2017 in the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, LILACS and registered trials (Clinicaltrials.gov October 28, 2017 and World Health Organization International Clinical Trials Registry Platform (ICTRP) 28 October 2017). Abstract books from major congresses addressing thromboembolism were handsearched from 1976 to 28 October 2017, as were reference lists from relevant studies. We assessed randomized controlled clinical trials (RCTs) comparing prolonged thromboprophylaxis (≥ fourteen days) with any LMWH agent with placebo, or other methods, or both to thromboprophylaxis during the admission period only. The population consisted of persons undergoing abdominal or pelvic surgery for both benign and malignant pathology. The outcome measures included VTE (deep venous thrombosis (DVT) or pulmonary embolism (PE)) as assessed by objective means (venography, ultrasonography, pulmonary ventilation/perfusion scintigraphy, spiral computed tomography (CT) scan or autopsy). We excluded studies exclusively reporting on clinical diagnosis of VTE without objective confirmation. Review authors identified studies and extracted data. Outcomes were VTE (DVT or PE) assessed by objective means. Safety outcomes were defined as bleeding complications and mortality within three months after surgery. Sensitivity analyses were also performed with unpublished studies excluded, and with study participants limited to those undergoing solely open and not laparoscopic surgery. We used a fixed-effect model for analysis. We identified seven RCTs (1728 participants) evaluating prolonged thromboprophylaxis with LMWH compared with control or placebo. The searches resulted in 1632 studies, of which we excluded 1528. One hundred and four abstracts, eligible for inclusion, were assessed of which seven studies met the inclusion criteria.For the primary outcome, the incidence of overall VTE after major abdominal or pelvic surgery was 13.2% in the control group compared to 5.3% in the patients receiving out-of-hospital LMWH (Mantel Haentzel (M-H) odds ratio (OR) 0.38, 95% confidence interval (CI) 0.26 to 0.54; I2 = 28%; moderate-quality evidence).For the secondary outcome of all DVT, seven studies, n = 1728, showed prolonged thromboprophylaxis with LMWH to be associated with a statistically significant reduction in the incidence of all DVT (M-H OR 0.39, 95% CI 0.27 to 0.55; I2 = 28%; moderate-quality evidence).We found a similar reduction when analysis was limited to incidence in proximal DVT (M-H OR 0.22, 95% CI 0.10 to 0.47; I2 = 0%; moderate-quality evidence).The incidence of symptomatic VTE was also reduced from 1.0% in the control group to 0.1% in patients receiving prolonged thromboprophylaxis, which approached significance (M-H OR 0.30, 95% CI 0.08 to 1.11; I2 = 0%; moderate-quality evidence).No difference in the incidence of bleeding between the control and LMWH group was found, 2.8% and 3.4%, respectively (M-H OR 1.10, 95% CI 0.67 to 1.81; I2 = 0%; moderate-quality evidence).No difference in mortality between the control and LMWH group was found, 3.8% and 3.9%, respectively (M-H OR 1.15, 95% CI 0.72 to 1.84; moderate-quality evidence).Estimates of heterogeneity ranged between 0% and 28% depending on the analysis, suggesting low or unimportant heterogeneity. Prolonged thromboprophylaxis with LMWH significantly reduces the risk of VTE compared to thromboprophylaxis during hospital admittance only, without increasing bleeding complications or mortality after major abdominal or pelvic surgery. This finding also holds true for DVT alone, and for both proximal and symptomatic DVT. The quality of the evidence is moderate and provides moderate support for routine use of prolonged thromboprophylaxis. Given the low heterogeneity between studies and the consistent and moderate evidence of a decrease in risk for VTE, our findings suggest that additional studies may help refine the degree of risk reduction but would be unlikely to significantly influence these findings. This updated review provides additional evidence and supports the previous results reported in the 2009 review.

Obstetric and neonatal outcomes in pregnant women treated with high-dose thromboprophylaxis: a retrospective, single-center study

Introduction It is well established that women with very high risk of developing antenatal thrombosis benefit from high-dose thromboprophylaxis, however data on outcomes and the safety and efficacy of thromboprophylaxis are scarce. The aim of the study was to evaluate the safety and effectiveness of the Swedish guidelines for high-dose thromboprophylaxis and the obstetric outcomes in a single-center patient cohort. Patients and methods Forty-seven women treated at the Department of Obstetrics and Gynecology, Karolinska University Hospital, Solna, Sweden, between 2004 and 2017 were included in this retrospective study. Data on treatment, obstetric, and neonatal outcomes and medical history were collected. Data derived from the Swedish Medical Birth Registry on women giving birth in Stockholm County 2004–2016 were used as controls. The protocol of the study was approved by the Regional Ethics Committee in Stockholm, Sweden. Results The initial thromboprophylaxis dose was 5000 IU dalteparin twice daily. No patient developed ablatio placentae or preeclampsia. One patient suffered antenatal muscle vein thrombosis. Six patients (12.7%) suffered postpartum hemorrhage (PPH); however only one patient had severe PPH. Forty-eight children were born. Three children (6%) were diagnosed with intrauterine growth retardation, five (10%) were born small for gestational age and seven (15%) were born premature, the majority of which (except for two premature) to women with thrombophilia. Discussion High-dose thromboprophylaxis was effective and safe. The incidence of preeclampsia and ablatio was lower than in controls; however, neonatal outcomes were worse, especially among mothers with thrombophilia. Due to the diversity of the thrombophilic traits, no thrombophilia-specific conclusion could be drawn. Stricter adherence to the guidelines could further decrease the risk for bleeding, whereas more frequent antenatal controls could possible improve neonatal outcomes.

Prolonged thromboprophylaxis with low molecular weight heparin for abdominal or pelvic surgery.

This an update of the review first published in 2009.Major abdominal and pelvic surgery carries a high risk of venous thromboembolism (VTE). The efficacy of thromboprophylaxis with low molecular weight heparin (LMWH) administered during the in-hospital period is well-documented, but the optimal duration of prophylaxis after surgery remains controversial. Some studies suggest that patients undergoing major abdominopelvic surgery benefit from prolongation of the prophylaxis up to 28 days after surgery. To evaluate the efficacy and safety of prolonged thromboprophylaxis with LMWH for at least 14 days after abdominal or pelvic surgery compared with thromboprophylaxis administered during the in-hospital period only in preventing late onset VTE. We performed electronic searches on 28 October 2017 in the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, LILACS and registered trials (Clinicaltrials.gov October 28, 2017 and World Health Organization International Clinical Trials Registry Platform (ICTRP) 28 October 2017). Abstract books from major congresses addressing thromboembolism were handsearched from 1976 to 28 October 2017, as were reference lists from relevant studies. We assessed randomized controlled clinical trials (RCTs) comparing prolonged thromboprophylaxis (≥ fourteen days) with any LMWH agent with placebo, or other methods, or both to thromboprophylaxis during the admission period only. The population consisted of persons undergoing abdominal or pelvic surgery for both benign and malignant pathology. The outcome measures included VTE (deep venous thrombosis (DVT) or pulmonary embolism (PE)) as assessed by objective means (venography, ultrasonography, pulmonary ventilation/perfusion scintigraphy, spiral computed tomography (CT) scan or autopsy). We excluded studies exclusively reporting on clinical diagnosis of VTE without objective confirmation. Review authors identified studies and extracted data. Outcomes were VTE (DVT or PE) assessed by objective means. Safety outcomes were defined as bleeding complications and mortality within three months after surgery. Sensitivity analyses were also performed with unpublished studies excluded, and with study participants limited to those undergoing solely open and not laparoscopic surgery. We used a fixed-effect model for analysis. We identified seven RCTs (1728 participants) evaluating prolonged thromboprophylaxis with LMWH compared with control or placebo. The searches resulted in 1632 studies, of which we excluded 1528. One hundred and four abstracts, eligible for inclusion, were assessed of which seven studies met the inclusion criteria.For the primary outcome, the incidence of overall VTE after major abdominal or pelvic surgery was 13.2% in the control group compared to 5.3% in the patients receiving out-of-hospital LMWH (Mantel Haentzel (M-H) odds ratio (OR) 0.38, 95% confidence interval (CI) 0.26 to 0.54; I2 = 28%; moderate-quality evidence).For the secondary outcome of all DVT, seven studies, n = 1728, showed prolonged thromboprophylaxis with LMWH to be associated with a statistically significant reduction in the incidence of all DVT (M-H OR 0.39, 95% CI 0.27 to 0.55; I2 = 28%; moderate-quality evidence).We found a similar reduction when analysis was limited to incidence in proximal DVT (M-H OR 0.22, 95% CI 0.10 to 0.47; I2 = 0%; moderate-quality evidence).The incidence of symptomatic VTE was also reduced from 1.0% in the control group to 0.1% in patients receiving prolonged thromboprophylaxis (M-H OR 0.30, 95% CI 0.08 to 1.11; I2 = 0%; moderate-quality evidence).No difference in the incidence of bleeding between the control and LMWH group was found, 2.8% and 3.4%, respectively (M-H OR 1.10, 95% CI 0.67 to 1.81; I2 = 0%; moderate-quality evidence).No difference in mortality between the control and LMWH group was found, 3.8% and 3.9%, respectively (M-H OR 1.15, 95% CI 0.72 to 1.84; moderate-quality evidence).Estimates of heterogeneity ranged between 0% and 28% depending on the analysis, suggesting low or unimportant heterogeneity. Prolonged thromboprophylaxis with LMWH significantly reduces the risk of VTE compared to thromboprophylaxis during hospital admittance only, without increasing bleeding complications or mortality after major abdominal or pelvic surgery. This finding also holds true for DVT alone, and for both proximal and symptomatic DVT. The quality of the evidence is moderate and provides moderate support for routine use of prolonged thromboprophylaxis. Given the low heterogeneity between studies and the consistent and moderate evidence of a decrease in risk for VTE, our findings suggest that additional studies may help refine the degree of risk reduction but would be unlikely to significantly influence these findings. This updated review provides additional evidence and supports the previous results reported in the 2009 review.

Prolonged thromboprophylaxis with low molecular weight heparin for abdominal or pelvic surgery.

This an update of the review first published in 2009.Major abdominal and pelvic surgery carries a high risk of venous thromboembolism (VTE). The efficacy of thromboprophylaxis with low molecular weight heparin (LMWH) administered during the in-hospital period is well-documented, but the optimal duration of prophylaxis after surgery remains controversial. Some studies suggest that patients undergoing major abdominopelvic surgery benefit from prolongation of the prophylaxis up to 28 days after surgery. To evaluate the efficacy and safety of prolonged thromboprophylaxis with LMWH for at least 14 days after abdominal or pelvic surgery compared with thromboprophylaxis administered during the in-hospital period only in preventing late onset VTE. We performed electronic searches on 28 October 2017 in the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, LILACS and registered trials (Clinicaltrials.gov October 28, 2017 and World Health Organization International Clinical Trials Registry Platform (ICTRP) 28 October 2017). Abstract books from major congresses addressing thromboembolism were handsearched from 1976 to 28 October 2017, as were reference lists from relevant studies. We assessed randomized controlled clinical trials (RCTs) comparing prolonged thromboprophylaxis (≥ fourteen days) with any LMWH agent with placebo, or other methods, or both to thromboprophylaxis during the admission period only. The population consisted of persons undergoing abdominal or pelvic surgery for both benign and malignant pathology. The outcome measures included VTE (deep venous thrombosis (DVT) or pulmonary embolism (PE)) as assessed by objective means (venography, ultrasonography, pulmonary ventilation/perfusion scintigraphy, spiral computed tomography (CT) scan or autopsy). We excluded studies exclusively reporting on clinical diagnosis of VTE without objective confirmation. Review authors identified studies and extracted data. Outcomes were VTE (DVT or PE) assessed by objective means. Safety outcomes were defined as bleeding complications within three months after surgery. Sensitivity analyses were also performed with unpublished studies excluded, and with study participants limited to those undergoing solely open and not laparoscopic surgery. We used a fixed-effect model for analysis. We identified seven RCTs (1728 participants) evaluating prolonged thromboprophylaxis with LMWH compared with control or placebo. The searches resulted in 1632 studies, of which we excluded 1528. One hundred and four abstracts, eligible for inclusion, were assessed of which seven studies met the inclusion criteria.For the primary outcome, the incidence of overall VTE after major abdominal or pelvic surgery was 13.2% in the control group compared to 5.3% in the patients receiving out-of-hospital LMWH (Mantel Haentzel (M-H) odds ratio (OR) 0.38, 95% confidence interval (CI) 0.26 to 0.54; I2 = 28%; seven studies, n = 1728; moderate-quality evidence).For the secondary outcome of all DVT, seven studies, n = 1728, showed prolonged thromboprophylaxis with LMWH to be associated with a statistically significant reduction in the incidence of all DVT (M-H OR 0.39, 95% CI 0.27 to 0.55; I2 = 28%; moderate-quality evidence).We found a similar reduction when analysis was limited to incidence in proximal DVT (M-H OR 0.22, 95% CI 0.10 to 0.47; I2 = 0%; moderate-quality evidence).The incidence of symptomatic VTE was also reduced from 1.0% in the control group to 0.1% in patients receiving prolonged thromboprophylaxis (M-H OR 0.30, 95% CI 0.08 to 1.11; I2 = 0%; moderate-quality evidence).No difference in the incidence of bleeding between the control and LMWH group was found, 2.8% and 3.4%, respectively (HM-H OR 1.10, 95% CI 0.67 to 1.81; I2 = 0%; seven studies, n = 2239; moderate-quality evidence).Estimates of heterogeneity ranged between 0% and 28% depending on the analysis, suggesting low or unimportant heterogeneity. Prolonged thromboprophylaxis with LMWH significantly reduces the risk of VTE compared to thromboprophylaxis during hospital admittance only, without increasing bleeding complications after major abdominal or pelvic surgery. This finding also holds true for DVT alone, and for both proximal and symptomatic DVT. The quality of the evidence is moderate and provides moderate support for routine use of prolonged thromboprophylaxis. Given the low heterogeneity between studies and the consistent and moderate evidence of a decrease in risk for VTE, our findings suggest that additional studies may help refine the degree of risk reduction but would be unlikely to significantly influence these findings. This updated review provides additional evidence and supports the previous results reported in the 2009 review.

Pediatric issues in thrombosis and hemostasis: The how and why of venous thromboembolism risk stratification in hospitalized children

Multiple observational studies have identified risk factors for venous thromboembolism (VTE) in hospitalized children, but very few interventional studies have assessed the safety and efficacy of thromboprophylaxis in this population. In recent years, however, evidence in pediatric VTE risk stratification has grown considerably. This has led to the conception of a pediatric subpopulation-specific risk-based paradigm for mechanical and pharmacological thromboprophylaxis in hospitalized children. More research is required to validate and further refine pediatric subpopulation-specific risk models and to subsequently investigate risk-stratified thromboprophylaxis strategies for hospitalized children.

Efficacy of thromboprophylaxis during pregnancy in women with a previous cerebral vein thrombosis.

Efficacy of thromboprophylaxis during pregnancy in women with a previous cerebral vein thrombosis.

Correlation of the Caprini Score and Venous Thromboembolism Incidence Following Primary Total Joint Arthroplasty—Results of a Single-Institution Protocol

BackgroundVenous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis, is a serious complication after total joint arthroplasty (TJA). Risk assessment models are increasingly used to provide patient-specific risk stratification. A recently implemented protocol mandates calculation of a Caprini Score for all surgical patients at our institution. We investigated the accuracy of the Caprini Score in predicting VTE events following TJA. MethodsA retrospective review of patients undergoing primary total hip (THA) and total knee arthroplasty (TKA) over a 1-year time period was performed. The 90-day postoperative incidence of emergency department evaluations, hospital readmissions, medical complications, need for revision surgery, and symptomatic VTE was recorded. “Preoperative” Caprini Scores routinely recorded per protocol and calculated during review (“Calculated”) were compared and assessed for relationship with VTE events. A “VTEstimator” Score was calculated for each patient. ResultsThree hundred seventy-six arthroplasties (151 TKA and 225 THA) meeting inclusion criteria were identified. Ten patients (2.5%) had symptomatic VTE postoperatively, with 3 pulmonary embolism (0.8%) and 7 deep vein thrombosis (1.8%). Eight VTE (5.3%) occurred following TKA and 2 (0.9%) occurred following THA. For each surgical characteristic evaluated, no significant difference was observed between mean Preoperative or Calculated Caprini Scores for patients with and without VTE (P > .05). Additionally, the distribution of VTEstimator Scores for patients with and without VTE was not significantly different (P = .93). ConclusionThe Caprini risk assessment model does not appear to provide clinically useful risk stratification for TJA patients. Alternative risk stratification protocols may provide assistance in balancing safety and efficacy of thromboprophylaxis.

TropicALL study: Thromboprophylaxis in Children treated for Acute Lymphoblastic Leukemia with Low-molecular-weight heparin: a multicenter randomized controlled trial

BackgroundVenous thromboembolism (VTE) is a common and severe complication during treatment of acute lymphoblastic leukemia (ALL). An important cause is the intensive use of asparaginase. Prospective cohort studies in which prophylactic low-molecular-weight heparin (LMWH) was used to prevent VTE showed lower VTE risk than in historic control cohorts, with a negligible bleeding risk. However, the efficacy of thromboprophylaxis with LMWH during ALL treatment has never been investigated in a randomized design. Here, we present the protocol of a randomized controlled trial in which the efficacy and safety of thromboprophylaxis with high prophylactic dose LMWH versus no thromboprophylaxis will be assessed in children treated for primary ALL with asparaginase.Methods/DesignThromboprophylaxis in Children treated for Acute Lymphoblastic Leukemia with Low-molecular-weight heparin (TropicALL) is a multicenter, randomized controlled open-label trial conducted in the Netherlands. Patients between 1 and 19 years of age with primary ALL, who are treated within the Dutch Childhood Oncology Group (DCOG) ALL-11 or 12 study will be randomized to thromboprophylaxis with LMWH once daily, (dose of 85 IU/kg (intervention arm A)), or to no thromboprophylaxis (arm B, standard of care) during asparaginase courses of ALL treatment. Primary efficacy endpoint is symptomatic objectified VTE during ALL treatment; secondary efficacy endpoints are overall survival and the composite of symptomatic and asymptomatic objectified VTE. Primary safety endpoints are major bleeding, clinically relevant non-major bleeding and minor bleeding. A total of 324 patients will be included to obtain a relative risk reduction of 75% with a power of 80%, using a two-sided test with significance level α = 0.05.DiscussionThis trial will be the first to assess efficacy and safety of thromboprophylaxis with LMWH during asparaginase treatment for ALL in children in a randomized design.Trail registrationNederlands Trial Register NTR4707. Registered 30 July 2014.

Lessons From the EThIGII Trial: Proper Putative Benefit Assessment of Low-Molecular-Weight Heparin Treatment in M2/ANXA5 Haplotype Carriers.

This study presents sample size considerations derived from the Efficacy of Thromboprophylaxis as an Intervention during Gravidity (EThIGII) trial (ClinicalTrials.gov: NCT00400387) to address the question of low-molecular-weight heparin (LMWH) treatment in women with recurrent pregnancy loss (RPL) depending on the M2/ANXA5 haplotype. To evaluate the possible influence of such treatment on miscarriage rates of trial participants, a post hoc analysis of ANXA5 promoter genotypes in the light of M2/ANXA5 (RPRGL3) distribution was performed using logistic models. DNA for genotyping was available from 129 LMWH and 95 control patients, 44 (19.6%) of whom were M2/ANXA5 carriers. Miscarriages occurred in 1 (4.0%) of 25 M2/ANXA5 carriers from the LMWH group compared to 4 (21.1%) of 19 in the control group, resulting in an odds ratio (95% confidence interval) for miscarriage of 0.16 (0.016-1.5) for women treated with LMWH. In noncarriers, miscarriage rates were 6 (5.8%) of 104 versus 7 (9.2%) of 76 for the LMWH and the control groups, respectively, corresponding to an odds ratio for miscarriage of 0.60 (0.19-1.9). The apparent beneficial effects of miscarriage rate reduction in M2/ANXA5 carriers with RPL concur with biological considerations about improvement in reduced ANXA5 function through LMWH treatment in an adequate murine model. The data obtained were instrumental to design proper assessment of the existence and magnitude of this effect.

Safety and efficacy of thromboprophylaxis using enoxaparin sodium after cesarean section: A multi-center study in Japan

ObjectivePulmonary embolism (PE) is the leading cause of maternal death in developed countries, and the prevention of venous thromboembolism (VTE) is a pivotal part of current obstetric care. This study evaluated the safety and efficacy of enoxaparin sodium for thromboprophylaxis after cesarean section (C/S), and analyzed the risk factors associated with VTE. Materials and methodsOne hundred and forty-three women deemed to be at high risk of postoperative deep vein thrombosis (DVT) were enrolled between January 2011 and May 2012 in seven institutions in Japan. Subcutaneous administration of enoxaparin 4000 units/d was initiated 24–36 hours after C/S for 5 days. Adverse events, based on the Common Terminology Criteria for Adverse Events, Version 4, were recorded. The diagnoses of PE and DVT were made on clinical signs. Venous ultrasonography in the lower extremities was performed in 102 patients. The association between VTE and various risk factors was evaluated using univariate analysis. ResultsThere were 10 (7.0%) Grade 1 adverse events: elevated aspartate aminotransferase or alanine aminotransferase levels in eight patients, chest pain in one patient, and subcutaneous hematoma in one patient. No patients showed clinical signs of PE and/or DVT. Among 102 patients who underwent venous ultrasonography, thrombus was detected in unilateral soleus veins in four (3.9%) patients. A body mass index (BMI) ≥ 25 kg/m2 before pregnancy was associated with asymptomatic DVT. ConclusionThe current study demonstrates the safety and efficacy of enoxaparin for thromboprophylaxis after C/S. Further studies are required to determine the best method of preventing asymptomatic DVT.

APOLLO I: Anticoagulation control in atrial fibrillation

Introduction and AimsAnticoagulation control as assessed by time in therapeutic range (TTR) correlates positively with the safety and efficacy of thromboprophylaxis in atrial fibrillation. We set out to assess TTR in our unit and to investigate determinants of better control. MethodsThis was a case series study of atrial fibrillation patients anticoagulated with warfarin or acenocoumarol at the Family Health Unit of Fânzeres. Sociodemographic and clinical data were collected and TTR was calculated by the Rosendaal method, based on international normalized ratio tests performed in external laboratories in the preceding six months. SPSS® 21.0 was used for the statistical analysis, with descriptive statistics, Spearman's correlation, and the Mann-Whitney U and Kruskal-Wallis tests. ResultsOf the 106 eligible patients, 70% participated in the study. Median TTR was 65.3% (P25=48.3%, P75=86.8%). We found a positive association between this variable and duration of atrial fibrillation (rho=0.477, p<0.001, r2=0.116) and with duration of anticoagulation (rho=0.5, p<0.001, r2=0.087). No association was found with age, gender, educational level or existence of a caregiver (p>0.05). ConclusionsMedian TTR in our unit is similar to that in southern European countries and close to the good control threshold (70%) proposed by the European Society of Cardiology. The duration of atrial fibrillation and of anticoagulation explains only a small part of the measure's variability. Other determinants of anticoagulation control must be investigated in future studies and comparative studies should be carried out in family health units monitoring anticoagulation on the premises.

APOLO I: controlo da hipocoagulação na fibrilhação auricular

Introduction and AimsAnticoagulation control as assessed by time in therapeutic range (TTR) correlates positively with the safety and efficacy of thromboprophylaxis in atrial fibrillation. We set out to assess TTR in our unit and to investigate determinants of better control. MethodsThis was a case series study of atrial fibrillation patients anticoagulated with warfarin or acenocoumarol at the Family Health Unit of Fânzeres. Sociodemographic and clinical data were collected and TTR was calculated by the Rosendaal method, based on international normalized ratio tests performed in external laboratories in the preceding six months. SPSS® 21.0 was used for the statistical analysis, with descriptive statistics, Spearman's correlation, and the Mann‐Whitney U and Kruskal‐Wallis tests. ResultsOf the 106 eligible patients, 70% participated in the study. Median TTR was 65.3% (P25=48.3%, P75=86.8%). We found a positive association between this variable and duration of atrial fibrillation (ρ=0.477, p<0.001, r2=0.116) and with duration of anticoagulation (ρ=0.5, p<0.001, r2=0.087). No association was found with age, gender, educational level or existence of a caregiver (p>0.05). ConclusionsMedian TTR in our unit is similar to that in southern European countries and close to the good control threshold (70%) proposed by the European Society of Cardiology. The duration of atrial fibrillation and of anticoagulation explains only a small part of the measure's variability. Other determinants of anticoagulation control must be investigated in future studies and comparative studies should be carried out in family health units monitoring anticoagulation on the premises.

Risk stratification and prevention of venous thromboembolic disease in cancerology

Patients with cancer are at high risk of venous thromboembolism (VTE), which leads to significantly increased morbidity and mortality. The rates of VTE vary between 0.5% and 20% per year and depend mainly on cancer-specific and treatment-related risk factors. Also individual risk factors related to patientś characteristics contribute to occurrence of cancer-associated VTE. Risk factors and biomarkers may help identify patients at high risk of developing VTE. In several clinical studies, risk factors for the occurrence of VTE events in patients with cancer have been investigated. The type and stage of cancer have been found to be amongst the most important risk factor for VTE occurrence. Also the histological grade of a tumor has been reported to be associated with the occurrence of VTE. In other investigations, venous diseases including a history of previous VTE, a history of superficial thrombophlebitis and the presence of varicose veins, have been associated with the risk of VTE. Some studies have recently focused on the identification of biomarkers or laboratory parameters predictive of future VTE occurrence. Parameters of blood count analysis (such as elevated leukocyte and platelet count and decreased hemoglobin) have turned out to be useful in risk stratification for VTE. In a prospective and observational cohort study, the Vienna Cancer and Thrombosis Study (CATS), associations between elevated levels and risk of future VTE have been found for D-dimer, prothrombin fragment 1 + 2, and soluble P-selectin and also for clotting factor VIII and the thrombin generation potential. The role of circulating microparticles for predicting risk of VTE in patients with cancer is unclear and has to be further investigated. Risk assessment models for prediction of VTE were developed including clinical and laboratory markers. First, Khorana and colleagues published a risk assessment score that incorporates readily available parameters: primary site of cancer, pre-chemotherapy platelet count of 350 × 109/L or more, haemoglobin level less than 10 g/dL and/or use of erythropoiesis stimulating agents, pre-chemotherapy leukocyte count of more than 11 × 109/L, and a body mass index of 35 kg/m2 or more. This score was validated in other studies. In CATS the score was expanded by adding two biomarkers (D-dimer and soluble P-selectin), and the prediction of VTE was considerably improved. In the high risk categories, patients with a VTE rate up to a 20% or higher within 6 months can be identified. In recent randomized controlled trials including cancer patients with different malignancies – without applying specific VTE risk assessment – it was shown that thromboprophylaxis is safe and effective. However, the overall VTE rates were low in these studies. To date, no data is available from interventional studies applying thromboprophylaxis in cancer patients categorized into high-risk groups on the basis of risk assessment scores. In conclusion, risk stratification for VTE is feasible in cancer patients. Further improvement in risk stratification would help better identify patients for VTE prevention using anticoagulant agents. However, interventional studies are needed to investigate the safety and efficacy of thromboprophylaxis in a high-risk cancer population.

A Multinational Study of Thromboprophylaxis Practice in Critically Ill Children*

Although critically ill children are at increased risk for developing deep venous thrombosis, there are few pediatric studies establishing the prevalence of thrombosis or the efficacy of thromboprophylaxis. We tested the hypothesis that thromboprophylaxis is infrequently used in critically ill children even for those in whom it is indicated. Prospective multinational cross-sectional study over four study dates in 2012. Fifty-nine PICUs in Australia, Canada, New Zealand, Portugal, Singapore, Spain, and the United States. All patients less than 18 years old in the PICU during the study dates and times were included in the study, unless the patients were 1) boarding in the unit waiting for a bed outside the PICU or 2) receiving therapeutic anticoagulation. None. Of 2,484 children in the study, 2,159 (86.9%) had greater than or equal to 1 risk factor for thrombosis. Only 308 children (12.4%) were receiving pharmacologic thromboprophylaxis (e.g., aspirin, low-molecular-weight heparin, or unfractionated heparin). Of 430 children indicated to receive pharmacologic thromboprophylaxis based on consensus recommendations, only 149 (34.7%) were receiving it. Mechanical thromboprophylaxis was used in 156 of 655 children (23.8%) 8 years old or older, the youngest age for that device. Using nonlinear mixed effects model, presence of cyanotic congenital heart disease (odds ratio, 7.35; p < 0.001) and spinal cord injury (odds ratio, 8.85; p = 0.008) strongly predicted the use of pharmacologic and mechanical thromboprophylaxis, respectively. Thromboprophylaxis is infrequently used in critically ill children. This is true even for children at high risk of thrombosis where consensus guidelines recommend pharmacologic thromboprophylaxis.