Primary Venous Thromboembolism Prophylaxis Research Articles

Primary prevention of venous thromboembolism with low molecular weight heparins in surgical patients – 2024: Council of Experts resolution

On March 15, 2024, in Moscow, the Russian Phlebological Association and the National Association of Specialists in Thrombosis, Clinical Hemostasiology and Hemorheology organized a meeting of the Council of Experts during the Russian Forum on Thrombosis and Hemostasis on the acute issues of venous thromboembolism (VTE) primary prevention using low molecular weight heparins (LMWH) in surgical patients with different body weight. The participants reviewed the relevance and prevalence of this problem in surgical practice, discussed risk factors and the frequency of VTE development, including bleeding in the postoperative period, and the Caprini risk score for complications. The discussion also focused on standard and personalized LMWH doses for primary prophylaxis of VTE in the perioperative period in surgical patients, depending on body weight, and the role of laboratory tests, including assessment of LMWH anti-Xa activity for monitoring the efficacy and safety of VTE primary prevention in clinical practice.

Factor XI inhibitors: a new option for the prevention and treatment of cancer-associated thrombosis

Venous thromboembolism (VTE) is a relatively common complication in cancer patients with potentially dire consequences. Anticoagulants are the mainstay of treatment of cancer-associated VTE. The anticoagulants most often used are low-molecular-weight heparin (LMWH) and direct oral factor (F) Xa inhibitors, which include apixaban, edoxaban, and rivaroxaban. Most guidelines recommend primary VTE prophylaxis with LMWH, apixaban, or rivaroxaban after abdominal or pelvic cancer surgery, or in high-risk ambulatory cancer patients. Both oral FXa inhibitors and LMWH have limitations. LMWH requires daily subcutaneous injections, and because of its renal clearance, its use may be problematic in patients with severe kidney disease. The risk of bleeding with oral FXa inhibitors may be higher than with LMWH in patients with intraluminal gastrointestinal or genitourinary cancers. Other problems with oral FXa inhibitors include potential drug-drug interactions and dosing issues in patients with thrombocytopenia or severe kidney or liver disease. Therefore, there remains a need for convenient and safer anticoagulants for VTE treatment in cancer patients. FXI has emerged as a potentially safer target for anticoagulants than FXa because FXI is essential for thrombosis, but mostly dispensable for hemostasis. This review summarizes the currently available therapeutic options for cancer-associated VTE, highlights knowledge gaps, and discusses the potential of FXI inhibitors to address key unmet clinical needs in this vulnerable patient population.

Prevention of Venous Thromboembolism in Medical Patients with Thrombocytopenia or with Platelet Dysfunction: The Last 10 Years.

Current guideline recommendations for primary prophylaxis of venous thromboembolism (VTE) are based on randomized clinical trials that usually exclude subjects at a potentially high risk of bleeding complications. For this reason, no specific guideline is available for thromboprophylaxis in hospitalized patients with thrombocytopenia and/or platelet dysfunction. However, except in patients with absolute contraindications to anticoagulant drugs, antithrombotic prophylaxis should always be considered, for example, in hospitalized cancer patients with thrombocytopenia, especially in those with multiple VTE risk factors. Low platelet number, platelet dysfunction, and clotting abnormalities are also very common in patients with liver cirrhosis, but these patients have a high incidence of portal venous thrombosis, implying that cirrhotic coagulopathy does not fully protect against thrombosis. These patients may benefit from antithrombotic prophylaxis during hospitalization. Patients hospitalized for COVID-19 need prophylaxis, but frequently experience thrombocytopenia or coagulopathy. In patients with antiphospholipid antibodies, a high thrombotic risk is usually present, even in the presence of thrombocytopenia. VTE prophylaxis in high-risk conditions is thus suggested in these patients. At variance with severe thrombocytopenia (< 50,000/mm3), mild/moderate thrombocytopenia (≥ 50,000/mm3) should not interfere with VTE prevention decisions. In patients with severe thrombocytopenia, pharmacological prophylaxis should be considered on an individual basis. Aspirin is not as effective as heparins in lowering the risk of VTE. Studies in patients with ischemic stroke demonstrated that thromboprophylaxis with heparins is safe in these patients also during antiplatelet treatment. The use of direct oral anticoagulants in the prophylaxis of VTE in internal medicine patients has been recently evaluated, but no specific recommendation exists for patients with thrombocytopenia. The need for VTE prophylaxis in patients on chronic treatment with antiplatelet agents should be evaluated after assessing the individual risk of bleeding complications. Finally, the selection of patients who require post-discharge pharmacological prophylaxis remains debated. New molecules currently under development (such as the inhibitors of factor XI) may contribute to improve the risk/benefit ratio of VTE primary prevention in this setting of patients.

The Saudi Consensus for the Management of Cancer-Associated Thromboembolism: A Modified Delphi-Based Study.

Background Cancer is a well-known risk factor of preventable thromboembolic disease. This study aims to provide guidance on the prevention and management of cancer-associated thrombosis (CT) that tailors prophylactic and therapeutic options for medical and surgical oncology patients presenting to health care settings in Saudi Arabia. Methods The present consensus was developed in concordance with the modified Delphi-based approach, which incorporates a face-to-face meeting between two voting rounds to gain experts' feedback on the proposed statements. All experts were either oncologists, hematologists, or hemato-oncologist with an active clinical and research profile in hemato-oncology. Results The experts highlighted that the comparatively high incidence of inherited thrombophilia among the Saudi population may account for a higher CT burden in the Kingdom than in other parts of the world. However, due to the lack of literature that assesses CT in Saudi Arabia, primary venous thromboembolism prophylaxis should be tailored according to a valid risk assessment of cancer patients and should be implemented in routine practice. For hospitalized medical oncology patients, the experts agreed that prophylaxis with low-molecular-weight heparin (LMWH) should be offered, regardless of the presence of acute illness. For ambulatory medical oncology patients, LMWH or direct oral anticoagulants (DOACs) prophylaxis should be offered for high-risk patients. Concerning surgical patients, they agreed that all oncology patients undergoing surgery should be offered thromboprophylaxis. In terms of secondary prophylaxis, the experts recommended continuing a prophylactic dose of anticoagulant (LMWH or DOAC), for an appropriate period depending on the cancer type and stage. Finally, they also provided a set of statements on management of CT in Saudi Arabia. Conclusion The present modified Delphi-based study combined the best available evidence and clinical experience with the current health care policies and settings in Saudi Arabia to build a consensus statement on the epidemiology, prevention, and management of CT.

Utilization of the Khorana score (KS) by hematology/oncology clinicians in the ambulatory setting.

31 Background: Patients with cancer are at an increased risk for venous thromboembolism (VTE). Though cancer-associated thrombosis is a major cause of mortality in patients, only second to disease progression, the optimal use of primary prophylaxis remains a clinical challenge. The KS, developed in 2008, is a validated tool to identify patients at low, intermediate, and high-risk for VTE. At the UConn Health Neag Comprehensive Cancer Center, we created a survey and administered it amongst our clinicians to assess KS knowledge and documentation practices. Methods: We conducted a 3-part quality improvement study that included a pre- and post-intervention retrospective chart review of eligible patients with cancer to examine rates of KS documentation. Eligibility included patients with cancer initiating a new chemotherapy. We excluded patients on anticoagulation, multiple myeloma, brain/central nervous system tumors, and patients in the Department of Corrections. The interventions included: 1) 9-question survey to assess clinician knowledge and utilization of KS; 2) KS education presented at a clinician meeting; 3) an electronic medical record (EMR) tool implemented to standardize KS documentation; and 4) reminder KS tip sheet created for clinicians. Descriptive statistics were used in data analysis. Results: Of 50 documented encounters, 40 met study criteria, with none having KS documentation. In a pre-tool implementation survey sent to 24 clinicians, of whom 20 had participated, 70% were physicians, 30% were advanced practice registered nurses (APRN), and 60% reported being in practice for 5 years or less. Most (90%) reported not using KS; only 10% reported being unfamiliar with the KS while 65% reported only sometimes talking to patients about VTE risk. Of the 10% of clinicians that did document KS, it was reported that they “document in the narrative of [the] note when appropriate.” The highest barriers to documentation were reported as “time constraints with extra documentation” and “not enough guidance.” Post-EMR tool implementation, a total of 58 of 99 (58.5%) encounters met study criteria and 1 KS was documented (1.7%). Conclusions: KS is underutilized in ambulatory clinical settings partly due to a lack of education and awareness despite availability of national guidelines which reflect the importance of primary VTE prophylaxis evaluation in all patients with cancer. This study demonstrates a continued deficiency in our clinical practice. We aim to further identify barriers and methods for improvement of KS documentation and VTE risk assessments. Additionally, a referral process is planned for all at-risk patients to enhance patient care, decrease hospital visits related to VTE, and attempt to reduce health-care costs related to VTE care.

Standard- versus extended-duration anticoagulation for primary venous thromboembolism prophylaxis in acutely ill medical patients

Standard- versus extended-duration anticoagulation for primary venous thromboembolism prophylaxis in acutely ill medical patients

Burden of venous thromboembolism in patients with pancreatic cancer.

Pancreatic cancer (PC) is a devastating malignancy with fewer than 10% of patients being alive at 5 years after diagnosis. Venous thromboembolism (VTE) occurs in approximatively 20% of patients with PC, resulting in increased morbidity, mortality and significant health care costs. The management of VTE is particularly challenging in these frail patients. Adequate selection of the most appropriate anticoagulant for each individual patient according to the current international guidelines is warranted for overcoming treatment challenges. The International Initiative on Thrombosis and Cancer multi-language web-based mobile application (downloadable for free at www.itaccme.com) has been developed to help clinicians in decision making in the most complex situations. In this narrative review, we will discuss the contemporary epidemiology and burden of VTE in PC patients, the performances and limitations of current risk assessment models to predict the risk of VTE, as well as evidence from recent clinical trials for the primary prophylaxis and treatment of cancer-associated VTE that support up-dated clinical practice guidelines.

Prophylactic anticoagulation in pancreatic adenocarcinoma patients: A single tertiary care center retrospective quality improvement project.

e16214 Background: Pancreatic ductal adenocarcinoma (PDAC) cancer portends a poor prognosis with a high case-fatality rate. Venous thromboembolism (VTE) is a common complication in PDAC, due expression of tissue factor on neoplastic cells. Per most recent guidelines, anticoagulation for primary prophylaxis (PPx) of VTE is to be considered based on the Khorana score. The purpose of this study is to identify patients with PDAC and compare the outcomes of those receiving anticoagulation for primary prophylaxis versus those who did not. Methods: We performed a retrospective review of all patients diagnosed with PDAC from 2017-2019 at Allegheny General Hospital. Data analysis was completed using IBM SPSS v23. Summary statistics were presented using percentages for categorical variables and medians with interquartile ranges for continuous variables. Univariable and multivariable logistic regression models were used to study the predictors of developing VTE, expressed as odds ratio (OR). Means and percentages were compared using t-test and Chi-square test, respectively. Results: Out of 171 patients, 121 received treatment at our institution and were included in the analysis. Median age was 69 years, 54 (45%) were male. The majority were white (88%). Only 92 patients had complete data regarding VTE PPx and events. 26 patients (28.2%) developed at least one VTE event. Out of 92 patients, 12 (13%) were on one form of VTE PPx and 1 had a contraindication to VTE PPx. One patient without VTE PPx died secondary to VTE. Of the patients on VTE PPx, only 3 (30%) experienced bleeding events. Seven patients were on VTE PPx prior to diagnosis of malignancy. 58 patients (63%) had a Khorana score of 2; 21 (23%) patients had a Khorana score of 3; 9 (10%) patients had a Khorana score of 4; and 4 (4%) patients had a Khorana score of 5. On univariable analysis, St. IV disease (OR 3.34, CI.22-8.40, P &lt; 0.01), planned surgery (OR 0.26, CI 0.12-0.55, p &lt; 0.01) and unresectable disease (OR 3.19, 95% CI 1.17-8.70, p 0.02) were predictors of developing VTE. On multivariate analysis, total pancreatectomy had a predictive association in the development of VTE (OR 5.01, 95% CI 1.65-23.60, p &lt; 0.01). There was no difference in average time to progression (months) between patients who had VTE vs those who did not (12.5 vs 11.4, p 0.60). Conclusions: Our analysis indicate that we may be underutilizing Khorana score to prescribe VTE PPx in patients with PDAC. Additionally, patients undergoing total pancreatectomy demonstrated predictive association with the development of VTE. With these findings, we believe education and increased awareness of the importance of the Khorana score may decrease the morbidity and mortality associated with VTE in patients with PDAC. The use of electronic medical records to prompt physicians to calculate the Khorana score will also likely be a helpful tool.

Aspirin as venous thromboembolism prophylaxis in total joint arthroplasty: a narrative review of the current evidence

The utilization of aspirin (acetylsalicylic acid [ASA]) as primary prophylaxis for venous thromboembolism (VTE) after total hip arthroplasty (THA) and total knee arthroplasty (TKA) in the United States has increased in concordance with the number of arthroplasty procedures being completed. The available literature regarding dosage, duration, efficacy, and safety varies considerably. This review assessed the recent published literature for both the efficacy and safety of aspirin as VTE prophylaxis. Overall, the rates of symptomatic VTE found in the literature ranged from 0.1% to 4.1%, of deep vein thrombosis (DVT) 0.1% to 3.0%, and of pulmonary embolism (PE) 0.1% to 1.5%. As for secondary outcome measures, the rate of major bleeding from either a gastrointestinal source or at the surgical site ranged from 0% to 3.2%, and the rate of transfusion between 7.0% to 20.0%. Among the studies that reported the infection rates, it ranged from 0.1% to 6.1%. The 90-day mortality rate was 0% to 0.23%. The available data and evidence remain inconclusive with regard to ASA dosage or the duration for patients after TKAs and THAs. However, ASA appears to be an effective option for VTE prevention when utilized as part of a multimodal approach to prophylaxis that includes early mobilization and mechanical compression devices.

Primary prophylaxis for venous thromboembolism in ambulatory cancer patients receiving chemotherapy.

Venous thromboembolism (VTE) often complicates the clinical course of cancer. The risk is further increased by chemotherapy, but the trade-off between safety and efficacy of primary thromboprophylaxis in cancer patients treated with chemotherapy is uncertain. This is the third update of a review first published in February 2012. To assess the efficacy and safety of primary thromboprophylaxis for VTE in ambulatory cancer patients receiving chemotherapy compared with placebo or no thromboprophylaxis, or an active control intervention. For this update, the Cochrane Vascular Information Specialist searched the Cochrane Vascular, CENTRAL, MEDLINE, Embase and CINAHL databases and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 3 August 2020. We also searched the reference lists of identified studies and contacted content experts and trialists for relevant references. Randomised controlled trials comparing any oral or parenteral anticoagulant or mechanical intervention to no thromboprophylaxis or placebo, or comparing two different anticoagulants. We extracted data on risk of bias, participant characteristics, interventions, and outcomes including symptomatic VTE and major bleeding as the primary effectiveness and safety outcomes, respectively. We applied GRADE to assess the certainty of evidence. We identified six additional randomised controlled trials (3326 participants) for this update, bringing the included study total to 32 (15,678 participants), all evaluating pharmacological interventions and performed mainly in people with locally advanced or metastatic cancer. The certainty of the evidence ranged from high to very low across the different outcomes and comparisons. The main limiting factors were imprecision and risk of bias. Thromboprophylaxis with direct oral anticoagulants (direct factor Xa inhibitors apixaban and rivaroxaban) may decrease the incidence of symptomatic VTE (risk ratio (RR) 0.43, 95% confidence interval (CI) 0.18 to 1.06; 3 studies, 1526 participants; low-certainty evidence); and probably increases the risk of major bleeding compared with placebo (RR 1.74, 95% CI 0.82 to 3.68; 3 studies, 1494 participants; moderate-certainty evidence). When compared with no thromboprophylaxis, low-molecular-weight heparin (LMWH) reduced the incidence of symptomatic VTE (RR 0.62, 95% CI 0.46 to 0.83; 11 studies, 3931 participants; high-certainty evidence); and probably increased the risk of major bleeding events (RR 1.63, 95% CI 1.12 to 2.35; 15 studies, 7282 participants; moderate-certainty evidence). In participants with multiple myeloma, LMWH resulted in lower symptomatic VTE compared with the vitamin K antagonist warfarin (RR 0.33, 95% CI 0.14 to 0.83; 1 study, 439 participants; high-certainty evidence), while LMWH probably lowers symptomatic VTE more than aspirin (RR 0.51, 95% CI 0.22 to 1.17; 2 studies, 781 participants; moderate-certainty evidence). Major bleeding was observed in none of the participants with multiple myeloma treated with LMWH or warfarin and in less than 1% of those treated with aspirin. Only one study evaluated unfractionated heparin against no thromboprophylaxis, but did not report on VTE or major bleeding. When compared with placebo or no thromboprophylaxis, warfarin may importantly reduce symptomatic VTE (RR 0.15, 95% CI 0.02 to 1.20; 1 study, 311 participants; low-certainty evidence) and may result in a large increase in major bleeding (RR 3.82, 95% CI 0.97 to 15.04; 4 studies, 994 participants; low-certainty evidence). One study evaluated antithrombin versus no antithrombin in children. This study did not report on symptomatic VTE but did report any VTE (symptomatic and incidental VTE). The effect of antithrombin on any VTE and major bleeding is uncertain (any VTE: RR 0.84, 95% CI 0.41 to 1.73; major bleeding: RR 0.78, 95% CI 0.03 to 18.57; 1 study, 85 participants; very low-certainty evidence). In ambulatory cancer patients, primary thromboprophylaxis with direct factor Xa inhibitors may reduce the incidence of symptomatic VTE (low-certainty evidence) and probably increases the risk of major bleeding (moderate-certainty evidence) when compared with placebo. LMWH decreases the incidence of symptomatic VTE (high-certainty evidence), but increases the risk of major bleeding (moderate-certainty evidence) when compared with placebo or no thromboprophylaxis. Evidence for the use of thromboprophylaxis with anticoagulants other than direct factor Xa inhibitors and LMWH is limited. More studies are warranted to evaluate the efficacy and safety of primary prophylaxis in specific types of chemotherapeutic agents and types of cancer, such as gastrointestinal or genitourinary cancer.

Primary prophylaxis for venous thromboembolism in ambulatory cancer patients: a systematic review and network meta-analysis.

Ambulatory cancer patients carry a high risk of venous thromboembolism (VTE). However, the optimal prophylaxis strategy remains controversial. This meta-analysis compared the effectiveness and safety of apixaban, rivaroxaban, low molecular weight heparin (LMWH), semuloparin, aspirin, and warfarin for the prevention of VTE in ambulatory cancer patients. A systematic review and network meta-analysis was performed. PubMed, the Cochrane Central Register of Controlled Trails (CENTRAL) and EMBASE electronic databases were searched from inception to 26 April 2019. In the meta-analysis, 19 randomized controlled trials (RCTs) in ambulatory cancer patients administrated venous thromboprophylaxis agents were included. The primary outcome was the risk of VTE. Safety outcomes included the occurrence of major-bleeding. Two investigators identified the studies and performed data extraction. A network meta-analysis was performed and agents were ranked using cumulative ranking (SUCRA) probabilities. We identified 19 studies, including 11,430 patients comparing 10 interventions. Compared to placebo controls, apixaban (5 mg) showed the highest efficacy for the prevention of VTE [odds ratio (OR) 0.36, 95% confidence interval (CI): 0.18-0.71, SUCRA=69.5] and was more effective than LMWH (OR 0.5, 0.39-0.63; SUCRA=52.1) or warfarin (OR 0.75, 95% CI: 0.35-1.59; SUCRA=25.6). Moreover, the safety of apixaban (5 mg) (OR 1.41, 95% CI: 0.33-5.93; SUCRA=58.5) was higher than LMWH (OR 1.96, 95% CI: 0.99-3.86; SUCRA=44.1) or warfarin (OR 3.06, 95% CI: 1.03-9.08; SUCRA=29.1). There were no significant differences between placebo and experimental groups in terms of patient deaths. Anticoagulation therapies in ambulatory cancer patients can significantly reduce the risk of VTE. However, this protective effect was associated with a significantly increased risk of major bleeding. Apixaban at the appropriate dose can decrease the risk of VTE without increasing the bleeding risk. These findings require validation in larger study cohorts.

Primary prophylaxis for venous thromboembolism in people undergoing major amputation of the lower extremity.

People undergoing major amputation of the lower limb are at increased risk of venous thromboembolism (VTE). Risk factors for VTE in amputees include advanced age, sedentary lifestyle, longstanding arterial disease and an identifiable hypercoagulable condition. Evidence suggests that pharmacological prophylaxis (e.g. heparin, factor Xa inhibitors, vitamin K antagonists, direct thrombin inhibitors, antiplatelets) is effective in preventing deep vein thrombosis (DVT), but is associated with an increased risk of bleeding. Mechanical prophylaxis (e.g. antiembolism stockings, intermittent pneumatic compression and foot impulse devices), on the other hand, is non-invasive and has minimal side effects. However, mechanical prophylaxis is not always appropriate for people with contraindications such as peripheral arterial disease (PAD), arteriosclerosis or bilateral lower limb amputations. It is important to determine the most effective thromboprophylaxis for people undergoing major amputation and whether this is one treatment alone or in combination with another. This is an update of the review first published in 2013. To determine the effectiveness of thromboprophylaxis in preventing VTE in people undergoing major amputation of the lower extremity. The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, Cochrane Central Register of Controlled Trials, MEDLINE, Embase and Cumulative Index to Nursing and Allied Health Literature databases, the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 5 November 2019. We planned to undertake reference checking of identified trials to identify additional studies. We did not apply any language restrictions. We included randomised controlled trials and quasi-randomised controlled trials which allocated people undergoing a major unilateral or bilateral amputation (e.g. hip disarticulation, transfemoral, knee disarticulation and transtibial) of the lower extremity to different types or regimens of thromboprophylaxis (including pharmacological or mechanical prophylaxis) or placebo. Two review authors independently selected studies, extracted data and assessed risk of bias. We resolved any disagreements by discussion. Outcomes of interest were VTE (DVT and pulmonary embolism (PE)), mortality, adverse events and bleeding. We used GRADE criteria to assess the certainty of the evidence. The two included studies compared different treatments, so we could not pool the data in a meta-analysis. We did not identify any eligible new studies for this update. Two studies with a combined total of 288 participants met the inclusion criteria for this review. Unfractionated heparin compared to low molecular weight heparin One study compared unfractionated heparin with low molecular weight heparin and found no evidence of a difference between the treatments in the prevention of DVT (odds ratio (OR) 1.23, 95% confidence interval (CI) 0.28 to 5.35; 75 participants; very low-certainty evidence). No bleeding events occurred in either group. Deaths and adverse events were not reported. This study was open-label and therefore at a high risk of performance bias. Additionally, the study did not report the method of randomisation, so the risk of selection bias was unclear. Heparin compared to placebo In the second study, there was no evidence of a benefit from heparin use in preventing PE when compared to placebo (OR 0.84, 95% CI 0.35 to 2.01; 134 participants; low-certainty evidence). Similarly, no evidence of improvement was detected when the level of amputation was considered, with a similar incidence of PE between the two treatment groups: above knee amputation (OR 0.79, 95% CI 0.31 to 1.97; 94 participants; low-certainty evidence); and below knee amputation (OR 1.53, 95% CI 0.09 to 26.43; 40 participants; low-certainty evidence). Ten participants died during the study; five underwent a post-mortem and three were found to have had a recent PE, all of whom had been on placebo (low-certainty evidence). Bleeding events were reported in less than 10% of participants in both treatment groups, but the study did not present specific data (low-certainty evidence). There were no reports of other adverse events. This study did not report the methods used to conceal allocation of treatment, so it was unclear whether selection bias occurred. However, this study appeared to be free from all other sources of bias. No study looked at mechanical prophylaxis. We did not identify any eligible new studies for this update. As we only included two studies in this review, each comparing different interventions, there is insufficient evidence to make any conclusions regarding the most effective thromboprophylaxis regimen in people undergoing lower limb amputation. Further large-scale studies of good quality are required.

Evaluation of Biomarkers for the Prediction of Venous Thromboembolism in Ambulatory Cancer Patients

Background: Venous thromboembolism (VTE) is a common complication of cancer. This study aimed to evaluate immature platelet fraction (IPF), mean platelet volume (MPV), P-selectin, D-dimer, and thrombin generation (TG) as predictive biomarkers for VTE and further the improvement of existing risk assessment models (RAMs). Methods: A prospective, observational, exploratory study was conducted on ambulatory cancer patients with indication for systemic chemotherapy. Baseline RAMs included the Khorana-, Vienna Cancer, Thrombosis-, Protecht-, ONKOTEV-, and Catscore. IPF, MPV, P-selectin, D-dimer, and TG were analysed at baseline and 3-month follow-up. Results: We enrolled 100 patients, of whom 89 completed the follow-up. Frequent tumour types were breast (30%), gastric (14%), gynaecological (14%), and colorectal (14%) cancer. Ten of the 89 patients (11.2%) developed VTE. The highest VTE rate was observed in patients with cholangiocarcinoma (3/5; 60%). Baseline D-dimer levels but not IPF, MPV, or P-selectin were associated with the risk of developing VTE (HR 6.9; p = 0.021). None of the RAMs showed statistical significance in predicting VTE. Peak thrombin and endogenous thrombin potential were lower in patients who developed VTE. Biomarker changes between baseline and follow-up were not associated with VTE risk. Conclusions: VTE risk was well predicted by baseline D-dimer levels. Adding D-dimer could improve existing RAMs to better identify patients who may benefit from primary VTE prophylaxis. The VTE risk among patients with cholangiocarcinoma should be further evaluated.

Rates of primary prophylaxis for venous thromboembolism in high-risk patients with pancreatic and gastric cancer: A single tertiary care academic center experience.

e19274 Background: Venous thromboembolism (VTE) causes significant morbidity and mortality in patients with cancer. The International Society of Thrombosis and Hemostasis published guidelines in 2014 recommending a risk-based approach to VTE prophylaxis in ambulatory cancer patients, but uptake in real-world clinical practice is unknown. This study's objective was to describe rates of primary VTE prophylaxis in ambulatory patients with gastric and pancreatic cancer receiving chemotherapy and at increased risk of VTE. Methods: We identified patients at a single academic tertiary care center who received chemotherapy from 1/1/2015 to 10/1/2018 for a diagnosis of pancreatic or gastric cancer through retrospective query of electronic health records. Data abstracted included the Khorana score components (body mass index, leukocyte, hemoglobin, and platelet counts) on day of chemotherapy initiation, anticoagulation prescription, and VTE diagnosis within 6 months of chemotherapy initiation. Patients were excluded if they had contraindications to anticoagulation or alternate indications for anticoagulation. Results: We identified 437 patients, of which 72% had pancreatic cancer and 29% had gastric cancer. Mean (standard deviation) age was 64.2 (11.7) years, and patients were predominately male (54%) and white (75%). Overall, only 13% of patients received a prescription for anticoagulation with similar rates in patients with pancreatic cancer (14%) compared to gastric cancer (9%). Anticoagulation prescription rates by Khorana score (2 or ≥3) are shown in Table. Approximately 10% of patients had a VTE within 6 months of chemotherapy initiation. Conclusions: Our results show that in a cohort of patients with gastric and pancreatic cancer at intermediate to high-risk of VTE by Khorana score (≥2), only 1 in 10 received a prescription for prophylactic anticoagulation. In addition, we observed high rates of incident VTE in 6-month follow-up confirming the high-risk nature of this group. Opportunity remains to enhance implementation of primary VTE prevention in clinical practice to reduce VTE morbidity and mortality in patients with cancer. [Table: see text]

The current approaches to the management of coronavirus disease 2019 associated coagulopathy

Coronavirus disease 2019 (COVID-19) is a highly infectious disease caused by the severe acute respiratory syndrome-CoV-2 virus that appeared in China and has spread globally. Accumulating evidence suggests that the development of specific prothrombotic changes in patients with COVID-19 reflected a high incidence of thrombotic complications. This paper is a narrative review of the diagnostic and management of COVID-19-associated coagulopathy and related venous thromboembolism (VTE). The consecutive search and review of relevant literature were carried out between March 23 and May 22, 2020. Eleven studies assessing the incidence of VTE and eleven guidelines on the management of coagulopathy were identified. The prevalence of VTE in patients with COVID-19 appeared to be unexpectedly high, reaching 8%–13% in the general ward and 9%–18% in the intensive care unit despite pharmacological prophylaxis. The current guidelines suggest prophylactic anticoagulation with low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH) in all inpatients. Intensified anticoagulation in the absence of VTE is not generally recommended but may be considered for patients with obesity, elevated D-dimer, an individually highest risk of VTE, or critical illness. The value of mechanical prophylaxis is underestimated. Extended prophylaxis after discharge may be indicated for patients with increased risk of VTE and low risk of bleeding. Increased D-dimer may be used as an indication for VTE screening by appropriate imaging tests. If VTE is highly suspected according to the clinical signs or D-dimer, then therapeutic anticoagulation may be initiated before VTE confirmation. For putative or confirmed VTE, therapeutic anticoagulation with LMWH or UFH is preferred during inpatient treatment, followed by switching to direct oral anticoagulants after discharge for 3 months. Primary VTE prophylaxis for outpatients is not generally recommended. Most of the guidelines are interim and ambiguous.

Incidence of Venous Thromboembolism in Patients With Newly Diagnosed Pancreatic Cancer and Factors Associated With Outcomes

Pancreatic ductal adenocarcinoma (PDAC) is associated with the highest incidence of venous thromboembolism (VTE) of any cancer type. However, little is known about risk factors for VTE or its outcomes in patients with PDAC. We collected data from a prospective, observational study performed at multiple centers in France from May 2014 through November 2018 (the Base Clinico-Biologique de l'Adénocarcinome Pancréatique [BACAP] study) linked to a database of patients with a new diagnosis of PDAC of any stage. Data were collected from 731 patients at baseline and during clinical follow-up or in the event of symptoms. The primary endpoint was the onset of VTE during follow-up. The secondary endpoints were progression-free survival (PFS) and overall survival (OS) times. During a median follow-up of 19.3 months, 152 patients (20.79%) developed a VTE. The median time from PDAC diagnosis to the onset of VTE was 4.49 months. Cumulative incidence values of VTE were 8.07% (95% confidence interval [CI], 6.31-10.29) at 3 months and 19.21% (95% CI, 16.27-22.62) at 12 months. In multivariate analysis, PDAC primary tumor location (isthmus vs head: hazard ratio [HR], 2.06; 95% CI, 1.09-3.91; P= .027) and stage (locally advanced vs resectable or borderline: HR, 1.66; 95% CI, 1.10-2.51, P= .016; metastatic vs resectable or borderline: HR, 2.50; 95% CI, 1.64-3.79; P < .001) were independent risk factors for the onset of VTE. Patients who developed VTE during follow-up had shorter times of PFS (HR, 1.74; 95% CI, 1.19-2.54; P= .004) and OS (HR, 2.02; 95% CI, 1.57-2.60; P < .001). In an analysis of data from the BACAP study, we found that frequent and early onsets of VTE after diagnoses of PDAC are associated with significant decreases in times of PFS and OS. Studies are needed to determine whether primary prophylaxis of VTE in patients with PDAC will improve morbidity and mortality related to VTE. (ClinicalTrials.gov, Number: clinicaltrials.gov as number NCT02818829).

Provider Practices Regarding Prophylactic Anticoagulation in Children with Leukemia

Venous thromboembolism (VTE) is a known complication in children with leukemia, with prevalence in acute lymphoblastic leukemia (ALL) reported as high as 37% (Mitchell, et al, Cancer, 2003). Indwelling catheters, hyperviscosity, mediastinal masses, and medications such as asparaginase, can all contribute to increased VTE risk. In addition to national interest in preventing VTE in hospitalized children, decreasing risk of VTE in children with cancer is of great importance to pediatric hematologist/oncologists. The International Society of Hemostasis and Thrombosis released a guidance statement (Tullius, et al, JTH, 2017) that suggested considering thromboprophylaxis on a case-by-case basis for children with cancer and multiple VTE risk factors, and suggested discontinuing anticoagulant prophylaxis when predisposing conditions resolve. Children with leukemia certainly may have multiple risk factors and therefore deserve consideration for prophylaxis. The Children's Oncology Group is currently conducting a clinical trial studying thromboprophylaxis during induction for ALL. Given the importance of reducing VTE and the interest in thromboprophylaxis, we sought to assess practitioners' practices regarding thromboprophylaxis in children with leukemia. We performed a cross sectional, anonymous survey of pediatric members of VENUS (the VTE Network of the Hemostasis and Thrombosis Research Society) and ASH (the American Society of Hematology) using Qualtrics, a secure online survey tool. Responses were excluded if physicians answered no to either of 2 screening questions (related to clinical practice and board certification/eligibility), or if no questions were answered after screening. A gift card incentive was offered anonymously. Institutional IRBs approved this study. 870 surveys were distributed, with a response rate of 17.7%; after exclusions, a total of 142 surveys were included. Demographics were well balanced regarding size of program and years in practice. When asked about which anticoagulant agents may be used for thromboprophylaxis (n=36), 92% of those responding reported using enoxaparin (Table 1). In addition, 36% use Apixaban and 14% use Rivaroxaban. When asked if they ever provide primary VTE prophylaxis to children with leukemia (n=127), 71% said no, while 29% answered yes (Table 1). When asked in what scenarios primary prophylaxis was used, the most common answer was in leukemia patients with a known inherited thrombophilia (57%). Also common were children with mediastinal masses with vessel compression, and children enrolled on the COG prophylaxis study. Some additional scenarios offered were AYA patients, and those with additional risk factors, such as obesity and immobility. When asked about duration of primary prophylaxis (n=36), the most common times for discontinuing therapy were resolution of mediastinal mass and/or vessel compression (58%), end of all asparaginase therapy (50%), and until the central line is removed (42%). A smaller number of physicians (22%) would consider continuing anticoagulant prophylaxis until the end of all cancer chemotherapy. When questioned about secondary prophylaxis following VTE (n=127), 8% of respondents never provide post-VTE prophylaxis, 11% always give post-VTE prophylaxis, and 81% used post-VTE prophylaxis in certain cases (Table 1.) The most common stopping point for secondary prophylaxis (n=116) was after central line removal (55%), followed by completion of all asparaginase therapy (41%). Our study is limited by a low response rate. Due to technical issues, we had missing data for many questions and could not obtain free-text answers for some of the prophylaxis questions, limiting full data acquisition. Despite these issues, our results provide some insights into current practices of pediatric hematologist/oncologists. This study shows that many physicians are not utilizing primary anticoagulant prophylaxis in their pediatric leukemia patients, despite the high-risk nature of these patients, possibly trying to balance bleeding risk due to thrombocytopenia. Duration of anticoagulant therapy varies, and it is likely that there are no clear definitions regarding resolution of predisposing factors. Given their unique set of risk factors, and the potential morbidity associated with VTE, further study of VTE prophylaxis is essential for development of pediatric leukemia-specific guidelines. Disclosures Cooley: off-label: Other: drug use. Acharya:Bayer Pharmaceuticals, LLC: Research Funding; Novonordisk: Membership on an entity's Board of Directors or advisory committees; BioProducts Laboratory: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: We surveyed physicians on which anticoagulants they use in their pediatric leukemia patients and the majority of drugs offered as answer choices are technically off-label.

3150 Deep Venous Thrombosis in Ulcerative Colitis

INTRODUCTION: Inflammatory bowel disease (IBD) has a variety of both intestinal and extraintestinal manifestations. Among the range of extraintestinal manifestations of IBD, venous thromboembolism (VTE) is a rare complication with high morbidity and mortality. VTE can present in patients with both active disease, which is more prevalent, or in well-controlled disease, which suggests a prothrombotic risk in patients with IBD. The case below is a classic presentation of VTE in IBD, and raises questions involving lifelong anticoagulation. CASE DESCRIPTION/METHODS: A 62 year old male with ulcerative colitis presented to the office with a 2-week history of constant, achy pain in his right leg associated with swelling and stiffness of his right lower extremity. A right lower extremity venous duplex ultrasound revealed extensive thrombosis from the popliteal vein up to the common femoral vein. Despite a discussion about possible sequelae of untreated VTE such as further clot extension, acute pulmonary embolism, and death, the patient opted for outpatient treatment with lifelong apixaban. His swelling improved, and although he has had prior IBD exacerbations with significant bleeding, since the patient has been on apixaban, he has not had any significant bleeding. DISCUSSION: Patients with IBD have a threefold higher risk of VTE than the general population. Research suggests that it may be due to a complex interplay between inflammation and coagulation. Treatment of acute VTE in IBD patients has not been clearly defined and currently is similar to most patients. Consequently, the duration of anticoagulation is not established, and it is imperative to establish specific guidelines due to the risk of recurrent VTE in IBD. Currently, there are no data on the role of primary VTE prophylaxis for IBD patients in the outpatient setting and no specific biomarkers to identify IBD patients at risk. Future research should assess the prothrombotic risk in IBD to assist clinicians in preventive measures. Additional studies are needed to address the use of screening tests such as ultrasound or biomarkers. In this case, the patient was placed on lifelong apixaban due to his underlying risk factor of ulcerative colitis and showed clinical improvement with no significant bleeding. This case helps highlight the concern for major bleeding in a patient who has had previous significant major bleeding episodes during IBD exacerbations. In conclusion, VTE is a significant complication that should not be overlooked in patients with IBD.

Aspirin for prevention of venous thromboembolism in recipients of major lower-limb orthopedic surgery: a systematic review of Level I evidence.

Major lower-limb orthopedic surgery recipients are at increased risk of venous thromboembolism (VTE). The optimal strategy for preventing VTE is a topic of ongoing debate. The use of aspirin has been implicated in reducing VTE events and is potentially advantageous compared to other agents in respect to cost, access, route of administration and reduced adverse effects such as bleeding. A systematic search for Level I evidence (systematic reviews and meta-analyses of randomised-controlled trials) was performed in April 2019 to evaluate the use of aspirin for primary and secondary VTE prophylaxis compared to alternative chemical and mechanical strategies. This search encompassed three electronic databases (Pubmed, Embase and the Cochrane Database of Systematic Reviews). All references of included studies were screened for additional studies. Data was compiled and compared to the recommendations and guidelines published by major institutions. Included studies were appraised with the aid of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. In total, 21 studies were included. Interventions and outcomes identified were heterogeneous across studies. Most statistical tests applied found no difference between aspirin and other interventions in regards to deep vein thrombosis, pulmonary embolism, bleeding and mortality outcomes. Aspirin may be a viable alternative to established thromboprophylactic regimes for primary prevention of VTE, however in the setting of secondary prevention it is generally less efficacious. Future studies should have clearly identified and comparable outcome measures, with direct comparisons and assessment of intervention combination, dosing and treatment duration.

Recent advances in the treatment and prevention of venous thromboembolism in cancer patients: role of the direct oral anticoagulants and their unique challenges.

Venous thromboembolism (VTE) is a common complication in patients with cancer and is associated with poor prognosis. Low-molecular-weight heparins (LMWHs) are the standard of care for the treatment of cancer-associated thrombosis. Primary VTE prophylaxis with LMWH is recommended after cancer surgery and in hospitalized patients with reduced mobility. However, owing to wide variations in VTE and bleeding risk, based on disease stage, anti-cancer treatments, and individual patient characteristics, routine primary prophylaxis is not recommended in ambulatory cancer patients undergoing chemotherapy. Efforts are under way to validate risk assessment models that will help identify those patients in whom the benefits of primary prophylaxis will outweigh the risks. In recent months, long-awaited dedicated clinical trials assessing the direct oral anticoagulants (DOACs) in patients with cancer have reported promising results. In comparison with the LMWHs, the DOACs were reported to be non-inferior to prevent VTE recurrence. However, there was an increased risk of bleeding, particularly in gastrointestinal cancers. Safe and optimal treatment with the DOACs in the patient with cancer will require vigilant patient selection based on patient characteristics, co-morbidities, and the potential for drug–drug interactions.