Risk of venous thromboembolism after discontinuing prophylactic or therapeutic anticoagulation in patients with haematologic malignancies because of thrombocytopenia.

EFFICACY AND SAFETY OF THERAPEUTIC VERSUS PROPHYLACTIC ANTICOAGULATION IN PATIENTS WITH COVID-19 INFECTION: A SYSTEMATIC REVIEW OF RANDOMIZED CONTROLLED TRIALS

520 Background: The Khorana score is the primary tool utilized to predict VTE risk in patients with cancer. This score incorporates primary cancer site, pretreatment hematologic parameters, and body mass index. GCT are considered high-risk for VTE. However, risk factors for VTE not included in the Khorana Score have been reported for GCT including retroperitoneal lymph node (RPLN) size, elevated LDH, and poor risk disease. Methods: A retrospective chart review was conducted to correlate known VTE risk factors with VTE incidence in male patients with GCT undergoing first-line chemotherapy. Variables included venous access type, RPLN size, LDH, chemotherapy regimen, procedure history, cancer stage and histology, Khorana risk factors, and pertinent demographics. VTE and superficial vein thrombosis (SVT) events that occurred within 1 month prior through 6 months after start of chemotherapy were recorded. Fisher’s Exact test was used for univariate analysis and logistic regression for multivariate analysis of the relationship between predictors and thrombosis. P-values are two-sided at an alpha level of 0.05. Results: 47 patients with GCT were identified. 12 VTE occurred (overall incidence 25.5%), 11 in patients with central lines (39.3% incidence) and 1 with a peripheral line (5.3% incidence). SVT were observed in 5 patients with peripheral lines compared to 1 patient with a central line (26.3% vs. 3.6%). Central line access was the primary variable associated with VTE risk in both univariate and multivariate analysis (p=0.01 and p=0.03, respectively). Conclusions: Venous access type is a significant but modifiable factor that can be targeted to reduce VTE risk. Due to small sample size there is limited statistical power to detect potentially meaningful differences in known risk factors. If validated, these results may identify specific patients to be treated with prophylactic anticoagulation. [Table: see text]

Venous Thromboembolism in Hospitalized Patients With COVID-19 Receiving Prophylactic Anticoagulation

Risk of Venous Thromboembolism in Multiple Myeloma Patients Undergoing Autologous Hematopoietic Cell Transplant

Personalized prophylactic anticoagulation decision analysis in patients with membranous nephropathy

Risk of venous thromboembolism in splenectomized patients compared with the general population and appendectomized patients: a 10-year nationwide cohort study.

Real-World Use of Therapeutic Anticoagulation in Patients with Paroxysmal Nocturnal Hemoglobinuria. Results of a Survey of Physicians in Australia

Baseline Thrombophilic Alterations and Risk of Venous Thromboembolism in 266 Multiple Myeloma Patients Primarily Treated with Thalidomide and High-Dose Dexamethasone.

Derivation of a Risk Prediction Model for Venous Thromboembolism in Adult Patients with Acute Myeloid Leukemia

Age-adjusted D-dimer cutoffs to guide anticoagulation in COVID-19 – Authors' reply

The risk of venous thromboembolism (VTE) is increased substantially in patients with malignant disease, most notably cancers of the pancreas, stomach, kidney, ovary, lung, and CNS, as well as certain hematologic malignancies. The risk of VTE is further increased in patients with cancer and certain demographic-, diseaseand treatment-related characteristics. Patients with major medical comorbidities such as infection, pulmonary disease, and renal failure are notably at increased risk. In addition to hospitalized patients with cancer and those in the perioperative period, patients receiving systemic therapies including chemotherapy, hormonal therapy, and certain targeted agents are at several-fold increased risk for VTE compared with the general population. Even certain supportive care measures, such as the use of the erythroidstimulating agents and blood transfusions, have been associated with an increased risk of VTE. The identification of several factors associated with cancerassociated VTE has led to the development of multivariable risk models for cancer-associated risk. A VTE risk model was developed on the basis of a prospective cohort of 2,701 ambulatory patients during their initial three to four cycles of chemotherapy for cancer, and was validated in a separate group of 1,365 patients using five readily available clinical and laboratory risk factors that were identified. On the basis of this model, points were assigned and patients were classified as low, intermediate, and high risk for VTE according to cancer type, severe obesity (body mass index 35 kg/m), elevations in pretreatment platelet count ( 350,000/ L) and leukocyte count ( 11,000/ L), and either anemia ( 10 g/dL) or erythroid-stimulating agent use. The risk score has now been validated by a number of independent investigators in the United States and Europe. In a prospective cohort of 819 patients with cancer, Ay et al observed a cumulative risk of VTE at 6 months that ranged from 1.5% to 17.7% (1.5%, score 0; 3.8%, score 1; 9.4%, score 2; and 17.7%, score 3). It should be noted that in both the original model-development population and the various validation studies, high-risk patients represent approximately 10% of ambulatory patients receiving cancer chemotherapy. Current guidelines from both the American Society of Clinical Oncology (ASCO) and the National Comprehensive Cancer Network recommend an evaluation of VTE risk and encourage the use of a validated risk score in ambulatory patients receiving cancer chemotherapy. Patients with cancers of the pancreas and upper GI tract have recently received particular attention because of the apparent greater risk for VTE than in other cancer types. A retrospective observational study of ambulatory patients with common solid malignancies initiating cancer chemotherapy reported overall rates of VTE at 3.5 months and 1 year of 7.3% and 13.5%, respectively. The greatest risk of VTE was observed in patients with advanced pancreatic cancer (APC) and was determined to be 11.6% and 21.3% at 3.5 and 12 months, respectively. It may be noted that patients who developed VTE in this cohort experienced more than twice the risk of major bleeding and had approximately 50% greater health care expenditures than similar patients who did not develop VTE. Although the prognosis of most patients with APC is poor, those with VTE have a particularly poor survival. Although the role of anticoagulation is well supported in the treatment of established VTE and for prevention of VTE in hospitalized patients with cancer, the role of thromboprophylaxis in ambulatory patients has not been firmly established. Several randomized controlled trials (RCTs) of thromboprophylaxis in ambulatory patients with cancer have been published, including 11 that compared low–molecular weight heparins (LMWHs) with either placebo or no prophylaxis. A meta-analysis estimated an overall relative risk for symptomatic VTE across published trials of 0.47 (95% CI, 0.36 to 0.61; P .001) but generally low rates of VTE and an overall absolute reduction in VTE risk of only 2.8% (95% CI, 1.8% to 3.7%; P .001). The largest RCT of an LMWH for thromboprophylaxis in patients with solid malignancies demonstrated a hazard ratio for VTE of 0.36 (95% CI, 0.21 to 0.60; P .001) but observed absolute rates of VTE of only 3.4% and 1.2% among control and LMWH-treated patients, respectively. At the same time, the largest absolute rates of VTE were observed in trials of patients with APC. The long-awaited publication of CONKO-004 (Prospective Randomized Trial of Simultaneous Pancreatic Cancer treatment With Enoxaparin and Chemotherapy) that accompanies this article provides the opportunity to reconsider the risk of VTE in patients with JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 33 NUMBER 18 JUNE 2

e14567 Background: Cancer and some anti-cancer therapies increase risk of VTE. ICIs cause immune activation and inflammation which are known to potentiate VTE formation. The risk of VTE associated with ICI is unclear, with conflicting evidence of association. Our study assessed the risk of VTE in patients treated with ICI compared to those receiving other cancer treatments. Methods: EPIC Slicer Dicer was used to collect data from three university-affiliated hospitals in New Orleans, LA. All patients >17 years of age, with an oncology treatment plan (TP) between January 1 2012 – January 31 2021 were considered the base population (n=6,894) for the study. The base population was divided into two cohorts - those that received ICI (n=794) versus those who did not (n=6,100). ICIs included pembrolizumab, nivolumab, avelumab, atezolizumab, durvalumab, cemiplimab, ipilimumab. An encounter diagnosis of deep venous thrombosis (DVT) or pulmonary embolism (PE) which was preceded by a TP in the last 1 year was used to identify patients with VTE after initiation of a TP. Categorical covariates compared across VTE groups using Chi-squared tests of independence. Two sample t-tests were used to compare continuous covariates based on VTE status. Logistic regression used to predict VTE as a function of ICIs and other potential confounders including age, BMI, gender, race and cancer subtypes. Results: Patients who experienced VTE were significantly more likely to have received ICI (1.43 times odds of VTE (95% CI = 1.12-1.83; p <0.005), be black or African American (p < 0.05 compared with White and Asian races), and have GI cancer (1.82 times odds, 95% CI= 1.41 – 2.36, p< 0.001), GU cancer (1.7 times odds, 95% CI = 1.3 – 2.23; p<0.001). Patients with VTE were significantly less likely to have breast cancer or other cancer types. Males had a decreased odd of VTE (0.73 odds, 95% CI= 0.62 – 0.85, p< 0.001). Conclusions: Based on the above results, there appears to be an increased likelihood of VTE in patients that receive ICI when compared to other types of cancer treatment. This study is a preliminary analysis and has limitations. At this time, it is unclear if prophylactic anticoagulation can reduce risk of VTE after ICI initiation. Further investigation is warranted in the form of individual chart review, or a prospective study.

Anticoagulation in COVID-19

Impact of Khorana Score, Tumor Histology, and Treatment Regimen on VTE Incidence in Lung Cancer

The Safety and Adherence To Prophylactic Anticoagulation During Induction Chemotherapy In Adults With Acute Lymphoblastic Leukemia