Use of Khorana score to predict VTE in patients undergoing chemotherapy for uterine cancer.

5589 Background: Gynecologic cancers are associated with a high risk of venous thromboembolism (VTE). The Khorana score is a clinically-validated tool to assess risk of VTE in cancer patients (using disease site, BMI and blood counts). Recent ASCO clinical practice guidelines have recommended patients with a Khorana score of 2 or greater be offered pharmacologic thromboprophylaxis during systemic chemotherapy. For women with uterine cancer, the utility of the Khorana score is still unknown. Methods: A retrospective cohort study was performed from January 2016 to January 2020. All patients with uterine cancer were screened. Patients receiving chemotherapy, both neoadjuvant (NACT) and adjuvant (ACT), were included. VTE was evaluated for 12 months following the first cycle of chemotherapy. The Khorana score was calculated for each patient using both a high risk score of ≥2 and ≥3 and the patients were stratified based on NACT vs ACT. Logistic regression and chi-square were used to evaluate the prognostic utility of the Khorana score as well as other clinico-pathologic criteria on development of VTE. Results: A total of 265 patients were included. The majority of patients were obese (160, 60.4%) and 60 years or older (188, 70.9%). The most common histology was endometrioid (107, 40.4%) followed by serous (71, 26.8%) and the majority were advanced-stage (169, 63.8%). Most women underwent hysterectomy during treatment (243, 91.7%) followed by ACT (228, 86.0%). 14% (37) had NACT. 24 patients developed VTE (9.1%), which was higher, but not statistically different, with NACT vs ACT (13.5% vs 8.3%, p = 0.35). Demographics including age, race and BMI nor pathologic data including histology, grade or stage significantly correlated with development of VTE. Similarly, treatment factors including undergoing hysterectomy and radiation treatment were not statistically significant in regards to VTE. The proportion of patients with high Khorana score (both ≥2 and ≥3) was similar between groups. In the whole cohort, high Khorana score (defined either as ≥2 or ≥3) did not significantly predict VTE; however, the model using ≥3 was more predictive (OR 1.154, 95%CI 0.402-2.907, p = 0.7326). In the NACT cohort, neither model was predictive of VTE (both with OR < 1). In the ACT group, Khorana ≥3 was a better prediction model, but was still not statistically significant (OR 1.557, 95%CI 0.480-4.343, p = 0.4213). Conclusions: Although validated in other cancer types, the Khorana score was found to be a poor predictor of VTE in this population. A defined high risk Khorana score of ≥3 (per the original validation study) better predicted VTE than a score of ≥2 (per guidelines). Independent of the Khorana score, demographic and pathologic data were poor predictors of VTE. At this time, use of the Khorana score to guide routine thromboprophylaxis in patients undergoing chemotherapy for uterine cancer should be used with caution.

Pharmacologic Thromboprophylaxis and Thrombosis in Hospitalized Patients with COVID-19: A Pooled Analysis

Background Coronavirus disease 2019 (COVID-19) increases thrombosis in hospitalized patients prompting adoption of different thromboprophylaxis strategies. Safety and efficacy of escalated-dose pharmacologic thromboprophylaxis are not established. Objectives To determine the pooled incidence of thrombosis/bleeding in hospitalized patients with COVID-19 for standard-dose, intermediate-dose, therapeutic anticoagulation, and no pharmacologic thromboprophylaxis. Methods MEDLINE, EMBASE, and Cochrane CENTRAL were searched up to August 29, 2020 for studies reporting pharmacologic thromboprophylaxis and thrombosis or bleeding. Pooled event rates were calculated using a random-effects model. Results Thirty-five observational studies were included. The pooled incidence rates of total venous thromboembolism (N = 4,685) were: no prophylaxis 41.9% (95% confidence interval [CI]: 28.1–57.2, I 2 = 76%), standard-dose prophylaxis 19.8% (95% CI: 13.2–28.6, I 2 = 95%), intermediate-dose prophylaxis 11.9% (95% CI: 4.3–28.6, I 2 = 91%), and therapeutic-dose anticoagulants 10.5% (95% CI: 4.2–23.8, I 2 = 82%, p = 0.003). The pooled incidence rates of arterial thrombosis (N = 1,464) were: no prophylaxis 11.3% (95% CI: 5.2–23.0, I 2 = 0%), standard-dose prophylaxis 2.5% (95% CI: 1.4–4.3, I 2 = 45%), intermediate-dose prophylaxis 2.1% (95% CI: 0.5–7.7, I 2 = 45%), and therapeutic-dose anticoagulants 1.3% (95% CI: 0.2–8.8, I 2 = 0, p = 0.009). The pooled bleeding event rates (N = 6,393) were nonsignificantly higher in therapeutic-dose anticoagulants compared with standard-dose prophylaxis, (6.3 vs. 1.7%, p = 0.083). Conclusion Thrombosis rates were lower in hospitalized COVID-19 patients who received pharmacologic thromboprophylaxis. Thrombosis and bleeding rates for patients receiving intermediate-dose thromboprophylaxis or therapeutic anticoagulation were similar to those who received standard-dose pharmacologic thromboprophylaxis.

Efficacy of pre-operative pharmacologic thromboprophylaxis on incidence of venous thromboembolism following major gynecologic and gynecologic oncology surgery: a systematic review and meta-analysis

IntroductionVenous thromboembolism remains a significant complication following major gynecologic surgery. Evidence is lacking on whether it is beneficial to give pharmacologic thromboprophylaxis pre-operatively. The aim of this meta-analysis was to assess the role of pre-operative pharmacologic thromboprophylaxis in preventing post-operative venous thromboembolism.MethodsPubMed, EMBASE, and the Cochrane Central Register of Clinical Trials were searched to find randomized controlled, cohort, and case–control trials comparing pre-operative pharmacologic thromboprophylaxis to no prophylaxis, mechanical prophylaxis, or only post-operative pharmacologic thromboprophylaxis for open and minimally invasive major gynecologic surgery (benign and malignant conditions). Two authors independently assessed abstracts, full-text articles, and methodological quality. Data were extracted and pooled using ORs for random effects meta-analysis. Heterogeneity was explored using forest plots, Q-statistic, and I2 statistics. Planned subgroup analysis of use of sequential compression devices, equivalent versus non-equivalent post-operative prophylaxis, cancer diagnosis, and methodological quality were performed.ResultsSome 503 unique studies were found, and 16 studies (28 806 patients) were included in the systematic review. Twelve studies (14 273 patients) were included in the meta-analysis. The OR for incidence of post-operative venous thromboembolism was 0.59 (95% CI 0.39, 0.89), favoring pre-operative pharmacologic thromboembolism prophylaxis compared with no pre-operative pharmacologic prophylaxis (Q=13.80, I2=20.30). In studies where post-operative care was equivalent between groups, the OR for venous thromboembolism was 0.56 (95% CI 0.22, 1.40). Pre-operative pharmacologic prophylaxis demonstrated greatest benefit when utilized with both intra-operative and post-operative sequential compression devices (OR 0.43, 95% CI 0.30, 0.64) compared with when no sequential compression devices were utilized (OR 1.27, 95% CI 0.63, 2.56). When looking at only studies determined to be of high quality, the results no longer reached significance (OR 0.73, 95% CI 0.36, 1.46).ConclusionsPre-operative pharmacologic thromboprophylaxis decreases the odds of venous thromboembolism in the peri-operative period for major gynecologic oncology surgery by approximately 40%. It remains unclear whether this benefit is present in benign and minor procedures. Adequately powered studies are needed.

Venous Thromboembolism Prophylaxis Practices for Patients with Sickle Cell Disease Pre and during the COVID-19 Pandemic

Background: The coronavirus disease pandemic of 2019 (COVID-19) has been associated with coagulopathy and an increased rate of thrombosis in adults. Medical practitioners have been prompted to consider prophylactic anticoagulation in special populations diagnosed with COVID-19. Patients with sickle cell disease (SCD) are predisposed to a hypercoagulable state. Despite the concern for development of venous thromboembolism (VTE) in these patients, there are no standardized guidelines for routine thromboprophylaxis in either adults or children with SCD. Thus, VTE management options are often extrapolated from guidelines for the general population. Methods: A cross-sectional electronic survey was distributed to pediatric and adult hematology oncology practitioners through 7 SCD specific interest groups. Pediatric and adult practitioners were defined as those who medically manage patients 0-21 years of age and &gt;21 years of age respectively. We examined responses to survey questions focused on routine thromboprophylaxis practices in children and adults with SCD prior to the pandemic and in patients with SCD admitted with COVID-19. Chi-square analyses or Fisher's exact tests for small samples were used to compare proportions as needed. Results: The survey was distributed to approximately 2,550 providers. Of 93 total responses, 14% (N=13) only treat patients &gt;21yo; 38.7% (N=36) only treat patients 0-21yo and 47.3% (N=44) treat both. Nearly all adult practitioners (96.6%) would recommend pharmacologic prophylaxis, mechanical prophylaxis or both for hospitalized adults, but only 76% of pediatric treaters would recommend any prophylaxis (PPX) in hospitalized children (p&lt;0.0001, Figure 1). Only 16% would recommend pharmacologic PPX only for patients 0-21yo, with 36% preferring non-pharmacologic only methods and 24% preferring both forms. In contrast, for the &gt;21yo patients, 51% preferred to use both pharmacologic and non-pharmacologic PPX, 25% preferred pharmacologic alone, with just 5.3% preferring non-pharmacologic PPX only. Enoxaparin was the most frequently used anticoagulant among both pediatric and adult practitioners [78% vs 89% respectively] (Figure 2). Direct oral anticoagulants (DOACS) were infrequently recommended (3.8% for SCD children and 10.9% for adults); of these, rivaroxaban was used most often. The most common indication for starting thromboprophylaxis for both 0-21yo and &gt;21yo patients was history of prior VTE [81% and 81% respectively], followed by hip replacement [57% and 75% respectively]. In patients admitted with COVID-19, prophylactic anticoagulation was recommended for adults by 94% of treaters. There was a significant increase in the use of prophylactic anticoagulation in children with COVID-19 vs. those without (84% vs. 40%; p=.0001). Figure 3 shows extended thromboprophylaxis practices upon discharge for COVID related admissions. Almost half of respondents (46%) would not recommend any thromboprophylaxis for children on discharge; 37% would recommend either 2-4 weeks or &gt;4weeks of post-discharge PPX. The majority of adult providers would recommend discharge thromboprophylaxis for adults with 2 weeks post discharge (33%), and 2-4 weeks (30%) being the most common regimens. Conclusion: This pilot survey describes the thromboprophylaxis practices used for adult and pediatric SCD patients by specialty practitioners. In general, practitioners were likely to prescribe pharmacologic thromboprophylaxis for adults while mechanical PPX was preferred for children. However, in the high-risk setting of COVID-19 infection, pediatric practitioners would modify their practice to include pharmacologic thromboprophylaxis. Interestingly, despite the long-term availability of direct oral anticoagulants in adults, and recent completion of pediatric studies, the most commonly used pharmacologic agent pre-COVID in adults and children was enoxaparin. Of note, this survey was conducted prior to release of the International Society on Thrombosis and Haemostasis guidelines regarding discharge PPX in COVID-19. (Spyropoulos AC, J Thromb Haemost, 2020) These results highlight the influence of COVID-19 on the use of pharmacologic thromboprophylaxis, specifically in the pediatric population. Due to frequent hospitalization, studies are needed to guide decision making surrounding VTE PPX for the adult and pediatric inpatient SCD population. Disclosures Davila: Spire Learning: Speakers Bureau; ATHN: Other: Grant Funding. Minniti:Bluebird bio: Consultancy, Research Funding; TauTona: Consultancy, Research Funding; Roche: Consultancy, Research Funding; Emmaus: Consultancy, Research Funding; CLS Bering: Consultancy; Novartis: Consultancy, Research Funding; Global Blood Therapeutics: Consultancy, Research Funding. Desai:Pfizer, Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding; GBT, Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Ironwood Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees; Rockpointe Continuing Medical Education Company: Consultancy. O'Brien:Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: Enoxaparin used as a form of thromboprophylaxis in children.

SARS-CoV-2 INFECTED PATIENTS: FROM A HEMATOLOGIST PERSPECTIVE

Introduction: According to the World Health Organization (WHO), COVID-19 has become a Public Health Emergency of International Concern (PHEIC). Understanding the hematologic findings of patients with SARS-CoV-2 infection is essential to promote their care and improve outcomes. Objective:In this review, we aim at summarizing changes in the hematopoietic system and hemostasis that occur in SARS-CoV-2 infected patients. Findings: COVID-19 infection is often associated with laboratory hematologic findings that can have important clinical implications. Careful revision of baseline hematologic findings at diagnosis can predict severity of illness and help clinicians tailor their management and approach to patients whose condition can be guarded or critical.This can be of therapeutic and prognostic value in severely ill patients and can reduce the mortality rate from COVID-19. Such markers include D-dimer, procalcitonin, C-reactive protein, viral load, cytokine storm, and lymphopenia.Studies have also shown an association between these markers and severe COVID-19 infection requiring admission to the intensive care unit or complicated by acute respiratory distress syndrome (ARDS). According to the American Society of Hematology (ASH), all hospitalized patients with COVID-19 should receive pharmacologic thromboprophylaxis with LMWH. Conclusion:Until more data arises, the summary we provide can be used by hematologists to better understand hemostasis in COVID-19 infected patients.We are in need for more studies to define appropriate management plans in the setting of hematologic findings.