“Life is short, art long, opportunity fleeting, experience treacherous, judgment difficult.”
To complement The ASCO Post’s continued comprehensive coverage of the 2020 American Society of Hematology (ASH) Annual Meeting & Exposition, here are several abstracts selected from the meeting proceedings focusing on bleeding disorders such as coagulopathy and venous thromboembolism in patients with cancer and COVID-19. For full details of these study abstracts, visit ashpublications.org.
Syed Ali Abutalib, MD
Jean M. Connors, MD
COVID-19 and Cancer Consortium (CCC19) Registry Analysis
ABSTRACT 204: Incidence of and risk factors for venous thromboembolism (VTE) among hospitalized adults with cancer (active or history) and COVID-19 (ClinicalTrials.gov identifier NCT04354701).1
Background: Hospitalized patients with COVID-19 may have an increased risk of VTE and pulmonary embolism. Cancer and anticancer therapies are well-known additional risk factors for VTE. The COVID-19 and CCC19 registry prospectively collects anonymized data about patients diagnosed with COVID-19 and cancer. The goal of the registry is to generate hypothesis-generating and hypothesis-supporting findings that are generalizable to the population at large.2
Methods: A prespecified subgroup analysis was performed to examine the interaction between intensive care unit (ICU) admission and recent anticancer therapy on VTE outcomes. Bivariable logistic regression analyses were conducted to assess the association between baseline variables and VTE.
Results: Among the 1,629 hospitalized patients, the median follow-up was 35 days. A history of VTE was reported in 9% of patients; the most common cancer types included prostate (18%), breast (15%), and lymphoma (14%). Based on the VTE risk grouping adapted from the original Khorana score, 34% were low risk, 29% were high risk, and 6% were very high risk. The receipt of anticancer therapy within 3 months of diagnosis was observed in 39% of patients (17% cytotoxic chemotherapy, 11% targeted therapy, 7% endocrine therapy, and 5% immunotherapy).
The overall incidence of in-hospital VTE and pulmonary embolism was 9.3% and 5.2%, respectively. The corresponding estimates were 13.4% and 7.9% in the ICU subgroup.
On bivariable analysis, significant predictors of VTE included ICU admission, recent anticancer therapy (within the past 3 months), active cancer status (active-progressive > active-stable), cancer subtype VTE risk grouping (esophageal, stomach and pancreatic, lung, ovarian, kidney, testicular and lymphoma, breast, colorectal, prostate, head and neck), and preadmission antiplatelet use.
Preadmission anticoagulant use had significant associations with pulmonary embolism but not with VTE.
Both ICU admission status and anticancer therapy increased the risk of VTE independently.
Clinical Implications: In this cohort study of hospitalized patients with cancer and COVID-19, recent anticancer therapy, active disease, high-risk VTE cancer subtypes, and ICU admission seem to be associated with an increased risk of VTE and pulmonary embolism, whereas preadmission anticoagulant/antiplatelet therapy may reduce the risk. This information should aid in developing a risk prediction tool for VTE in hospitalized patients with cancer and COVID-19. Additional data collection and analyses are ongoing. Longer follow-up is needed to better understand the effect of COVID-19 on outcomes in patients with cancer, including the ability to continue specific cancer treatments.2
Early Data From the Prospective Northwell CORE-19 Registry
ABSTRACT 443: Thromboembolic outcomes of hospitalized patients with COVID-19 in the 90-day postdischarge period.3
Background: The actual rate of arterial and venous thromboembolic events in hospitalized patients with COVID-19, especially in the immediate posthospital discharge period, has not been fully elucidated, with most of the data derived from retrospective studies with small sample sizes.
Methods: The study has implemented an ongoing prospective registry (CORE-19) consisting of 11,249 consecutive hospitalized patients with COVID-19 from March 1, 2020, through May 31, 2020. It is using data derived from the Northwell Health System and the COVID-19 Research Consortium to study through 90 days after discharge the rate of arterial and venous thromboembolic events, major bleeding, all-cause mortality, and other complications.
Results: As of August 7, 2020, data consist of complete follow-up in 4,100 patients, with a mean age of 61.0 years (standard deviation = 17.0). Preliminary data show an all-cause mortality rate of 4.3%, an overall thromboembolic rate of 3.5% (2.4% for venous and 1.1% for arterial), a major bleeding rate of 1.6%, and a rehospitalization rate of 12.9%. Of patients with either deep-vein thrombosis or pulmonary embolism after discharge, 13.4% (9 of 67) died.
Clinical Implications: Few data on the rates of postdischarge thromboembolic events exist. This work signifies the importance of postdischarge surveillance and, potentially, postdischarge extended thromboprophylaxis in this acutely ill medical population. However, the risks and benefits need to be assessed for the COVID-19 population. Clinical trials are in progress.
Retrospective Multicenter Study From Southeast Michigan
ABSTRACT 577: Increasing doses of anticoagulation are associated with improved survival in hospitalized patients with COVID-19.4
Background: Evidence on clinical outcomes among patients with COVID-19 receiving therapeutic anticoagulation compared with prophylactic dose anticoagulation is limited.
Methods: Participants were assigned to three groups based on whether they received no anticoagulation, prophylactic anticoagulation throughout most of their hospitalization, or at least 3 days of therapeutic anticoagulation. A total of 3,480 patients were included, with 18.5% (n = 642) treated in the ICU. About 60.9% received prophylactic anticoagulation (n = 2,121), 28.7% received at least 3 days of therapeutic anticoagulation (n = 998), and 10.4% (n = 361) did not receive anticoagulation.
Results: A propensity score–weighted Kaplan-Meier plot demonstrated a statistical difference in the 25-day survival probability in the therapeutic anticoagulation group compared with the prophylactic anticoagulation group (57.5% vs 50.7%). In a propensity score–weighted multivariate proportional hazards model adjusting for age, body mass index, and ICU status, anticoagulation was associated with a reduced risk of death at both prophylactic (hazard ratio [HR] = 0.35 [confidence interval (CI) = 0.22–0.54]) and therapeutic doses (HR = 0.14 [CI = 0.05–0.23]) compared with no anticoagulation. Major bleeding occurred more frequently among patients given therapeutic anticoagulation (n = 81 [8.1%]) than in those who received no anticoagulation (n = 20 [5.5%]) or prophylactic anticoagulation (n = 46 [2.2%]).
Clinical Implications: Higher doses of anticoagulation appear to be associated with lower mortality in hospitalized patients with COVID-19. The lowest hazard ratio was observed in ICU patients, but the risk was also significantly lower in non-ICU hospitalized patients. Bleeding occurred more frequently with higher doses of anticoagulation. There are limitations with the data and analyses, as with any single-center retrospective study. Randomized trials to prospectively evaluate the efficacy and risk of therapeutic anticoagulation in patients with COVID-19 are under way.
Male sex, severe obesity, and elevated D-dimer levels on ICU admission were independent predictors of VTE.— Syed Ali Abutalib, MD, and Jean M. Connors, MD
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Nationally Representative Multicenter Study in Critically Ill Patients
ABSTRACT 581: Thrombosis, bleeding, and the effect of anticoagulation on survival in critically ill patients with COVID-19 in the United States.5
Background: Hypercoagulability may be a key mechanism of death in patients with COVID-19, yet data on thrombosis, bleeding, and therapeutic anticoagulation in this population are limited.
Methods: The investigators analyzed data from 3,239 critically ill adults with COVID-19 at 67 hospitals across the United States, for the incidence of VTE, major bleeding, and other coagulation-associated complications within 14 days of ICU admission. In the primary analysis, investigators estimated the effect of therapeutic anticoagulation on 28-day survival by emulating a target trial in which critically ill patients with COVID-19 were assigned to receive or not receive therapeutic anticoagulation within the first 2 days of ICU admission.
Results: During the first 14 days of ICU admission, a total of 204 patients (6.3%) developed radiographically confirmed VTE, 90 (2.8%) had a major bleeding event (of which 66.7% occurred while receiving therapeutic anticoagulation), 48 (1.5%) developed disseminated intravascular coagulation, and 18 (0.6%) developed heparin-induced thrombocytopenia. Although mortality in patients with VTE (38.2%) was similar to that in the cohort overall, 71.1% of patients with major bleeding died within 28 days.
In a multivariable logistic model, independent predictors of VTE were male sex (odds ratio [OR] = 1.70; CI = 1.05–2.77), severe obesity (OR = 2.08; CI = 1.17–3.70 for body mass index ≥ 40 vs < 30 kg/m2), and higher D-dimer levels (OR = 4.20; CI = 2.17–8.14 for > 10,000 vs ≤ 1,000 ng/mL).
In the primary analysis, during a median follow-up of 27 days, patients who received therapeutic anticoagulation had a similar risk of death as those who did not (HR = 1.12; 95% CI = 0.92–1.35).
Clinical Implications: Among critically ill adults with COVID-19, the 14-day rates of radiographically confirmed VTE and major bleeding were 6.3% and 2.8%, respectively. Major bleeding was highly morbid. Male sex, severe obesity, and elevated D-dimer levels on ICU admission were independent predictors of VTE. In a target trial emulation controlling for 22 baseline characteristics and severity-of-illness covariates, receipt of therapeutic anticoagulation early after ICU admission did not appear to affect survival. The data from this analysis confirm known risk factors for poor outcomes. Study limitations include those of health claims database analyses, which also inform the simulated effect of anticoagulation. Randomized controlled trials are needed.
COVID-19 is associated with increased microvascular and macrovascular thrombotic events. Although data presented at the ASH meeting give us a look at the current status from observations at individual centers or from large claims, hospital databases can shed light on events and outcomes with different anticoagulant practices. Randomized controlled clinical trials are truly needed to determine the best clinical practice and associated benefits and risks. Such studies are now in progress, and we await the results.
Dr. Abutalib is Associate Director of the Hematology and BMT/Cellular Therapy Programs and Director of the Clinical Apheresis Program at the Cancer Treatment Centers of America, Zion, Illinois; Associate Professor at Rosalind Franklin University of Medicine and Science; and Founder and Co-Editor of Advances in Cell and Gene Therapy. Dr. Connors is Associate Professor and Medical Director of the Anticoagulation Management Service in the Hematology Division Brigham and Women’s Hospital, Harvard Medical School, Boston.
DISCLOSURE: Dr. Abutalib has served on the advisory board for AstraZeneca. Dr. Connors has served as a consultant or advisor to Bristol Myers Squibb/Pfizer and Portola Pharmaceuticals and has received institutional research funding from CSL Behring.
1. Li A, Kuderer NM, Warner JL, et al: Incidence of and risk factors for venous thromboembolism among hospitalized patients with cancer and COVID-19: Report from the COVID-19 and Cancer Consortium (CCC19) Registry. 2020 ASH Annual Meeting & Exposition. Abstract 204. Presented December 5, 2020.
2. Kuderer NM, Choueiri TK, Shah DP, et al: Clinical impact of COVID-19 on patients with cancer (CCC19): A cohort study. Lancet 395:1907-1918, 2020.
3. Giannis D, Allen SL, Davidson A, et al: Thromboembolic outcomes of hospitalized COVID-19 patients in the 90-day post-discharge period: Early data from the Northwell CORE-19 Registry. 2020 ASH Annual Meeting & Exposition. Abstract 443. Presented December 6, 2020.
4. Ionescu F, Nair GB, Petrescu I, et al: Increasing doses of anticoagulation are associated with improved survival in hospitalized COVID-19 patients. 2020 ASH Annual Meeting & Exposition. Abstract 577. Presented December 7, 2020.
5. Al-Samkari, H, Gupta S, Leaf RK, et al: Thrombosis, bleeding, and the effect of anticoagulation on survival in critically ill patients with COVID-19 in the United States. 2020 ASH Annual Meeting & Exposition. Abstract 581. Presented December 7, 2020.