Arterial Thrombotic Events Research Articles

Estimated plasma volume status in COVID-19 patients and its relation to comorbidities and clinical outcomes.

Blood plasma is a large reservoir of circulating mediators of inflammation and its expansion has been associated with unfavorable outcomes in patients with inflammatory and cardiovascular diseases. The aim of this study was to determine clinical and prognostic value of estimated plasma volume status (ePVS) in hospitalized patients with COVID-19. We retrospectively investigated 5871 consecutive COVID-19 patient hospitalized in our tertiary-level institution in period 3/2020-6/2021. ePVS was determined using the Strauss-derived Duarte formula and was correlated with clinical characteristics and unwanted outcomes. Median ePVS was 4.77dl/g with interquartile range 4.11-5.74. Higher ePVS was significantly associated with older age, female sex, higher comorbidity burden, worse functional status, less severe COVID-19 clinical presentation with lower severity and longer duration of symptoms, but more pronounced inflammatory profile with higher C-reactive protein, interleukin-6 and D-dimer levels (P < 0.05 for all analyses). In the multivariate regression analysis U shaped relationship of ePVS with mortality was revealed, present independently of age, sex, COVID-19 severity and comorbidity burden. In addition, higher ePVS was independently associated with higher tendency for mechanical ventilation, intensive care unit treatment, venous thromboembolism, major bleeding and bacteriemia and lower ePVS was independently associated with tendency for arterial thrombotic events. Higher ePVS, indicative of plasma volume expansion and inflammatory cytokine accumulation, may predispose respiratory deterioration and venous thromboembolism, despite less severe initial clinical presentation. Lower ePVS, indicative of hemoconcentration, may predispose arterial thrombotic events. Both may be associated with higher mortality in hospitalized COVID-19 patients.

Anticoagulation for the Prevention of Arterial Thrombosis in Ambulatory Cancer Patients: Systematic Review and Meta-Analysis.

The risk of arterial thrombotic events (ATEs) is high among patients on systemic anticancer therapies. Despite the efficacy of anticoagulants in the prevention of cancer-associated venous thromboembolism, it is unknown whether anticoagulation is effective to prevent ATEs. This study sought to examine the efficacy and safety of anticoagulants in ATE prevention among ambulatory cancer patients. We performed a systematic review using Medline, Embase, Scopus, and Cochrane Central Register of Controlled Trials (CENTRAL) from inception to May 21, 2022, and included studies comparing oral or parenteral anticoagulation with no anticoagulation among ambulatory patients receiving systemic anticancer therapy with no other indication for anticoagulation. The primary outcome was ATE (myocardial infarction, ischemic stroke, intra-abdominal arterial embolism, or peripheral artery occlusion). The secondary outcomes were major and nonmajor bleeding and all-cause mortality. Fourteen randomized trials involving low-molecular-weight heparins, direct oral anticoagulants, and warfarin were included. ATEs were captured as coefficacy endpoints or adverse events. Anticoagulant use was not associated with a reduction in ATEs compared with placebo or standard treatment (RR: 0.73, 95% CI: 0.50-1.04; P = 0.08; I2=0%). RRs of major and minor bleeding were 1.56 (95% CI: 1.12-2.17) and 2.25 (95% CI: 1.45-3.48) with anticoagulant use. In 13 trials that reported all-cause mortality, risk of death was not reduced with anticoagulants (RR: 0.99; 95% CI: 0.95-1.02; P = 0.38; I2 = 0%). Anticoagulants did not reduce ATE risk among ambulatory patients on systemic anticancer therapy and were associated with increased bleeding. Based on the current data, anticoagulants have a limited role in ATE prevention in this population as a whole.

Real world utilization of Andexanet alfa in the management of oral factor Xa inhibitor-associated gastrointestinal bleeding

BackgroundAndexanet alfa (AA) is approved for reversal of factor Xa inhibitor (FXaI) bleeds; however, there are limited reports of its use for gastrointestinal bleeding (GIB) in real-world populations. The objective of this study was to report real-world utilization and evaluation of the effectiveness of AA for FXaI-associated GIB. MethodsThis retrospective cohort study including consecutive patients receiving AA for FXaI-associated GIB (7/2018–2/2021). Demographics, blood product administration, hemostatic efficacy, rebleeding, thrombosis, and mortality rates were collected. Hemostatic efficacy (HE), based on corrected hemoglobin at 12 h compared to baseline, was categorized as excellent (<10% decrease), good (≤ 20% decrease), or poor (>20% decrease, > 2 units of additional coagulation intervention or death prior to repeat hemoglobin). Comparative transfusion requirements between efficacy groups was assessed by Wilcoxon-Rank test. ResultsTwenty-two patients were included (64% male, median (IQR) age 76 years (67, 80). Most patients (59%, n = 13) were on apixaban, and the primary anticoagulation indication was atrial fibrillation (64%, n = 14). Median initial hemoglobin was 7.5 g/dL (IQR 6.4, 8.8) and 50% (n = 11) were upper GIB. Hemostatic efficacy was excellent in 46% (n = 10), good in 23% (n = 5), and poor in 32% (n = 7). There was no statistically significant difference in red blood cells (RBCs) received between those with excellent/good hemostasis (median 2, IQR 1 to 2) and those with poor hemostasis (median 4, IQR 1.5 to 4.5). Two patients (9%) had arterial thrombotic events within 30 days of reversal. ConclusionIn this multicenter, single arm, real-world observational analysis of patients with factor Xa inhibitor associated GIB most patients achieved good hemostasis following administration of AA. There was a 9% 30-day thrombotic event rate. The lack of a control group limits the strength of the conclusions that can be drawn from this study.

Post-COVID-19 Arterial Thrombotic Events among Three Major Permutations of COVID-19.

Post-COVID-19 thrombotic events are a crucial trouble of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, affecting hundreds of thousands of people internationally. Further proof is needed at the chance of putting up COVID-19 thrombotic activities after infection with specific editions of COVID-19. In the gift state of affairs, when the maximum of human beings gets vaccinated, COVID-19 sickness is less likely. However, the remnants of preceding COVID-19 infections are nonetheless a sizeable fitness burden. This prospective, observational, comparative, and analytical look at a total of 3,220 COVID-19 sufferers who visited the medical institution. We covered 1,050 sufferers of α-variants; 1,275 sufferers of δ-variants; 895 sufferers of Omicron variations; from June to November 2020, March to July 2021, and January to April 2022, respectively. The affected person's records concerning demography, clinical profile, comorbidities, the severity of the disorder, clinic stay, and vaccination repute were accrued and all sufferers have been accompanied up for 6 months of duration. The sufferers who evolved post-COVID-19 thrombotic events have been approached to gather records regarding demography, comorbidities, the severity of the disease, and vaccination assay. All accumulated information has been tabulated, compiled, and analyzed to examine the post-COVID-19 thrombotic occasions among exceptional variants of COVID-19. A complete of 246 (7.48%) patients [190 (14.90%) of the δ-variant, 41 (3.90%) of the α-variant, and 15 (1.68%) of Omicron version] evolved post-COVID-19 thrombotic occasions at some stage in their comply with-up period. In this observation, distinctly popular post-COVID-19 thrombotic occasions changed into coronary artery ailment (50.00%) which turned followed via cerebral vascular sickness (38.61%), abdominal vessels disease (5.69%), and peripheral artery disease (5.69%). These thrombotic occasions were not unique to any variations of SARS-CoV-2. The distinction of implying the age of patients suffering from post-COVID-19 thrombotic activities became statistically giant (p &lt; 0.05) in comparison amongst all versions. At the time of analysis of COVID-19, 86.17% of sufferers with put-up COVID-19 thrombotic occasions had slight to excessive sickness whilst 13.82% had slight to asymptomatic disorder. The common time length to develop and publish COVID-19 thrombotic events for δ 137.18, Omicron 145.18, and α-version turned 149.85 days. Sufferers inflamed with the δ-variant of COVID-19 are greater vulnerable to developing submit COVID-19 thrombotic events with minimum hazard within the Omicron version and intermediate risk within the α-version. The hazard of submitting COVID-19 thrombotic activities is directly proportional to the severity of the sickness.

Acute Myocardial Infarction in Patients with Hereditary Thrombophilia-A Focus on Factor V Leiden and Prothrombin G20210A.

Factor V (FV) Leiden and prothrombin G20210A are the most common hereditary thrombophilias. While their role in venous thromboembolism is well known, there are still uncertainties regarding their relationship with arterial thrombotic events, especially coronary ones. Our research, based on an in-depth analysis of the available literature, provides up-to-date information on the relationship between FV Leiden and prothrombin G20210A and acute myocardial infarction. FV Leiden and prothrombin G20210A screening should be implemented only in select cases, such as acute coronary syndrome in young individuals and/or in the absence of traditional cardiovascular risk factors and/or in the absence of significant coronary artery stenosis at angiography. Their identification should be followed by the implementation of optimal control of modifiable traditional cardiovascular risk factors to reduce the risk of recurrent events and genotyping and genetic counseling of all family members of affected cases for proper prophylaxis. An extended dual antiplatelet therapy (DAPT) may be considered, given the lower risk of bleeding under DAPT conferred by FV Leiden.

Arterial Thrombosis in Patients with Acute Myeloid Leukemia: Incidence and Risk Factors.

Patients with hematological malignancies have an increased risk of arterial thrombotic events (ATEs) after diagnosis, compared to matched controls without cancer. However, data about incidence and risk factors for ATE development in patients with acute myeloid leukemia (AML) are missing. The objectives of this study were to determine the incidence of ATE in non-promyelocytic-AML patients and to define the potential risk factors for ATE development. We conducted a retrospective cohort study of adult patients with newly diagnosed AML. The primary outcome was the occurrence of confirmed ATE, defined as myocardial infarction, stroke or critical limb ischemia. Out of 626 eligible AML patients, 18 (2.9%) patients developed ATE in the median time of 3 (range: 0.23-6) months. Half of these patients died due to ATE complications. Five parameters were predictors of ATE: BMI > 30 (p = 0.000, odds ratio [OR] 20.488, 95% CI: 6.581-63.780), prior history of TE (p = 0.041, OR 4.233, 95% CI: 1.329-13.486), presence of comorbidities (p = 0.027, OR 5.318, 95% CI: 1.212-23.342), presence of cardiovascular comorbidities (p < 0.0001, OR 8.0168, 95% CI: 2.948-21.800) and cytogenetic risk score (p = 0.002, OR 2.113, 95% CI: 1.092-5.007). Our study showed that patients with AML are at increased risk of ATE. The risk was increased in patients with cardiovascular comorbidities, previous thrombosis, adverse cytogenetic risk as well as BMI > 30.

The particularities of hemostasis in patients with non-ST elevation myocardial infarction and some comorbidities

The formation of an obstructive thrombus within an artery remains a major cause of mortality and morbidity worldwide. [1] Despite effective inhibition of platelet function by modern antiplatelet therapies, these agents fail to fully eliminate atherothrombotic risk. This may well be related to extensive vascular disease, beyond the protective abilities of the treatment agents used. However, recent evidence suggests that residual vascular risk in those treated with modern antiplatelet therapies is related, at least in part, to impaired fibrin clot lysis. Along these lines, thrombosis is the result of several changes in local homeostasis: endothelial dysfunction, changes in the fibrinolytic system, increased content of some coagulation factors, decreased natural inhibitors, platelet hyperactivity [2] [3]. In this review, we attempt to shed more light on the role of hypofibrinolysis in predisposition to arterial vascular events. We provide a brief overview of the coagulation system followed by addressing the role of impaired coagulation, anticoagulation, and fibrinolysis in acute vascular conditions, including coronary artery disease. We also discuss the prognostic implications of coagulation biomarkers regarding arterial thrombotic events, addressing, in particular, people who are exposed to metabolic risks (hyperlipidemia, hypertension, and diabetes). We conclude that affecting coagulation appears to contribute to residual thrombosis risk in individuals with arterial disease on antiplatelet therapy, and targeting proteins in the fibrinolytic and coagulant system represents a viable strategy to improve outcomes in this population. Future work is required to refine the antithrombotic approach by modulating pathological abnormalities in the fibrinolytic and anticoagulant system and tailoring the therapy according to the need of each individual

The impact of renin-angiotensin-aldosterone system inhibitors on immune checkpoint inhibitor-associated adverse cardiovascular events.

2605 Background: Immune checkpoint inhibitors (ICIs) are associated with adverse cardiovascular events that impair patient outcomes. Previous observational studies showed that renin-angiotensin-aldosterone system inhibitors (RAASi) may mitigate the cardiotoxicity associated with chemotherapeutic agents. However, the effects of RAASi on ICI-associated adverse cardiovascular events are unknown. Methods: We conducted a 1:1 propensity score-matched cohort study involving ICI-treated patients at two tertiary referral centers in Taiwan. The propensity score matching model includes age, sex, hypertension, diabetes mellitus, chronic kidney disease, Eastern Cooperative Oncology Group (ECOG) Performance Scale, cancer stage, and cancer type. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of myocardial infarction (MI), ischemic stroke, peripheral arterial occlusive disease (PAOD), pulmonary embolism (PE), deep venous thrombosis (DVT), heart failure, pericardial disease, myocarditis, and cardiac arrhythmias. The secondary outcomes were arterial thrombotic events (MI, ischemic stroke, PAOD) and venous thrombotic events (PE and DVT). Results: We identified 684 patients eligible for inclusion, from which 164 patients who received RAASi were matched to patients who did not receive RAASi. Over a median follow-up of 9.1 months, the incidence rate of MACE for RAASi and non-RAASi recipients was 6.5 and 13.9 per 100 patient-years, respectively, resulting in an incidence rate ratio of 0.47 [95% CI: 0.21–1.00] (p = 0.038). In a multivariate Cox proportional hazard model adjusting for cancer therapy, RAASi recipients had an approximately 60% reduction in the risk for MACE (HR, 0.37 [95% CI: 0.16-0.86], p = 0.021). In the secondary analysis, RAASi were associated with a reduction in venous thrombotic events (HR, 0.11 [95% CI: 0.02-0.63], p = 0.013), but not for arterial thrombotic events (HR, 0.47 [95% CI: 0.06-3.38], p = 0.45). Conclusions: In patients receiving ICI therapy, the use of RAASi is associated with a decreased cardiovascular risk, particularly for venous thrombotic events. [Table: see text]

Major cardiovascular events after COVID-19, event rates post-vaccination, antiviral or anti-inflammatory therapy, and temporal trends: Rationale and methodology of the CORONA-VTE-Network study

BackgroundCoronavirus disease 2019 (COVID-19) is associated with excess risk of cardiovascular and thrombotic events in the early post-infection period and during convalescence. Despite the progress in our understanding of cardiovascular complications, uncertainty persists with respect to more recent event rates, temporal trends, association between vaccination status and outcomes, and findings within vulnerable subgroups such as older adults (aged 65 years or older), or those undergoing hemodialysis. Sex-informed findings, including results among pregnant and breastfeeding women, as well as adjusted comparisons between male and female adults are similarly understudied. MethodsAdult patients, aged ≥18 years, with polymerase chain reaction-confirmed COVID-19 who received inpatient or outpatient care at the participating centers of the registry are eligible for inclusion. A total of 10,000 patients have been included in this multicenter study, with Brigham and Women's Hospital (Boston, MA) serving as the coordinating center. Other sites include Beth Israel Deaconess Medical Center, Anne Arundel Medical Center, University of Virginia Medical Center, University of Colorado Health System, and Thomas Jefferson University Health System. Data elements will be ascertained manually for accuracy. The two main outcomes are 1) a composite of venous or arterial thrombotic events, and 2) a composite of major cardiovascular events, defined as venous or arterial thrombosis, myocarditis or heart failure with inpatient treatment, new atrial fibrillation/flutter, or cardiovascular death. Clinical outcomes are adjudicated by independent physicians. Vaccination status and time of inclusion in the study will be ascertained for subgroup-specific analyses. Outcomes are pre-specified to be reported separately for hospitalized patients versus those who were initially receiving outpatient care. Outcomes will be reported at 30-day and 90-day follow-up. Data cleaning at the sites and the data coordinating center and outcomes adjudication process are in-progress. ConclusionsThe CORONA-VTE-Network study will share contemporary information related to rates of cardiovascular and thrombotic events in patients with COVID-19 overall, as well as within key subgroups, including by time of inclusion, vaccination status, patients undergoing hemodialysis, the elderly, and sex-informed analyses such as comparison of women and men, or among pregnant and breastfeeding women.

Arterial events in cancer patients treated with apixaban for venous thrombosis

IntroductionIn a recent interventional study of cancer patients with newly diagnosed venous thrombosis (VT), we found a high risk of arterial thrombotic events (AT) during treatment with therapeutic doses of apixaban. MethodsTotal 298 cancer patients with VT received apixaban as treatment and secondary prophylaxis for up to 36 months. AT was registered as a serious adverse event, and this is a post hoc analysis of risk factors for AT. Clinical risk factors and concomitant medication were assessed through odds ratios (OR) with 95 % confidence interval using multivariate logistic regression. Biomarkers were assessed by non-parametric testing. ResultsAT occurred in 16/298 patients (5.4 %, 95 % confidence interval (CI) 3.1–8.6 %). Median leucocyte count at baseline was higher in patients with AT compared with patients without AT (11 vs. 6.8·109/L, p < 0.01). Clinical factors associated with AT were pancreatic cancer (OR 13.7, 95 % CI 4.3–43.1), ovarian cancer (OR 19.3, 95 % CI 2.3–164.4), BMI <25 percentile (OR 3.1, 95 % CI 1.1–8.8) and previous VT (OR 4.4, 95 % CI 1.4–13.7). Pancreatic cancer had a cumulative incidence of AT of 36 % compared with 0.8 % for all other cancers at 6 months (p < 0.01). Non-steroidal anti-inflammatory drugs (OR 4.9, 95 % CI 1.0–26) and antiplatelet treatment (OR 3.8, 95 % CI 1.2–12.2) were associated with AT. ConclusionIn cancer patients with apixaban treated VT, pancreatic cancer was strongly associated with AT. In addition, ovarian cancer, BMI < 25 percentile, previous VT, antiplatelet treatment, non-steroidal anti-inflammatory drug use and high leucocyte count at baseline were associated with AT.The CAP study is registered with the unique identifier NCT02581176 in ClinicalTrials.gov.

Outcomes associated with sodium glucose co-transporter 2 inhibitors in anticoagulated atrial fibrillation patients

Abstract Funding Acknowledgements Type of funding sources: None. Background Sodium glucose co-transporter 2 inhibitors (SGLT2i) have been associated with favourable outcomes in patients with heart failure. Studies also indicate a reduced risk of atrial fibrillation (AF). Purpose We performed an exploratory analysis to evaluate the impact of SGLT2 inhibitors in anticoagulated patients with AF. Method All anticoagulated patients with AF and type 2 diabetes between January 2014 and December 2018 were identified from a federated electronic medical record database (TriNetX), and followed up for 3 years. A 1:1 propensity score matched (PSM) analysis was performed to balance the SGLT-2i and non-SGLT-2i cohorts. The primary outcome was ischaemic stroke/ transient ischaemic attack (TIA), bleeding events, hospitalisation for AF and composite of cardioversion and ablations. Secondary outcomes included all-cause mortality, haemorrhagic stroke, ventricular arrhythmias, cardiac arrest, incident heart failure and composite of arterial and venous thrombotic events. Results A total of 236,493 and 20,841 were identified from the non-SGLT2 and SGLT2 inhibitor groups respectively. After PSM, each group had 17,968 patients. In anticoagulated AF patients, SGLT2 inhibitor use was associated with a significantly lower risk of ischaemic stroke/ TIA, hazard ratio (HR) 0.759 (95% CI 0.719-0.802), bleeding HR 0.657 (95% CI 0.619-0.697), hospitalisation for AF HR 0.875 (95% CI 0.855-0.897), and composite of cardioversion/ablations HR 0.705 (95% CI 0.655-0.759). A lower risk of all-cause mortality HR 0.481 (95% CI 0.453-0.510), haemorrhagic stroke HR 0.54 (95% CI 0.454-0.642), ventricular arrhythmias HR 0.766 (95% CI 0.719-0.816), cardiac arrests HR 0.539 (95% CI 0.476-0.611), incident heart failure HR 0.709 (95% CI 0.661-0.760) and composite of arterial and venous thrombotic events HR 0.737 (95% CI 0.712-0.763) were also observed with SGLT2 inhibitor use. Conclusion Our findings suggest that SGLT2i use is associated with a lower risk of AF-related complications such as ischaemic stroke/ TIA, bleeding, ventricular arrhythmias and reduced need for procedures such as cardioversion and ablations. Further studies are required to confirm this association.

Remdesivir use in severe and critical COVID-19 patients might be associated with lower incidence of arterial thrombotic events

IntroductionVenous thromboembolism (VTE) and arterial thrombotic (AT) events are a striking feature of severe COVID-19, however, relationship of remdesivir use and the risk of thrombotic events is unknown and has not been investigated before. MethodsWe retrospectively analyzed a cohort of 876 consecutive hospitalized severe and critical COVID-19 patients who were treated with remdesivir and compared them to 876 case-matched control patients. All patients were treated in our tertiary-level institution in period from 10/2020 to 6/2021. VTE and AT were diagnosed by objective imaging and laboratory methods. ResultsAfter exclusion of 71 VTE and 37 AT events present at the time of hospital admission, there were a total of 70 VTE (35 in the remdesivir and 35 in the control group) and 38 AT events occurring during hospitalization (13 in the remdesivir and 25 in the control group). There was a similar cumulative post-admission VTE incidence among both remdesivir and matched control patients (P = 0.287). Significantly lower cumulative post-admission AT incidence was observed among patients treated with remdesivir than among matched control patients (1.7% vs 3.3%, HR = 0.51, P = 0.035). Tendency for lower AT rates was evident in subgroups of patients stratified according to the type of AT, as well as according to the intensity of required oxygen supplementation at the time of remdesivir use. ConclusionRemdesivir use in severe and critical COVID-19 patients might be associated with lower occurrence of AT during hospitalization, whereas similar rates of VTE events were observed among both patients treated with remdesivir and control patients.

The Pattern of Thrombosis in Patients with JAK2 V617F Mutation

Background: JAK2V617F mutation is recurrent in MPN and reported as a marker for occult MPN in patients with splanchnic vein thrombosis. Objective: To better estimate the pattern of arterial and venous thrombosis in a Lebanese series in order to define the potential risk and to evaluate the current treatment. Methods: Ninety-five consecutive patients were included and all arterial and venous thrombotic events were documented, altogether with the clinical and demographic data. Results: Twenty-eight % of patients developed arterial thrombosis and 29% venous thrombosis with PV predilection for DVT and BCS. 27% and 5% of patients had thrombosis at presentation or history of thrombosis. However; subsequent thrombosis may develop in 20% of cases and may be the cause of death in 12.6%. Two cases with family aggregation were observed. Conclusion: Close surveillance should be carried out in JAK2V617F-mutated patients with special attention to subsequent thrombosis development. Familial clustering should be looked for.

Venous thromboembolism secondary to hospitalization for COVID-19: patient management and long-term outcomes

BackgroundVenous thromboembolism (VTE) is a complication of COVID-19 in hospitalized patients. Little information is available on long-term outcomes of VTE in this population. ObjectivesWe aimed to compare the characteristics, management strategies, and long-term clinical outcomes between patients with COVID-19–associated VTE and patients with VTE provoked by hospitalization for other acute medical illnesses. MethodsThis is an observational cohort study, with a prospective cohort of 278 patients with COVID-19–associated VTE enrolled between 2020 and 2021 and a comparison cohort of 300 patients without COVID-19 enrolled in the ongoing START2-Register between 2018 and 2020. Exclusion criteria included age <18 years, other indications to anticoagulant treatment, active cancer, recent (<3 months) major surgery, trauma, pregnancy, and participation in interventional studies. All patients were followed up for a minimum of 12 months after treatment discontinuation. Primary end point was the occurrence of venous and arterial thrombotic events. ResultsPatients with VTE secondary to COVID-19 had more frequent pulmonary embolism without deep vein thrombosis than controls (83.1% vs 46.2%, P <.001), lower prevalence of chronic inflammatory disease (1.4% and 16.3%, P <.001), and history of VTE (5.0% and 19.0%, P <.001). The median duration of anticoagulant treatment (194 and 225 days, P = 0.9) and the proportion of patients who discontinued anticoagulation (78.0% and 75.0%, P = 0.4) were similar between the 2 groups. Thrombotic event rates after discontinuation were 1.5 and 2.6 per 100 patient-years, respectively (P = 0.4). ConclusionThe risk of recurrent thrombotic events in patients with COVID-19–associated VTE is low and similar to the risk observed in patients with VTE secondary to hospitalization for other medical diseases.

Immune checkpoint inhibitor-associated thrombosis in patients with bladder and kidney cancer: a study of the Spanish Society of Medical Oncology (SEOM) thrombosis and cancer group

PurposeBoth venous and arterial thrombotic events (VTE/AT) can be associated with immune checkpoint inhibitors (ICI). However, there is a paucity of information apropos patients in routine clinical practice.Methods/patientsRetrospective, multicenter study promoted by the Thrombosis and Cancer Section of the Spanish Society of Medical Oncology (SEOM). Individuals with kidney or bladder cancer who initiated ICI between 01/01/2015 and 12/31/2020 were recruited. Minimum follow-up was 6 months (except in cases of demise). The primary objective was to calculate the incidence of ICI-associated VTE/AT and secondary objectives included to analyze their impact on survival and identify variables predictive of VTE/AT.Results210 patients with kidney cancer were enrolled. The incidence of VTE/AT during follow-up (median 13 months) was 5.7%. Median overall survival (OS) was relatively lower among subjects with VTE/AT (16 months, 95% CI 0.01–34.2 vs. 27 months, 95% CI 22.6–31.4; p = 0.43). Multivariate analysis failed to reveal predictive variables for developing VTE/ AT.197 patients with bladder were enrolled. There was a 9.1% incidence rate of VTE/AT during follow-up (median 8 months). Median OS was somewhat higher in patients with VTE/AT (28 months, 95% CI 18.4–37.6 vs 25 months, 95% CI 20.7–29.3; p = 0.821). Serum albumin levels < 3.5 g/dl were predictive of VTE/ AT (p < 0.05).ConclusionsThere appears to be no association between developing VTE/AT and ICI use in patients with renal or bladder cancer. Serum albumin levels are a predictive factor in individuals with bladder cancer.

Abstract 3217: Risk of thromboembolism in patients with non-small lung cancer (NSCLC) treated with immune check point inhibitors (ICIs) versus chemoimmunotherapy (ChemoIO)

Abstract Background: Immune checkpoint inhibitors with or without chemotherapy form the backbone of treatment for patients with advanced NSCLC without an actionable driver mutation. Emerging literature shows that ICIs increase the risk of venous thromboembolism (VTE), which is a major cause of death in patients with NSCLC. The mechanism is yet to be elucidated but is likely secondary to inflammation. Since chemotherapy is immunosuppressive, we sought to understand if the addition of chemotherapy to ICIs impacted the incidence of VTEs. Methods: We performed a retrospective cohort study to evaluate thromboembolic outcomes in patients diagnosed with advanced NSCLC between 2012 and 2018 and treated with either ICIs or chemo immunotherapy at Cleveland Clinic Foundation. Diagnosis of thrombotic events (TE) (arterial/deep vein thrombosis and/or pulmonary embolism) was confirmed by imaging. Overall survival (OS) was estimated by Kaplan-Meier and compared using log rank test. Odds of developing TE was estimated and compared between ICI and ChemoIO groups, using Fisher's Exact Test. Results: A total of 367 NSCLC patients (242 pts on ICI only and 125 pts on ChemoIO regimen), were identified with a median age 65 years ( range 58-72), 52% were men, 82% white, 85.3% smokers, 91.8% had ECOG ≤2, 73 % had adenocarcinoma and 18% had squamous cell carcinoma, 34% with brain metastasis and the distribution of PDL1expression was as follows- &amp;lt;1 (26.4%), 1-49% (48%) and ≥50% (25.6%). Adjusted response rates to treatment were (N, %): Complete Response (CR) (6/367, 1.9%), Partial Response (PR) (96/367, 30%), Stable Disease (SD) (76/367, 24%) and PD (143/367, 45%). TE was detected in 19% of the cohort (n=70) (8.4% DVT, 4.9% PE, 5.2 % both, and 0.5 % arterial TE. Rate of TE in NSCLC pts on ICI alone was 18% (44/242) Vs. 21% (26/125) for those on ChemoIO (OR 1.5, 95% CI 0.66-2.1, P 0.6). Development of TEs was not associated with survival differences with either regimen (P &amp;gt;0.05). Conclusion: Rates of TE were high in patients with advanced NSCLC who received ICI therapy, but no different if treated with ICIs alone or ChemoIO. Further studies to better understand the pathophysiology of TE in patients treated with ICIs might allow us to identify subgroups of patients that are at the highest risk for TEs. Citation Format: Doaa Attia, Ran Zhao, Alok A. Khorana, Prandya Patil. Risk of thromboembolism in patients with non-small lung cancer (NSCLC) treated with immune check point inhibitors (ICIs) versus chemoimmunotherapy (ChemoIO) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3217.

In thrombotic antiphospholipid syndrome, DOACs vs. VKAs increase arterial thrombotic events but not major bleeding.

Khairani CD, Bejjani A, Piazza G, et al. Direct oral anticoagulants vs vitamin K antagonists in patients with antiphospholipid syndromes: meta-analysis of randomized trials. J Am Coll Cardiol. 2023;81:16-30. 36328154.

The APSANTICO Study: A Prospective Observational Study to Evaluate Antiphospholipid Antibody Profiles in Patients with Thromboembolic Antiphospholipid Syndrome (APS) after COVID-19 Infection and/or Vaccination

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new virus discovered in December 2019 that causes coronavirus disease 19 (COVID-19) and various vaccinations have been developed. The extent to which COVID-19 infections and/or COVID-19 vaccinations alter antiphospholipid antibodies (aPL) in patients with thromboembolic antiphospholipid syndrome (APS) remains unclear. Eighty-two patients with confirmed thromboembolic APS were included in this prospective non-interventional trial. Blood parameters including lupus anticoagulants, anticardiolipin IgG- and IgM-antibodies, and anti-ß2-glycoprotein I IgG- and IgM-antibodies were assessed prior to and after COVID-19 vaccination and/or COVID-19 infection. No increases in aPL in the total study population were detected. In fact, low but significant decreases were observed for anticardiolipin IgG- and anti-β2-glycoprotein I IgG-antibodies, while anticardiolipin IgM- and anti-b2-glycoprotein I IgM-antibodies slightly increased only in patients with COVID-19 infection and vaccination. Although the investigated patient group is known to have a high risk of recurrent thrombosis, only one arterial thrombotic event was diagnosed (1.2%, 1/82). This low recurrence rate was probably due to the high vaccination rates prior to infections and a high rate of effective anticoagulation. Our data show that COVID-19 infections and/or vaccinations do not deteriorate the clinical course of anticoagulated thromboembolic APS patients.

An investigation to find the correlation between lupus anticoagulant and coagulation abnormalities in COVID-19 patients; a narrative review

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19) which is associated with nonspecific respiratory syndromes, varying from mild symptoms of upper airway to required mechanical ventilation hypoxemia. A unique feature of this disease is COVID-19-associated coagulopathy (CAC) that linked with disease severity and hospital mortality. These patients have a profound hypercoagulable state and in patients with severe type arterial and venous thrombotic events are frequent. Abnormal coagulation parameters such as activated partial thromboplastin time (aPTT) were observed in patients with COVID-19. Regarding the above finding it could be considered as a reason to avoid anticoagulation at the both doses of therapeutic and prophylactic. A prolonged aPTT may indicate a coagulation factor deficiency or inhibitor of coagulation, which can be specific (antibody to factor VIII) or nonspecific (lupus anticoagulant, LA). LA can affect laboratory tests of blood coagulation, but is not usually associated with bleeding; however, it can be associated with thrombotic risk as a part of the antiphospholipid syndrome. In a phospholipid concentration-dependent manner LA recognizes a type of antiphospholipid antibodies (aPLs) that prolong clotting tests. In patients with antiphospholipid syndrome (APS) LA is considered as one of the laboratory criteria representing a significant risk factor of both thrombosis and pregnancy morbidity. Similarities between some of the pathophysiological features of COVID-19 and APS has been focused in several reports particularly in the most severe form, catastrophic APS. This study aimed to evaluate the effect of LA on the incidence of thrombophilia in patients with COVID-19, as well as its impact on the inflammation and finally the mortality final rate.

Emicizumab prophylaxis in haemophilia A with inhibitors: Three years follow-up from the UK Haemophilia Centre Doctors' Organisation (UKHCDO).

The UK National Haemophilia Database (NHD) collects data from all UK persons with haemophilia A with inhibitors (PwHA-I). It is well-placed to investigate patient selection, clinical outcomes, drug safety and other issues not addressed in clinical trials of emicizumab. To determine safety, bleeding outcomes and early effects on joint health of emicizumab prophylaxis in a large, unselected cohort using national registry and patient reported Haemtrack (HT) data between 01 January 2018 and 30 September 2021. Prospectively collected bleeding outcomes were analysed in people with ≥6 months emicizumab HT data and compared with previous treatment if available. Change in paired Haemophilia Joint Health Scores (HJHS) were analysed in a subgroup. Adverse events (AEs) reports were collected and adjudicated centrally. This analysis includes 117 PwHA-I. Mean annualised bleeding rate (ABR) was .32 (95% CI, .18; .39) over a median 42 months treatment with emicizumab. Within-person comparison (n = 74) demonstrated an 89% reduction in ABR after switching to emicizumab and an increase in zero treated bleed rate from 45 to 88% (p < .01). In a subgroup of 37 people, total HJHS improved in 36%, remained stable in 46% and deteriorated in 18%, with a median (IQR) within-person change of -2.0 (-9, 1.5) (p = .04). Three arterial thrombotic events were reported, two possibly drug related. Other AEs were generally non-severe and usually limited to early treatment, included cutaneous reactions (3.6%), headaches (1.4%), nausea (2.8%) and arthralgia (1.4%). Emicizumab prophylaxis is associated with sustained low bleeding rates and was generally well-tolerated in people with haemophilia A and inhibitors.