Anticoagulation In Cancer Patients Research Articles

Usage pattern of anticoagulants in oncology patients receiving active anticancer therapies in Europe and Asia.

e23297 Background: Risks and benefits associated with use of anticoagulants (ACs) in cancer patients should be carefully assessed due to an increased risk of both thrombotic recurrences and bleeding events. Vitamin K antagonists (AVK) have been the most used ACs for patients with atrial fibrillation and venous thromboembolism for many years. Low molecular weight heparins (LMWH) and direct oral anticoagulants (DOACs) are preferred over AVK for cancer associated thrombosis. To better define the current scenario for ACs in cancer patients we propose to use market research data to describe treatment patterns in Europe and Asia. Methods: This study was conducted using Oncology Dynamics, an online secondary market research survey collecting anonymized patient data, from a representative panel of physicians. Data for 11,568 drug-treated oncology patients (p) (9,178 Europe p; 2,390 Asia p) with active cancer and anticoagulant therapies, collected between Q3 2021 and Q3 2023, from 5 European (France, Spain, Germany, Italy, & UK) and 3 Asian countries (China, Japan, & S. Korea), were analyzed. Patients with Genitourinary (GU) tumors were 36%, Lung 19%, Gastrointestinal (GI) 18%, Hepatobiliary/pancreas 12%, Gynecologic (Gyn) 12%, and Melanoma and Brain < 5%. Results: 94% p were aged > 50 years and 49% > 70 years. 64% p were male and 36% female. 67% p showed advanced/metastatic stage vs 33% local/locally advanced stage. Globally, DOACs use was 55%, LMWH 35%, and AVK < 10%; DOACs were the preferred ACs in Europe (64% p) and LMWH in Asia (59% p). Prescription of AVKs in Asia population was higher (17% p) compared with Europe (7% p). Difference in use of ACs by tumor type in European countries in favor of DOACs vs LMWH was noticeable in GU (75% p vs 13% p), GI (61% vs 34%) and Melanoma (71% vs 22%). In Asia population, predominance of LMWH vs DOACs was observable in Gyn (86% p vs 5% p), GI (57% vs 24%) and Hepatobiliary/pancreas (56% vs 35%). AVK were administered in 53% of GU Asia p and DOACs in 31%. Overall, bleeding was more frequently associated with AVK (32% p), compared to DOACs (15% p) and LMWH (9% p). Conclusions: This research highlights the differences in ACs prescription in oncology patients between Asia and Europe, with a preference for LMWH in former and DOACs in the latter. DOACs are the most common ACs prescribed overall, while AVK, associated with higher incidence of bleeding, are used in a small population. A more comprehensive analysis of the included variables will be shared.

Anticoagulation in cancer patients with atrial fibrillation and grade 3–4 thrombocytopenia

IntroductionAtrial fibrillation or flutter (AF) is prevalent in cancer patients. Many of these patients have an indication for anticoagulation (AC) but are also at risk for developing chemotherapy-induced thrombocytopenia. There are scarce data regarding management of AC and risk of bleeding and thrombosis in cancer patients with AF and thrombocytopenia. AimTo assess anticoagulation management and incidence of bleeding and arterial thromboembolism (ATE) in cancer patients with AF and grade 3–4 thrombocytopenia (platelets <50 × 109/L). MethodsA retrospective cohort study included adults with active cancer, grade 3–4 thrombocytopenia and AF with CHA2DS2-VASc score ≥ 1. Patients were stratified according to AC discontinuation (No-AC) or continuation (Continue-AC) when platelets dropped below 50 × 109/L and followed for 30 days. The study outcomes were ATE (ischemic stroke, transient ischemic attack or systemic emboli) and major bleeding. Cox proportional hazards model was used to calculate hazard ratios (HR) with death as a competing risk (Fine and Gray model). ResultsThe cohort included 131 patients; 90 in the No-AC group and 41 in the Continue-AC group. Patient characteristics were balanced between the groups. The 30-day cumulative incidence of ATE was 2 % [95 % CI 0.4 %–7 %] in the No-AC group and 2 % [0.2 %–11 %] in the Continue-AC group (HR 0.92 [95 % CI 0.09–9.88]). The 30-day cumulative incidence of major bleeding was 7.8 % [95 % CI 3.40 %–14.52 %] and 2.44 % [95 % CI 0.18 %–11.22 %] in the No-AC and Continue-AC groups, respectively (HR 3.29 [95 % CI 0.42–26.04]). ConclusionsThe high rate of bleeding and low rate of ATE in thrombocytopenic cancer patients with AF suggests that holding AC during time-limited periods may be a reasonable approach.

Relationships, Current Issues, Safety and Efficacy of Oral Anticoagulation in Cancer Patients with Atrial Fibrillation.

A relationship between malignancy and impaired hemostasis has been proven, and balancing clotting and bleeding risks can be challenging. Half of cancer patients with atrial fibrillation (AF) do not receive any oral anticoagulation (OAC). Using PubMed on the relationship between cancer and AF and their association with hemostasis, targeting studies comparing vitamin K antagonists (VKAs) and direct OAC (DOAC) strategies in AF cancer patients, three RCTs (>3000 patients) and eight observational studies (>250,000 patients) comparing different OACs were retrieved. The VKA prescribed was always warfarin. Dabigatran was the only DOAC not analyzed in the RCTs but the most used in non-randomized studies, whereas edoxaban-treated patients were the majority in the RCTs. Overall, the DOAC patients showed similar or lower rates of efficacy (thromboembolic) and safety (bleeding) outcomes compared to the VKA patients. DOACs are subject to fewer interactions with antineoplastic agents. DOACs may be preferable to VKAs as a thromboembolic prophylaxis in cancer patients with non-valvular AF.

Heparins are potent inhibitors of ectonucleotide pyrophosphatase/phospho-diesterase-1 (NPP1) - a promising target for the immunotherapy of cancer.

Heparins, naturally occurring glycosaminoglycans, are widely used for thrombosis prevention. Upon application as anticoagulants in cancer patients, heparins were found to possess additional antitumor activities. Ectonucleotidases have recently been proposed as novel targets for cancerimmunotherapy. In the present study, we discovered that heparin and its derivatives act as potent, selective, allosteric inhibitors of the poorly investigated ectonucleotidase NPP1 (nucleotide pyrophosphatase/phosphodiesterase-1, CD203a). Structure-activity relationships indicated that NPP1 inhibition could be separated from the compounds' antithrombotic effect. Moreover, unfractionated heparin (UFH) and different low molecular weight heparins (LMWHs) inhibited extracellular adenosine production by the NPP1-expressing glioma cell line U87 at therapeutically relevant concentrations. As a consequence, heparins inhibited the ability of U87 cell supernatants to induce CD4+ T cell differentiation into immunosuppressive Treg cells. NPP1 inhibition likely contributes to the anti-cancer effects of heparins, and their specific optimization may lead to improved therapeutics for the immunotherapy of cancer.

Direct-Acting Oral Anticoagulant Therapy in Cancer Patients-A Review.

Venous thromboembolism (VTE) is an important aspect in cancer patients. There are various pharmacological methods used for thrombotic event treatment. DOACs (direct-acting oral anticoagulants) are gaining popularity among both physicians and researchers and are slowly starting to replace VKAs (vitamin K antagonists), thus becoming a substitute or alternative option for LMWHs (low-molecular-weight heparins). In this article, we present DOACs' main therapeutic advantages and disadvantages in patients with cancer. The only major concern with using DOACs is the higher risk of bleeding; however, there are discrepancies in this matter. There are still some types of cancer for which DOACs are not recommended. Specific cancer types may influence the efficacy of DOAC therapy. Additionally, race and ethnicity may affect therapy in cancer patients with DOACs. A sizeable number of clinical trials are focused on comparing DOACs with other anticoagulants. The current guidelines of different scientific associations are not unanimous in their DOAC assessments. There is still a need for more evidence of DOACs' potential advantages over other methods of anticoagulation in cancer patients to facilitate their position in this recommendation. This literature review presents the current state of knowledge about the use of DOACs in patients with neoplastic growth.

Outcome of antithrombotic therapy in cancer patients with catheter-related thrombosis: a systematic review.

The guidelines' recommendations for anticoagulation in cancer patients with catheter-related thrombosis are unclear. The aim of this systematic review was to assess anticoagulation management in cancer patients with catheter-related thrombosis (CRT) based on previously published studies. As of June 10, 2023,we searched databases including PubMed, Embase, and Cochrane and included 11 observational studies that met the criteria. We evaluated 770 adults with active cancer and objectively confirmed patients with CRT who were using drugs including warfarin, LMWH, and new oral anticoagulants as antithrombotic therapy. We extracted outcome data, including thrombosis recurrence, catheter dysfunction, major bleeding, and death, and performed a meta-analysis. In this study we found that the risk of VTE recurrence was higher with rivaroxaban, the risk of bleeding and death appeared to be greater with warfarin, and although the risk of catheter dysfunction due to LMWH is a concern, it is still a more reasonable option for cancer patients with catheter-related thrombosis. http://www.clinicaltrials.gov, identifier (CRD42022367979).

Effectiveness and Safety of Anticoagulants in Cancer Patients with VTE and Kidney Disease

Introduction: Cancer patients with kidney disease are at increased risk for having venous thromboembolism (VTE) and bleeding than those without kidney disease. There is a lack of evidence about the effectiveness and safety of anticoagulants in cancer patients with VTE and kidney disease. Purpose: To evaluate the effectiveness and safety of different anticoagulants among VTE cancer patients with or without kidney disease. Methods: Adult VTE patients with any active cancer identified between 01SEP2014 and 29SEP2020 who initiated apixaban, low molecular weight heparin (LMWH), or warfarin within 30-days following a VTE were identified from 4 commercial databases and Medicare database. Cancer status was identified in the 6-months prior through 30-days post VTE. Kidney disease (chronic kidney disease plus acute kidney disease) was defined based on diagnosis codes and was identified in the 6-months prior to VTE. Stabilized inverse probability treatment weighting (IPTW) was used to balance patient characteristics between treatment cohorts. After IPTW, VTE cancer patients were stratified by those with and without kidney disease. Incidence rates (IRs) were determined for major bleeding (MB), clinically relevant non-major (CRNM) bleeding and recurrent VTE events within the first 6-months of follow-up. Cox proportional hazard models were used to evaluate interactions between treatments (apixaban or warfarin or LMWH) and kidney disease status on the risk of MB, CRNM bleeding and recurrent VTE events. Interactions with P<0.10 were considered statistically significant. Results: Among the 30,586 VTE cancer patients who met all study criteria 8,858 (29.0%) had kidney disease. Use of warfarin, LMWH and apixaban was similar between those with kidney disease (40.2%, 31.6%, and 28.1%) and without kidney disease (36.9%, 38.6%, and 24.4%, respectively). After IPTW, patient characteristics were balanced between treatment cohorts. Analyses stratified by kidney disease status showed that treatment effects were not significantly different for patients with and without kidney disease (figure). The incidence rates of major bleeding, CRNM bleeding and recurrent VTE events trended lower in the apixaban cohort compared to warfarin or LMWH for both kidney disease and no kidney disease patients (figure). Generally, there were no significant interactions between kidney disease status and treatments on any of the outcomes (figure). Conclusion: Effects of apixaban, LMWH and warfarin on recurrent VTE and bleeding were generally consistent in VTE cancer patients with or without kidney disease. Additional research is needed to identify optimal anticoagulant treatment strategy for VTE cancer patients with kidney disease. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Impact of Thrombocytopenia on Bleeding and Recurrent Thrombosis in Cancer Associated Thrombosis: A Post Hoc Analysis of Hokusai VTE Cancer Study

Background: Thrombosis and thrombocytopenia are both frequent complications in patients with active cancer. Thrombocytopenia can complicate decisions around anticoagulation in cancer associated thrombosis (CAT) but data to guide clinicians is limited. Much of the data on the safety and efficacy of anticoagulation in patients with CAT and thrombocytopenia have been retrospective, single-center, cohort studies. The benefit and risk of direct oral anticoagulants in cancer patients with acute venous thromboembolism (VTE) and thrombocytopenia is incompletely understood. The HOKUSAI VTE Cancer study was a randomized open-label, non-inferiority, phase III trial in CAT that compared dalteparin with edoxaban for at least 6 months. We conducted a post hoc analysis of this trial to investigate the impact of platelet count on bleeding and recurrent thrombosis. Methods: Patients with platelet counts less than 100,000/µL at specified time points (enrollment, day 31 or day 90) were compared with patients with platelet count > 100,000/µL on all three time points. The primary outcomes for these analyses was major bleeding; secondary outcomes were clinically relevant non-major bleeding (CRNMB), recurrent thrombosis and survival. Cumulative incidences of bleeding and thrombosis outcomes were calculated with death as a competing risk. Results: A total of 1045 patients were included in the analyses. , The median age was 65 years and 52% were male. Most common malignancies included colorectal (16%), lung (15%), genitourinary (13%), breast (12%), and hematologic malignancies (11%). Of patients with solid cancers, 53% had metastatic disease and 30% recurrent disease at enrollment. Qualifying thrombotic events included pulmonary embolism for 63% and isolated deep vein thrombosis in 37%. Thrombocytopenia (<100,000/µL) was present in 101 patients (9.6%) of the total cohort. Only 14 patients had a platelet count <50,000/µL at any of the three time points. For the overall trial period the rates of major bleeding were significantly higher in patients with platelet count <100,000/µL (11.9% vs. 4.8%, HR 2.5 P=0.004). (Table 1) Rates of CRNMB were similarly higher in patients with platelet count <100,000/ µL (21.8% vs. 11.9%, HR 1.93, P=0.005), however there was no significant difference in rates of recurrent VTE (11.9% vs. 9.2%, HR 1.28 P=0.42) or overall mortality (37.6% vs. 38%, HR 0.98, P=0.90). Cumulative incidence of major bleeding at 180 days was higher 8.9% (95% CI 3.4-14.5%) in patients with platelet count <100,000/ µL compared to 3.9% (95% CI 2.7-5.2%) in those higher than 100,000/µL. (Figure 1) Conclusion: In this post hoc analysis of a randomized controlled study in CAT, thrombocytopenia (<100,000/µL) was associated with an increased risk of major bleeding by two-fold. No difference in the risk of recurrent thrombosis was detected. These data highlight the importance of recognizing even mild thrombocytopenia as an important risk factor for bleeding in patients being anticoagulated for CAT. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Optimizing antithrombotic therapy for atrial fibrillation in cancer

Atrial fibrillation (AF) may be a pre-existing disease before cancer diagnosis, may be a direct effect of the neoplasm or, more often, appears as a post-surgical complication, especially after thoracic surgery. AF may also develop as a consequence of chemotherapy or radiotherapy. The management of the anticoagulation in cancer patients with AF is challenging, and data on these patients are lacking. The use of vitamin K antagonists (VKAs) may be problematic because of the unpredictable therapeutic response and high bleeding risk in patients with active cancer who are undergoing chemotherapy and who may experience thrombocytopenia and/or changes in renal or hepatic function. Low molecular weight heparins and direct oral anticoagulants (DOACs) could be preferred. However, the possible pharmacological interactions of DOACs with anti-cancer and anti-arrhythmic drugs and the bleeding risks in thrombocytopenic patients should be considered. Based on these considerations, a careful evaluation of the antithrombotic strategy with the best efficacy/safety ratio is always needed in cancer patients and anticoagulation for AF should be tailored individually. An ongoing consultation of oncologists/hematologists with cardiologists and coagulation experts in a multidisciplinary approach, with a periodic re-assessment of the benefits of anticoagulation with changes in cancer status/advancement and treatment plans is needed.

Absorption of Direct Oral Anticoagulants in Cancer Patients after Gastrectomy.

Direct oral anticoagulants (DOACs) are safe and effective in cancer patients treated for venous thromboembolism (VTE) or atrial fibrillation (AF). Gastrectomy is the treatment of choice in patients with localized upper gastrointestinal cancer. DOACs are absorbed in the upper gastrointestinal tract, but to what extent is unclear. In a retrospective analysis, hospital data were searched for adult patients who underwent gastrectomy for gastroesophageal or pancreatic cancer, and DOAC therapy for VTE or AF after gastrectomy. DOAC blood levels were determined by chromogenic assays before and after administration, and thromboembolic and bleeding complications were recorded. Eleven patients (median age 76 years) received a factor Xa inhibitor (FXaI; apixaban (3), edoxaban (3), rivaroxaban (4)) or the factor IIa inhibitor dabigatran (1) for VTE (7) or AF (4) after gastrectomy. Eight patients on FXaI had anti-Xa (aXa) trough levels within the expected range (ER). In all of them, aXa levels increased upon DOAC administration. Two patients on 30 mg edoxaban had low aXa trough levels. Administration of 20 mg of rivaroxaban resulted in trough levels in the ER in one of them. None of the FXaI patients had thromboembolism, while two experienced bleeding (arterial puncture site, gastrointestinal). One dabigatran AF patient with trough and peak concentrations below the ER had strokes during 110 mg and 150 mg dabigatran administration. While on apixaban, aXa levels were in the ER, and no clinical complications occurred. DOACs, particularly FXaI, were adequately absorbed in cancer patients after gastrectomy. Our observation of recurrent thromboembolic events in a patient treated with dabigatran warrants cautious use in this specific patient population.

Anticoagulation in Cancer Patients with Atrial Fibrillation and Grade 3-4 Thrombocytopenia

Introduction: Atrial fibrillation (AF) is not uncommon in cancer patients with grade 3-4 thrombocytopenia (platelets <50x10 9/L). The risk of bleeding appears to outweigh the risk of thrombosis in acute leukemia patients. There are no published data regarding management of anticoagulation (AC) and rates of bleeding and thrombosis in other cancer types.Aim: To assess AC management and incidence of bleeding and thrombosis in thrombocytopenic cancer patients with AF.Methods: Single-center retrospective cohort study. The study included adults with active cancer, grade 3-4 thrombocytopenia (platelets <50x10 9/L) and AF with CHA 2DS 2-VASc ≥1, irrespective of AC status prior index. Patients with acute leukemia were excluded. Patients were indexed when platelets <50x10 9/L. AC management was classified as either “No-AC”, if AC was withheld (i.e., stopped or not started) at index, or “Continue-AC”, if AC was continued. Arterial thromboembolism (ATE; ischemic stroke, transient ischemic attack or systemic embolism) and ISTH-defined major bleeding were recorded over 30 days. The 30-day cumulative incidence of composite and individual outcomes with corresponding 95% confidence intervals (CI) was calculated for each management group (death as competing risk). A Cox proportional hazards model was used to calculate hazard ratios (HR) and corresponding 95% CI for outcomes between the No-AC and Continue-AC groups, with death as a competing risk (Fine and Gray model).Results: The eligibility criteria were met by 131 patients. At study index, AC was not given in 90 (69%) patients and continued in 41 (31%). Table 1 shows patient characteristics overall and stratified for management. The median age was 80 years )IQR 70-82) and 55 (42%) were females. Most patients were inpatients at index (70%) and had newly diagnosed cancer (70%). 64% had solid malignancy, and the remainder had hematological malignancy. The majority (92%) had AF prior to study index, while 8% had AF newly diagnosed at index. The median CHA 2DS 2-VASc score was 4 [IQR 3-5] and 18% had a prior stroke. Median platelet counts were 42 x 10 9/L at index and the median HASBLED score was 5 [3-5].Only 44% of the No-AC group were receiving AC prior index, compared with 95% in the Continue-AC group, at shorter median duration. The type of prior AC differed between groups. Antiplatelet therapy (54%) and major bleeding prior index (13%) were more frequent in the No-AC group.There was a median [IQR] of 4 [0-60] and 4 [1-26] days of grade 3-4 thrombocytopenia in the No-AC and Continue-AC groups, respectively. Platelet nadirs (x10 9/L) were numerically higher in the No-AC group (31 [3-50] vs. 21 [6-50]; p=0.09). A median [IQR] of 12 [6-17.25] and 10 [5-12] platelet transfusions were given to 29 (32.2%) patients in the No-AC group and 11 (26.8%) in the Continue-AC group, respectively (p>0.2). In the Continue-AC group, AC was subsequently held in 12/41 (29%) and dose-reduced in 4/41 (10%) during the 30 days post-index.The 30-day cumulative incidence [95% CI] of the composite outcome (major bleeding or ATE) was 10% [4.88-17.27] in the No-AC group and 4.88% [0.86-14.7] in the Continue-AC group (HR 2.142 [0.47-9.609]). The 30-day cumulative incidence of ATE (Figure 1A) was 3.33% [0.88-8.66] in the No-AC group (n=3), and 4.88% [0.85-14.7] in the Continue-AC group (n=2), corresponding with a HR of 0.70 [0.12-4.10]. The 30-day cumulative incidence of major bleeding (Figure 1B) was 7.8% [3.40-14.52] in the No-AC group, and 2.44% [0.18-11.22] in the Continue-AC group (HR 3.29 [0.42-26.04]). The 30-day overall survival was 64.4% in the No-AC and 73.2% in the Continue-AC groups (HR 1.39 (95% CI 0.7-2.76).Conclusions: In a cohort of cancer patients with grade 3-4 thrombocytopenia (<50x10 9/L) and AF (median CHA 2DS 2-VASc = 4), the majority had anticoagulation held. Baseline thrombotic and bleeding risk factors were generally balanced, but a higher rate of prior bleeding and lower rates of anticoagulation prior index in the No-AC group, suggest confounding by indication. No statistically significant difference in outcomes was detected between management groups, but 95% CI's were wide. The high bleeding and low ATE incidence in the No-AC group suggests that holding AC during time-limited periods of grade 3-4 thrombocytopenia may be a reasonable approach in many cancer patients with AF. Continuing AC should be investigated in a subset of patients with lower bleeding and higher thrombotic risk. [Display omitted] DisclosuresFalanga: Pfizer: Honoraria; Bayer: Honoraria; Sanofi: Honoraria; Leo Pharma: Honoraria. ten Cate: Bayer AG: Other; Pfizer: Other; LEO Pharma: Other; Gideon Pharmaceuticals: Other; Alveron Pharma: Other. Leader: Bayer: Honoraria; Leo Pharma: Honoraria; Novartis: Honoraria; Pfizer: Consultancy, Honoraria; Sanofi: Honoraria.

SAFETY AND EFFECTIVENESS OF ANTICOAGULATION BASED ON AN INSTITUTIONAL RECOMMENDATION ON THE MANAGEMENT OF CANCER ASSOCIATED VENOUS THROMBOSIS

Cancer associated venous thrombosis (CAT) can affect 20% of oncologic patients. Its management is challenging due to coexistent risk of bleeding and thrombosis (VTE) recurrence, that are 6 and approximately 4 fold higher compared to non-cancer patients, respectively. Anticoagulant choice needs to be careful and can be guided by a recommendation to avoid those complications. To evaluate effectiveness and safety of anticoagulation according to a public cancer institution recommendation on CAT management. This is a retrospective cohort study carried out from October 2018 to January 2020. The recommendation on CAT management included defined criteria to select the proper anticoagulant for each patient, to make adjustments and to handle anticoagulation in challenging situations, like thrombocytopenia, in the perioperative period and facing bleeding and thrombosis recurrence. A 3-month ambulatory was scheduled to evaluate eligibility of outpatients on enoxaparin to switch to rivaroxaban (new at the institution), based on criteria defined by the recommendation. All consecutive adult oncologic outpatients on therapeutic enoxaparin in the institution were considered eligible for the ambulatory. Retrospective data on cancer, comorbidities, bleeding, VTE recurrence and death during 1 year since the first visit were captured from an electronic recording. Cumulative incidence of bleeding and VTE recurrence were calculated by Kaplan-Meier method and log-rank test. 326 patients were referred to the ambulatory and 268 were included in the analyses, with a median age of 63 years (IQR 53-71). Sixty-one percent were female and 86% had solid tumours (53% metastatic). The main sites were the gastrointestinal tract (27%), breast (12%) and lungs (10%). Forty-six percent of the patients switched to rivaroxaban and 6% were able to stop anticoagulation. From the 85 patients who remained on enoxaparin, 51.7% had some dosing adjustment (to 1.5 mg/kg/day or to prophylactic dose). The main reason for not switching to rivaroxaban was drug-drug interaction (27%). One-year cumulative incidence of VTE recurrence was 11.2% (95% CI 7.7-16.2) and of overall bleeding was 13.4% (95% CI 9.4-18.7). Major bleeding occurred in 8 out of 268 patients (2.9%). Death rate was 32%, with no one due to bleeding. No significant difference in outcomes was observed between patients who had switched or not. Severity of cancer status was considered relevant for the high rate of deaths. Cumulative incidence of bleeding as well as thrombosis recurrence were similar to the described in the literature, although many clinical trials on direct oral anticoagulants in cancer patients had a shorter period of follow-up. Recommendation-based decision on anticoagulant choice and management showed similar effectiveness and safety independently of the chosen anticoagulant. No relevant hazards due to anticoagulation were observed during the follow-up period.

Direct oral anticoagulants in cancer patients: which help from the specialist hemostasis and thrombosis laboratory?

Oncologists continue to prefer traditional low molecular weight heparins over direct oral anticoagulants (DOAC) for the treatment of venous thromboembolism (VTE) cancer-related. Recently published studies supporting the use DOACs in this patient setting confirm the safety and efficacy of the treatment, but this still does not seem to be enough. The major obstacles to their use are interaction with chemotherapeutic agents, fear of haemorrhage, poor habit of using DOACs for VTE prophylaxis. But what if the haemostasis and thrombosis laboratory reassured oncologists? In this short report we talk about this topic in order to stimulate a fruitful discussion between expert.

Mortality associated with the use of non-vitamin K antagonist oral anticoagulants in cancer patients: Dabigatran versus rivaroxaban.

ObjectiveThis study assesses the mortality outcomes of non‐vitamin K antagonist oral anticoagulants (NOACs) in cancer patients with venous thromboembolism (VTE) and atrial fibrillation (AF).MethodsMedical records of cancer patients receiving NOACs for VTE or AF between January 1, 2011, and December 31, 2016, were retrieved from Taiwan's National Health Institute Research Database. NOACs were compared using the inverse probability of treatment weighting (IPTW) method. The primary outcome was cancer‐related death. Secondary outcomes were all‐cause mortality, major bleeding, and gastrointestinal (GI) bleeding.ResultsAmong 202,754 patients who received anticoagulants, 3591 patients (dabigatran: 907; rivaroxaban: 2684) with active cancers were studied. Patients who received dabigatran were associated with lower risks of cancer‐related death at one year (HR = 0.71, 95% CI = 0.54–0.93) and at the end of follow‐ups (HR = 0.79, 95% CI = 0.64–0.98) compared with rivaroxaban. Patients who received dabigatran were also associated with lower risks of all‐cause mortality (HR = 0.81, 95% CI = 0.67–0.97), major bleeding (HR = 0.64, 95% CI = 0.47–0.88), and GI bleeding (HR = 0.57, 95% CI = 0.39–0.84) at the end of follow‐ups compared with rivaroxaban.ConclusionCompared with rivaroxaban, the use of dabigatran may be associated with a lower risk of cancer‐related death and all‐cause mortality.

Selección de lo mejor del año 2020 sobre el tratamiento antitrombótico para el cardiólogo clínico

In recent months, therapeutic novelties have appeared in the area of antithrombotic treatment with important repercussions for our activity. In the field of anticoagulation of atrial fibrillation, the publication of new guidelines that continue prioritizing the use of direct-acting anticoagulants collide with our clinical practice possibilities, due to the limitations imposed by the approval of these drugs. Regarding chronic coronary syndromes, double antithrombotic treatment will become a preferential option for a high percentage of patients; hence it will be very useful to be able to identify them. In patients with peripheral arterial disease, double antithrombotic treatment will also play a very important role. In heart failure, the results are conflicting and the new studies will help us to choose the best candidate. Percutaneous aortic prostheses is an area in continuous growth, but antithrombotic treatment in these patients has not been clarified and important developments have emerged in recent months. Finally, anticoagulation in cancer patients continues to be a challenge in our clinical practice.

The Choice of Anticoagulation Among Internal Medicine Residents to Treat/Prevent Venous Thromboembolism in Cancer Patients

Introduction: Venous thromboembolism (VTE) is the second most common cause of death in cancer patients next to disease progression. The patients with cancer are not only at increased risk to develop VTE but are also at increased risk of recurrence and bleeding complications from treatment. Hence, anticoagulation is of utmost importance in this population. The International Society of Thrombosis and Hemostasis (ISTH) and American Society of clinical oncology (ASCO) propose guidelines for treatment and prophylaxis of VTE in cancer patients frequently. We aimed to assess the choice and ease among internal medicine residents at different levels of postgraduate training in a teaching community hospital regarding the use of anticoagulation for the prevention and treatment of VTE in medical cancer patients. This study also determines the awareness of the 2019 guidelines of ISTH and ASCO among these residents. Methods: A Cross-sectional study including a web-based survey of five clinical scenarios was designed to determine the anticoagulation of choice as per the 2019 ASCO and ISTH guidelines. The scenarios consisted of non-gastrointestinal cancer patients with a diagnosis of VTE with and without normal kidney function, upper gastrointestinal cancer patents with recent VTE, and VTE prophylaxis in hospitalized and ambulatory cancer patients. Also, four questions were included to determine the ease of residents to start anticoagulation in cancer patients and to assess the difference in choices based on their postgraduate year (PGY) level making a total of nine questions. Results: 58 (77%) of the total residents (75) responded to the questionnaire who included, 18 PGY-1, 18 PGY-2, and 22 PGY-3. The average correct answers were 1.9 (Mean 39%; SD 21%) out of the five questions that were scored i.e the clinical scenario questions based on guidelines. In the scenario of VTE in non-gastrointestinal cancer, the majority of residents chose Lower Molecular Weight Heparin (LMWH) (60.34%), followed by rivaroxaban (24.14%). For a patient with impaired renal function, although a majority of residents preferred warfarin (41.38%), quite a few picked LMWH (29.31%). For upper gastrointestinal cancer, LMWH was the favored option (41.38%) and apixaban was second (31.03%). For VTE prophylaxis, LMWH had 63.16% of preference vs 35.09% of other options. In an ambulatory, fully functional patient with cancer, only 26% of residents believed anticoagulation is not required. 87.72% of the residents said they were unaware of the current guidelines and a total of 65.38% PGY-3 residents did not feel very comfortable starting anticoagulants on their patients without guidance. For the individual answers based on the PGY level see Figure 1. Conclusion: Most of the internal medicine residents preferred LMWH for cancer patients over direct oral anticoagulants. However, they picked the wrong choices in other common scenarios; such as one third preferred to start apixaban in a gastrointestinal cancer patient, or the majority would give prophylactic anticoagulation to ambulatory patients, which is not required per guidelines. These mistakes were supported by the majority of them saying that they were unaware of the treatment recommendations for VTE in cancer patients. Also more than half of the PGY-3 residents are not very comfortable initiating anticoagulants on their own. Based on the above study, we concluded that all residents should be educated on current VTE guidelines on cancer patients, and emphasis should be on including them in the Internal Medicine curriculum. This action will help the residents be more confident and highlight the importance of keeping up with new guidelines. Disclosures No relevant conflicts of interest to declare.

Treatment of venous thromboembolism in patients with cancer: from clinical trials to real life

Approximately one-fifth of all cases of venous thromboembolism (VTE) are related to cancer. VTE complications may have a substantial impact on prognosis, quality of life and care in patients with cancer. Patients with cancer-related VTE are at increased risk of developing recurrent VTE compared to patients without cancer, but also have a higher risk of major bleeding. In the last years, direct oral anticoagulants (DOACs) have been evaluated in a head-to-head comparison with low molecular weight heparin (LMWH) in two randomized trials for the long-term treatment of VTE in patients with advanced cancer. The results of these trials show that DOACs have a similar efficacy profile, but probably higher risk of bleeding, compared to LMWH dalteparin. Because DOACs offer a simple oral treatment regimen without the need for anticoagulation monitoring, they could be attractive alternatives to LMWHs in these setting. The American Society of Clinical Oncology guidelines, published in August 2019, recommend LMWH, edoxaban and rivaroxaban as first-choice therapies for long-term anticoagulation in cancer patients with VTE. However, several practical issues should be considered concerning the long-term use of DOAC treatment in patients with cancer. Major concerns have been highlighted about the gastrointestinal bleeding risk in patients with gastrointestinal cancers and the potential drug-drug interactions in combination for some specific anticancer therapies. Several studies comparing DOACs with LMWH are currently ongoing to refine our knowledge concerning treatment with DOACs in patients with cancer-associated VTE.

Direct Oral Anticoagulants in Cancer Patients. Time for a Change in Paradigm

Thrombosis is a more common occurrence in cancer patients compared to the general population and is one of the main causes of death in these patients. Low molecular weight heparin (LMWH) has been the recognized standard treatment for more than a decade, both in cancer-related thrombosis and in its prevention. Direct oral anticoagulants (DOACs) are a new option for anticoagulation therapy. Recently published results of large randomized clinical trials have confirmed that DOAC may be a reasonable alternative to LMWH in cancer patients. The following review summarizes the current evidence on the safety and efficacy of DOAC in the treatment and prevention of cancer-related thrombosis. It also draws attention to the limitations of this group of drugs, knowledge of which will facilitate the selection of optimal therapy.

DOACs for stroke prevention in patients with AF and cancer.

Stroke prophylaxis in atrial fibrillation is an important consideration in patients with cancer. However, there is little consensus on the choice of anticoagulation, due to the numerous difficulties associated with active cancer. Direct oral anticoagulants (DOACs) have been shown to be a promising option. Here, we conduct a simple cross-sectional analysis of 29 cancer patients receiving DOACs for stroke prophylaxis in atrial fibrillation at a tertiary-care institution in London. Our study demonstrates an encouraging efficacy and safety profile of DOACs used in this setting. We conclude by suggesting that, while DOACs may be useful, anticoagulation in cancer patients should continue to be individualised.

In-hospital outcomes of catheter-directed thrombolysis versus anticoagulation in cancer patients with proximal deep venous thrombosis

ObjectiveThe objective of this study was to determine the rate of complications of catheter-directed thrombolysis (CDT) in cancer patients with deep venous thrombosis (DVT) compared with anticoagulation therapy alone. MethodsThis observational study used the National Inpatient Sample database to screen for any cancer patients who were admitted with a principal discharge diagnosis of proximal lower extremity or caval DVT between January 2005 and December 2013. Patients treated with CDT plus anticoagulation were compared with those treated with anticoagulation alone using propensity score matching for comorbidities and demographic characteristics. The primary end point was in-hospital mortality. Secondary end points were acute intracranial hemorrhage, inferior vena cava filter placement, acute renal failure, blood transfusion rates, length of stay, and hospital charges. ResultsWe identified 31,124 cancer patients with lower extremity proximal or caval DVT, and 1290 (4%) patients were treated with CDT. Comparative outcomes as assessed in the two matched groups of 1297 patients showed that there was no significant difference in in-hospital mortality of patients undergoing CDT plus anticoagulation compared with those treated with anticoagulation alone (2.6% vs 1.9%; P = .23). However, CDT was associated with increased risk of intracranial hemorrhage (1.3% vs 0.4%; P = .017), greater blood transfusion rates (18.6% vs 13.1 %; P < .001), and higher rates of procedure-related hematoma (2.4% vs 0.4%; P < .001). The length of stay (6.0 [4.0-10.0] days vs 4.0 [2.0-7.0] days; P < .001) and hospital charges ($81,535 [$50,968-$127,045] vs $22,320 [$11,482-$41,005]; P < .001) were also higher in the CDT group compared with the control group. ConclusionsThere was no significant difference in in-hospital mortality of cancer patients who underwent CDT plus anticoagulation compared with anticoagulation alone. CDT was associated with increased in-hospital morbidity and resource utilization compared with anticoagulation alone. Further studies are needed to examine the effect of CDT on the development of PTS in this population.