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  • 1
    In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 1252-1254
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2022
    detail.hit.zdb_id: 1468538-3
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  • 2
    Online Resource
    Online Resource
    American Society of Hematology ; 2015
    In:  Blood Vol. 126, No. 23 ( 2015-12-03), p. 1124-1124
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 1124-1124
    Abstract: Introduction: Multiple studies have shown an association between aspirin treatment and a reduced incidence of cancer. An antiplatelet effect is one of the hypotheses explaining these results. Whether the antiplatelet thienopyridine drug, clopidogrel, influences the incidence of cancer is unknown. Objective: To assess the effect of clopidogrel on the incidence of cancer. Methods: A population-based historical cohort study within the HMO-Clalit Health Services population was performed. Members living in the Sharon-Shomron district ≥ 50 years were included in this cohort between January 2000 and January 2012, and followed until December 2014. We excluded patients treated with prasugrel or ticagrelor, and those diagnosed with cancer prior to or within 1 year of study inclusion. The study population was divided into 4 groups based on antiplatelet treatment with aspirin, clopidogrel, both (defined as ≥ 1 monthly prescription at any stage) or neither. To determine whether long-term antiplatelet treatment (i.e. follow-up for ≥ 5 years since the first antiplatelet dose) is associated with decreased rates of cancer (defined by ICD-9 codes), we applied a logistic regression model. With this model, the Exp(ß) was used to calculate the odds ratio (OR) and the 95% confidence interval (CI) of each type of antiplatelet treatment compared to the reference group of patients who did not receive treatment. Cox proportional hazards regression models were fitted to assess the association between the duration of time until cancer developed and the different anti-platelet treatments. Results: The study cohort included 184,781 patients with a median age of 54.9 years (range: 50-100.1), 53.7% female, 19.6% past or current smokers, and mean BMI of 31±8.3 kg/m2. Patients receiving antiplatelet drugs were older, had higher BMI and were more likely to be men and smokers, compared to patients receiving no treatment (p 〈 0.001 for all). Long-term (≥5 years) follow up from antiplatelet treatment with clopidogrel, aspirin or both was associated with a lower risk of cancer, compared to no antiplatelet treatment (median follow up: 155 months (range, 12-179)), before and after adjustment for baseline variables (Table 1). Any duration of treatment with clopidogrel (HR 0.42, 95% CI: 0.33-0.53), aspirin (HR 0.76, 95% CI: 0.74-0.78) or both (HR 0.49, 95% CI: 0.47-0.52) was also associated with a lower risk of incident cancer (p 〈 0.001), compared to patients who received no treatment, in multivariate analysis. The reduction in cancer incidence with clopidogrel alone was maintained in a subgroup analysis of solid cancers (OR 0.53, p=0.001) as well as gastrointestinal (GI; OR 0.45, p=0.02) and non-GI malignancies (OR 0.43, p 〈 0.01). In an exploratory secondary analysis after adjustment for baseline variables and duration of antiplatelet treatment, patients receiving clopidogrel only, had a lower risk of cancer than the aspirin only group (HR 0.57, 95% CI: 0.36-0.91, p=0.018), on long term follow-up. Conclusions: Clopidogrel treatment, with or without aspirin, was associated with a lower risk of cancer when compared to no antiplatelet treatment. The risk of cancer was reduced with aspirin only, similar to prior studies. The effect of clopidogrel alone was at least comparable to that of aspirin, despite shorter median exposure to clopidogrel (Table 1). Our results supports the antiplatelet role in reducing the risk of cancer. Table 1. The long-term risk of cancer* in subjects treated with aspirin, clopidogrel or both, compared with no antiplatelet treatment Long-term follow-up Study Groups (N) No anti-platelet (75,624) Clopidogrel only (271) Aspirin only (64,362) Combined anti-platelet (15,103) Incidence of cancer, % (n) 11.7 (8816) 6.6 (18) 8.8 (5692) 8.5 (1286) No. of cancer cases / 1000 patient years 12.8 5.6 7.6 7.0 Median duration of follow up (range), months 119 (12-179) 179 (24-179) 179 (12-179) 179 (12-179) Median duration of antiplatelet treatment (range), months NA 43 (1-168) 87 (1-172) Aspirin: 117 (1-170); Clopidogrel 13 (1-170) Risk of cancer, HR (95% CI) Unadjusted 1 (ref.) 0.32 (0.20-0.51)** 0.48 (0.46-0.49)** 0.40 (0.37-0.42)** adjusted for: age, gender, BMI, smoking status 1 (ref.) 0.37 (0.23-0.58)** 0.54 (0.52-0.56)** 0.46 (0.44-0.49)** *More than 5 years follow up from first anti platelet prescription. **p 〈 0.001 NA, not applicable Disclosures Leader: Novartis: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
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  • 3
    In: Thrombosis Research, Elsevier BV, Vol. 166 ( 2018-06), p. 106-112
    Type of Medium: Online Resource
    ISSN: 0049-3848
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2018
    detail.hit.zdb_id: 1500780-7
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  • 4
    In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 27-27
    Abstract: Introduction: The risk of venous thromboembolism (VTE) is increased in cancer patients, compared to subjects without cancer. The Khorana score (KS) is used to stratify VTE risk in cancer outpatients and recent society guidelines recommend thromboprophylaxis for patients with KS≥2. The burden of VTE in cancer, current use of thromboprophylaxis and performance of the KS in the Israeli setting are lacking. This data is needed to drive health-care policies regarding risk stratification and thromboprophylaxis. Aim: Define the clinical need for thromboprophylaxis in an Israeli population of cancer outpatients by determining the cumulative VTE incidence, VTE risk factors and anticoagulation (AC) use. Methods: This retrospective cohort study was conducted using the comprehensive computerized patient-level databases of Maccabi Healthcare Services (MHS), a nationwide healthcare insurer-provider organization for a quarter of the population in Israel, including 2.4 million members. All newly diagnosed cancer patients aged ≥18 years identified from the MHS cancer registry (excluding non-melanoma skin cancer) who initiated systemic anti-cancer treatment between 2010 and 2018 were included in the study. The cancer registry includes patients with cancer diagnostic codes from the Israel Ministry of Health, linked to cancer medication approvals and pathology reports. Subjects with prior VTE or AC within 3 months prior index were excluded. Patients were indexed on the first day of anti-cancer treatment and baseline variables were extracted, as well as data on AC post-index. The KS was used to stratify VTE risk as low (0-1) or high (≥2) at index. The main outcome was VTE at any site, defined using a validated algorithm based on diagnostic codes and AC prescription data (Sanfilippo et al, Thrombosis Research 135 (2015)). Cumulative incidence of VTE (95% confidence intervals [CI]) at 12 months was calculated and stratified for KS risk group. Univariate and multivariate analysis identified associations between baseline variables and VTE within 12 months. Results: The study cohort included 15,388 cancer patients of whom 35% were female with a mean age 58.8 (SD 13.6) years, 85% had a solid tumor, and 46% received chemotherapy as the index anti-cancer therapy. Of these, 338 (2.2%) had a VTE within one year after cancer diagnosis (24% pulmonary embolism with or without deep vein thrombosis [DVT], 76% DVT). Table 1 shows baseline characteristics according to VTE status at 12 months. The 12-month cumulative incidence of VTE (95% CI) was 2.3% (2.1%-2.6%) overall, 1.6% (1.3%-1.8%) in the low-risk KS group and 5.6% (4.7%-6.4%) in the high-risk KS group, as shown in Figure 1. A multivariate model considered baseline variables shown in Table 1, as well as socioeconomic status, year of diagnosis, district and use of granulocyte colony stimulating factors. In this multivariate model, the following variables were associated with increased risk of VTE in the first year since index date: females, subjects living in the south of Israel, older age, increasing co-morbidity, and high KS. All non-chemotherapy anti-cancer treatments were associated with decreased VTE risk, compared to chemotherapy. Table 2 shows the hazard ratios with 95% CI. A total of 2896 patients (19%) initiated prophylactic AC after index date (LMWH/unfractionated heparin (UFH) in 2452 (85%)). Among patients with a VTE at any time post-index, 574 (90%) started AC within a median of 2 days (IQR: 0,7) after VTE diagnosis. AC used to treat cancer-associated VTE (defined as AC class 30-days post VTE diagnosis) included LMWH/UFH in 341(74%), direct oral anticoagulant in 74 (16%) and vitamin K antagonists in 43 (9%). Median time on AC after index VTE was 22.1 months (95% CI 17.2-38.4). Conclusion: This study confirms that the Khorana score identifies a population of cancer outpatients at higher risk of VTE, and that patients receiving chemotherapy are at highest risk. The association between VTE risk and geographical location in Israel suggests possible health care disparities. The majority of cancer patients with VTE received long term therapy with LMWH. Funding: This research was sponsored by Pfizer Conflict of Interest Statement: A. Leader is an employee of Rabin Medical Center who was paid as a consultant to Pfizer in connection with this study. O. Friedman-Mazursky & M. Tirosh are employees of Pfizer Israel. The remaining authors declare no conflict of interest. Disclosures Friedman: Pfizer Pharmaceuticals Israel Ltd.: Current Employment. Tirosh:Pfizer Pharmaceuticals Israel Ltd.: Current Employment. Chodick:Novartis Pharma AG: Other: Institutional grant. Leader:Bayer Healthcare: Other: personal fees ; Pfizer Pharmaceuticals Israel Ltd.: Consultancy, Honoraria, Other: personal fees .
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2020
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  • 5
    In: Journal of Thrombosis and Haemostasis, Elsevier BV, Vol. 19, No. 5 ( 2021-05), p. 1250-1258
    Type of Medium: Online Resource
    ISSN: 1538-7836
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 2099291-9
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  • 6
    In: European Journal of Internal Medicine, Elsevier BV, Vol. 77 ( 2020-07), p. 86-96
    Type of Medium: Online Resource
    ISSN: 0953-6205
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 2026166-4
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  • 7
    In: Journal of Thrombosis and Haemostasis, Elsevier BV, Vol. 20, No. 3 ( 2022-03), p. 635-647
    Type of Medium: Online Resource
    ISSN: 1538-7836
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
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  • 8
    In: Thrombosis and Haemostasis, Georg Thieme Verlag KG, Vol. 119, No. 01 ( 2019-01), p. 163-174
    Abstract: Data on anti-platelet therapy (APT) for prevention of atherothrombotic events in thrombocytopaenic cancer patients is lacking. We aimed to identify patient and physician characteristics associated with APT management in thrombocytopaenic patients with haematological malignancy. A clinical vignette-based experiment was designed. Eleven haematologists were interviewed, identifying five variable categories. Next, 18 hypothetical vignettes were generated. Each physician received three vignettes and chose to: hold all APT; continue APT without platelet transfusion support; or continue APT with platelet transfusion support. The survey was distributed to haematologists and thrombosis specialists in three countries. Multivariate cluster robust Poisson regression models were used to calculate relative risks (RRs) of using one management option (over the other) for each variable in comparison to a reference variable. A total of 145 physicians answered 434 cases. Clinicians were more likely to hold APT in case of 20,000/µL platelets (vs. 40,000/µL; RR for continuing: 0.82 [95% confidence interval: 0.75–0.91]), recent major gastrointestinal bleeding (vs. none; RR 0.81 [0.72–0.92] ) and when the physician worked at a university-affiliated community hospital (vs. non-academic community hospital; RR 0.84 [0.72–0.98]). Clinicians were more likely to continue APT in ST elevation myocardial infarction with dual APT (vs. unstable angina with single APT; RR 1.31 [1.18–1.45] ) and when there were institutional protocols guiding management (vs. none; RR 1.15 [1.03–1.27]). When APT was continued, increased platelet transfusion targets were used in 34%. In summary, the decision process is complex and affected by multiple patient and physician characteristics. Platelet transfusions were frequently chosen to support APT, although no evidence supports this practice.
    Type of Medium: Online Resource
    ISSN: 0340-6245 , 2567-689X
    Language: English
    Publisher: Georg Thieme Verlag KG
    Publication Date: 2019
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  • 9
    Online Resource
    Online Resource
    Elsevier BV ; 2022
    In:  Thrombosis Research Vol. 213 ( 2022-05), p. S127-S132
    In: Thrombosis Research, Elsevier BV, Vol. 213 ( 2022-05), p. S127-S132
    Type of Medium: Online Resource
    ISSN: 0049-3848
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
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  • 10
    Online Resource
    Online Resource
    American Society of Hematology ; 2021
    In:  Blood Vol. 138, No. Supplement 1 ( 2021-11-05), p. 1053-1053
    In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 1053-1053
    Abstract: Introduction: There are knowledge gaps regarding splenic infarcts (SI), given the heterogenic patient population and wide range of clinical presentation. Comprehensive data on the frequency, management and outcomes of cryptogenic SI are lacking. Aim: To assess the etiology, treatment patterns and outcome of patients with SI, with an emphasis on cryptogenic SI. Methods: Single-center retrospective cohort study including adults with acute symptomatic or incidental SI. Patients were indexed at SI diagnosis and records were followed for 12 months. Patients were identified by ICD-9 diagnoses and an electronic search of the text in all radiology reports, and confirmed by manual review. Thrombotic risk-factors were classified as "baseline" if known at index or as "newly-diagnosed" if identified in diagnostic tests that were performed or recommended during hospitalization for the index SI. Diagnostic work-up was performed according to the clinician's discretion. The clinical context as well as baseline and newly-diagnosed thrombotic risk factors were used to determine SI etiology at baseline. Patients with no clear SI etiology after workup were classified as cryptogenic. Imaging studies of patients with cryptogenic SI were manually reviewed by an abdominal radiologist to identify possible etiology. The study exposure was the type of antithrombotic therapy defined as the prescribed antithrombotic regimen at discharge from hospitalization for the index SI, and classified as follows: none; anticoagulation (AC) only; antiplatelet (APT) only; AC & APT. AC was defined as intermediate or full dose AC. Prophylactic dose AC was classified as no AC. The primary outcome was arterial thromboembolism (ATE; acute coronary syndrome, ischemic stroke; transient ischemic attack; systemic embolism including recurrent SI) or venous thromboembolism (VTE) during 12-month follow-up. The cumulative incidence of the primary outcome over 12 months and corresponding 95% confidence intervals (CI) was calculated for each antithrombotic therapy group and a Cox proportional hazards model was used to calculate hazard ratios (HR), with death as a competing risk. Results: The eligibility criteria were met by 255 patients. The median age was 66 years and 130 (51%) were female. At least one cardiovascular risk factor was present in 221 (87%) patients. while 44 (17%) had previously diagnosed atrial fibrillation. 30 (12%) patients had prior VTE and 83 (33%) had acute concurrent ATE or VTE diagnosed at another site during hospital admission for the index SI. The SI etiology after initial diagnostic work-up, stratified for type of antithrombotic therapy at hospital discharge, is shown in Table 1. The most prevalent presumed etiologies were active malignancy in 92 (36%), cardioembolic in 69 (27%), infection in 48 (19%), shock/hypoperfusion in 47 (18%) and abdominal surgery in 46 (18%). Myeloproliferative neoplasms (2%) and antiphospholipid syndrome (6%) were rare causes. Only 15 cases (6%) were cryptogenic. Radiology review identified a possible etiology that was missed on initial review in 5 (33%) of the 15 cryptogenic SI's. These etiologies were cardioembolic [n=3], infectious [1] and malignancy [1]. Diagnostic work-up post-SI led to identification of a previously undiagnosed thrombotic risk factor in 58 cases (23%), especially atrial fibrillation (8%) and malignancy (10%), as shown in Table 2. The yield of antiphospholipid antibody testing was 10%, after confirmatory testing (Table 2). 148 patients (58.0%) were discharged from hospital with antithrombotic therapy (Table 1). The overall 12-month cumulative incidence of ATE or VTE was 18% [95% CI 13.5-23%]. Figure 1 shows the cumulative incidence of VTE or ATE stratified for type of antithrombotic therapy. The APT only and AC & APT groups had the highest 12-month incidence of ATE/VTE (22% [11.7-34.4%] and 27.4% [14.1-42.6%] , respectively). In the cryptogenic SI group, 9 (60%) received AC and 4 (27%) patients had ATE/VTE. Conclusions: SI is associated with a wide spectrum of clinical disorders. Cryptogenic SI is rare and imaging review may identify possible etiologies in such cases. Diagnostic workup leads to identification of new thrombotic risk factors in 1 in 4 patients and should be pursued. The rate of ATE or VTE at 12-months post-SI is high despite antithrombotic therapy. Further research is needed to identify the optimal antithrombotic therapy in these patients. Figure 1 Figure 1. Disclosures Leader: Leo Pharma: Honoraria; Pfizer: Consultancy, Honoraria; Novartis: Honoraria; Bayer: Honoraria; Sanofi: Honoraria.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2021
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