Jason E Smith, Rebecca Cardigan, Emily Sanderson, Laura Silsby, Claire Rourke, Ed B G Barnard, Peter Basham, Grazia Antonacci, Richard Charlewood, Nikki Dallas, Jane Davies, Elizabeth Goodwin, Annie Hawton, Cara Hudson, Joanne Lucas, Katie Keen, Richard M Lyon, Brodie Nolan, Gavin D Perkins, Viona Rundell, Laura Smith, Simon J Stanworth, Anne Weaver, Tom Woolley, Laura Green
Background: Whole-blood transfusion has recently gained favor in the management of severe hemorrhage; however, data from large clinical trials evaluating its clinical effectiveness and safety are lacking.
Methods: We conducted a pragmatic, phase 3, multicenter, unblinded, randomized, superiority trial across 10 air ambulance services in England. Patients with major traumatic hemorrhage who were attended by a participating air ambulance service were randomly assigned to receive either whole-blood transfusion (up to 2 units) or standard care with blood components (up to 2 units each of red cells and plasma) before arrival at the hospital. The primary outcome was a composite of death from any cause or massive transfusion (≥10 units of blood components or products) within 24 hours after randomization.
Results: A total of 942 patients underwent randomization. After the exclusion of participants with nontraumatic hemorrhage or traumatic cardiac arrest, 616 were included in the analysis (314 in the whole-blood group and 302 in the standard-care group). A primary-outcome event occurred in 48.7% of the participants in the whole-blood group and in 47.7% of those in the standard-care group (relative risk, 1.02; 95% confidence interval, 0.80 to 1.31; P = 0.84). The incidence of death from any cause at all time points, massive transfusion, and other secondary outcomes appeared to be similar in the two groups. Prothrombin times were above the normal range in 40.7% of the participants in the whole-blood group and in 30.5% of those in the standard-care group. More serious adverse events occurred in the standard-care group than in the whole-blood group (37 and 31, respectively). The incidence of thrombotic events appeared to be similar in the two groups.
Conclusions: Among participants with life-threatening hemorrhage, prehospital transfusion of 2 units of whole blood was not superior to standard care in reducing the risk of death or massive transfusion within 24 hours. (Funded by NHS Blood and Transplant and others; ISRCTN Registry number, ISRCTN23657907.).
{"title":"Prehospital Whole Blood in Traumatic Hemorrhage - a Randomized Controlled Trial.","authors":"Jason E Smith, Rebecca Cardigan, Emily Sanderson, Laura Silsby, Claire Rourke, Ed B G Barnard, Peter Basham, Grazia Antonacci, Richard Charlewood, Nikki Dallas, Jane Davies, Elizabeth Goodwin, Annie Hawton, Cara Hudson, Joanne Lucas, Katie Keen, Richard M Lyon, Brodie Nolan, Gavin D Perkins, Viona Rundell, Laura Smith, Simon J Stanworth, Anne Weaver, Tom Woolley, Laura Green","doi":"10.1056/NEJMoa2516043","DOIUrl":"https://doi.org/10.1056/NEJMoa2516043","url":null,"abstract":"<p><strong>Background: </strong>Whole-blood transfusion has recently gained favor in the management of severe hemorrhage; however, data from large clinical trials evaluating its clinical effectiveness and safety are lacking.</p><p><strong>Methods: </strong>We conducted a pragmatic, phase 3, multicenter, unblinded, randomized, superiority trial across 10 air ambulance services in England. Patients with major traumatic hemorrhage who were attended by a participating air ambulance service were randomly assigned to receive either whole-blood transfusion (up to 2 units) or standard care with blood components (up to 2 units each of red cells and plasma) before arrival at the hospital. The primary outcome was a composite of death from any cause or massive transfusion (≥10 units of blood components or products) within 24 hours after randomization.</p><p><strong>Results: </strong>A total of 942 patients underwent randomization. After the exclusion of participants with nontraumatic hemorrhage or traumatic cardiac arrest, 616 were included in the analysis (314 in the whole-blood group and 302 in the standard-care group). A primary-outcome event occurred in 48.7% of the participants in the whole-blood group and in 47.7% of those in the standard-care group (relative risk, 1.02; 95% confidence interval, 0.80 to 1.31; P = 0.84). The incidence of death from any cause at all time points, massive transfusion, and other secondary outcomes appeared to be similar in the two groups. Prothrombin times were above the normal range in 40.7% of the participants in the whole-blood group and in 30.5% of those in the standard-care group. More serious adverse events occurred in the standard-care group than in the whole-blood group (37 and 31, respectively). The incidence of thrombotic events appeared to be similar in the two groups.</p><p><strong>Conclusions: </strong>Among participants with life-threatening hemorrhage, prehospital transfusion of 2 units of whole blood was not superior to standard care in reducing the risk of death or massive transfusion within 24 hours. (Funded by NHS Blood and Transplant and others; ISRCTN Registry number, ISRCTN23657907.).</p>","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":""},"PeriodicalIF":78.5,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147500730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Genetic Variation in Clinical Cohorts.","authors":"Stephen F Kingsmore","doi":"10.1056/NEJMc2518638","DOIUrl":"https://doi.org/10.1056/NEJMc2518638","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"394 11","pages":"1142"},"PeriodicalIF":78.5,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147437845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lauren V Collen, Dermot P B McGovern, Scott B Snapper
{"title":"Genetic Variation in Clinical Cohorts.","authors":"Lauren V Collen, Dermot P B McGovern, Scott B Snapper","doi":"10.1056/NEJMc2518638","DOIUrl":"https://doi.org/10.1056/NEJMc2518638","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"394 11","pages":"1140-1141"},"PeriodicalIF":78.5,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147437869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Thrombopoietin-Receptor Agonists in Chemotherapy-Induced Thrombocytopenia.","authors":"George Goshua, Alfred Ian Lee","doi":"10.1056/NEJMe2517578","DOIUrl":"https://doi.org/10.1056/NEJMe2517578","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"394 11","pages":"1125-1126"},"PeriodicalIF":78.5,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147437927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lana A Castellucci,Vivien M Chen,Michael J Kovacs,Alejandro Lazo-Langner,Peter Greenstreet,Susan Kahn,Benoit Côté,Sam Schulman,Kerstin de Wit,James Douketis,Deepa Suryanarayan,Tony Wan,Erik Yeo,Genevieve Le Templier,Huyen A Tran,Abbey Willcox,Helen J Crowther,Ritam Prasad,Sudeep Shivakumar,Etimbuk Umana,Fionnuala Ni Ainle,Tobias Tritschler,Stefano Barco,Jean-Philippe Galanaud,Marc Blondon,Lisa Baumann Kreuziger,Susan Solymoss,Clive Kearon,Erin Thomas,Tim Ramsay,Gregoire Le Gal,Marc Rodger,
BACKGROUNDApixaban and rivaroxaban are the oral anticoagulants most frequently used to treat acute venous thromboembolism. However, uncertainty remains about the difference in bleeding risk between the two medications.METHODSIn an international trial with a prospective, randomized, open-label, blinded end-point design, we assigned, in a 1:1 ratio, eligible patients with acute symptomatic pulmonary embolism or proximal deep-vein thrombosis to receive apixaban or rivaroxaban for 3 months. Apixaban was given at a dose of 10 mg twice daily for 7 days followed by 5 mg twice daily, and rivaroxaban was given at a dose of 15 mg twice daily for 21 days followed by 20 mg daily. The primary outcome was clinically relevant bleeding, a composite of major bleeding or clinically relevant nonmajor bleeding, as defined according to the International Society on Thrombosis and Haemostasis, during the 3-month trial period. Secondary outcomes included death from any cause.RESULTSA total of 2760 patients underwent randomization: 1370 to the apixaban group and 1390 to the rivaroxaban group. A primary-outcome event occurred in 44 of 1345 patients (3.3%) in the apixaban group and 96 of 1355 patients (7.1%) in the rivaroxaban group (relative risk, 0.46; 95% confidence interval [CI], 0.33 to 0.65; P<0.001). Death from any cause occurred in 1 patient (0.1%) in the apixaban group and in 4 patients (0.3%) in the rivaroxaban group (relative risk, 0.25; 95% CI, 0.03 to 2.26). Serious adverse events unrelated to bleeding or venous thrombosis occurred in 36 patients (2.7%) in the apixaban group and in 30 patients (2.2%) in the rivaroxaban group.CONCLUSIONSAmong patients with acute venous thromboembolism, the risk of clinically relevant bleeding was significantly lower with apixaban than with rivaroxaban during the 3-month treatment period. (Funded by the Canadian Institutes of Health Research and others; COBRRA ClinicalTrials.gov number, NCT03266783.).
{"title":"Bleeding Risk with Apixaban vs. Rivaroxaban in Acute Venous Thromboembolism.","authors":"Lana A Castellucci,Vivien M Chen,Michael J Kovacs,Alejandro Lazo-Langner,Peter Greenstreet,Susan Kahn,Benoit Côté,Sam Schulman,Kerstin de Wit,James Douketis,Deepa Suryanarayan,Tony Wan,Erik Yeo,Genevieve Le Templier,Huyen A Tran,Abbey Willcox,Helen J Crowther,Ritam Prasad,Sudeep Shivakumar,Etimbuk Umana,Fionnuala Ni Ainle,Tobias Tritschler,Stefano Barco,Jean-Philippe Galanaud,Marc Blondon,Lisa Baumann Kreuziger,Susan Solymoss,Clive Kearon,Erin Thomas,Tim Ramsay,Gregoire Le Gal,Marc Rodger, ","doi":"10.1056/nejmoa2510703","DOIUrl":"https://doi.org/10.1056/nejmoa2510703","url":null,"abstract":"BACKGROUNDApixaban and rivaroxaban are the oral anticoagulants most frequently used to treat acute venous thromboembolism. However, uncertainty remains about the difference in bleeding risk between the two medications.METHODSIn an international trial with a prospective, randomized, open-label, blinded end-point design, we assigned, in a 1:1 ratio, eligible patients with acute symptomatic pulmonary embolism or proximal deep-vein thrombosis to receive apixaban or rivaroxaban for 3 months. Apixaban was given at a dose of 10 mg twice daily for 7 days followed by 5 mg twice daily, and rivaroxaban was given at a dose of 15 mg twice daily for 21 days followed by 20 mg daily. The primary outcome was clinically relevant bleeding, a composite of major bleeding or clinically relevant nonmajor bleeding, as defined according to the International Society on Thrombosis and Haemostasis, during the 3-month trial period. Secondary outcomes included death from any cause.RESULTSA total of 2760 patients underwent randomization: 1370 to the apixaban group and 1390 to the rivaroxaban group. A primary-outcome event occurred in 44 of 1345 patients (3.3%) in the apixaban group and 96 of 1355 patients (7.1%) in the rivaroxaban group (relative risk, 0.46; 95% confidence interval [CI], 0.33 to 0.65; P<0.001). Death from any cause occurred in 1 patient (0.1%) in the apixaban group and in 4 patients (0.3%) in the rivaroxaban group (relative risk, 0.25; 95% CI, 0.03 to 2.26). Serious adverse events unrelated to bleeding or venous thrombosis occurred in 36 patients (2.7%) in the apixaban group and in 30 patients (2.2%) in the rivaroxaban group.CONCLUSIONSAmong patients with acute venous thromboembolism, the risk of clinically relevant bleeding was significantly lower with apixaban than with rivaroxaban during the 3-month treatment period. (Funded by the Canadian Institutes of Health Research and others; COBRRA ClinicalTrials.gov number, NCT03266783.).","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"57 34 1","pages":"1051-1060"},"PeriodicalIF":158.5,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147393928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Patrick T O'Gara,Rachel L Goldberg,Jennifer S N Tang,Evan D Gale,Eric M Isselbacher,Serguei Melnitchouk,Anthony R Russo
{"title":"Case 8-2026: A 57-Year-Old Woman with Chest Pain, Dyspnea, and Syncope.","authors":"Patrick T O'Gara,Rachel L Goldberg,Jennifer S N Tang,Evan D Gale,Eric M Isselbacher,Serguei Melnitchouk,Anthony R Russo","doi":"10.1056/nejmcpc2517857","DOIUrl":"https://doi.org/10.1056/nejmcpc2517857","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"1 1","pages":"1111-1121"},"PeriodicalIF":158.5,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147393993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-12Epub Date: 2026-03-07DOI: 10.1056/NEJMicm2509511
Francisco Javier Castro-Apodaca, Adrian Canizalez-Roman
{"title":"Vulvar Melanoma with Vaginal Extension.","authors":"Francisco Javier Castro-Apodaca, Adrian Canizalez-Roman","doi":"10.1056/NEJMicm2509511","DOIUrl":"10.1056/NEJMicm2509511","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":"1110"},"PeriodicalIF":78.5,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147379487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hanny Al-Samkari,César Muñoz,Çağlayan Geredeli,Ippokratis Korantzis,Beatriz González Astorga,Cagatay Arslan,Johnny Francisco Cordeiro Camargo,Florian Scotté,Giuliano Borges,Kejia Wang,Melissa Eisen,David J Kuter,Gerald A Soff
BACKGROUNDChemotherapy-induced thrombocytopenia (CIT) is a common complication of chemotherapy that is associated with bleeding, reduced relative dose intensity, and potentially worse outcomes. No widely available therapies are approved for CIT.METHODSWe conducted a phase 3, international, double-blind, randomized, placebo-controlled trial involving patients with persistent CIT (platelet count, ≤85×109 per liter on trial day 1) who were receiving oxaliplatin-based multiagent cytotoxic chemotherapy for gastrointestinal cancers. Patients were randomly assigned in a 2:1 ratio to receive romiplostim or placebo for three chemotherapy cycles. The primary end point was the absence of CIT-induced modifications of the chemotherapy dose (reduction, delay, omission, or discontinuation) in both the second and third chemotherapy cycles.RESULTSOf the 165 patients who underwent randomization (109 in the romiplostim group and 56 in the placebo group), 75% had colorectal cancer, 13% had gastroesophageal cancer, and 12% had pancreatic cancer; 72% of the patients in the romiplostim group and 61% of those in the placebo group had stage 4 disease. The percentage of patients with no CIT-induced modifications of the chemotherapy dose was 84% (92 of 109 patients) with romiplostim and 36% (20 of 56 patients) with placebo, which corresponded to an odds ratio of 10.16 (95% confidence interval [CI], 4.44 to 23.72; P<0.001) and a risk ratio of 2.77 (95% CI, 1.78 to 4.30; P<0.001). Adverse events of grade 3 or higher occurred in 37% of the patients who received romiplostim and in 22% of those who received placebo, which primarily reflected chemotherapy effects. Adverse events that were considered by the investigator to be related to romiplostim or placebo occurred in 12% of patients who received romiplostim and in 7% who received placebo, with the most frequent being nausea (2% in each group) and headache (2% in the romiplostim group); none were serious or led to death or discontinuation of romiplostim, placebo, or chemotherapy. Thromboembolic events occurred in 2% of patients who received romiplostim and in no patients who received placebo.CONCLUSIONSIn this phase 3, placebo-controlled trial, romiplostim was efficacious in treating CIT. (Funded by Amgen and the Biomedical Advanced Research and Development Authority; RECITE ClinicalTrials.gov number, NCT03362177.).
{"title":"Romiplostim versus Placebo for Chemotherapy-Induced Thrombocytopenia.","authors":"Hanny Al-Samkari,César Muñoz,Çağlayan Geredeli,Ippokratis Korantzis,Beatriz González Astorga,Cagatay Arslan,Johnny Francisco Cordeiro Camargo,Florian Scotté,Giuliano Borges,Kejia Wang,Melissa Eisen,David J Kuter,Gerald A Soff","doi":"10.1056/nejmoa2511882","DOIUrl":"https://doi.org/10.1056/nejmoa2511882","url":null,"abstract":"BACKGROUNDChemotherapy-induced thrombocytopenia (CIT) is a common complication of chemotherapy that is associated with bleeding, reduced relative dose intensity, and potentially worse outcomes. No widely available therapies are approved for CIT.METHODSWe conducted a phase 3, international, double-blind, randomized, placebo-controlled trial involving patients with persistent CIT (platelet count, ≤85×109 per liter on trial day 1) who were receiving oxaliplatin-based multiagent cytotoxic chemotherapy for gastrointestinal cancers. Patients were randomly assigned in a 2:1 ratio to receive romiplostim or placebo for three chemotherapy cycles. The primary end point was the absence of CIT-induced modifications of the chemotherapy dose (reduction, delay, omission, or discontinuation) in both the second and third chemotherapy cycles.RESULTSOf the 165 patients who underwent randomization (109 in the romiplostim group and 56 in the placebo group), 75% had colorectal cancer, 13% had gastroesophageal cancer, and 12% had pancreatic cancer; 72% of the patients in the romiplostim group and 61% of those in the placebo group had stage 4 disease. The percentage of patients with no CIT-induced modifications of the chemotherapy dose was 84% (92 of 109 patients) with romiplostim and 36% (20 of 56 patients) with placebo, which corresponded to an odds ratio of 10.16 (95% confidence interval [CI], 4.44 to 23.72; P<0.001) and a risk ratio of 2.77 (95% CI, 1.78 to 4.30; P<0.001). Adverse events of grade 3 or higher occurred in 37% of the patients who received romiplostim and in 22% of those who received placebo, which primarily reflected chemotherapy effects. Adverse events that were considered by the investigator to be related to romiplostim or placebo occurred in 12% of patients who received romiplostim and in 7% who received placebo, with the most frequent being nausea (2% in each group) and headache (2% in the romiplostim group); none were serious or led to death or discontinuation of romiplostim, placebo, or chemotherapy. Thromboembolic events occurred in 2% of patients who received romiplostim and in no patients who received placebo.CONCLUSIONSIn this phase 3, placebo-controlled trial, romiplostim was efficacious in treating CIT. (Funded by Amgen and the Biomedical Advanced Research and Development Authority; RECITE ClinicalTrials.gov number, NCT03362177.).","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"7 1","pages":"1061-1073"},"PeriodicalIF":158.5,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147393932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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