title: Prophylactic platelet transfusion plus supportive care versus supportive care alone in adults with dengue and thrombocytopenia: a multicentre, open-label, randomised, superiority trial.
abstract: Dengue is the commonest vector-borne infection worldwide. It is often associated with thrombocytopenia, and prophylactic platelet transfusion is widely used despite the dearth of robust evidence. We aimed to assess the efficacy and safety of prophylactic platelet transfusion in the prevention of bleeding in adults with dengue and thrombocytopenia.
  
  
  
  We did an open-label, randomised, superiority trial in five hospitals in Singapore and Malaysia. We recruited patients aged at least 21 years who had laboratory-confirmed dengue (confirmed or probable) and thrombocytopenia (≤20 000 platelets per μL), without persistent mild bleeding or any severe bleeding. Patients were assigned (1:1), with randomly permuted block sizes of four or six and stratified by centre, to receive prophylactic platelet transfusion in addition to supportive care (transfusion group) or supportive care alone (control group). In the transfusion group, 4 units of pooled platelets were given each day when platelet count was 20 000 per μL or lower; supportive care consisted of bed rest, fluid therapy, and fever and pain medications. The primary endpoint was clinical bleeding (excluding petechiae) by study day 7 or hospital discharge (whichever was earlier), analysed by intention to treat. Safety outcomes were analysed according to the actual treatment received. This study was registered with ClinicalTrials.gov, number NCT01030211, and is completed.
  
  
  
  Between April 29, 2010, and Dec 9, 2014, we randomly assigned 372 patients to the transfusion group (n=188) or the control group (n=184). The intention-to-treat analysis included 187 patients in the transfusion group (one patient was withdrawn immediately) and 182 in the control group (one was withdrawn immediately and one did not have confirmed or probable dengue). Clinical bleeding by day 7 or hospital discharge occurred in 40 (21%) patients in the transfusion group and 48 (26%) patients in the control group (risk difference -4·98% [95% CI -15·08 to 5·34]; relative risk 0·81 [95% CI 0·56 to 1·17]; p=0·16). 13 adverse events occurred in the transfusion group and two occurred in the control group (5·81% [-4·42 to 16·01]; 6·26 [1·43 to 27·34]; p=0·0064). Adverse events that were possibly, probably, or definitely related to transfusion included three cases of urticaria, one maculopapular rash, one pruritus, and one chest pain, as well as one case each of anaphylaxis, transfusion-related acute lung injury, and fluid overload that resulted in serious adverse events. No death was reported.
  
  
  
  In adult patients with dengue and thrombocytopenia, prophylactic platelet transfusion was not superior to supportive care in preventing bleeding, and might be associated with adverse events.
  
  
  
  National Medical Research Council, Singapore.
authors.affiliation: Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Electronic address: david_lye@ttsh.com.sg.
authors.forename: David C
authors.initials: DC
authors.lastname: Lye
authors.affiliation: Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Division of Infectious Diseases, National University Hospital, National University Health System, Singapore.
authors.forename: Sophia
authors.initials: S
authors.lastname: Archuleta
authors.affiliation: University Malaya Medical Centre, Kuala Lumpur, Malaysia.
authors.forename: Sharifah F
authors.initials: SF
authors.lastname: Syed-Omar
authors.affiliation: Singapore General Hospital, Singapore; Duke-NUS Medical School, Singapore.
authors.forename: Jenny G
authors.initials: JG
authors.lastname: Low
authors.affiliation: Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Changi General Hospital, Singapore.
authors.forename: Helen M
authors.initials: HM
authors.lastname: Oh
authors.affiliation: Singapore Clinical Research Institute, Singapore.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Division of Infectious Diseases, National University Hospital, National University Health System, Singapore.
authors.forename: Dale
authors.initials: D
authors.lastname: Fisher
authors.affiliation: University Malaya Medical Centre, Kuala Lumpur, Malaysia.
authors.forename: Sasheela S L
authors.initials: SSL
authors.lastname: Ponnampalavanar
authors.affiliation: Singapore General Hospital, Singapore.
authors.forename: Limin
authors.initials: L
authors.lastname: Wijaya
authors.affiliation: Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, Singapore.
authors.forename: Linda K
authors.initials: LK
authors.lastname: Lee
authors.affiliation: Duke-NUS Medical School, Singapore.
authors.forename: Eng-Eong
authors.initials: EE
authors.lastname: Ooi
authors.affiliation: University Malaya Medical Centre, Kuala Lumpur, Malaysia.
authors.forename: Adeeba
authors.initials: A
authors.lastname: Kamarulzaman
authors.affiliation: University Malaya Medical Centre, Kuala Lumpur, Malaysia.
authors.forename: Lucy C
authors.initials: LC
authors.lastname: Lum
authors.affiliation: Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Division of Infectious Diseases, National University Hospital, National University Health System, Singapore.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Tambyah
authors.affiliation: Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Saw Swee Hock School of Public Health, National University of Singapore, Singapore; Lee Kong Chian School of Medicine, Singapore.
authors.forename: Yee-Sin
authors.initials: YS
authors.lastname: Leo
mesh_terms: D000328:Adult; D003715:Dengue / Q000150:complications*; D000074099:Equivalence Trials as Topic; D005260:Female; D006470:Hemorrhage / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D008296:Malaysia; D008297:Male; D008875:Middle Aged; D017713:Platelet Transfusion; D012846:Singapore; D013921:Thrombocytopenia / Q000150:complications*; D016896:Treatment Outcome