1.
Predictors and Clinical Outcomes of Poor Platelet Recovery in Adult Dengue With Thrombocytopenia: A Multicenter, Prospective Study
Archuleta, S., Chia, P. Y., Wei, Y., Syed-Omar, S. F., Low, J. G., Oh, H. M., Fisher, D., Ponnampalavanar, S. S. L., Wijaya, L., Kamarulzaman, A., et al
Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America. 2020;71(2):383-389
Abstract
BACKGROUND Platelet transfusion is common in dengue patients with thrombocytopenia. We previously showed in a randomized clinical trial that prophylactic platelet transfusion did not reduce clinical bleeding. In this study, we aimed to characterize the predictors and clinical outcomes of poor platelet recovery in transfused and nontransfused participants. METHODS We analyzed patients from the Adult Dengue Platelet Study with laboratory-confirmed dengue with ≤20 000 platelets/μL and without persistent mild bleeding or any severe bleeding in a post hoc analysis. Poor platelet recovery was defined as a platelet count of ≤20 000/μL on Day 2. We recruited 372 participants from 5 acute care hospitals located in Singapore and Malaysia between 29 April 2010 and 9 December 2014. Of these, 188 were randomly assigned to the transfusion group and 184 to the control group. RESULTS Of 360 patients, 158 had poor platelet recovery. Age, white cell count, and day of illness at study enrollment were significant predictors of poor platelet recovery after adjustment for baseline characteristics and platelet transfusion. Patients with poor platelet recovery had longer hospitalizations but no significant difference in other clinical outcomes, regardless of transfusion. We found a significant interaction between platelet recovery and transfusion; patients with poor platelet recovery were more likely to bleed if given a prophylactic platelet transfusion (odds ratio 2.34, 95% confidence interval 1.18-4.63). CONCLUSIONS Dengue patients with thrombocytopenia who were older or presented earlier and with lower white cell counts were more likely to have poor platelet recovery. In patients with poor platelet recovery, platelet transfusion does not improve outcomes and may actually increase the risk of bleeding. The mechanisms of poor platelet recovery need to be determined. CLINICAL TRIALS REGISTRATION NCT01030211.
2.
Prophylactic platelet transfusion plus supportive care versus supportive care alone in adults with dengue and thrombocytopenia: a multicentre, open-label, randomised, superiority trial
Lye DC, Archuleta S, Syed-Omar SF, Low JG, Oh HM, Wei Y, Fisher D, Ponnampalavanar SS, Wijaya L, Lee LK, et al
Lancet (London, England). 2017;389((10079):):1611-1618. 1611
Abstract
BACKGROUND 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. METHODS 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 muL), 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 muL 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. FINDINGS 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. INTERPRETATION 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. FUNDING National Medical Research Council, Singapore.
3.
Effectiveness of platelet transfusion in dengue fever: a randomized controlled trial
Khan Assir MZ, Kamran U, Ahmad HI, Bashir S, Mansoor H, Anees SB, Akram J
Transfusion Medicine & Hemotherapy. 2013;40((5):):362-8.
Abstract
BACKGROUND Scientific data regarding effects of platelet transfusion on platelet count in dengue-related thrombocytopenia is scanty. METHODS A single center, randomized non-blinded trial was conducted on adult patients with dengue fever and platelet counts less than 30,000/mul. Patients were randomized to treatment and control group. Treatment group received single donor platelets. Patients with post-transfusion platelet increment (PPI) >=10,000/mul and/or corrected count increment (CCI) >=5,000/mul 1 h post-transfusion were considered responders. Primary outcome was platelet count increments at 24 and 72 h. RESULTS 87 patients were enrolled, and 43 (48.2%) received platelet transfusion. Mean PPI and CCI at 1 h post-transfusion in the treatment group were 18,800/mul and 7,000/mul respectively. 22 (53.6%) patients in the treatment group were non-responders. Mean platelet increments at 24 and 72 h were higher in the treatment group as compared to the control group. Responders showed significantly higher increments when compared to non-responders and the control group at 24 h (p = 0.004 and p <= 0.001, respectively) and 72 h (p = 0.001 and p <= 0.001, respectively). Significant differences were found between non-responders and the control group at 24 h (p <= 0.001), but not at 72 h (p = 0.104). Patients with lower baseline platelet count were more likely to be non-responders. Platelet transfusion neither prevented development of severe bleeding nor shortened time to cessation of bleeding. Three severe transfusion reactions and two deaths occurred in treatment group. CONCLUSION In this trial, almost half the patients showed no response to a high-dose platelet transfusion. Platelet transfusion did not prevent development of severe bleeding or shorten time to cessation of bleeding and was associated with significant side effects. Therefore, platelet transfusion should not be routinely done in the management of dengue fever.