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1.
Effectiveness and safety of autologous platelet-rich plasma therapy with total contact casting versus total contact casting alone in treatment of trophic ulcer in leprosy: An observer-blind, randomized controlled trial
Saha S, Patra AC, Gowda SP, Mondal N, Rahaman S, Ahmed SK, Debbarma S, Kumar Vitthal KP, Sarkar S, Sil A, et al
Indian journal of dermatology, venereology and leprology. 2020
Abstract
Background: Trophic ulcers secondary to leprosy pose a great stigma to patients and remain a challenge to the treating dermatologists. Platelet-rich plasma (PRP) introduces growth factors directly into the wound and aids in rapid healing. The role of PRP in the treatment of trophic ulcers in leprosy patients has not yet been established by randomized controlled trials. Aims: To study the effectiveness and safety of autologous PRP therapy with total contact casting versus total contact casting alone in the treatment of trophic ulcers in leprosy. Methods: In an observer-blind, randomized (1:1) controlled study, 118 patients were enrolled. PRP was prepared by the manual double-spin method (1600 rpm for 10 min followed by 4000 rpm for 10 min). After wound bed preparation, activated PRP was injected intra- and perilesionally, and platelet-poor plasma gel was applied over the ulcer bed. Occlusive dressings and total contact casting were then applied in Group A, and only total contact casting was applied in Group B. The same procedure was repeated every 2 weeks for 8 weeks. Results: In all, 56 patients were analyzable in Group A and 52 in Group B. The surface area of the ulcer decreased significantly from first follow-up onward in both the groups (P < 0.001 in both the groups). Intergroup comparison showed that the reduction in the surface area of the ulcer was significantly more in Group A than in Group B from the first follow-up onward (P = 0.038) and the difference was maintained till the fifth follow-up (P < 0.001). At the end of the study, 91.10 +/- 9.65% ulcer surface area reduction had occurred in Group A, whereas it was 79.77 +/- 17.91% in Group B (P < 0.001). Trophic ulcers healed completely more often in paucibacillary leprosy patients (P < 0.001) and in those with a lower initial surface area of the ulcer (P < 0.001). Limitation: Short duration of treatment (8 weeks). Conclusion: PRP combined with total contact casting accelerates the healing of trophic ulcers of leprosy and is more effective than total contact casting alone. Complete remission is more likely to occur when the duration and surface area of ulcer are less and in the paucibacillary spectrum.
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2.
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.
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3.
Anti-influenza immune plasma for the treatment of patients with severe influenza A: a randomised, double-blind, phase 3 trial
Beigel JH, Aga E, Elie-Turenne MC, Cho J, Tebas P, Clark CL, Metcalf JP, Ozment C, Raviprakash K, Beeler J, et al
The Lancet. Respiratory medicine. 2019
Abstract
BACKGROUND Infection with influenza virus causes substantial morbidity and mortality globally, although antiviral treatments are available. Previous studies have suggested that anti-influenza immune plasma could be beneficial as treatment, but they were not designed as randomised, blinded, placebo-controlled trials. Therefore, we aimed to prospectively evaluate the clinical efficacy of high-titre immune plasma compared with standard low-titre plasma to improve outcomes in patients with severe influenza A infection. METHODS We did this randomised, double-blind, phase 3 trial at 41 US medical centres to assess the efficacy of high-titre anti-influenza plasma (haemagglutination inhibition antibody titre ≥1:80) compared with low-titre plasma (≤1:10). Children and adults with PCR-confirmed influenza A infection, a National Early Warning score of 3 or greater, and onset of illness within 6 days before randomisation were eligible. Patients were randomly assigned (2:1) using an interactive web response system to receive either two units (or paediatric equivalent) of high-titre plasma (high-titre group) or low-titre plasma (low-titre group), and were followed up for 28 days from randomisation. High-titre and low-titre plasma had the same appearance. Randomisation was stratified by severity (in intensive care unit, not in intensive care but requiring supplemental oxygen, or not in intensive care and not requiring supplemental oxygen) and age (<18 years and ≥18 years). All participants, site staff, and the study team were masked to treatment allocation until after the final database lock. The primary endpoint was clinical status assessed by a six-point ordinal scale on day 7 (death, in intensive care, hospitalised but requiring supplemental oxygen, hospitalised not requiring supplemental oxygen, discharged but unable to resume normal activities, and discharged with full resumption of normal activities) analysed in a proportional odds model (an odds ratio [OR] >1 indicates improvement in clinical status across all categories for the high-titre vs the low-titre group). The primary analysis was done in the intention-to-treat population, excluding two participants who did not receive plasma. This trial is registered with ClinicalTrials.gov, NCT02572817. FINDINGS Participants were recruited between Jan 26, 2016, and April 19, 2018. Of 200 participants enrolled (177 adults and 23 children), 140 met the criteria for randomisation and were assigned to the high-titre group (n=92) or to the control low-titre group (n=48). One participant from each group did not receive plasma. At baseline, 60 (43%) of 138 participants were in intensive care and 55 (71%) of 78 participants who were not in intensive care required oxygen. 93% of planned plasma infusions were completed. The study was terminated in July, 2018, when independent efficacy analysis showed low conditional power to detect an effect of high-titre plasma even if full accrual (150 participants) was achieved. The proportional OR for improved clinical status on day 7 was 1.22 (95% CI 0.65-2.29, p=0.54). 47 (34%) of 138 participants experienced 88 serious adverse events: 32 (35%) with 60 events in the high-titre group and 15 (32%) with 28 events in the low-titre group. The most common serious adverse events were acute respiratory distress syndrome (ARDS; four [4%] vs two [4%]), allergic transfusion reactions (two [2%] vs two [4%]), and respiratory distress (three [3%] vs none). 65 (47%) participants experienced 183 adverse events: 42 (46%) with 126 events in the high-titre group and 23 (49%) with 57 events in the low-titre group. The most common adverse events were anaemia (four [3%] vs two [4%]) and ARDS (four [3%] vs three [5%]). Ten patients died during the study (six [7%] in the high-titre group vs four [9%] in the low-titre group, p=0.73). The most common cause of death was worsening of acute respiratory distress syndrome (two [2%] vs two [4%] patients). INTERPRETATION High-titre anti-influenza plasma conferred no significant benefit over non-immune plasma. Although our study did not have the precision to rule out a small, clinically relevant effect, the benefit is insufficient to justify the use of immune plasma for treating patients with severe influenza A. FUNDING National Institute of Allergy and Infectious Diseases of the National Institutes of Health (Bethesda, MD, USA).
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4.
WBC alloimmunization: effects on the laboratory and clinical endpoints of therapeutic granulocyte transfusions
Price T H, McCullough J, Strauss R G, Ness P M., Hamza T H, Harrison R W, Assmann S F
Transfusion. 2018;58((5):):1280-1288
Abstract
BACKGROUND Although the subject of many previous studies, the importance of white blood cell (WBC) alloimmunization in granulocyte transfusion therapy has not been settled. In this study, we report the results of the effects of WBC antibodies in the RING (Resolving Infection in Neutropenia with Granulocytes) study, a randomized controlled trial comparing the efficacy of daily granulocyte transfusion therapy plus antimicrobials versus antimicrobials alone; the primary outcome results have been published previously. STUDY DESIGN AND METHODS One hundred fourteen subjects were enrolled in the study. Serum samples for WBC antibody determination were obtained from each subject at baseline and at 2 and 6 weeks. One hundred subjects had at least one antibody test result. Samples were tested for human leukocyte antigen (HLA) Class I and Class II antibodies as well as for granulocyte-specific antibodies using granulocyte agglutination and immunofluorescence techniques. All testing was performed at a central laboratory. RESULTS Baseline WBC alloimmunization was modest, depending somewhat on the assay. Seroconversion during the study was slightly higher in the granulocyte transfusion arm, but the differences were not statistically significant. There was no demonstrable effect of the presence of alloimmunization on the primary outcome (survival and microbial response at 42 days), the occurrence of transfusion reactions (either overall or pulmonary), or posttransfusion neutrophil increments. CONCLUSION The presence or development of WBC antibodies had no demonstrable effect on any clinical aspect of granulocyte transfusion therapy. It appears that, at least in the patient population studied, there is no evidence suggesting need for concern about recipient WBC alloimmunization when prescribing granulocyte transfusions.
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5.
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.
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6.
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.
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7.
The effect of blood storage age on treatment of lactic acidosis by transfusion in children with severe malarial anaemia: a pilot, randomized, controlled trial
Dhabangi A, Mworozi E, Lubega IR, Cserti-Gazdewich CM, Maganda A, Dzik WH
Malaria Journal. 2013;12:55
Abstract
BACKGROUND Severe malarial anaemia requiring blood transfusion is a life-threatening condition affecting millions of children in sub-Saharan Africa. Up to 40% of children with severe malarial anaemia have associated lactic acidosis. Lactic acidosis in these children is strongly associated with fatal outcomes and is corrected by blood transfusion. However, it is not known whether the storage age of blood for transfusion affects resolution of lactic acidosis. The objective of this pilot study was to evaluate the effect of blood storage age on resolution of lactic acidosis in children with severe malarial anaemia and demonstrate feasibility of conducting a large trial. METHODS Children aged six to 59 months admitted to Acute Care Unit of Mulago Hospital (Kampala, Uganda) with severe malarial anaemia (haemoglobin<=5g/dL) and lactic acidosis (blood lactate >=5mmol/L), were randomly assigned to receive either blood of short storage age (one to 10 days) or long storage age (21-35days) by gravity infusion. Seventy-four patients were enrolled and randomized to two equal-sized study arms. Physiological measurements, including blood lactate, oxygen saturation, haemoglobin, and vital signs, were taken at baseline, during and after transfusion. The primary outcome variable was the proportion of children whose lactic acidosis resolved by four hours after transfusion. RESULTS Thirty-four of 37 (92%) of the children in the short storage treatment arm compared to 30/37 (81%) in the long storage arm achieved a blood lactate <5mmol/L by four hours post transfusion (p value=0.308). The mean time to lactic acidosis resolution was 2.65hours (95% CI; 2.25-3.05) in the short storage arm, compared to 3.35hours (95% CI; 2.60-4.10) in the long storage arm (p value=0.264). CONCLUSION Pilot data suggest that among children with severe malarial anaemia and lactic acidosis transfused with packed red blood cells, the storage age of blood does not affect resolution of lactic acidosis. The results support a larger and well-powered study which is under way. TRIAL REGISTRATION clinicaltrials.gov NCT01580111.
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8.
Is fresh frozen plasma effective for thrombocytopenia in adults with dengue fever? A prospective randomised double blind controlled study
Sellahewa KH, Samaraweera N, Thusita KP, Fernando JL
The Ceylon Medical Journal. 2008;53((2):):36-40.
Abstract
RATIONALE Thrombocytopenia is a common problem which causes concern and complications in dengue fever. If proven effective, intravenous fresh frozen plasma is a simple and widely available therapeutic option to manage thrombocytopenia. OBJECTIVE To test the efficacy of fresh frozen plasma (FFP) on thrombocytopenia in patients with dengue fever. DESIGN 109 serologically confirmed dengue patients with platelet counts <40 000/mm3 were randomised into two groups. Group A (treatment) comprised 53 patients and group B (control) 56 patients. Group A received an intravenous infusion of 3 units (600 ml) of FFP over 90 minutes. Group B received an intravenous infusion of an equal volume of isotonic saline over the same period. The primary outcome measure was the difference between pre- and post-interventional platelet counts at 12, 24 and 48 hours. RESULTS Following Intervention, the mean platelet count was significantly higher in Group Athan in Group B at 12 hours (p=0. 04; t-test). The mean platelet counts continued to be higher in Group A than in Group B at 24 and 48 hours post-intervention, but the differences were not statistically significant. CONCLUSIONS In dengue patients with thrombocytopenia, infusion of 600 ml FFP may contribute to a significant increase in platelet count in the first 12 hours, but not thereafter.
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9.
Absence of activation of CMV by blood transfusion to HIV-infected, CMV-seropositive patients
Drew WL, Chou S, Mohr BA, Assmann SF, Miner RC, Laycock ME, Busch MP, Viral Activation Transfusion Study Group
Transfusion. 2003;43((10):):1351-7.
Abstract
BACKGROUND The Viral Activation Transfusion Study (VATS) afforded an opportunity to determine whether blood transfusions, and in particular exogenous WBCs, activateCMV replication in HIV-infected, CMV-seropositive patients, and whether such patients can be superinfected by additional strains of CMV transmitted via blood transfusions. STUDY DESIGN AND METHODS A total of 531 patients were randomized to receive either WBC-reduced (WBCR) or non-WBC-reduced (NWBCR) RBC units. Plasma CMV PCR assays were performed before transfusion and weekly after transfusion for 4 weeks. NWBCR cases with evidence of possible reactivation and/or superinfection were further studied for donor viremia by DNA PCR of frozen retention segments and new genotype acquisition using gB envelope sequence analysis of pre- and posttransfusion recipient specimens. RESULTS VATS patients received a median of two RBC units during their initial transfusion. Whether positive or negative for CMV DNA at baseline, there were no significant treatment-arm differences in the percentage of patients who had positive qualitative CMV PCR or increases in CMV viral load at follow-up. Of 50 recipients randomized to NWBCR RBC and meeting criteria for possible CMV superinfection, 25 had sufficient CMV DNA load in a baseline and one or more viremic follow-up sample to permit comparison of gB genotypes. Only two recipients showed genotype shifts. Of 125 WBC pellets prepared from the seropositive units transfused into these 50 cases, only 1 tested weakly PCR positive for CMV DNA (insufficient copy number for genotyping). CONCLUSION There was no evidence of activationof CMV by blood transfusion. Among the NWBCR RBC recipients, there was little evidence of possible transmission of new CMV strains. Hence, the current policy for transfusion support of HIV-infected patients, which allows transfusion of CMV-antibody-positive blood to CMV-seropositive patients, is appropriate.
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10.
The transfusion trigger and number of units transfused in patients with HIV: associations with disease stage and functional status
Kennedy MS, Kalish LA, Mohandas K, Gernsheimer T, Townsend-McCall D, Viral Activation Transfusion Study Group
Transfusion. 2002;42((4):):456-61.
Abstract
BACKGROUND The influence of quality of life (QOL), physical functioning, and HIV disease stage on the transfusion trigger and the number of units transfused was investigated. STUDY DESIGN AND METHODS The Viral Activation Transfusion Study, a randomized, double-blind study at 11 participating sites, enrolled HIV-positive patients with anemia who required RBC transfusion; 428 patients were included in the analysis of the first transfusion. The QOL scores, Perceived Health Index, Karnofsky score, CD4+ cell count, HIV viral load, and site were analyzed for relationships with the Hb level and the number of units transfused. RESULTS The transfusion trigger was lower in patients with higher levels of Karnofsky score, Perceived Health Index, CD4+ cell count, and a number of QOL scales. Both the Hb trigger and the number of units transfused had a significant site variation. Males were transfused at a significantly lower Hb level than females. In multivariate analysis, the CD4+ cell count remained significant, but the Karnofsky score or the Perceived Health Index did not. The number of RBC units transfused was associated with the Hb level, CD4+ cell counts, and Karnofsky scores in unadjusted analysis but with only Hb in adjusted analysis. CONCLUSIONS In this group of HIV+ patients, lower CD4+ cell counts prompted transfusion at higher Hb levels. However, after controlling for the Hb level, the number of units transfused was associated with only the Hb level. The HIV stage appears to influence the decision to transfuse at a particular Hb level but not to influence the number of RBC units transfused. The functional status does not appear to influence the decision to transfuse.