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1.
Platelet Transfusion before CVC Placement in Patients with Thrombocytopenia
van Baarle FLF, van de Weerdt EK, van der Velden Wjfm, Ruiterkamp RA, Tuinman PR, Ypma PF, van den Bergh WM, Demandt AMP, Kerver ED, Jansen AJG, et al
The New England journal of medicine. 2023;388(21):1956-1965
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Editor's Choice
Abstract
BACKGROUND Transfusion guidelines regarding platelet-count thresholds before the placement of a central venous catheter (CVC) offer conflicting recommendations because of a lack of good-quality evidence. The routine use of ultrasound guidance has decreased CVC-related bleeding complications. METHODS In a multicenter, randomized, controlled, noninferiority trial, we randomly assigned patients with severe thrombocytopenia (platelet count, 10,000 to 50,000 per cubic millimeter) who were being treated on the hematology ward or in the intensive care unit to receive either one unit of prophylactic platelet transfusion or no platelet transfusion before ultrasound-guided CVC placement. The primary outcome was catheter-related bleeding of grade 2 to 4; a key secondary outcome was grade 3 or 4 bleeding. The noninferiority margin was an upper boundary of the 90% confidence interval of 3.5 for the relative risk. RESULTS We included 373 episodes of CVC placement involving 338 patients in the per-protocol primary analysis. Catheter-related bleeding of grade 2 to 4 occurred in 9 of 188 patients (4.8%) in the transfusion group and in 22 of 185 patients (11.9%) in the no-transfusion group (relative risk, 2.45; 90% confidence interval [CI], 1.27 to 4.70). Catheter-related bleeding of grade 3 or 4 occurred in 4 of 188 patients (2.1%) in the transfusion group and in 9 of 185 patients (4.9%) in the no-transfusion group (relative risk, 2.43; 95% CI, 0.75 to 7.93). A total of 15 adverse events were observed; of these events, 13 (all grade 3 catheter-related bleeding [4 in the transfusion group and 9 in the no-transfusion group]) were categorized as serious. The net savings of withholding prophylactic platelet transfusion before CVC placement was $410 per catheter placement. CONCLUSIONS The withholding of prophylactic platelet transfusion before CVC placement in patients with a platelet count of 10,000 to 50,000 per cubic millimeter did not meet the predefined margin for noninferiority and resulted in more CVC-related bleeding events than prophylactic platelet transfusion. (Funded by ZonMw; PACER Dutch Trial Register number, NL5534.).
PICO Summary
Population
Patients with severe thrombocytopenia enrolled in the PACER randomised controlled trial (n= 338).
Intervention
Placement of a central venous catheter (CVC) with one unit of prophylactic platelet transfusion (188 placements).
Comparison
Placement of an CVC without a platelet transfusion (185 placements).
Outcome
A total of 373 episodes of CVC placement involving 338 patients were included in the per-protocol primary analysis. Catheter-related bleeding of grade 2 to 4 occurred in 9 of 188 patients (4.8%) in the transfusion group and in 22 of 185 patients (11.9%) in the no-transfusion group (relative risk, 2.45; 90% confidence interval (CI), [1.27, 4.70]). Catheter-related bleeding of grade 3 or 4 occurred in 4 of 188 patients (2.1%) in the transfusion group and in 9 of 185 patients (4.9%) in the no-transfusion group (relative risk, 2.43; 95% CI [0.75, 7.93]). There were 15 adverse events, of these events 13 (all grade 3 catheter-related bleeding [4 in the transfusion group and 9 in the no-transfusion group]) were categorized as serious. The net savings of withholding prophylactic platelet transfusion before CVC placement was $410 per catheter placement.
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Risk of HLA antibody generation after receipt of Mirasol versus standard platelets in the MIPLATE randomized trial
Kaidarova Z, Di Germanio C, Custer B, Norris PJ
Transfusion. 2023
Abstract
BACKGROUND Human leukocyte antigen (HLA) alloimmunization can occur after platelet transfusion. These antibodies can complicate future platelet transfusions or organ transplantation. Animal data suggest that Mirasol pathogen reduction treatment (PRT) can prevent alloimmunization after transfusion. STUDY DESIGN AND METHODS The MIPLATE trial enrolled 330 of a planned 660 participants with hematological malignancies at risk for grade 2 or greater bleeding. The study was halted early for futility after a planned interim analysis. Participants were randomized to receive PRT versus standard control platelets. Serum samples were collected from participants at baseline (pretransfusion), weekly for the first 4 weeks, then at days 42 and 56. HLA antibody levels were determined using a commercial multianalyte bead-based assay. HLA antibody levels were analyzed using low, medium, and high cutoffs based on prior studies. RESULTS The rate of alloimmunization was low in both arms of the study, particularly at the high HLA antibody cutoff (total of 6 of 277 subjects at risk, or 2.2%). The risk of alloimmunization did not differ between study arms, nor did the risk of immune refractoriness to platelet transfusion. CONCLUSIONS The data do not support the conclusion that Mirasol exerted a protective effect against alloimmunization after platelet transfusion in the MIPLATE trial.
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A randomized cross-over study of cryopreserved platelets in prophylactic transfusions of thrombocytopenic patients
Ang, A. L., Gan, L. S. H., Tuy, T. T., Ang, C. H., Tan, C. W., Tan, H. H., Shu, P. H., Zhang, Q., Cao, Y., Moorakonda, R. B., et al
Transfusion. 2023
Abstract
BACKGROUND The short shelf-life of liquid-stored platelets (LP) at 20-24°C poses shortage and wastage challenges. Cryopreserved platelets have significantly extended shelf-life, and were safe and efficacious for therapeutic transfusions of bleeding patients in the Afghanistan conflict and phase 2 randomized studies. Although hematology patients account for half of platelets demand, there is no randomized study on prophylactic cryopreserved platelet transfusions in them. METHODS We performed a phase 1b/2a randomized cross-over study comparing the safety and efficacy of cryopreserved buffy coat-derived pooled platelets (CP) to LP in the prophylactic transfusions of thrombocytopenic hematology patients. RESULTS A total of 18 adults were randomly assigned 1:1 to CP and LP for their first thrombocytopenic period (TP) of up to 28-days. A total of 14 crossed over to the other platelet-arm for the second TP. Overall, 17 subjects received 51 CP and 15 received 52 LP. CP-arm had more treatment emergent adverse event (29.4% vs. 13.3% of subjects, 9.8% vs. 3.8% of transfusions) than LP-arm but all were mild. No thromboembolism was observed. Both arms had similar bleeding rates (23.5% vs. 26.7% of subjects) which were all mild. Subjects in CP-arm had lower average corrected count increments than LP-arm (mean [SD] 5.6 [4.20] vs. 22.6 [9.68] ×10(9) /L at 1-4 h, p < .001; 5.3 [4.84] vs. 18.2 [9.52] ×10(9) /L at 18-30 h, p < .001). All TEG parameters at 1-4 h and maximum amplitude (MA) at 18-30 h improved from baseline post-CP transfusion (p < .05) though improvements in K-time and MA were lower than LP (p < .05). DISCUSSION During shortages, CP may supplement LP in prophylactic transfusions of thrombocytopenic patients.
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The impact of pathogen-reduced platelets in acute leukaemia treatment on the total blood product requirement: a subgroup analysis of an EFFIPAP randomised trial
Garban F, Vilotitch A, Tiberghien P, Bosson JL
Transfusion medicine (Oxford, England). 2022
Abstract
OBJECTIVE To evaluate the impact of pathogen-reduced (PR) platelet transfusions on blood products requirement for clinical practice. BACKGROUND PR platelets are increasing in use as standard blood products. However, few randomised trials have evaluated their impact on bleeding control or prevention. Furthermore, PR platelets recirculate less than untreated platelets. METHODS A subgroup study of the randomised clinical trial EFFIPAP compared three arms of platelet preparations (PR: P-PRP/PAS, additive solution: P-PAS and plasma P-P arms respectively). The subgroup of acute leukaemia patients, in their chemotherapy induction phase, included 392 patients (133 P-PRP/PAS arm, 132 P-PAS arm and 130 P-P arm). Blood requirements were analysed across over periods of 7 days. RESULTS The number of platelet transfusions per week was significantly higher in the P-PRP/PAS group 2.3 [1.6-3.3] compared to the control groups 1.9 [1.3-2.8] and 2.0 [1.3-3.0] for P-P and P-PAS groups respectively (p < 0.0001). However, the total number of platelets transfused per week was not different. The number of red blood cell concentrates (RBC) transfusion per week did not differ either. CONCLUSION In a homogeneous group of patients, platelet pathogen reduction resulted in an increased number of platelet units transfused per week while having no impact on the total number of platelets transfused or the number of RBC transfusion; resulting to an average requirement of 2 RBC and 2-3 platelets transfusions per week of marrow aplasia.
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Expected individual benefit of prophylactic platelet transfusions in hemato-oncology patients based on bleeding risks
Cornelissen LL, Caram-Deelder C, Fustolo-Gunnink SF, Groenwold RHH, Stanworth SJ, Zwaginga JJ, van der Bom JG
Transfusion. 2021
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Free full text
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Editor's Choice
Abstract
BACKGROUND Prophylactic platelet transfusions prevent bleeding in hemato-oncology patients, but it is unclear how any benefit varies between patients. Our aim was to assess if patients with different baseline risks for bleeding benefit differently from a prophylactic platelet transfusion strategy. STUDY DESIGN AND METHODS Using the data from the randomized controlled TOPPS trial (Trial of Platelet Prophylaxis), we developed a prediction model for World Health Organization grades 2, 3, and 4 bleeding risk (defined as at least one bleeding episode in a 30 days period) and grouped patients in four risk-quartiles based on this predicted baseline risk. Predictors in the model were baseline platelet count, age, diagnosis, disease modifying treatment, disease status, previous stem cell transplantation, and the randomization arm. RESULTS The model had a c-statistic of 0.58 (95% confidence interval [CI] 0.54-0.64). There was little variation in predicted risks (quartiles 46%, 47%, and 51%), but prophylactic platelet transfusions gave a risk reduction in all risk quartiles. The absolute risk difference (ARD) was 3.4% (CI -12.2 to 18.9) in the lowest risk quartile (quartile 1), 7.4% (95% CI -8.4 to 23.3) in quartile 2, 6.8% (95% CI -9.1 to 22.9) in quartile 3, and 12.8% (CI -3.1 to 28.7) in the highest risk quartile (quartile 4). CONCLUSION In our study, generally accepted bleeding risk predictors had limited predictive power (expressed by the low c-statistic), and, given the wide confidence intervals of predicted ARD, could not aid in identifying subgroups of patients who might benefit more (or less) from prophylactic platelet transfusion.
PICO Summary
Population
Haemato-oncology patients enrolled in the TOPPS trial (n= 600).
Intervention
Platelet transfusions based on a threshold of 10 × 10 9/L (Prophylactic arm, n= 299).
Comparison
Platelet transfusions in case of active bleeding (Therapeutic arm, n= 301).
Outcome
47% of patients (279) developed at least one WHO grade 2, 3, or 4 bleeding during 30-day follow-up. The model had a c-statistic of 0.58. There was little variation in predicted risks (quartiles 46%, 47%, and 51%), but prophylactic platelet transfusions gave a risk reduction in all risk quartiles. The absolute risk difference was 3.4% in the lowest risk quartile (quartile 1), 7.4% in quartile 2, 6.8% in quartile 3, and 12.8% in the highest risk quartile (quartile 4).
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An epitope-based approach of HLA-matched platelets for transfusion: a noninferiority crossover randomized trial
Marsh JC, Stanworth SJ, Pankhurst LA, Kallon D, Gilbertson AZ, Pigden C, Deary AJ, Mora AS, Brown J, Laing ES, et al
Blood. 2021;137(3):310-322
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Editor's Choice
Abstract
Platelet transfusion refractoriness results in adverse outcomes and increased health care costs. Managing refractoriness resulting from HLA alloimmunization necessitates the use of HLA antigen-matched platelets but requires a large platelet donor pool and does not guarantee full matching. We report the first randomized, double-blind, noninferiority, crossover trial comparing HLA epitope-matched (HEM) platelets with HLA standard antigen-matched (HSM) platelet transfusions. Alloimmunized, platelet-refractory, thrombocytopenic patients with aplastic anemia, myelodysplastic syndrome, or acute myeloid leukemia were eligible. HEM platelets were selected using HLAMatchMaker epitope (specifically eplet) matching. Patients received up to 8 prophylactic HEM and HSM transfusions provided in random order. The primary outcome was 1-hour posttransfusion platelet count increment (PCI). Forty-nine patients were randomized at 14 UK hospitals. For intention to treat, numbers of evaluable transfusions were 107 and 112 for HEM and HSM methods, respectively. Unadjusted mean PCIs for HEM and HSM methods were 23.9 (standard deviation [SD], 15) and 23.5 (SD, 14.1), respectively (adjusted mean difference, -0.1; 95% confidence interval [CI], -2.9 to 2.8). Because the lower limit of the 95% CI was not greater than the predefined noninferiority limit, the HEM approach was declared noninferior to the HSM approach. There were no differences in secondary outcomes of platelet counts, transfusion requirements, and bleeding events. Adequate 1-hour PCI was more frequently observed, with a mean number of 3.2 epitope mismatches, compared with 5.5 epitope mismatches for inadequate 1-hour increments. For every additional epitope mismatch, the likelihood of an adequate PCI decreased by 15%. Epitope-matched platelets should be considered to support HLA alloimmunized patients. This trial was registered at www.isrctn.com as #ISRCTN23996532.
PICO Summary
Population
Alloimmunized, platelet-refractory, thrombocytopenic patients with aplastic anemia, myelodysplastic syndrome, or acute myeloid leukemia (n= 49).
Intervention
HLA epitope-matched (HEM) platelet transfusions.
Comparison
HLA standard antigen-matched (HSM) platelet transfusions.
Outcome
For intention to treat, numbers of evaluable transfusions were 107 and 112 for HEM and HSM methods, respectively. Unadjusted mean platelet count increments (PCI) for HEM and HSM methods were 23.9 (standard deviation [SD], 15) and 23.5 (SD, 14.1), respectively. There were no differences in secondary outcomes of platelet counts, transfusion requirements, and bleeding events. Adequate 1-hour PCI was more frequently observed, with a mean number of 3.2 epitope mismatches, compared with 5.5 epitope mismatches for inadequate 1-hour increments.
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Preterm neonates benefit from low prophylactic platelet transfusion threshold despite varying risk of bleeding or death
Fustolo-Gunnink SF, Fijnvandraat K, van Klaveren D, Stanworth S, Curley AE, Onland W, Steyerberg EW, de Kort E, d'Haens E, Hulzebos C, et al
Blood. 2019
Abstract
The Platelets for Neonatal Thrombocytopenia (PlaNeT-2) trial reported an unexpected overall benefit of a prophylactic platelet transfusion threshold of 25x109/L compared to 50x109/L for major bleeding and/or mortality in preterm neonates (7% absolute risk reduction). However, some neonates in the trial may have experienced little benefit or even harm from the 25x109/L threshold. We aimed to assess this heterogeneity of treatment effect in the PlaNet-2 trial, in order to investigate whether all preterm neonates benefit from the low threshold. We developed a multivariable logistic regression model in the PlaNet-2 data to predict baseline risk of major bleeding and/or mortality for all 653 neonates. We then ranked the neonates based on their predicted baseline risk and categorized them into four risk quartiles. Within these quartiles we assessed absolute risk difference between the 50x109/L and 25x109/L threshold group. A total of 146 neonates died or developed major bleeding. The internally validated C-statistic of the model was 0.63 (95% confidence interval 0.58 - 0.68). The 25x109/L threshold was associated with absolute risk reduction in all risk groups, varying from 4.9% in the lowest to 12.3% in the highest risk group. These results suggest that a 25x109/L prophylactic platelet count threshold can be adopted in all preterm neonates, irrespective of predicted baseline outcome risk. Future studies are needed to improve the predictive accuracy of the baseline risk model. Current Controlled Trials number ISRCTN87736839.
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Platelet Transfusion for PDA Closure in Preterm Infants: A Randomized Controlled Trial
Kumar J, Dutta S, Sundaram V, Saini SS, Sharma RR, Varma N
Pediatrics. 2019
Abstract
BACKGROUND AND OBJECTIVES Thrombocytopenia is associated with late closure of patent ductus arteriosus (PDA). There are few studies evaluating platelet transfusions to treat PDA. We compared liberal platelet-transfusion criteria (to maintain a platelet count >100 000 per microL) versus standard criteria achieve earlier PDA closure among thrombocytopenic preterm neonates (<35 weeks' gestation) with hemodynamically significant PDA (hs-PDA) presenting within the first 2 weeks of life. METHODS Thrombocytopenic (<100 000 per microL) preterm neonates with hs-PDA were enrolled and randomly allocated to the liberal and standard transfusion groups: 22 in each arm. They underwent echocardiography daily until closure of PDA, completion of 120 hours follow-up, or death. All subjects received standard cotreatment with nonsteroidal antiinflammatory drugs. Primary outcome of time to PDA closure was compared by survival analysis. Multivariate Cox proportional hazard regression was performed with randomization group, baseline platelet count, gestational age, and age at enrollment as predictor variables. RESULTS Median time to PDA closure was 72 (95% confidence interval [CI] 55.9-88.1) versus 72 (95% CI 45.5-98.4) hours in the liberal versus restrictive transfusion groups, respectively (unadjusted hazard ratio 0.88 [95% CI 0.4-1.9]; P = .697). Despite adjusting for potential confounders, there was no significant difference in time to PDA closure. In the liberal transfusion group, 41% of infants had any grade of intraventricular hemorrhage compared with 4.5% in the restrictive group (P = .009). CONCLUSIONS Attempting to maintain a platelet count >100 000 per microL by liberally transfusing platelets in preterm thrombocytopenic neonates with hs-PDA does not hasten PDA closure.
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Efficacy of cross-match compatible platelets in multi transfused haemato-oncology patients refractory to platelet transfusion
Chavan A, Sharma RR, Saikia B, Malhotra P, Prakash S, Hans R, Marwaha N
Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis. 2019;:102657
Abstract
BACKGROUND Platelet refractoriness, which leads to platelet transfusion failure resulting in significant morbidity and long hospital stay, is routinely not investigated. AIMS To determine the efficacy of cross-match compatible platelets in multi-transfused alloimmunized hemato-oncological patients refractory to platelet transfusion. MATERIALS AND METHOD 149 ABO compatible single donor apheresis platelet transfusions given to 38 alloimmunized refractory patients. Corrected Count Increment (CCI) <5000 (1h) was taken to define refractoriness. Solid-phase red cell adherence assay was used to determine the alloimmunization status and platelet cross-matching. Post Transfusion Platelet Increment, CCI and the Percentage Platelet Recovery were used to monitor the effectiveness of platelet transfusion. ANOVA test followed by Post hoc test Tukey HSD used to compare group means and classified into three groups depending upon the cross-matching and compatibility status. Categorical data was analysed for various outcomes using Pearson's chi square test or Fischer exact test. RESULT Patients showed statistically significant recovery in terms of PPI, CCI and PPR at 1h post SDAP transfusions when they received cross-matched compatible platelets. The one-hour CCI was significantly higher for cross-match-compatible platelets (19173+/-2692) than for incompatible (5888+/-1526) and for uncross-matched (8140+/-1480). Forty four (97.8%) of 45 cross-matched compatible platelet transfusion episodes showed a satisfactory response in terms of PPI and CCI values as compared to 50 % and 53.9% in uncross-matched group respectively (p<0.0001). CONCLUSION Platelet cross-matching is an effective intervention in the management of multi-transfused alloimmunized Haemato-oncological patients, refractory to platelet transfusion.
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The role of pathogen-reduced platelet transfusions on HLA alloimmunization in hemato-oncological patients
Saris A, Kerkhoffs JL, Norris PJ, van Ham SM, Ten Brinke A, Brand A, van der Meer PF, Zwaginga JJ
Transfusion. 2018
Abstract
BACKGROUND Platelet transfusions can induce alloimmunization against HLA antigens. The use of pathogen-reduced platelet concentrates (PCs) was suggested to reduce HLA alloimmunization and concomitant transfusion refractoriness. METHODS This study investigated HLA alloimmunization in available samples from 448 hemato-oncological patients who were randomized for the Pathogen Reduction Evaluation and Predictive Analytical Rating Score (PREPAReS) trial to receive either untreated or pathogen-reduced PCs (Mirasol, Terumo BCT Inc.). Anti-HLA Class I and II antibodies were determined before the first platelet transfusion and weekly thereafter using multiplex assay with standard cutoffs to detect low- as well as high-level antibodies. RESULTS When using the lower cutoff, in patients who were antibody negative at enrollment, 5.4% (n = 12) developed anti-HLA Class I antibodies after receiving untreated PCs, while this was significantly higher in patients receiving pathogen-reduced PCs, 12.8% (n = 29; p = 0.009, intention-to-treat [ITT] analysis). A similar but nonsignificant trend was observed in the per-protocol (PP) analysis (5.4% vs. 10.1%; p = 0.15). HLA class II antibody formation was similar between both types of PCs in the ITT analysis, while the PP analysis showed a trend toward lower immunization after receiving pathogen-reduced PCs. Multivariate analysis identified receiving pathogen-reduced platelets as an independent risk factor for HLA Class I alloimmunization (ITT: odds ratio [95% confidence interval] = 3.02 [1.42-6.51], PP: odds ratio [95% confidence interval] = 2.77 [1.00-5.40]), without affecting HLA Class II alloimmunization. When using the high cutoff value, the difference in HLA Class I alloimmunization between study arms remained significant in the ITT analysis and again was not significant in the PP analysis. CONCLUSION Our data clearly indicate that Mirasol pathogen inactivation does not prevent HLA Class I or II alloimmunization after platelet transfusions.