The clinical efficacy of 4℃ stored platelet: a randomized controlled feasibility trial conducted in surgical patients with related bleeding

The clinical efficacy of 4℃ stored platelet: a randomized controlled feasibility trial conducted in surgical patients with related bleeding | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article The clinical efficacy of 4℃ stored platelet: a randomized controlled feasibility trial conducted in surgical patients with related bleeding Yang Sun, Jiameng Niu, Lili Xing, Ting Ma, Shengli Yan, Gongliang Du, and 12 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4341873/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Platelets play an important role in acute bleeding.Whether 4℃cold stored platelets (CSPs) can be an effective substitute for platelets at room temperature (RTPs) is rarely reported, we carried out the clinical application observation trial of CSPs in China for the first time. Method A prospective, double-blind, randomized clinical trial was conducted on surgical patients with related bleedingto assess the hemostatic potential of CSPs compared with RTPs. The primary outcomes measured were drainage volume, platelet counts, and Thrombelastography-maximum amplitude. Secondary outcomes included hospital stays, length of stay in the intensive care unit, medical expenses. Results A total of 62 patients were completed the final clinical observation. There were 31 cases ineach of the CSPs group and RTPs group. With in 1–12 hours, 13–24 hours, 25–48 hours, and 49–72 hours after platelet transfusion, drainage volume: 8.5ml/h vs 20.83ml/h ,0.52ml/h vs 5.0ml/h, 3.5ml/h vs 5.0ml/h, 0.63ml/h vs 4.1ml/h. platelet counts:58×10 9 /L vs 79×10 9 /L, 54×10 9 /Lvs77×10 9 /L,63×10 9 /L vs 75×10 9 /L, 66×10 9 /Lvs79×10 9 /L. TEG-MA: 50.1mm vs 52.0mm ,50.1mm vs 54.8mm, 53.0mm vs 56.6, 56.0mm vs 53.2mm.There was no overall difference between the two groups by Generalized estimation equation at different times (P drainage =0.933,P PLT counts =0.473,P TEG−MA =0.246). The secondary outcomes (hospital stay, ICU stay time, medical cost, discharge outcome) were no difference between the CSPs group and RTPs group (P > 0.05). There were no significant differences in adverse platelet transfusion events between the groups (P > 0.05). Conclusion CSPs and RTP have equivalent efficacy and safety in the treatment of surgery-related bleeding. This trial provides reliable evidence to support the clinical application of CSPs. Trial registration Chinese Clinical Trial Registry: ChiCTR2000036353;Principal investigator's name: Jiangcun Yang. Date of registration: 22/08/2020. Platelet Platelet storage Cold-stored platelets Bleeding Hemostasis Figures Figure 1 Introduction Platelet transfusion plays an irreplaceable role in the treatment of massive bleeding, especially in cases such as traumatic hemorrhage, postoperative bleeding, and thrombocytopenia caused by platelet functional disorders 1–2 .Timely platelet transfusion after massive bleeding during initial resuscitation can significantly reduce mortality 3 . Currently, the standard storage limit for platelets in China is 5 days at room temperature. Faced with an increasingly severe shortage of platelet supply, researchers have never stopped exploring solutions to the problem of platelet shortage, from studying the addition of preservatives for internal storage to exploring external storage environments. In-depth research on platelet ultrastructure provides new evidence: refrigerated storage does not affect the hemostatic function of platelets when they into the bod, despite potential functional losses. Based on this, researchers have regained interest in refrigerated platelets and have proposed their application in trauma and other bleeding patient. In 1969, Murphy and Gardner showed that cryopreserved platelets would be quickly cleared by blood circulation after input into the human body 4.5 . This conclusion had a profound impact on the preservation of platelets. Since then, domestically and internationally, platelets have been stored at room temperature under gentle agitation. Over the past decades, the use of platelets in blood transfusion has increased significantly, especially in patients with trauma or surgery. In recent years, the advantages of CSPs, such as long storage time, less bacterial growth, and strong coagulation ability 6 , have attracted renewed attention. The ability to release platelets of patients with massive surgical bleeding is usually not affected, and immediate hemostasis after platelets entry into the body is the primary consideration. The hemostasis advantage of refrigerated platelet preservation is just applicable to patients with surgical massive bleeding. Eker et al. 7 and our previous in- vitro studies 8,9 confirmed that CSPs, had higher and faster thrombin generation capacity than RTPs and could be stored for 10–14 d. The FDA approved the use of CSPs for 3 days in 2015. In August 2019, the U.S. Army Blood Program received approval to store CSPs for 14 days to treat patients with bleeding when RTPs are not available or not practical to use 10 . In February 2020, the US FDA granted the South Texas Blood and Tissue Center permission to use 14 day refrigerated platelets 11 . Torres Filho et al. constructed an animal model of in vivo bleeding and thrombosis which demonstrated that CSPs performed as well as RTPs in platelet adhesion and thrombosis in normal blood volume and hemorrhagic hypotension 12 . Strandenes G et al. completed clinical trials on platelets stored in cold storage for 7 days and 8–14 days in cardiac surgery patients in 2016 and 2020 respectively, supporting the feasibility of CSPs in clinical use 13 14 . In order to solve the problem of platelet shortage and make the application of CSPs in Chinese medical institutions as soon as possible, we carried out the therapeutic efficacy and adverse reactions observation trial of CSPs transfusion in patients with surgical-related bleeding in China for the first time. This study is a non-inferiority clinical trial, assuming no significant difference in clinical efficacy between the two treatment regimens. Materials And Methods Design This prospective, double-blind, randomized, controlled trial(RCT), was independently completed by the Shaanxi Provincial People's Hospital and approved by the Shaanxi Provincial People's Hospital’s Medical Ethics Committee [(2020) R005]. All written informed consents have been obtained from the study participants or their legal representatives. The trial was pre-registered with Chinese Clinical Trial Registry: ChiCTR2000036353. 22/08/2020. The trial protocol and statistical analysis plan are available in Supplement 1 and Supplement 2. Study Population Patients were recruited from the departments of emergency surgery, obstetrics, and cardiac surgery. The study was conducted between January 1, 2021, and June 30, 2022. Follow-up assessments were completed on July 15, 2022, encompassing a total of 121 cases. Inclusion criteria Following clinical evaluation by the attending physician, the patient must meet the conditions of ( 1 ) and ( 2 ), and meet the conditions of ( 3 ) or ( 4 ). ( 1 ) voluntary signing of informed consent for transfusion of therapy products (CSPs), either by the patient or their legal representative. ( 2 ) age range: 18–80 years; gender: not specified. ( 3 ) patients exhibiting platelet transfusion indications, including: ① massive blood loss(massive blood loss is replacement of the patient’s total blood volume or transfusion of more than ten units of blood within 24 hours;A replacement of 50% of circulating blood volume in less than three hours or more than 150 ml per minute.); ② platelet count ≤ 50×10 9 /L with active bleeding. ( 4 ) patients experiencing obstetric hemorrhage; Exclusion criteria ( 1 ) Age falling outside the range of 18 to 80 years. ( 2 ) Patients with hyper-coagulable diseases such as myocardial infarction or stroke. ( 3 ) Patients with severe surgical trauma expected to have a risk of mortality within 24 hours. ( 4 ) Those participating in concurrent clinical trials. ( 5 ) The physician identifies additional contraindications for platelet use, including severe pulmonary infection, liver cirrhosis, pregnancy with thrombocytopenia, renal failure with thrombocytopenia, and others. Data Extraction Two researchers according to the SAP ( statistical analysis plan) and filled in the case report form (CRF)encompassing a total of 238 items covering baseline characteristics, vital signs as clinical features, five categories of laboratory tests, surgical details such as surgery time along and surgery type; Blood transfusion before platelet transfusion;Platelet infusion start and stop time༛Pre- and post-transfusion platelet drainage volume༛Application of blood products after platelet transfusion; Other medical interventions, such as the use of anticoagulants and hemostatic agents; Discharge outcomes; Adverse reactions to blood transfusion༛Application Scenarios of platelets༈Preoperative traumatic hemorrhage, Massive bleeding during the operation, Postoperative thrombocytopenia). Platelet collection and transfusion In this study, single-donor platelets were utilized and all were sourced from the Blood Center of Xi'an. Informed consent was obtained from the donors, ensuring compliance with the national standard of the People's Republic of China (GB18467-2011) 15 . Platelet transfusion was performed by trained nurses following established protocols, while closely monitoring and documenting both the transfusion process and any associated responses. The platelets used in this study were autologous(donor) plasma platelets (AS). ( 1 ) CSPs: The platelets used in this study were first stored at 22℃ for 18-24h, then kept at 4℃ for 10–14 days. ( 2 ) RTPs: Agitation preservation platelets at 22℃ for 5 days (20–24℃). Outcome Measures Primary outcomes In order to comprehensively evaluate the hemostatic effect of platelets on surgical bleeding patients, we employed three indicators, including drainage volume, platelet count, and TEG-MA value, for a comprehensive assessment as the primary outcome. ( 1 ) Drainage volume: serves as an objective indicator for assessing the hemostatic efficacy of platelet transfusion. Collection volume: the sum of all drainage tubes of patients (thoracic drainage, abdominal drainage, intracranial drainage, etc.) ( 2 ) Platelet count: it is a laboratory index to evaluate the number of platelets after platelet transfusion. ( 3 ) TEG-MA value: it is employed as a laboratory index to assess post-transfusion platelet function. Secondary outcomes ( 1 ) Hospital stays. ( 2 ) ICU stay. ( 3 ) Medical expenses. ( 4 ) Discharge outcomes. ( 5 ) Utilization of various blood components following platelet transfusion. Efficacy evaluation of blood test indicators ( 1 ) Complete blood count, ( 2 ) Coagulation markers, ( 3 ) Thromboelastography indicators. Safety evaluation ( 1 ) Adverse platelet transfusion events, such as transfusion reactions and the incidence of deep vein thrombosis, were assessed. ( 2 ) Other clinical evaluation indicators included monitoring vital signs, assessing blood routine indicators, liver function test indicators, renal function test indicators, as well as analyzing urine and feces samples. Study termination and withdrawal A total of 121 cases were observed from January 2021 to July 2022. During the study period, 55 cases were excluded before inclusion (16 cases with severe pulmonary infection, 18 cases with cirrhosis bleeding, 6 cases with pregnancy complicated with thrombocytopenia, 4 cases with age less than 18 years old, 5 cases with age over 80 years old, 6 cases with renal failure complicated with thrombocytopenia). A total of 4 cases were terminated and not included. According to the CSPs group and RTPs group, 62 patients were statistically analyzed(Figure 1 ). Randomization and blinding A randomization table was generated using SPSS software to allocate subjects into the experimental group or control group in a 1:1 ratio (Fig. 1 , Supplement 2). To ensure double-blind conditions, subjects were numbered sequentially based on platelet application order and platelets were distributed accordingly using a random number table. The appearance and preparation methods of platelets in both groups remained consistent, with their preparation date and expiration date concealed for uniform packaging. After taking the CSPs out of the refrigerator, they are left at room temperature for half an hour to ensure that the temperature of their outer packaging is consistent with that of RTPs, thus ensuring double-blind conditions. Unblinding After the completion of the trial and thorough data cleaning, the dataset was securely locked and submitted to the School of Epidemiology and Public Health Statistics staff at Xi'an Jiao Tong University. It successfully met all requirements for clinical drug efficacy observation, enabling final statistical analysis and unblinding on September 18, 2022. Statistical analysis The demographic characteristics and baseline indicators were compared using appropriate statistical tests. The measurement data were summarized as mean, standard deviation, and median, and the difference between the two groups was assessed using either a T-test or Mann-Whitney U test based on the distribution of the data. For categorical data, proportions were calculated, and differences between the two datasets were determined using either a Chi-square test or Fisher's exact probability test. Statistical analyses were conducted using SPSS Version 26.0 (IBM SPSS Statistics for Windows, Armonk, NY: IBM Corp) and Prism 6 (GraphPad Software Inc., San Diego, CA). The analysis of the main outcome indicators involved the utilization of a generalized estimation equation (GEE) for statistical assessment of various indicators, including drainage, PLT counts, and TEG-MA, in order to compare the hemostatic efficacy between the two groups. Comparisons of this frequency were made using either a Chi-square test or Fisher's exact probability method. All statistical tests conducted in this study were two-tailed with significance set at P < 0.05. Results Study Population A total of 121 patients were enrolled in the randomized clinical trial, 55 cases were excluded before inclusion, 4 cases being terminated and withdrawn. Therefore, a total of 62 cases completed the final clinical observation. Both the CSPs and RTPs groups consisted of 31 cases each (Fig. 1 ). The mean age for patients in the CSPs group was 51 years, while it was 57 years for those in the RTPs group. In terms of gender distribution, there were 23 males (74.2%) in the CSPs group and 15 males (48.4%) in the RTPs group. The detailed baseline characteristics of both groups can be found in Table 1 . In view of our study population consisting mainlyof patients with traumatic bleeding, postpartum bleeding, and surgical-related bleeding,the stratified statistical results regarding baseline data are providedin Supplement 3 Part 2,eTable s1 -1-3. Table 1 Demographic and Clinical Characteristics of the Patients at Baseline CSPs group(n = 31) RTPs group(n = 31) Age,median(IQR),y 51(36–63) 57(45–63) Sex,Male,No.(%) 23(74.2) 15(48.4) Female,No,(%) 8(25.8) 16(51.6) Height,median(IQR),cm 170(162–174) 169 (161–173) Weight,median(IQR),kg 68(60–79) 68(60–80) Hospital stay,median(IQR),d 24(18–30) 24(14–29) Classification of diseases,No.(%) Trauma bleeding 16(51.60) 16(51.60) Postpartum bleeding 4(12.90) 4(12.90) Surgical releated bleeding 11(35.50) 11(35.50) Condition on admission,No.(%) Danger 12(38.7) 14(45.2) Urgent 12(38.7) 10(32.3) General 7(22.6) 7(22.5) Pre-operative VTE,Mean ± SD,scores 6.68 ± 3.24 6.77 ± 2.62 Anticoagulant drugs,No.(%) Unused 1(3.2) 3(9.7) Used 30(96.8) 28(90.3) Adjuvant therapy for hemostasis,No.(%) Unused 1(3.2) 3(9.7) Used 30(96.8) 28(90.3) Application Scenarios of platelets,No.(%) Preoperative traumatic hemorrhage 9(29.0) 10(32.3) Massive bleeding during the operation 13(42.0) 8(25.8) Postoperative thrombocytopenia 9(29.0) 13(41.9) Platelet storage time, Mean ± SD(day) 8.2 ± 3.6 2.4 ± 0.8 Blood transfusion of before platelet infusion,Median(IQR) Red blood cell(U) 8( 4 – 16 ) 8( 4 – 26 ) Fresh frozen plasma(ml) 750(400-2,000.00) 700(400-1,900.00) Platelet(U) 0(0–1) 0(0–2) Blood test indicators of before platelet transfusion,median(IQR) White blood cell count(×10 9 /L) 9.9(6.9–13.9) 9.1(6.5–12) Red blood cell count(×10 12 /L) 2.9(2.4–3.2) 3.2(2.6–3.7) Haemoglobin(g/L) 90(75–98) 96(82–115) Haematocrit 0.3(0.2–0.3) 0.3(0.2–0.3) Platelet count(×10 9 /L) 52(43–75) 51(32–140) Platelet crit 0.1(0.1–0.1) 0.1(0-0.2) Mean platelet volume(fL) 12.1(11.4–12.7) 12.4(11-12.8) Platelet distribution width(fL) 15.1(12.5–16.6) 16.8(12.2–18.9) Coagulation and fibrinolysis test indicators of before platelet transfusion,median(IQR) Prothrombin time(s) 13.7(12.5–17.2) 14.5(13.3–17.5) International normalized ratio 1.2(1-1.4) 1.2(1.1–1.4) Activated partial thromboplatin time(s) 33.6(30.5–39.2) 38.2(30.4–42.8) Fibrinogen(g/L) 2.6(1.7–4.9) 3.2(2.2–4.1) Thrombin time(s) 18(16.4–19.8) 17.1(16.2–17.9) Fibrin degradation product(mg/L) 12.1(6.5–46.6) 33.8(10.7–56.4) D-dimer(mg/L) 7.6(2.2–25) 15.6(4.2–26.7) Thrombelastography test indicators of before platelet transfusion,median(IQR) R(min) 6(4.4–8.5) 5.9(4.8-9) K(min) 3.5(2.7–5.1) 3.5(2.5–5.3) Angle(deg) 54.6(41.3–57.6) 55.1(42.1–60.5) MA(mm) 44.8(40.2–51.6) 45.4(39.6–52.5) CI -2.6(-6.2–1.4) -3.5(-5.9–1.7) Abbreviations: IQR, interquartile range. VTE: venous thrombus embolism. SD: standard deviation. Primary outcomes ( 1 ) The drainage volume in the CSPs and RTPs groups during 1–12 hours, 13–24 hours, 25–48 hours, and 49–72 hours after platelet transfusion were as follows: 8.5 ml/h vs 20.83ml/h, 0.52 ml/h vs 5.0 ml/h, 3.5 ml/h vs 5.0 ml/h, and 0.63 ml/h vs 4.1ml /h respectively.There was no significant difference between the two groups overall (P = 0.933), nor within each of the four time periods (P > 0 .05). ( 2 ) The platelet counts of the CSPs and RTPs groups during four post-transfusion periods were as follows: 58×10 9 /L vs 79×10 9 /L,54×10 9 /L vs 77×10 9 /L,63×10 9 /L vs 75×10 9 /L,and 66×10 9 /L vs 79 ×10 9 /L.Overall there was no significant difference between the two groups ( P = 0.473). However, at both the first period (1–12 hours) and second period (13–24 hours) after platelet transfusion,the CSPs group had lower platelet counts compared to the RTPs group (P = 0 .037; P = 0 .043). ( 3 ) The MA values of CSPs and RTPsgroups during four post-transfusion periods were respectively: 50.1 mm vs 52.0 mm, 50.1 mm vs 54.8 mm, 53.0 mm vs 56.6 mm, and 56.0 mm vs 53.2 mm.There was no significant difference between the two groups overall (P = 0.246), nor within each of the four time periods (P > 0.005) (Table 2 ). Table 2 Primary outcomes indicators after platelet therapy CSPs group(n = 31) RTPs group(n = 31) P * Drainage volume ,median (IQR),(ml/h) Before platelet transfusion 0(0-31.3) 0(0–50) 0.816 1-12h 8.5(0-37.5) 20.83(9.4–45.8) 0.560 13-24h 0.52(0–16.0) 5(0-17.8) 0.367 25-48h 3.5(0-6.3) 5(1.7–12.5) 0.791 49-72h 0.63(0-9.4) 4.1(0-12.5) 0.827 P ** 0.933 Platelet count ,median (IQR),(×10 9 /L) Before platelet transfusion 52(43–75) 51(32–140) 0.882 1-12h 58(46–85) 79(60–103) 0.037* 13-24h 54(42–69) 77(45–91) 0.043* 25-48h 63(50–87) 75(48–111) 0.186 49-72h 66(58–94) 79(55–113) 0.486 P ** 0.473 Thrombelastography-MA ,median (IQR),(mm) Before platelet transfusion 44.8(40.2–51.6) 45.4(39.6–52.5) 0.873 1-12h 50.1(43.4–53.3) 52.0(46.5–60.9) 0.124 13-24h 50.1(44.6–56.2) 54.8(46.5–60.4) 0.165 25-48h 53.0(46.3–59.1) 56.6(46.9–62.3) 0.216 49-72h 56.0(49.9–60.6) 53.2(44.5–61.7) 0.869 P ** 0.246 Abbreviations: IQR, interquartile range. CSPs, cold stored platelets. RTPs, room temperature stored platelets. The Mann-Whitney U test was used to compare the differences between the two groups at each measurement period (P*was the probability value of Mann-Whitney U test).Generalized estimation equation (GEE) was used to compare the global difference between the two groups (CSPs VS RTPs) at different times (P**was the difference in GEE analysis). Statistical analysis was performed using IBMSPSS26.0. Secondary Outcomes The secondary outcomes of the the CSPs group and RTPs group: There were no significant differences between the two group’ hospital stays, ICU stays, medical expenses, discharge outcome (P > 0.05). The transfusion volume within 72 hours after platelet transfusion in the two groups was RBC (U) / FFP (ml)/ PLT (therapeutic volume) = 2.03/216/0.42 vs 3.19/213/0.41, respectively, and there was no statistically significant difference in the transfusion ratio between the two groups, Platelet transfusion repeated at 72 hours: 9 vs 11 (P > 0.05). (Table 3 ). Table 3 Secondary outcomes after platelet therapy CSPs group(n = 31) RTPs group(n = 31) Test value P Hospital stay,median(IQR),d 24(18–30) 24(14–29) 454.00 0.709 ※ ICU stay, median(IQR),h 144.7(39–336) 160.7(52–349) 222.00 0.481 ※ Medical expenses median (IQR), 191.070.9 (124.916.0-238.354.7) 163.395.1 (121.761.2-227.499.2) 438.00 0.550 ※ Discharge Outcome Cure &Improved,No.(%) 31(100) 27(87.1) - 0.118 # Death + other,No.(%) 0(0) 4(12.9) RBC usage (U), mean ± SD Within 72 hours 2.03 ± 1.17 3.19 ± 1.94 -0.204 0.839* After 72 hours 1.32 ± 0.63 2.13 ± 0.69 -1.265 0.211* FFP usage (ml), mean ± SD Within 72 hours 216.29 ± 34.65 213.35 ± 39.25 0.036 0.972* After 72 hours 112.90 ± 24.25 309.94 ± 58.06 0.03 0.976* Platele usage (U), mean ± SD Within 72 hours 0.42 ± 0.12 0.41 ± 0.13 -1.416 0.162* After 72 hours 0.03 ± 0.01 0.29 ± 0.08 -1.563 0.123* Platelet usage repeated at 72 hours Infusion,No.(%) 9(29.0) 11(35.5) 0.295 0.587 § No infusion,No.(%) 22(71.0) 20(64.5) Abbreviations: IQR, interquartile range. ※ Rank sum test.* Two-sample T test. # Fisher exact probability method. § Chi square test. Evaluation of the efficacy of blood test indicators Blood test indicators; The differences between the two groups were compared before transfusion and during four periods after platelet transfusion. The Mann-Whitney U test was employed to compare the differences between the groups at each time point, revealing no statistically significant differences between the groups in any period. Additionally, considering the linear effect of time, Generalized Estimating Equation (GEE) analysis was conducted to compare the longitudinal data of blood routine indicators during treatment in both groups, which still showed no significant statistical difference (P > 0.05). (Supplement 3 Part 1,eTable 2) Safety evaluation outcomes The CSPs group presented with one case of intermuscular venous thrombosis affecting both calves and another case of intermuscular venous thrombosis specifically in the right calf, as detected by B-ultrasound. In the RTPs group, there was no significant difference observed between one case of double calf muscle venous thrombosis and one case of left calf muscle venous thrombosis identified through B-ultrasound (P > 0.05). Furthermore, no transfusion reactions such as hemolysis reaction, fever reaction, allergy, transfusion associated circulatory overload (TACO) and transfusion related acute lung injury (TRALI) were reported following platelet transfusion in either group (Supplement 3 Part 1,eTable 3). The vital signs were assessed within 72 hours following platelet transfusion in both groups, and no significant differences were observed between the two groups (P > 0.05) (Supplement 3 Part 1, eTable 4). Liver function indicators and renal function indicators were compared and evaluated before and after platelet transfusion at the 72-hour mark, with no statistically significant differences found (P > 0.05) (Supplement 3 Part 1, eTable 5). Routine urinary fecal indicators including urine protein levels and fecal occult blood tests were compared before and after platelet transfusion at the 72-hour mark, revealing no significant differences (P > 0.05) (Supplement 3 Part 1, eTable 6). Stratification statistics were conducted for patients with traumatic bleeding, postpartum bleeding and cardiac surgery Primary outcomes: There were no significant differences observed between the CSPs and RTPs groups in terms of drainage volume, platelet count, and TEG-MA for the treatment of the three diseases (P > 0.05). Additionally, there were no significant differences observed between the two groups during the four measurement periods (P > 0.05) (Supplement 3 Part 2, eTable 2 − 1, 2–2, 2–3). The secondary outcomes: There were no significant differences between the two groups’ hospitalization time, ICU treatment time, hospitalization cost, discharge outcome, transfusion of different blood components within and after 72 hours of platelet transfusion(P > 0.05) (Supplement 3 Part 2, eTable 3 − 1, 3 − 2, 3–3). Blood test indicators: No statistically significant differences were observed between the two groups (P > 0.05), and there were also no significant differences observed in each indicator's five measurement periods between both groups (P > 0.05) (Supplement 3 Part 2,eTable4 -1 ,4 − 2 ,4 − 3 )2. Safety evaluation outcomes: Intermuscular venous calf thrombosis occurred in patients with traumatic bleeding in both CSPs and RTPs groups ( Supplement 3 Part 2, eTable 5 − 1,5 − 2,5 − 3). Vital signs: Overall there was no statistically significant difference observed between the two groups(P > 0.05) (Supplement 3 Part 2, eTable 6 − 1,6 − 2,6 − 3). Liver function indicators and renal function indicators before and after platelet transfusion at a duration of seventy-two hours showed no statistically significance (P > 0.05) ( Supplement 3 Part 2, eTable 7 − 1,7 − 2,7 − 3). Discussion The results indicated that there was no statistically significant difference observed in the clinical efficacy between CSPs and RTPs for the management of bleeding. This study demonstrated the feasibility of utilizing platelets stored at 4℃ for 10–14 days in clinical settings, providing a foundation for future promotion and application of refrigerated platelets. In the past three decades, there have been significant advancements in our understanding of platelet application. Firstly, for patients with thrombocytopenia caused by myelosuppression, ensuring longer platelet survival in blood circulation is crucial, making room temperature-stored platelets (RTPs) the optimal choice. Secondly, for patients with war wounds, trauma, and surgical massive bleeding where bone marrow inhibition is not a concern but coagulopathy poses a major problem 17–19 , rapid hemostasis becomes paramount. Cold-stored platelets (CSPs) offer strong hemostatic properties and facilitate thrombosis and clot formation 20–21 ; thus timely infusion of CSPs can be considered for such patients. To evaluate the efficacy of CSPs compared to RTPs after platelet transfusion over a period of 72 hours, we conducted longitudinal data analysis encompassing five observation periods. Key indicators, including drainage flows, platelet counts, and TEG-MA measurements, were consistently monitored. Analysis using generalized estimation equations revealed no statistically significant differences in key evaluation indicators between the two groups from post-transfusion up to 72 hours later. However, during the first 12 hours and from hour 13 to hour 24 after platelet transfusion, the CSPs group exhibited lower platelet counts compared to the RSP group due to potentially more active aggregation and hemostasis upon entry into the body. Nevertheless, no significant differences were detected in segmental drainage flow rates or MA values between both groups during these time intervals, thereby validating the excellent immediate hemostatic efficacy attributed to the use of CSP. Supporting evidence is derived from clinical trials conducted by Strandenes G et al., wherein their studies in 2016 and 2020 respectively demonstrated a superior aggregation response following transfusion using cold-stored platelets compared to room temperature stored platelets (RTPs) in cardiac surgery patients 12–13,22 . In our study, all 31 cases in the CSPs group achieved complete cure or improvement, while 27 cases in the RTPs group showed effectiveness (one case resulted in mortality and three cases did not recover), with no statistically significant difference observed. However, further clinical case verification is required to determine whether CSPs can effectively reduce mortality caused by extensive surgical bleeding. Stratified analysis of conditions and comparison of secondary outcomes between the two groups revealed consistent trends in evaluating traumatic bleeding, postpartum bleeding, and surgery-related bleeding. The patient population receiving RTPs demonstrated a higher risk profile indicating increased susceptibility to mortality. Although no differences were observed in complications, it should be noted that the limited sample size of this study prevents definitive conclusions regarding similarity in risk profiles between CSPs and RTPs. Our study showed that there were 2 cases of intermuscular venous calf thrombosis in each of the trauma bleeding patients in the CSPs and RTPs group. These 4 patients had relatively serious multiple systemic injuries, where the lower extremity intermuscular venous thrombosis was related to their conditions. There were no blood transfusion reactions such as hemolysis, fever, allergy, cardiac overload or transfusion-related lung injury after platelet transfusion. Vital signs were detected within 72 hours after platelet transfusion between the two groups. Liver function indicators and renal function indicators were compared and evaluated before and after discharge, and there were no significant differences. From these indicators, we believe that cold storage of platelets is safe for clinical use. Our results were consistent with the conclusions of Strandenes 13 , Warner, M.A 23 and Leeper C.M 24 . The platelets used in this study were autologous plasma platelets (AS), which were stored at room temperature (22℃) for 18–24 hours and then transferred to cold storage. The Getz TM 25 study suggested that CSP clumping is caused by the binding of fibrinogen to activated PLT, and this process can be mitigated by the use of PLT additive solution (PAS). The Wagner 26 study found that platelets stored at room temperature for 8 hours at 20–24℃ before storage at 1–6℃ showed less aggregation responses to collagen, ADP and TRAP than platelets stored at room temperature for 1–2 hours before refrigeration. The Mayo Clinic Donation Center optimized its platelet inventory in April 2020 to allow pathogen-treated RTPs normally stored at five days to be refrigerated for up to nine days 23 .Wood et al. 27 extended the shelf life of platelets when they were routinely stored until near expiration (4 days) and then transferred to cold storage. The results showed that the metabolism and activation of delayed cold platelets was similar to that of cold platelets. Therefore, delayed-cold storage method may also serve as a viable alternative for applications aimed at maximizing platelet functionality. Conclusion In this study, CSPs were clinically applied for the first time in China. No significant difference was observed in the therapeutic efficacy between CSPs and RTP. There were no disparities found in primary efficacy indicators, secondary efficacy indicators, and safety evaluation indicators between the two groups. Considering the substantial advantages of extended storage time offered by CSPs, they exhibit promising prospects for clinical applications. Limitations The present study was conducted at a single center and had a limited sample size. It is important to note that our study population exclusively consisted of individuals aged 18 years or above, thus necessitating further investigation into pediatric and neonatal cases. Abbreviations CSPs = Cold- Stored Platelets; RTPs = Room Temperature-Stored Platelets; TEG = Thrombelastography；MA=Maximum Amplitude；VTE=Venous Thromboembolism Declarations Acknowledgements We would like to thank Dr. Ning Peng and Dr. Min Wu (Department of Scientific Contributions, Shaanxi Provincial People's Hospital); Yaojun Song BM, Miaoni Wang BM, Jingyan Chang BM(Department of Transfusion Medicine, Shaanxi Provincial People's Hospital); Prof. Lingxia Zeng(School of Public Health, Xi 'an Jiaotong University Health Science Center); Prof. Xiaoli Cao(Shaanxi Provincial Blood Center); Prof. Wen Yin(Xijing Hospital, Military Medical University, PLA Air Force). No one received compensation in connection with this study. 2.Author Contributions Jiangcun Yang: Conceptualization, Methodology, Conceptualization, Methodology, Writing- Reviewing and Editing,Supervision,Writing - Review & Editing,Funding acquisition,Writing - Original Draft,Supervision,Supervision,Formal analysis. Yuan Shen: Conceptualization, Methodology, Writing- Reviewing and Editing, Supervision, Writing - Review & Editing, Data Curation, Formal analysis. Yang Sun: Investigation, Writing - Review & Editing, Data Curation, Funding acquisition, Formal analysis. Jiameng Niu: Investigation.,Writing - Review & Editing,Data Curation,Writing - Review & Editin. Lili Xing:Investigation,Writing-Review&Editing,Data Curation, Visualization, Writing - Review & Editing. Ting Ma: Investigation,Writing - Review & Editing. Gongliang Du:Resources.Xuewen Li:Resources.Yaqin Wang:Resources.Hengxin Li:Resources.hengli Yan:Resources.Kangshe Guo: Resources. Liqin Wang: Writing - Review & Editing. Ping Chen: Writing - Review & Editing. Wenhua Wang: Writing - Review & Editing.Yingqun Yang: Writing - Review & Editing. Xinxin Xie: Writing - Review & Editing. Aowei Song: Writing - Review & Editing. All authors have read and approved the final version of the manuscript for submission. The order of authorship is based on the level of contribution to the research and preparation of the manuscript. 3.Conflicts of Interest All authors declare no competing interests. 4.Funding Statement This research was funded by key project 2019CGHJ-09 of Science and Technology Department of Shaanxi Province (Yang Sun) and Leading Talents Fund Project 2021LJ-14 of Shaanxi Provincial People's Hospital (Jiangcun Yang). Role of the Funder/Sponsor The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. 5.T rial r egistration Chinese Clinical Trial Registry: ChiCTR2000036353; Principal investigator's name: Jiangcun Yang. Date of registration:22/08/2020. 6.Ethics approval and consent to participate Shaanxi Provincial People's Hospital and approved by its Medical Ethics Committee [(2020) R005]. All participants or their legal representatives provided written informed consent. 7.Consent for publication The final manuscript has been approved by all authors. 8.Availability of data and materials See Supplement 4 9.Running Heads Clinical Study on Platelets Stored at 4℃ in China 10.Additional information Prior Presentations No any presentation/s of the work at conferences for meetings. Preprint Server No References Borgman MA, Spinella PC, Perkins JG, Grathwohl KW, Repine T, Beekley AC, Sebesta J, Jenkins D, Wade CE, Holcomb JB. The ratio of blood products transfused affects mortality in patients receiving massive transfusions at a combat support hospital. J Trauma. 2007 Oct;63(4):805-13. doi: 10.1097/TA.0b013e3181271ba3. PMID: 18090009. Holcomb JB, Jenkins D, Rhee P, Johannigman J, Mahoney P, Mehta S, Cox ED, Gehrke MJ, Beilman GJ, Schreiber M, Flaherty SF, Grathwohl KW, Spinella PC, Perkins JG, Beekley AC, McMullin NR, Park MS, Gonzalez EA, Wade CE, Dubick MA, Schwab CW, Moore FA, Champion HR, Hoyt DB, Hess JR. Damage control resuscitation: directly addressing the early coagulopathy of trauma. J Trauma. 2007 Feb;62(2):307-10. doi: 10.1097/TA.0b013e3180324124. PMID: 17297317. Pidcoke HF, Aden JK, Mora AG, Borgman MA, Spinella PC, Dubick MA, Blackbourne LH, Cap AP. Ten-year analysis of transfusion in Operation Iraqi Freedom and Operation Enduring Freedom: increased plasma and platelet use correlates with improved survival. J Trauma Acute Care Surg. 2012 Dec;73(6 Suppl 5):S445-52. doi: 10.1097/TA.0b013e3182754796. PMID: 23192068. Murphy S, Gardner FH. Effect of storage temperature on maintenance of platelet viability--deleterious effect of refrigerated storage. N Engl J Med. 1969 May 15;280(20):1094-8. doi: 10.1056/NEJM196905152802004. PMID: 5778424. Becker GA, Tuccelli M, Kunicki T, Chalos MK, Aster RH. Studies of platelet concentrates stored at 22 C nad 4 C. Transfusion. 1973 Mar;13(2):61-8. doi: 10.1111/j.1537-2995.1973.tb05442.x. PMID: 4695593. Currie LM, Harper JR, Allan H, Connor J. Inhibition of cytokine accumulation and bacterial growth during storage of platelet concentrates at 4 degrees C with retention of in vitro functional activity. Transfusion. 1997 Jan;37(1):18-24. doi: 10.1046/j.1537-2995.1997.37197176946.x. PMID: 9024485. Eker I, Yilmaz S, Cetinkaya RA, Unlu A, Pekel A, Acikel C, Yilmaz S, Gursel O, Avci İY. Is one-size-fits-all strategy adequate for platelet storage? Transfus Apher Sci. 2016 Dec;55(3):323-328. doi: 10.1016/j.transci.2016.08.006. Epub 2016 Sep 28. PMID: 27743710. Yang J, Yin W, Zhang Y, Sun Y, Ma T, Gu S, Gao Y, Zhang X, Yuan J, Wang W. Evaluation of the advantages of platelet concentrates stored at 4°C versus 22°C. Transfusion. 2018 Mar;58(3):736-747. doi: 10.1111/trf.14462. Epub 2017 Dec 21. PMID: 29266276. Yang JC, Liu FH, Sun Y, Ma T, Xu CX, Wang WH, Chen P, Xie XX, Song YJ, Yin W. Good hemostatic effect of platelets stored at 4°C in an in vitro model of massive blood loss and thrombocytopenia. Medicine (Baltimore). 2019 May;98(18):e15454. doi: 10.1097/MD.0000000000015454. PMID: 31045818; PMCID: PMC6504340. FDA Action Makes Blood product more accessible to warfighters in combat. September 11, 2019 FDA. Available from https:// www.fda.gov/media/130671/download. 2019. FDA grants South Texas Blood & Tissue Center first license for new process that triples shelf life of critically needed platelets Feb. 28, 2020: FDA. 2020; https://www.globenewswire.com/news-release/2020/02/28/1992715/0/en/FDA-grants-SouthTexas-Blood-Tissue-Center-first-license-for-new-process-thattriples-shelf-life-of-critically-needed-platelets.html. Torres Filho IP, Torres LN, Valdez C, Salgado C, Cap AP, Dubick MA. Refrigerated platelets stored in whole blood up to 5 days adhere to thrombi formed during hemorrhagic hypotension in rats. J Thromb Haemost. 2017 Jan;15(1):163-175. doi: 10.1111/jth.13556. Epub 2016 Dec 18. PMID: 27797452. Strandenes G, Kristoffersen EK, Bjerkvig CK, Fosse TK, Apelseth T. Cold-stored Apheresis Platelets in Treatment of Postoperative Bleeding in Cardiothoracic Surgery. Paper presented at: AABB Annual Meeting 2016. Strandenes G, Sivertsen J, Bjerkvig CK, Fosse TK, Cap AP, Del Junco DJ, Kristoffersen EK, Haaverstad R, Kvalheim V, Braathen H, Lunde THF, Hervig T, Hufthammer KO, Spinella PC, Apelseth TO. A Pilot Trial of Platelets Stored Cold versus at Room Temperature for Complex Cardiothoracic Surgery. Anesthesiology. 2020 Dec 1;133(6):1173-1183. doi: 10.1097/ALN.0000000000003550. PMID: 32902572. National Health Commission of the People’s Republic of China.whole blood and component donor selection requirements. GB18467-2011. (2011-12-30). Accessed November 30, 2022. http://www.nhc.gov.cn/wjw/s9493/201207/55286.shtml. Xia Jie-Lai. Statistical considerations for non-inferiority clinical trials[J]. (China Health Statistics,2012,29(02):270-274.) Levy JH, Neal MD, Herman JH. Bacterial contamination of platelets for transfusion: strategies for prevention. Crit Care. 2018;22(1):271. Published 2018 Oct 27. doi:10.1186/s13054-018-2212-9 Ketter PM, Kamucheka R, Arulanandam B, Akers K, Cap AP. Platelet enhancement of bacterial growth during room temperature storage: mitigation through refrigeration. Transfusion. 2019;59(S2):1479-1489. doi:10.1111/trf.15255 Cap AP. Platelet storage: a license to chill!. Transfusion. 2016;56(1):13-16. doi:10.1111/trf.13433 Dutton RP, Mackenzie CF, Scalea TM. Hypotensive resuscitation during active hemorrhage: impact on in-hospital mortality. J Trauma. 2002;52(6):1141-1146. doi:10.1097/00005373-200206000-00020 Pidcoke HF, Spinella PC, Ramasubramanian AK, Strandenes G, Hervig T, Ness PM, Cap AP. Refrigerated platelets for the treatment of acute bleeding: a review of the literature and reexamination of current standards. Shock. 2014 May;41 Suppl 1:51-3. doi: 10.1097/SHK.0000000000000078. PMID: 24662779. Cap AP, Reddoch-Cardenas KM. Can't get platelets to your bleeding patients? Just chill… the solution is in your refrigerator!. Transfus Clin Biol. 2018;25(3):217-219. doi:10.1016/j.tracli.2018.06.008 Warner MA, Kurian EB, Hammel SA, van Buskirk CM, Kor DJ, Stubbs JR. Transition from room temperature to cold-stored platelets for the preservation of blood inventories during the COVID-19 pandemic. Transfusion. 2021;61(1):72-77. doi:10.1111/trf.16148 Leeper CM, Yazer MH, Cladis FP, Saladino R, Triulzi DJ, Gaines BA. Cold-stored whole blood platelet function is preserved in injured children with hemorrhagic shock. J Trauma Acute Care Surg. 2019;87(1):49-53. doi:10.1097/TA.0000000000002340 Getz T, Cap AP. Storage of Platelets at 4 degrees C in Platelet Additive Solutions Prevents Aggregate Formation and Preserves Platelet Functional Responses. Paper presented at: AABB Annual Meeting 2014. Wagner SJ, Getz TM, Thompson-Montgomery D, Turgeon A. Preliminary characterization of the properties of cold-stored apheresis platelets suspended in PAS-III with and without an 8-hour room temperature hold. Transfusion. 2020;60(11):2489-2493. doi:10.1111/trf.15964 Wood B, Johnson L, Hyland RA, Marks DC. Maximising platelet availability by delaying cold storage [published online ahead of print, 2018 Apr 6]. Vox Sang. 2018;10.1111/vox.12649. doi:10.1111/vox.12649 Additional Declarations No competing interests reported. Supplementary Files Supplement1TrialProtocol.docx Supplement 1：Trial Protocol Supplement2TrialSAP.docx Supplement 2：Trial SAP supplement3DataAnalysis.docx Supplement 3：Data analysis Part 1 0ver all data for study Part 2 Sub-group data according to bleeding causes Supplement4DataSharingStatement.docx Supplement 4：Data Sharing Statement Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4341873","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":301337677,"identity":"ed4a484f-7199-452e-afff-e41de7ed90e3","order_by":0,"name":"Yang Sun","email":"","orcid":"","institution":"Shaanxi Provincial People’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yang","middleName":"","lastName":"Sun","suffix":""},{"id":301337678,"identity":"f3184bdc-2839-4edc-a9ec-6fb6396d65b5","order_by":1,"name":"Jiameng Niu","email":"","orcid":"","institution":"Shaanxi Provincial People’s 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09:46:03","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4341873/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4341873/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":56677589,"identity":"0e1a93c6-bbbf-4a9b-98ab-013fdd4923e3","added_by":"auto","created_at":"2024-05-17 16:35:46","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1002368,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e1. CONSORT\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 121 patients were included in the randomized clinical trial.During the study period, 55 cases were excluded before inclusion (16 cases with severe pulmonary infection, 18 cases with cirrhosis bleeding, 6 cases with pregnancy complicated with thrombocytopenia, 4 cases with age less than 18 years old, 5 cases with age over 80 years old, 6 cases with renal failure complicated with thrombocytopenia，and 4 cases were terminated and withdrawn, so 62 cases were finally completed clinical observation. According to the randomization table, patients were divided into CSPs group and RTPs group in a 1:1 ratio. Finally, there were 31 cases in CSPs group and RTPs group, 16 cases in each group for traumatic bleeding, 4 cases in each group for postpartum bleeding, and 11 cases in each group for surgical releated bleeding\u003c/p\u003e","description":"","filename":"Figure1CONSORT.png","url":"https://assets-eu.researchsquare.com/files/rs-4341873/v1/747391850a120ad8763e7328.png"},{"id":58198113,"identity":"56a2d633-17a6-486a-a9cb-bc6f79d16adb","added_by":"auto","created_at":"2024-06-12 09:59:30","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1795824,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4341873/v1/200dbfb1-8682-423c-acc3-31632b8148ae.pdf"},{"id":56677590,"identity":"ebb4c367-f9f4-48d5-9306-715aacebf237","added_by":"auto","created_at":"2024-05-17 16:35:46","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":18946,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplement 1：Trial Protocol\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Supplement1TrialProtocol.docx","url":"https://assets-eu.researchsquare.com/files/rs-4341873/v1/9cf0ceda9fa9bed3147de7da.docx"},{"id":56677591,"identity":"ac7ebfb0-b1f7-40c4-b40e-67e9751c38e9","added_by":"auto","created_at":"2024-05-17 16:35:46","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":64281,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplement 2：Trial SAP\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Supplement2TrialSAP.docx","url":"https://assets-eu.researchsquare.com/files/rs-4341873/v1/ea8d4b710b6973f58bba21d8.docx"},{"id":56677592,"identity":"929a2cdf-505c-427a-a152-f4692cb9bab9","added_by":"auto","created_at":"2024-05-17 16:35:46","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":241776,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplement 3：Data analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePart 1 0ver all data for study\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePart 2 Sub-group data according to bleeding causes\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"supplement3DataAnalysis.docx","url":"https://assets-eu.researchsquare.com/files/rs-4341873/v1/529ce852040ef85c04a28adc.docx"},{"id":56677594,"identity":"6aa33060-0775-4a9d-9ba6-bd83760f0d6c","added_by":"auto","created_at":"2024-05-17 16:35:46","extension":"docx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":10966,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplement 4：Data Sharing Statement\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Supplement4DataSharingStatement.docx","url":"https://assets-eu.researchsquare.com/files/rs-4341873/v1/a50929680d981a5f911aace1.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"The clinical efficacy of 4℃ stored platelet: a randomized controlled feasibility trial conducted in surgical patients with related bleeding","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePlatelet transfusion plays an irreplaceable role in the treatment of massive bleeding, especially in cases such as traumatic hemorrhage, postoperative bleeding, and thrombocytopenia caused by platelet functional disorders\u003csup\u003e1\u0026ndash;2\u003c/sup\u003e.Timely platelet transfusion after massive bleeding during initial resuscitation can significantly reduce mortality\u003csup\u003e3\u003c/sup\u003e. Currently, the standard storage limit for platelets in China is 5 days at room temperature. Faced with an increasingly severe shortage of platelet supply, researchers have never stopped exploring solutions to the problem of platelet shortage, from studying the addition of preservatives for internal storage to exploring external storage environments. In-depth research on platelet ultrastructure provides new evidence: refrigerated storage does not affect the hemostatic function of platelets when they into the bod, despite potential functional losses. Based on this, researchers have regained interest in refrigerated platelets and have proposed their application in trauma and other bleeding patient.\u003c/p\u003e \u003cp\u003eIn 1969, Murphy and Gardner showed that cryopreserved platelets would be quickly cleared by blood circulation after input into the human body\u003csup\u003e4.5\u003c/sup\u003e. This conclusion had a profound impact on the preservation of platelets. Since then, domestically and internationally, platelets have been stored at room temperature under gentle agitation. Over the past decades, the use of platelets in blood transfusion has increased significantly, especially in patients with trauma or surgery. In recent years, the advantages of CSPs, such as long storage time, less bacterial growth, and strong coagulation ability\u003csup\u003e6\u003c/sup\u003e, have attracted renewed attention. The ability to release platelets of patients with massive surgical bleeding is usually not affected, and immediate hemostasis after platelets entry into the body is the primary consideration. The hemostasis advantage of refrigerated platelet preservation is just applicable to patients with surgical massive bleeding. Eker et al.\u003csup\u003e7\u003c/sup\u003e and our previous in- vitro studies\u003csup\u003e8,9\u003c/sup\u003e confirmed that CSPs, had higher and faster thrombin generation capacity than RTPs and could be stored for 10\u0026ndash;14 d.\u003c/p\u003e \u003cp\u003eThe FDA approved the use of CSPs for 3 days in 2015. In August 2019, the U.S. Army Blood Program received approval to store CSPs for 14 days to treat patients with bleeding when RTPs are not available or not practical to use\u003csup\u003e10\u003c/sup\u003e. In February 2020, the US FDA granted the South Texas Blood and Tissue Center permission to use 14 day refrigerated platelets\u003csup\u003e11\u003c/sup\u003e. Torres Filho et al. constructed an animal model of in vivo bleeding and thrombosis which demonstrated that CSPs performed as well as RTPs in platelet adhesion and thrombosis in normal blood volume and hemorrhagic hypotension\u003csup\u003e12\u003c/sup\u003e. Strandenes G et al. completed clinical trials on platelets stored in cold storage for 7 days and 8\u0026ndash;14 days in cardiac surgery patients in 2016 and 2020 respectively, supporting the feasibility of CSPs in clinical use \u003csup\u003e13 14\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn order to solve the problem of platelet shortage and make the application of CSPs in Chinese medical institutions as soon as possible, we carried out the therapeutic efficacy and adverse reactions observation trial of CSPs transfusion in patients with surgical-related bleeding in China for the first time. This study is a non-inferiority clinical trial, assuming no significant difference in clinical efficacy between the two treatment regimens.\u003c/p\u003e"},{"header":"Materials And Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eDesign\u003c/h2\u003e \u003cp\u003e This prospective, double-blind, randomized, controlled trial(RCT), was independently completed by the Shaanxi Provincial People's Hospital and approved by the Shaanxi Provincial People's Hospital\u0026rsquo;s Medical Ethics Committee [(2020) R005]. All written informed consents have been obtained from the study participants or their legal representatives. The trial was pre-registered with Chinese Clinical Trial Registry: ChiCTR2000036353. 22/08/2020. The trial protocol and statistical analysis plan are available in Supplement 1 and Supplement 2.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStudy Population\u003c/h2\u003e \u003cp\u003ePatients were recruited from the departments of emergency surgery, obstetrics, and cardiac surgery. The study was conducted between January 1, 2021, and June 30, 2022. Follow-up assessments were completed on July 15, 2022, encompassing a total of 121 cases.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eInclusion criteria\u003c/h2\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eFollowing clinical evaluation by the attending physician, the patient must meet the conditions of (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) and (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e), and meet the conditions of (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) or (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003e(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) voluntary signing of informed consent for transfusion of therapy products (CSPs), either by the patient or their legal representative. (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) age range: 18\u0026ndash;80 years; gender: not specified. (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) patients exhibiting platelet transfusion indications, including: ① massive blood loss(massive blood loss is replacement of the patient\u0026rsquo;s total blood volume or transfusion of more than ten units of blood within 24 hours;A replacement of 50% of circulating blood volume in less than three hours or more than 150 ml per minute.); ② platelet count\u0026thinsp;\u0026le;\u0026thinsp;50\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L with active bleeding. (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) patients experiencing obstetric hemorrhage;\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section3\"\u003e \u003ch2\u003eExclusion criteria\u003c/h2\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) Age falling outside the range of 18 to 80 years. (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) Patients with hyper-coagulable diseases such as myocardial infarction or stroke. (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) Patients with severe surgical trauma expected to have a risk of mortality within 24 hours. (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) Those participating in concurrent clinical trials. (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) The physician identifies additional contraindications for platelet use, including severe pulmonary infection, liver cirrhosis, pregnancy with thrombocytopenia, renal failure with thrombocytopenia, and others.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eData Extraction\u003c/h2\u003e \u003cp\u003eTwo researchers according to the SAP ( statistical analysis plan) and filled in the case report form (CRF)encompassing a total of 238 items covering baseline characteristics, vital signs as clinical features, five categories of laboratory tests, surgical details such as surgery time along and surgery type; Blood transfusion before platelet transfusion;Platelet infusion start and stop time༛Pre- and post-transfusion platelet drainage volume༛Application of blood products after platelet transfusion; Other medical interventions, such as the use of anticoagulants and hemostatic agents; Discharge outcomes; Adverse reactions to blood transfusion༛Application Scenarios of platelets༈Preoperative traumatic hemorrhage, Massive bleeding during the operation, Postoperative thrombocytopenia).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003ePlatelet collection and transfusion\u003c/h2\u003e \u003cp\u003eIn this study, single-donor platelets were utilized and all were sourced from the Blood Center of Xi'an. Informed consent was obtained from the donors, ensuring compliance with the national standard of the People's Republic of China (GB18467-2011)\u003csup\u003e15\u003c/sup\u003e. Platelet transfusion was performed by trained nurses following established protocols, while closely monitoring and documenting both the transfusion process and any associated responses.\u003c/p\u003e \u003cp\u003eThe platelets used in this study were autologous(donor) plasma platelets (AS). (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) CSPs: The platelets used in this study were first stored at 22℃ for 18-24h, then kept at 4℃ for 10\u0026ndash;14 days. (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) RTPs: Agitation preservation platelets at 22℃ for 5 days (20\u0026ndash;24℃).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eOutcome Measures\u003c/h2\u003e \u003cdiv id=\"Sec10\" class=\"Section3\"\u003e \u003ch2\u003ePrimary outcomes\u003c/h2\u003e \u003cp\u003eIn order to comprehensively evaluate the hemostatic effect of platelets on surgical bleeding patients, we employed three indicators, including drainage volume, platelet count, and TEG-MA value, for a comprehensive assessment as the primary outcome.\u003c/p\u003e \u003cp\u003e(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) Drainage volume: serves as an objective indicator for assessing the hemostatic efficacy of platelet transfusion. Collection volume: the sum of all drainage tubes of patients (thoracic drainage, abdominal drainage, intracranial drainage, etc.) (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) Platelet count: it is a laboratory index to evaluate the number of platelets after platelet transfusion. (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) TEG-MA value: it is employed as a laboratory index to assess post-transfusion platelet function.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eSecondary outcomes\u003c/h2\u003e \u003cp\u003e(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) Hospital stays. (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) ICU stay. (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) Medical expenses. (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) Discharge outcomes. (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) Utilization of various blood components following platelet transfusion.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eEfficacy evaluation of blood test indicators\u003c/h2\u003e \u003cp\u003e(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) Complete blood count, (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) Coagulation markers, (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) Thromboelastography indicators.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eSafety evaluation\u003c/h2\u003e \u003cp\u003e(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) Adverse platelet transfusion events, such as transfusion reactions and the incidence of deep vein thrombosis, were assessed. (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) Other clinical evaluation indicators included monitoring vital signs, assessing blood routine indicators, liver function test indicators, renal function test indicators, as well as analyzing urine and feces samples.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eStudy termination and withdrawal\u003c/h2\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eA total of 121 cases were observed from January 2021 to July 2022. During the study period, 55 cases were excluded before inclusion (16 cases with severe pulmonary infection, 18 cases with cirrhosis bleeding, 6 cases with pregnancy complicated with thrombocytopenia, 4 cases with age less than 18 years old, 5 cases with age over 80 years old, 6 cases with renal failure complicated with thrombocytopenia). A total of 4 cases were terminated and not included. According to the CSPs group and RTPs group, 62 patients were statistically analyzed(Figure \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eRandomization and blinding\u003c/h2\u003e \u003cp\u003eA randomization table was generated using SPSS software to allocate subjects into the experimental group or control group in a 1:1 ratio (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, Supplement 2). To ensure double-blind conditions, subjects were numbered sequentially based on platelet application order and platelets were distributed accordingly using a random number table. The appearance and preparation methods of platelets in both groups remained consistent, with their preparation date and expiration date concealed for uniform packaging. After taking the CSPs out of the refrigerator, they are left at room temperature for half an hour to ensure that the temperature of their outer packaging is consistent with that of RTPs, thus ensuring double-blind conditions.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eUnblinding\u003c/h2\u003e \u003cp\u003eAfter the completion of the trial and thorough data cleaning, the dataset was securely locked and submitted to the School of Epidemiology and Public Health Statistics staff at Xi'an Jiao Tong University. It successfully met all requirements for clinical drug efficacy observation, enabling final statistical analysis and unblinding on September 18, 2022.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eThe demographic characteristics and baseline indicators were compared using appropriate statistical tests. The measurement data were summarized as mean, standard deviation, and median, and the difference between the two groups was assessed using either a T-test or Mann-Whitney U test based on the distribution of the data. For categorical data, proportions were calculated, and differences between the two datasets were determined using either a Chi-square test or Fisher's exact probability test. Statistical analyses were conducted using SPSS Version 26.0 (IBM SPSS Statistics for Windows, Armonk, NY: IBM Corp) and Prism 6 (GraphPad Software Inc., San Diego, CA).\u003c/p\u003e \u003cp\u003eThe analysis of the main outcome indicators involved the utilization of a generalized estimation equation (GEE) for statistical assessment of various indicators, including drainage, PLT counts, and TEG-MA, in order to compare the hemostatic efficacy between the two groups. Comparisons of this frequency were made using either a Chi-square test or Fisher's exact probability method. All statistical tests conducted in this study were two-tailed with significance set at P\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003eStudy Population\u003c/h2\u003e \u003cp\u003eA total of 121 patients were enrolled in the randomized clinical trial, 55 cases were excluded before inclusion, 4 cases being terminated and withdrawn. Therefore, a total of 62 cases completed the final clinical observation. Both the CSPs and RTPs groups consisted of 31 cases each (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The mean age for patients in the CSPs group was 51 years, while it was 57 years for those in the RTPs group. In terms of gender distribution, there were 23 males (74.2%) in the CSPs group and 15 males (48.4%) in the RTPs group. The detailed baseline characteristics of both groups can be found in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. In view of our study population consisting mainlyof patients with traumatic bleeding, postpartum bleeding, and surgical-related bleeding,the stratified statistical results regarding baseline data are providedin Supplement 3 Part 2,eTable\u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003es1\u003c/span\u003e-1-3.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic and Clinical Characteristics of the Patients at Baseline\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCSPs group(n\u0026thinsp;=\u0026thinsp;31)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRTPs group(n\u0026thinsp;=\u0026thinsp;31)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge,median(IQR),y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51(36\u0026ndash;63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e57(45\u0026ndash;63)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex,Male,No.(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23(74.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15(48.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale,No,(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8(25.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16(51.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeight,median(IQR),cm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e170(162\u0026ndash;174)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e169 (161\u0026ndash;173)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeight,median(IQR),kg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e68(60\u0026ndash;79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e68(60\u0026ndash;80)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospital stay,median(IQR),d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24(18\u0026ndash;30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24(14\u0026ndash;29)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eClassification of diseases,No.(%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTrauma bleeding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16(51.60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16(51.60)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostpartum bleeding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4(12.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4(12.90)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgical releated bleeding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11(35.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11(35.50)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eCondition on admission,No.(%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDanger\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12(38.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14(45.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrgent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12(38.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10(32.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGeneral\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7(22.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7(22.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePre-operative VTE,Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD,scores\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.68\u0026thinsp;\u0026plusmn;\u0026thinsp;3.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.77\u0026thinsp;\u0026plusmn;\u0026thinsp;2.62\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eAnticoagulant drugs,No.(%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnused\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3(9.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUsed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30(96.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28(90.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eAdjuvant therapy for hemostasis,No.(%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnused\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3(9.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUsed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30(96.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28(90.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eApplication Scenarios of platelets,No.(%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative traumatic hemorrhage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9(29.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10(32.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMassive bleeding during the operation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13(42.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8(25.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative thrombocytopenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9(29.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13(41.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelet storage time, Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD(day)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.2\u0026thinsp;\u0026plusmn;\u0026thinsp;3.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eBlood transfusion of before platelet infusion,Median(IQR)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRed blood cell(U)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8(\u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8 CR9 CR10 CR11 CR12 CR13 CR14 CR15\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8(\u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8 CR9 CR10 CR11 CR12 CR13 CR14 CR15 CR16 CR17 CR18 CR19 CR20 CR21 CR22 CR23 CR24 CR25\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFresh frozen plasma(ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e750(400-2,000.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e700(400-1,900.00)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelet(U)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0(0\u0026ndash;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0(0\u0026ndash;2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eBlood test indicators of before platelet transfusion,median(IQR)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWhite blood cell count(\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.9(6.9\u0026ndash;13.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.1(6.5\u0026ndash;12)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRed blood cell count(\u0026times;10\u003csup\u003e12\u003c/sup\u003e/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.9(2.4\u0026ndash;3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.2(2.6\u0026ndash;3.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHaemoglobin(g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e90(75\u0026ndash;98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e96(82\u0026ndash;115)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHaematocrit\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.3(0.2\u0026ndash;0.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.3(0.2\u0026ndash;0.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelet count(\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52(43\u0026ndash;75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51(32\u0026ndash;140)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelet crit\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.1(0.1\u0026ndash;0.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.1(0-0.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean platelet volume(fL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.1(11.4\u0026ndash;12.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.4(11-12.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelet distribution width(fL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15.1(12.5\u0026ndash;16.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16.8(12.2\u0026ndash;18.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eCoagulation and fibrinolysis test indicators of before platelet transfusion,median(IQR)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProthrombin time(s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13.7(12.5\u0026ndash;17.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14.5(13.3\u0026ndash;17.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInternational normalized ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.2(1-1.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.2(1.1\u0026ndash;1.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eActivated partial thromboplatin time(s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33.6(30.5\u0026ndash;39.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38.2(30.4\u0026ndash;42.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFibrinogen(g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.6(1.7\u0026ndash;4.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.2(2.2\u0026ndash;4.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThrombin time(s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18(16.4\u0026ndash;19.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17.1(16.2\u0026ndash;17.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFibrin degradation product(mg/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.1(6.5\u0026ndash;46.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33.8(10.7\u0026ndash;56.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eD-dimer(mg/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.6(2.2\u0026ndash;25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15.6(4.2\u0026ndash;26.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eThrombelastography test indicators of before platelet transfusion,median(IQR)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR(min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6(4.4\u0026ndash;8.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.9(4.8-9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eK(min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.5(2.7\u0026ndash;5.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.5(2.5\u0026ndash;5.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAngle(deg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e54.6(41.3\u0026ndash;57.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55.1(42.1\u0026ndash;60.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMA(mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44.8(40.2\u0026ndash;51.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45.4(39.6\u0026ndash;52.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-2.6(-6.2\u0026ndash;1.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-3.5(-5.9\u0026ndash;1.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003eAbbreviations: IQR, interquartile range. VTE: venous thrombus embolism. SD: standard deviation.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec20\" class=\"Section2\"\u003e \u003ch2\u003ePrimary outcomes\u003c/h2\u003e \u003cp\u003e(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) The drainage volume in the CSPs and RTPs groups during 1\u0026ndash;12 hours, 13\u0026ndash;24 hours, 25\u0026ndash;48 hours, and 49\u0026ndash;72 hours after platelet transfusion were as follows: 8.5 ml/h vs 20.83ml/h, 0.52 ml/h vs 5.0 ml/h, 3.5 ml/h vs 5.0 ml/h, and 0.63 ml/h vs 4.1ml /h respectively.There was no significant difference between the two groups overall (P\u0026thinsp;=\u0026thinsp;0.933), nor within each of the four time periods (P\u0026thinsp;\u0026gt;\u0026thinsp;0 .05).\u003c/p\u003e \u003cp\u003e(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) The platelet counts of the CSPs and RTPs groups during four post-transfusion periods were as follows: 58\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L vs 79\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L,54\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L vs 77\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L,63\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L vs 75\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L,and 66\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L vs 79 \u0026times;10\u003csup\u003e9\u003c/sup\u003e /L.Overall there was no significant difference between the two groups ( P\u0026thinsp;=\u0026thinsp;0.473). However, at both the first period (1\u0026ndash;12 hours) and second period (13\u0026ndash;24 hours) after platelet transfusion,the CSPs group had lower platelet counts compared to the RTPs group (P\u0026thinsp;=\u0026thinsp;0 .037; P\u0026thinsp;=\u0026thinsp;0 .043).\u003c/p\u003e \u003cp\u003e(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) The MA values of CSPs and RTPsgroups during four post-transfusion periods were respectively: 50.1 mm vs 52.0 mm, 50.1 mm vs 54.8 mm, 53.0 mm vs 56.6 mm, and 56.0 mm vs 53.2 mm.There was no significant difference between the two groups overall (P\u0026thinsp;=\u0026thinsp;0.246), nor within each of the four time periods (P\u0026thinsp;\u0026gt;\u0026thinsp;0.005) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePrimary outcomes indicators after platelet therapy\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCSPs group(n\u0026thinsp;=\u0026thinsp;31)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRTPs group(n\u0026thinsp;=\u0026thinsp;31)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e*\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eDrainage volume ,median (IQR),(ml/h)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBefore platelet transfusion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0(0-31.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0(0\u0026ndash;50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.816\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1-12h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.5(0-37.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20.83(9.4\u0026ndash;45.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.560\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e13-24h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.52(0\u0026ndash;16.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5(0-17.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.367\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e25-48h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.5(0-6.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5(1.7\u0026ndash;12.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.791\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e49-72h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.63(0-9.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.1(0-12.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.827\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e**\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003e0.933\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePlatelet count ,median (IQR),(\u0026times;10\u003c/b\u003e\u003csup\u003e\u003cb\u003e9\u003c/b\u003e\u003c/sup\u003e\u003cb\u003e/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBefore platelet transfusion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52(43\u0026ndash;75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51(32\u0026ndash;140)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.882\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1-12h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e58(46\u0026ndash;85)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e79(60\u0026ndash;103)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.037*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e13-24h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e54(42\u0026ndash;69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e77(45\u0026ndash;91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.043*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e25-48h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e63(50\u0026ndash;87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e75(48\u0026ndash;111)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.186\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e49-72h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e66(58\u0026ndash;94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e79(55\u0026ndash;113)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.486\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e**\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003e0.473\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eThrombelastography-MA ,median (IQR),(mm)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBefore platelet transfusion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44.8(40.2\u0026ndash;51.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45.4(39.6\u0026ndash;52.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.873\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1-12h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50.1(43.4\u0026ndash;53.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52.0(46.5\u0026ndash;60.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.124\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e13-24h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50.1(44.6\u0026ndash;56.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e54.8(46.5\u0026ndash;60.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.165\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e25-48h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e53.0(46.3\u0026ndash;59.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56.6(46.9\u0026ndash;62.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.216\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e49-72h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e56.0(49.9\u0026ndash;60.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e53.2(44.5\u0026ndash;61.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.869\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e**\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003e0.246\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eAbbreviations: IQR, interquartile range. CSPs, cold stored platelets. RTPs, room temperature stored platelets.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eThe Mann-Whitney U test was used to compare the differences between the two groups at each measurement period (P*was the probability value of Mann-Whitney U test).Generalized estimation equation (GEE) was used to compare the global difference between the two groups (CSPs VS RTPs) at different times (P**was the difference in GEE analysis). Statistical analysis was performed using IBMSPSS26.0.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec21\" class=\"Section2\"\u003e \u003ch2\u003eSecondary Outcomes\u003c/h2\u003e \u003cp\u003eThe secondary outcomes of the the CSPs group and RTPs group: There were no significant differences between the two group\u0026rsquo; hospital stays, ICU stays, medical expenses, discharge outcome (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). The transfusion volume within 72 hours after platelet transfusion in the two groups was RBC (U) / FFP (ml)/ PLT (therapeutic volume)\u0026thinsp;=\u0026thinsp;2.03/216/0.42 vs 3.19/213/0.41, respectively, and there was no statistically significant difference in the transfusion ratio between the two groups, Platelet transfusion repeated at 72 hours: 9 vs 11 (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSecondary outcomes after platelet therapy\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCSPs group(n\u0026thinsp;=\u0026thinsp;31)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRTPs group(n\u0026thinsp;=\u0026thinsp;31)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTest value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospital stay,median(IQR),d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24(18\u0026ndash;30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24(14\u0026ndash;29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e454.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.709\u003csup\u003e※\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eICU stay, median(IQR),h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e144.7(39\u0026ndash;336)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e160.7(52\u0026ndash;349)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e222.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.481\u003csup\u003e※\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedical expenses median (IQR),\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e191.070.9\u003c/p\u003e \u003cp\u003e(124.916.0-238.354.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e163.395.1\u003c/p\u003e \u003cp\u003e(121.761.2-227.499.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e438.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.550\u003csup\u003e※\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003eDischarge Outcome\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCure \u0026amp;Improved,No.(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31(100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27(87.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.118\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeath\u0026thinsp;+\u0026thinsp;other,No.(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0(0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4(12.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003eRBC usage (U), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWithin 72 hours\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.03\u0026thinsp;\u0026plusmn;\u0026thinsp;1.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.19\u0026thinsp;\u0026plusmn;\u0026thinsp;1.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.204\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.839*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAfter 72 hours\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.32\u0026thinsp;\u0026plusmn;\u0026thinsp;0.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.13\u0026thinsp;\u0026plusmn;\u0026thinsp;0.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-1.265\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.211*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003eFFP usage (ml), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWithin 72 hours\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e216.29\u0026thinsp;\u0026plusmn;\u0026thinsp;34.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e213.35\u0026thinsp;\u0026plusmn;\u0026thinsp;39.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.036\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.972*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAfter 72 hours\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e112.90\u0026thinsp;\u0026plusmn;\u0026thinsp;24.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e309.94\u0026thinsp;\u0026plusmn;\u0026thinsp;58.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.976*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003ePlatele usage (U), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWithin 72 hours\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.42\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.41\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-1.416\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.162*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAfter 72 hours\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.03\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.29\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-1.563\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.123*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003ePlatelet usage repeated at 72 hours\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInfusion,No.(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9(29.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11(35.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.295\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.587\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo infusion,No.(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22(71.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20(64.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eAbbreviations: IQR, interquartile range.\u003csup\u003e※\u003c/sup\u003e Rank sum test.* Two-sample T test. \u003csup\u003e#\u003c/sup\u003e Fisher exact probability method. \u003csup\u003e\u0026sect;\u003c/sup\u003e Chi square test.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec22\" class=\"Section2\"\u003e \u003ch2\u003eEvaluation of the efficacy of blood test indicators\u003c/h2\u003e \u003cp\u003eBlood test indicators; The differences between the two groups were compared before transfusion and during four periods after platelet transfusion. The Mann-Whitney U test was employed to compare the differences between the groups at each time point, revealing no statistically significant differences between the groups in any period. Additionally, considering the linear effect of time, Generalized Estimating Equation (GEE) analysis was conducted to compare the longitudinal data of blood routine indicators during treatment in both groups, which still showed no significant statistical difference (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). (Supplement 3 Part 1,eTable 2)\u003c/p\u003e \u003cdiv id=\"Sec23\" class=\"Section3\"\u003e \u003ch2\u003eSafety evaluation outcomes\u003c/h2\u003e \u003cp\u003eThe CSPs group presented with one case of intermuscular venous thrombosis affecting both calves and another case of intermuscular venous thrombosis specifically in the right calf, as detected by B-ultrasound. In the RTPs group, there was no significant difference observed between one case of double calf muscle venous thrombosis and one case of left calf muscle venous thrombosis identified through B-ultrasound (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Furthermore, no transfusion reactions such as hemolysis reaction, fever reaction, allergy, transfusion associated circulatory overload (TACO) and transfusion related acute lung injury (TRALI) were reported following platelet transfusion in either group (Supplement 3 Part 1,eTable 3).\u003c/p\u003e \u003cp\u003eThe vital signs were assessed within 72 hours following platelet transfusion in both groups, and no significant differences were observed between the two groups (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05) (Supplement 3 Part 1, eTable 4). Liver function indicators and renal function indicators were compared and evaluated before and after platelet transfusion at the 72-hour mark, with no statistically significant differences found (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05) (Supplement 3 Part 1, eTable 5). Routine urinary fecal indicators including urine protein levels and fecal occult blood tests were compared before and after platelet transfusion at the 72-hour mark, revealing no significant differences (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05) (Supplement 3 Part 1, eTable 6).\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec24\" class=\"Section2\"\u003e \u003ch2\u003eStratification statistics were conducted for patients with traumatic bleeding, postpartum bleeding and cardiac surgery\u003c/h2\u003e \u003cp\u003ePrimary outcomes: There were no significant differences observed between the CSPs and RTPs groups in terms of drainage volume, platelet count, and TEG-MA for the treatment of the three diseases (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Additionally, there were no significant differences observed between the two groups during the four measurement periods (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05) (Supplement 3 Part 2, eTable 2\u0026thinsp;\u0026minus;\u0026thinsp;1, 2\u0026ndash;2, 2\u0026ndash;3).\u003c/p\u003e \u003cp\u003eThe secondary outcomes: There were no significant differences between the two groups\u0026rsquo; hospitalization time, ICU treatment time, hospitalization cost, discharge outcome, transfusion of different blood components within and after 72 hours of platelet transfusion(P\u0026thinsp;\u0026gt;\u0026thinsp;0.05) (Supplement 3 Part 2, eTable 3\u0026thinsp;\u0026minus;\u0026thinsp;1, 3\u0026thinsp;\u0026minus;\u0026thinsp;2, 3\u0026ndash;3).\u003c/p\u003e \u003cp\u003eBlood test indicators: No statistically significant differences were observed between the two groups (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05), and there were also no significant differences observed in each indicator's five measurement periods between both groups (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05) (Supplement 3 Part 2,eTable4 -1 ,4\u0026thinsp;\u0026minus;\u0026thinsp;2 ,4\u0026thinsp;\u0026minus;\u0026thinsp;3 )2.\u003c/p\u003e \u003cp\u003eSafety evaluation outcomes: Intermuscular venous calf thrombosis occurred in patients with traumatic bleeding in both CSPs and RTPs groups ( Supplement 3 Part 2, eTable 5\u0026thinsp;\u0026minus;\u0026thinsp;1,5\u0026thinsp;\u0026minus;\u0026thinsp;2,5\u0026thinsp;\u0026minus;\u0026thinsp;3).\u003c/p\u003e \u003cp\u003eVital signs: Overall there was no statistically significant difference observed between the two groups(P\u0026thinsp;\u0026gt;\u0026thinsp;0.05) (Supplement 3 Part 2, eTable 6\u0026thinsp;\u0026minus;\u0026thinsp;1,6\u0026thinsp;\u0026minus;\u0026thinsp;2,6\u0026thinsp;\u0026minus;\u0026thinsp;3).\u003c/p\u003e \u003cp\u003eLiver function indicators and renal function indicators before and after platelet transfusion at a duration of seventy-two hours showed no statistically significance (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05) ( Supplement 3 Part 2, eTable 7\u0026thinsp;\u0026minus;\u0026thinsp;1,7\u0026thinsp;\u0026minus;\u0026thinsp;2,7\u0026thinsp;\u0026minus;\u0026thinsp;3).\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe results indicated that there was no statistically significant difference observed in the clinical efficacy between CSPs and RTPs for the management of bleeding. This study demonstrated the feasibility of utilizing platelets stored at 4℃ for 10\u0026ndash;14 days in clinical settings, providing a foundation for future promotion and application of refrigerated platelets.\u003c/p\u003e \u003cp\u003eIn the past three decades, there have been significant advancements in our understanding of platelet application. Firstly, for patients with thrombocytopenia caused by myelosuppression, ensuring longer platelet survival in blood circulation is crucial, making room temperature-stored platelets (RTPs) the optimal choice. Secondly, for patients with war wounds, trauma, and surgical massive bleeding where bone marrow inhibition is not a concern but coagulopathy poses a major problem \u003csup\u003e17\u0026ndash;19\u003c/sup\u003e, rapid hemostasis becomes paramount. Cold-stored platelets (CSPs) offer strong hemostatic properties and facilitate thrombosis and clot formation \u003csup\u003e20\u0026ndash;21\u003c/sup\u003e; thus timely infusion of CSPs can be considered for such patients.\u003c/p\u003e \u003cp\u003eTo evaluate the efficacy of CSPs compared to RTPs after platelet transfusion over a period of 72 hours, we conducted longitudinal data analysis encompassing five observation periods. Key indicators, including drainage flows, platelet counts, and TEG-MA measurements, were consistently monitored. Analysis using generalized estimation equations revealed no statistically significant differences in key evaluation indicators between the two groups from post-transfusion up to 72 hours later. However, during the first 12 hours and from hour 13 to hour 24 after platelet transfusion, the CSPs group exhibited lower platelet counts compared to the RSP group due to potentially more active aggregation and hemostasis upon entry into the body. Nevertheless, no significant differences were detected in segmental drainage flow rates or MA values between both groups during these time intervals, thereby validating the excellent immediate hemostatic efficacy attributed to the use of CSP. Supporting evidence is derived from clinical trials conducted by Strandenes G et al., wherein their studies in 2016 and 2020 respectively demonstrated a superior aggregation response following transfusion using cold-stored platelets compared to room temperature stored platelets (RTPs) in cardiac surgery patients\u003csup\u003e12\u0026ndash;13,22\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn our study, all 31 cases in the CSPs group achieved complete cure or improvement, while 27 cases in the RTPs group showed effectiveness (one case resulted in mortality and three cases did not recover), with no statistically significant difference observed. However, further clinical case verification is required to determine whether CSPs can effectively reduce mortality caused by extensive surgical bleeding. Stratified analysis of conditions and comparison of secondary outcomes between the two groups revealed consistent trends in evaluating traumatic bleeding, postpartum bleeding, and surgery-related bleeding. The patient population receiving RTPs demonstrated a higher risk profile indicating increased susceptibility to mortality. Although no differences were observed in complications, it should be noted that the limited sample size of this study prevents definitive conclusions regarding similarity in risk profiles between CSPs and RTPs.\u003c/p\u003e \u003cp\u003eOur study showed that there were 2 cases of intermuscular venous calf thrombosis in each of the trauma bleeding patients in the CSPs and RTPs group. These 4 patients had relatively serious multiple systemic injuries, where the lower extremity intermuscular venous thrombosis was related to their conditions. There were no blood transfusion reactions such as hemolysis, fever, allergy, cardiac overload or transfusion-related lung injury after platelet transfusion. Vital signs were detected within 72 hours after platelet transfusion between the two groups. Liver function indicators and renal function indicators were compared and evaluated before and after discharge, and there were no significant differences. From these indicators, we believe that cold storage of platelets is safe for clinical use. Our results were consistent with the conclusions of Strandenes\u003csup\u003e13\u003c/sup\u003e, Warner, M.A\u003csup\u003e23\u003c/sup\u003e and Leeper C.M\u003csup\u003e24\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe platelets used in this study were autologous plasma platelets (AS), which were stored at room temperature (22℃) for 18\u0026ndash;24 hours and then transferred to cold storage. The Getz TM\u003csup\u003e25\u003c/sup\u003e study suggested that CSP clumping is caused by the binding of fibrinogen to activated PLT, and this process can be mitigated by the use of PLT additive solution (PAS). The Wagner\u003csup\u003e26\u003c/sup\u003e study found that platelets stored at room temperature for 8 hours at 20\u0026ndash;24℃ before storage at 1\u0026ndash;6℃ showed less aggregation responses to collagen, ADP and TRAP than platelets stored at room temperature for 1\u0026ndash;2 hours before refrigeration. The Mayo Clinic Donation Center optimized its platelet inventory in April 2020 to allow pathogen-treated RTPs normally stored at five days to be refrigerated for up to nine days\u003csup\u003e23\u003c/sup\u003e.Wood et al.\u003csup\u003e27\u003c/sup\u003e extended the shelf life of platelets when they were routinely stored until near expiration (4 days) and then transferred to cold storage. The results showed that the metabolism and activation of delayed cold platelets was similar to that of cold platelets. Therefore, delayed-cold storage method may also serve as a viable alternative for applications aimed at maximizing platelet functionality.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn this study, CSPs were clinically applied for the first time in China. No significant difference was observed in the therapeutic efficacy between CSPs and RTP. There were no disparities found in primary efficacy indicators, secondary efficacy indicators, and safety evaluation indicators between the two groups. Considering the substantial advantages of extended storage time offered by CSPs, they exhibit promising prospects for clinical applications.\u003c/p\u003e \u003cdiv id=\"Sec27\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eThe present study was conducted at a single center and had a limited sample size. It is important to note that our study population exclusively consisted of individuals aged 18 years or above, thus necessitating further investigation into pediatric and neonatal cases.\u003c/p\u003e \u003c/div\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCSPs = Cold- Stored Platelets; RTPs = Room Temperature-Stored Platelets;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTEG = Thrombelastography；MA=Maximum Amplitude；VTE=Venous Thromboembolism\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to thank Dr. Ning Peng and Dr. Min Wu (Department of Scientific Contributions, Shaanxi Provincial People\u0026apos;s Hospital); Yaojun Song BM, \u0026nbsp;Miaoni Wang BM, \u0026nbsp;Jingyan Chang BM(Department of Transfusion Medicine, Shaanxi Provincial People\u0026apos;s Hospital); Prof. Lingxia Zeng(School of Public Health, Xi \u0026apos;an Jiaotong University Health Science Center); Prof. Xiaoli Cao(Shaanxi Provincial Blood Center); Prof. Wen Yin(Xijing Hospital, Military Medical University, PLA Air Force). No one received compensation in connection with this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e2.Author Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJiangcun Yang: Conceptualization, Methodology, Conceptualization, Methodology, Writing- Reviewing and Editing,Supervision,Writing - Review \u0026amp; Editing,Funding acquisition,Writing - Original Draft,Supervision,Supervision,Formal analysis. Yuan Shen: Conceptualization, Methodology, Writing- Reviewing and Editing, Supervision, Writing - Review \u0026amp; Editing, Data Curation, Formal analysis. Yang Sun: Investigation, Writing - Review \u0026amp; Editing, Data Curation, Funding acquisition, \u0026nbsp;Formal analysis. Jiameng Niu: Investigation.,Writing - Review \u0026amp; Editing,Data Curation,Writing - Review \u0026amp; Editin. Lili Xing:Investigation,Writing-Review\u0026amp;Editing,Data Curation, Visualization, Writing - Review \u0026amp; Editing. Ting Ma: Investigation,Writing - Review \u0026amp; Editing. Gongliang Du:Resources.Xuewen Li:Resources.Yaqin Wang:Resources.Hengxin Li:Resources.hengli Yan:Resources.Kangshe Guo: Resources. Liqin Wang: Writing - Review \u0026amp; Editing. Ping Chen: Writing - Review \u0026amp; Editing. Wenhua Wang: Writing - Review \u0026amp; Editing.Yingqun Yang: Writing - Review \u0026amp; Editing. Xinxin Xie: Writing - Review \u0026amp; Editing. Aowei Song: Writing - Review \u0026amp; Editing.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;All authors have read and approved the final version of the manuscript for submission. The order of authorship is based on the level of contribution to the research and preparation of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e3.Conflicts of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e4.Funding Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research was funded by key project 2019CGHJ-09 of Science and Technology Department of Shaanxi Province (Yang Sun) and Leading Talents Fund Project 2021LJ-14 of Shaanxi Provincial People\u0026apos;s Hospital (Jiangcun Yang).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eRole of the Funder/Sponsor\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e5.T\u003c/strong\u003e\u003cstrong\u003erial\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003er\u003c/strong\u003e\u003cstrong\u003eegistration\u0026nbsp;\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eChinese Clinical Trial Registry: ChiCTR2000036353; Principal investigator\u0026apos;s name: Jiangcun Yang. Date of registration:22/08/2020.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e6.Ethics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eShaanxi Provincial People\u0026apos;s Hospital and approved by its Medical Ethics Committee [(2020) R005].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll participants or their legal representatives provided written informed consent.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e7.Consent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe final manuscript has been approved by all authors.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e8.Availability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSee Supplement 4\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e9.Running Heads\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eClinical Study on Platelets Stored at 4℃\u0026nbsp;in China\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003e10.Additional information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003ePrior Presentations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo any presentation/s of the work at conferences for meetings.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003ePreprint Server\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBorgman MA, Spinella PC, Perkins JG, Grathwohl KW, Repine T, Beekley AC, Sebesta J, Jenkins D, Wade CE, Holcomb JB. The ratio of blood products transfused affects mortality in patients receiving massive transfusions at a combat support hospital. J Trauma. 2007 Oct;63(4):805-13. doi: 10.1097/TA.0b013e3181271ba3. PMID: 18090009.\u003c/li\u003e\n\u003cli\u003eHolcomb JB, Jenkins D, Rhee P, Johannigman J, Mahoney P, Mehta S, Cox ED, Gehrke MJ, Beilman GJ, Schreiber M, Flaherty SF, Grathwohl KW, Spinella PC, Perkins JG, Beekley AC, McMullin NR, Park MS, Gonzalez EA, Wade CE, Dubick MA, Schwab CW, Moore FA, Champion HR, Hoyt DB, Hess JR. Damage control resuscitation: directly addressing the early coagulopathy of trauma. J Trauma. 2007 Feb;62(2):307-10. doi: 10.1097/TA.0b013e3180324124. PMID: 17297317.\u003c/li\u003e\n\u003cli\u003ePidcoke HF, Aden JK, Mora AG, Borgman MA, Spinella PC, Dubick MA, Blackbourne LH, Cap AP. Ten-year analysis of transfusion in Operation Iraqi Freedom and Operation Enduring Freedom: increased plasma and platelet use correlates with improved survival. J Trauma Acute Care Surg. 2012 Dec;73(6 Suppl 5):S445-52. doi: 10.1097/TA.0b013e3182754796. PMID: 23192068.\u003c/li\u003e\n\u003cli\u003eMurphy S, Gardner FH. Effect of storage temperature on maintenance of platelet viability--deleterious effect of refrigerated storage. N Engl J Med. 1969 May 15;280(20):1094-8. doi: 10.1056/NEJM196905152802004. PMID: 5778424.\u003c/li\u003e\n\u003cli\u003eBecker GA, Tuccelli M, Kunicki T, Chalos MK, Aster RH. Studies of platelet concentrates stored at 22 C nad 4 C. Transfusion. 1973 Mar;13(2):61-8. doi: 10.1111/j.1537-2995.1973.tb05442.x. PMID: 4695593.\u003c/li\u003e\n\u003cli\u003eCurrie LM, Harper JR, Allan H, Connor J. Inhibition of cytokine accumulation and bacterial growth during storage of platelet concentrates at 4 degrees C with retention of in vitro functional activity. Transfusion. 1997 Jan;37(1):18-24. doi: 10.1046/j.1537-2995.1997.37197176946.x. PMID: 9024485.\u003c/li\u003e\n\u003cli\u003eEker I, Yilmaz S, Cetinkaya RA, Unlu A, Pekel A, Acikel C, Yilmaz S, Gursel O, Avci İY. Is one-size-fits-all strategy adequate for platelet storage? Transfus Apher Sci. 2016 Dec;55(3):323-328. doi: 10.1016/j.transci.2016.08.006. Epub 2016 Sep 28. PMID: 27743710.\u003c/li\u003e\n\u003cli\u003eYang J, Yin W, Zhang Y, Sun Y, Ma T, Gu S, Gao Y, Zhang X, Yuan J, Wang W. Evaluation of the advantages of platelet concentrates stored at 4\u0026deg;C versus 22\u0026deg;C. Transfusion. 2018 Mar;58(3):736-747. doi: 10.1111/trf.14462. Epub 2017 Dec 21. PMID: 29266276.\u003c/li\u003e\n\u003cli\u003eYang JC, Liu FH, Sun Y, Ma T, Xu CX, Wang WH, Chen P, Xie XX, Song YJ, Yin W. Good hemostatic effect of platelets stored at 4\u0026deg;C in an in vitro model of massive blood loss and thrombocytopenia. Medicine (Baltimore). 2019 May;98(18):e15454. doi: 10.1097/MD.0000000000015454. PMID: 31045818; PMCID: PMC6504340.\u003c/li\u003e\n\u003cli\u003eFDA Action Makes Blood product more accessible to warfighters in combat. September 11, 2019 FDA. Available from https:// www.fda.gov/media/130671/download. 2019.\u003c/li\u003e\n\u003cli\u003eFDA grants South Texas Blood \u0026amp; Tissue Center first license for new process that triples shelf life of critically needed platelets Feb. 28, 2020: FDA. 2020; https://www.globenewswire.com/news-release/2020/02/28/1992715/0/en/FDA-grants-SouthTexas-Blood-Tissue-Center-first-license-for-new-process-thattriples-shelf-life-of-critically-needed-platelets.html.\u003c/li\u003e\n\u003cli\u003eTorres Filho IP, Torres LN, Valdez C, Salgado C, Cap AP, Dubick MA. Refrigerated platelets stored in whole blood up to 5 days adhere to thrombi formed during hemorrhagic hypotension in rats. J Thromb Haemost. 2017 Jan;15(1):163-175. doi: 10.1111/jth.13556. Epub 2016 Dec 18. PMID: 27797452.\u003c/li\u003e\n\u003cli\u003eStrandenes G, Kristoffersen EK, Bjerkvig CK, Fosse TK, Apelseth T. Cold-stored Apheresis Platelets in Treatment of Postoperative Bleeding in Cardiothoracic Surgery. Paper presented at: AABB Annual Meeting 2016.\u003c/li\u003e\n\u003cli\u003eStrandenes G, Sivertsen J, Bjerkvig CK, Fosse TK, Cap AP, Del Junco DJ, Kristoffersen EK, Haaverstad R, Kvalheim V, Braathen H, Lunde THF, Hervig T, Hufthammer KO, Spinella PC, Apelseth TO. A Pilot Trial of Platelets Stored Cold versus at Room Temperature for Complex Cardiothoracic Surgery. Anesthesiology. 2020 Dec 1;133(6):1173-1183. doi: 10.1097/ALN.0000000000003550. PMID: 32902572.\u003c/li\u003e\n\u003cli\u003eNational Health Commission of the People\u0026rsquo;s Republic of China.whole blood and component donor selection requirements. GB18467-2011. (2011-12-30). Accessed November 30, 2022. http://www.nhc.gov.cn/wjw/s9493/201207/55286.shtml.\u003c/li\u003e\n\u003cli\u003eXia Jie-Lai. Statistical considerations for non-inferiority clinical trials[J]. (China Health Statistics,2012,29(02):270-274.) \u003c/li\u003e\n\u003cli\u003eLevy JH, Neal MD, Herman JH. Bacterial contamination of platelets for transfusion: strategies for prevention. Crit Care. 2018;22(1):271. Published 2018 Oct 27. doi:10.1186/s13054-018-2212-9\u003c/li\u003e\n\u003cli\u003eKetter PM, Kamucheka R, Arulanandam B, Akers K, Cap AP. Platelet enhancement of bacterial growth during room temperature storage: mitigation through refrigeration. Transfusion. 2019;59(S2):1479-1489. doi:10.1111/trf.15255\u003c/li\u003e\n\u003cli\u003eCap AP. Platelet storage: a license to chill!. Transfusion. 2016;56(1):13-16. doi:10.1111/trf.13433\u003c/li\u003e\n\u003cli\u003eDutton RP, Mackenzie CF, Scalea TM. Hypotensive resuscitation during active hemorrhage: impact on in-hospital mortality. J Trauma. 2002;52(6):1141-1146. doi:10.1097/00005373-200206000-00020\u003c/li\u003e\n\u003cli\u003ePidcoke HF, Spinella PC, Ramasubramanian AK, Strandenes G, Hervig T, Ness PM, Cap AP. Refrigerated platelets for the treatment of acute bleeding: a review of the literature and reexamination of current standards. Shock. 2014 May;41 Suppl 1:51-3. doi: 10.1097/SHK.0000000000000078. PMID: 24662779.\u003c/li\u003e\n\u003cli\u003eCap AP, Reddoch-Cardenas KM. Can\u0026apos;t get platelets to your bleeding patients? Just chill\u0026hellip; the solution is in your refrigerator!. Transfus Clin Biol. 2018;25(3):217-219. doi:10.1016/j.tracli.2018.06.008\u003c/li\u003e\n\u003cli\u003eWarner MA, Kurian EB, Hammel SA, van Buskirk CM, Kor DJ, Stubbs JR. Transition from room temperature to cold-stored platelets for the preservation of blood inventories during the COVID-19 pandemic. Transfusion. 2021;61(1):72-77. doi:10.1111/trf.16148\u003c/li\u003e\n\u003cli\u003eLeeper CM, Yazer MH, Cladis FP, Saladino R, Triulzi DJ, Gaines BA. Cold-stored whole blood platelet function is preserved in injured children with hemorrhagic shock. J Trauma Acute Care Surg. 2019;87(1):49-53. doi:10.1097/TA.0000000000002340\u003c/li\u003e\n\u003cli\u003eGetz T, Cap AP. Storage of Platelets at 4 degrees C in Platelet Additive Solutions Prevents Aggregate Formation and Preserves Platelet Functional Responses. Paper presented at: AABB Annual Meeting 2014.\u003c/li\u003e\n\u003cli\u003eWagner SJ, Getz TM, Thompson-Montgomery D, Turgeon A. Preliminary characterization of the properties of cold-stored apheresis platelets suspended in PAS-III with and without an 8-hour room temperature hold. Transfusion. 2020;60(11):2489-2493. doi:10.1111/trf.15964\u003c/li\u003e\n\u003cli\u003eWood B, Johnson L, Hyland RA, Marks DC. Maximising platelet availability by delaying cold storage [published online ahead of print, 2018 Apr 6]. Vox Sang. 2018;10.1111/vox.12649. doi:10.1111/vox.12649\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Platelet, Platelet storage, Cold-stored platelets, Bleeding, Hemostasis","lastPublishedDoi":"10.21203/rs.3.rs-4341873/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4341873/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003ePlatelets play an important role in acute bleeding.Whether 4℃cold stored platelets (CSPs) can be an effective substitute for platelets at room temperature (RTPs) is rarely reported, we carried out the clinical application observation trial of CSPs in China for the first time.\u003c/p\u003e\u003ch2\u003eMethod\u003c/h2\u003e \u003cp\u003eA prospective, double-blind, randomized clinical trial was conducted on surgical patients with related bleedingto assess the hemostatic potential of CSPs compared with RTPs. The primary outcomes measured were drainage volume, platelet counts, and Thrombelastography-maximum amplitude. Secondary outcomes included hospital stays, length of stay in the intensive care unit, medical expenses.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 62 patients were completed the final clinical observation. There were 31 cases ineach of the CSPs group and RTPs group. With in 1\u0026ndash;12 hours, 13\u0026ndash;24 hours, 25\u0026ndash;48 hours, and 49\u0026ndash;72 hours after platelet transfusion, drainage volume: 8.5ml/h vs 20.83ml/h ,0.52ml/h vs 5.0ml/h, 3.5ml/h vs 5.0ml/h, 0.63ml/h vs 4.1ml/h. platelet counts:58\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L vs 79\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L, 54\u0026times;10\u003csup\u003e9\u003c/sup\u003e/Lvs77\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L,63\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L vs 75\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L, 66\u0026times;10\u003csup\u003e9\u003c/sup\u003e/Lvs79\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L. TEG-MA: 50.1mm vs 52.0mm ,50.1mm vs 54.8mm, 53.0mm vs 56.6, 56.0mm vs 53.2mm.There was no overall difference between the two groups by Generalized estimation equation at different times (P\u003csub\u003edrainage\u003c/sub\u003e=0.933,P\u003csub\u003ePLT counts\u003c/sub\u003e=0.473,P\u003csub\u003eTEG\u0026minus;MA\u003c/sub\u003e=0.246). The secondary outcomes (hospital stay, ICU stay time, medical cost, discharge outcome) were no difference between the CSPs group and RTPs group (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). There were no significant differences in adverse platelet transfusion events between the groups (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eCSPs and RTP have equivalent efficacy and safety in the treatment of surgery-related bleeding. This trial provides reliable evidence to support the clinical application of CSPs.\u003c/p\u003e\u003ch2\u003eTrial registration\u003c/h2\u003e \u003cp\u003eChinese Clinical Trial Registry: ChiCTR2000036353;Principal investigator's name: Jiangcun Yang. Date of registration: 22/08/2020.\u003c/p\u003e","manuscriptTitle":"The clinical efficacy of 4℃ stored platelet: a randomized controlled feasibility trial conducted in surgical patients with related bleeding","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-05-17 16:35:42","doi":"10.21203/rs.3.rs-4341873/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"14a66a12-016d-4cd7-8fd8-3b0cc7ff5c2b","owner":[],"postedDate":"May 17th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-06-12T09:51:23+00:00","versionOfRecord":[],"versionCreatedAt":"2024-05-17 16:35:42","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4341873","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4341873","identity":"rs-4341873","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}