Efficacy Of Platelet Transfusion Research Articles

Platelet transfusion.

Platelet transfusions, used as prophylaxis or treatment for bleeding, are potentially life-saving. In many countries, demand for platelet transfusion is rising. Platelets are a limited and costly resource, and it is vital that they are used appropriately. This study will explore the evidence behind platelet transfusions in different contexts, in particular recent and important research in this area. Recent randomized clinical trials demonstrate the efficacy of platelet transfusions in some contexts but potential detrimental effects in others. Platelet transfusions also carry risk of transfusion reactions, bacterial contamination and platelet transfusion refractoriness. Observational and clinical studies, which highlight approaches to mitigate these risks, will be discussed. There is growing interest in cold-stored or cryopreserved platelet units, which may improve platelet function and availability. Clinical trials also highlight the efficacy of other supportive measures such as tranexamic acid or thrombopoietin receptor agonists in patients with bleeding. Although platelet transfusions are beneficial in many patients, there remain many settings in which the optimal use of platelet transfusions is unclear, and some situations in which they may have detrimental effects. Future clinical trials are needed to determine optimal use of platelet transfusions in different patient populations.

Analysis of platelet transfusion efficacy during extracorporeal membrane oxygenation (ECMO) treatment in pediatric patients post-cardiac surgery-a retrospective cohort study.

Postoperative extracorporeal membrane oxygenation (ECMO) may be necessary for pediatric patients following cardiac surgery, with associated risks of thrombocytopenia and bleeding. Prophylactic platelet transfusions are utilized to mitigate these risks, but the effectiveness of platelet transfusion cannot be reliably predicted. The aim of this study was to investigate the effect of platelet transfusion during postoperative treatment with ECMO in children undergoing cardiac surgery and to explore the optimal transfusion thresholds to reduce the number of platelet transfusions in patients and reduce the risk of death. We included in our study patients from the Pediatric Cardiac Surgery Department at the First Affiliated Hospital of Tsinghua University who underwent cardiac surgery and received ECMO treatment from January 1, 2019, to December 31, 2023, and received platelets transfusion at least once during the ECMO therapy. The platelet counts were determined both before and 24 hours posttransfusion of the platelet product. The corrected count increment (CCI) was calculated for the effectiveness estimation of platelet transfusion. The research subjects were divided into 3 groups based on the platelet count before transfusion (pretransfusion platelet count ≤30×109/L was the low-threshold group, pretransfusion count 31-50×109/L was the medium-threshold group, and ≥51×109/L was the high-threshold group) and the effective rates of each group were calculated. A total of 11 patients received 47 platelet transfusions, an average of 4.27 ± 1.67 per patient. According to the 24-hour postinfusion platelet (Plt) corrected critical control increase index (24-hour CCI) ≥4500, the infusion was considered to be effective, and ineffective when the CCI was <4500. Out of these, 22 transfusions (46.8%) proved effective, whereas 25 (53.2%) were deemed ineffective. The effective transfusion rates across the 3 groups were 69.2%, 50%, and 27.7%, respectively. The efficacy of platelet transfusion may be higher if a low threshold of platelet transfusion is chosen during ECMO treatment, on the premise of ensuring life safety.

Establishment and clinical application of the HLA genotype database of platelet-apheresis donors in Suzhou

The establishment of a platelet-apheresis donor database may provide a feasible solution to improve the efficacy of platelet transfusion in patients with immune platelet transfusion refractoriness (PTR). This study aimed to establish HLA genotype database in Suzhou, to provide HLA-I compatible platelets for PTR patients to ensure the safety and effectiveness of platelet transfusions. We used a polymerase chain reaction sequence-based typing (PCR-SBT) method to establish the database by performing high-resolution HLA-A, -B, and –C genotyping on 900 platelet-apheresis donors. HLA-I antibody was detected in patients using a Luminex device, and HLA-I gene matching was performed by an HLA-Matchmaker. We found that the highest frequency of the HLA-A allele was A*11:01 (17.06 %), followed by A*24:02 (14.67 %) and A*02:01 (13.61 %). The highest frequency of the HLA-B allele was B*46:01 (9.78 %), followed by B*40:01 (8.39 %) and B*13:02 (33 %). After the detection of platelet antibodies in 74 patients with immune PTR, we found 30 HLA-A antibodies and 48 HLA-B antibodies, and there were a variety of high frequency antibodies whose alleles were low in the donor database, such as HLA-A*68:02, and B*57:01. After avoiding donor-specific antibodies (DSA) matching, 102 of 209 platelet-compatible transfusions were effective, resulting in an effective rate of 48.8 %, which significantly improved the efficacy of platelet transfusion. The establishment of a platelet donor database is of great significance to improve the therapeutic effect of platelet transfusion in patients with hematologic disorder, and save blood resources, and it is also the premise and guarantee of precise platelet transfusion.

Establish a Graded Method to Avoid HLA Class I Antibodies Corresponding Antigen and Combining HLAMatchmaker Application in Improving the CCI Value after Platelet Transfusion for Patients with IPTR

To establish a graded method to avoid mean fluorescence intensity (MFI) threshold of HLA Class I antibodies corresponding antigen, and the HLAMatchmaker program has been used to select the minimum mismatch value of donor-patient epitopes. Evaluate the application value of combining both methods in selecting HLA compatible platelets (PTL) for patients with immune platelet transfusion failure (IPTR) in improving platelet the corrected count increment (CCI). A total 7 807 PLT cross-matching compatible were performed by the solid-phase red cell adherence (SPRCA) method for 51 IPTR patients. The Luminex single antigen flow cytometry was used to detect HLA Class I antibodies in patients, and detected the MFI value for different specificity antigens of HLA Class I antibodies, was graded into strong positive group (MFI>4 000, level 1), medium positive group (1 000< MFI≤4 000, 2), weak positive group (500< MFI≤1 000, 3), and one negative control group (MFI≤500). The results of 7 807 SPRCA their negative/positive reaction wells were enrolled and statistically analyzed in different grades and the four groups, the statistical differences between the four groups were compared. Multiple applications for the select HLA Class I compatible donor events were made for patients in two cases, and HLAMatchmaker program was used to calculate the number of HLA Class I epitopes mismatches between the donors and patients. The donor with the minimum number of epitopes mismatches was selected, while avoiding the corresponding antigens of HLA Class I antibodies in levels 1 and 2, the provision of HLA compatible platelets for IPTR. After the transfusions, the CCI value of the platelet transfusion efficacy evaluation index was calculated, and the clinical evaluation of the transfusion effect was obtained through statistical analysis. There were statistically significant differences in the positive results of SPRCA immunoassay among the strong positive group, medium positive group, and weak positive group of 51 IPTR patients with different specific of HLA -I class antibodies and corresponding antigens(all P <0.001). The positive results showed a range from high to low, with strong positive group>medium positive group>weak positive group. There were a statistical difference among between the strongly positive or moderately positive groups and the negative control group(P <0.001). There was no statistical difference between the weakly positive group and the negative control group(P >0.05). The strong positive group was set as the corresponding specific HLA Class I site corresponding antigen grade 1 avoidance threshold, the medium positive group as the grade 2 avoidance thresholds, and the weak positive group as the grade 3 avoidance threshold. In the case of donor platelet shortage, it is not necessary to avoid the weak positive group. Avoiding the strategy of donor antigens and HLAMatchmaker program scores ≤7 corresponding to HLA Class I antibodies of levels 1 and 2, with CCI values>4.5×109/L within 24 hours, can obtain effective clinical platelet transfusion conclusions. When selecting HLA Class I compatible donors for IPTR patients, the grading avoids HLA Class I antibodies corresponding to donor antigens, and the donor selection strategy with the minimum scores of HLAMatchmaker program is comprehensively selected. The negative result confirmed by platelet cross-matching experiments has certain practical application value for improving platelet count in IPTR patients.

Real-World Evidence of Hetrombopag for Cancer Therapy-Induced Thrombocytopenia Among Patients with Gynecologic Malignancies

Background: Despite the widespread use of platinum-based combination chemotherapy, particularly when complemented with taxanes, for the treatment of gynecologic malignancies, its administration often results in myelosuppression. This effect can be potentiated across cumulative chemotherapy cycles, thereby inducing a more persistent condition known as cancer therapy-induced thrombocytopenia (CTIT). Traditionally, preferred treatments for CTIT entail platelet transfusion or the use of recombinant human thrombopoietin (rhTPO), or recombinant human interleukin-11 (rhIL-11). However, the efficacy of platelet transfusion tends to decrease with repetitive administration, and it carries inherent risks of infectious diseases. Additionally, rhIL-11 may induce severe hypersensitivity reactions, necessitating permanent discontinuation of the drug. Emerging as an appealing alternative, thrombopoietin-receptor agonists (TPO-RAs) present a promising approach for CTIT treatment. Among these, hetrombopag, an orally administered small-molecule TPO-RA, has demonstrated notable platelet-boosting effects and a favorable safety profile not only in patients with immune thrombocytopenia and severe aplastic anemia but also in those suffering from persistent CTIT. This study aims to appraise the real-world effectiveness and safety of hetrombopag, administered either alone or in conjunction with other platelet-boosting agents, for the management of CTIT in patients diagnosed with gynecologic malignancies. Methods: In this retrospective study conducted from January 2022 to June 2023, we examined the role of hetrombopag in treating CTIT among patients with gynecologic malignancies. The patients, aged 18 years and above, had experienced thrombocytopenia (platelet counts&amp;lt;100×10 9/L) following platinum-based chemotherapy or other antitumor treatments and subsequently received hetrombopag either as monotherapy or in combination with other platelet-boosting agents, such as rhTPO or rhIL-11. The primary outcome was platelet response within 14 days, denoted by a recovery in platelet counts to ≥100×10 9/L or an increase of ≥50×10 9/L or at least double from the baseline. Results: This study comprised 38 patients, with 55.3% diagnosed with ovarian cancer, 36.8% with cervical cancer, 5.3% with endometrial cancer, and 2.6% with other types. The median age was 58 years, with the majority (73.7%) at clinical stages III/IV. As for the antitumor regimens, 89.5% incorporated platinum, 68.4% included taxanes, 26.3% used antiangiogenic agents, and 15.8% employed PD-1 inhibitors. Among the patients, 15.8% received hetrombopag 2.5 mg/day monotherapy, while the remainder received hetrombopag in combination with rhTPO or rhIL-11. Baseline platelet counts prior to hetrombopag therapy averaged 46.5±24.9×10 9/L. Encouragingly, the 14-day platelet response rate was 71.1%, with a median time to response of 10 days (95% confidence interval, 5-14). Following treatment with hetrombopag, patients exhibited a gradual increase in platelet levels, recording mean platelet counts of 48.7, 67.1, 95.5, 108.5, 146.5, and 131.9×10 9/L on days 3, 5, 7, 9, 11, and 14 respectively. Importantly, hetrombopag was well-tolerated, with no treatment-related adverse events observed during the treatment course. Conclusion: In conclusion, our findings suggest hetrombopag, either alone or in combination with other therapies, displays preliminary effectiveness and safety in treating CTIT. Given its convenient oral administration and promising platelet-boosting effects observed in this study, prospective investigations of hetrombopag monotherapy for CTIT in gynecologic malignancies are warranted.

Liposomal Resveratrol Alleviates Platelet Storage Lesion via Antioxidation and the Physical Buffering Effect.

Platelet transfusion is essential in the treatment of platelet-related diseases and the prevention of bleeding in patients with surgical procedures. Platelet transfusion efficacy and shelf life are limited mainly by the development of platelet storage lesion (PSL). Mitigating PSL is the key to prolonging the platelet shelf life and reducing wastage. Excess intracellular reactive oxygen species (ROS) are one of the main factors causing PSL. In this study, we explored a nanomedicine strategy to improve the quality and functions of platelets in storage. Resveratrol (Res), a natural plant product, is known for its antioxidative effect. However, medical applications of Res are limited due to its low water solubility and stability. Therefore, we used a resveratrol-loaded liposomal system (Res-Lipo) to better utilize the antioxidant effect of the drug. This study aimed to evaluate the effect of Res-Lipo on platelet oxidative stress and alleviation of PSL during the storage time. Res-Lipo scavenged intracellular ROS and inhibited platelet apoptosis and activation during storage. Res-Lipo not only maintained mitochondrial function but also improved platelet aggregation in response to adenosine 5'-diphosphate. These results revealed that Res-Lipo ameliorated PSL and prolonged the platelet survival time in vivo. The strategy provides a potential method for extending the platelet storage time and might be considered a potential and safe additive to alleviate PSL.

Omics markers of platelet transfusion in trauma patients.

Even in the era of the COVID-19 pandemic, trauma remains the global leading cause of mortality under the age of 49. Trauma-induced coagulopathy is a leading driver of early mortality in critically ill patients, and transfusion of platelet products is a life-saving intervention to restore hemostasis in the bleeding patient. However, despite extensive functional studies based on viscoelastic assays, limited information is available about the impact of platelet transfusion on the circulating molecular signatures in trauma patients receiving platelet transfusion. To bridge this gap, we leveraged metabolomics and proteomics approaches to characterize longitudinal plasma samples (n = 118; up to 11 time points; total samples: 759) from trauma patients enrolled in the Control Of Major Bleeding After Trauma (COMBAT) study. Samples were collected in the field, in the emergency department (ED), and at intervals up to 168 h (7 days) post-hospitalization. Transfusion of platelet (PLT) products was performed (n = 30; total samples: 250) in the ED through 24 h post-hospitalization. Longitudinal plasma samples were subjected to mass spectrometry-based metabolomics and proteomics workflows. Multivariate analyses were performed to determine omics markers of transfusion of one, two, three, or more PLT transfusions. Higher levels of tranexamic acid (TXA), inflammatory proteins, carnitines, and polyamines were detected in patients requiring PLT transfusion. Correlation of PLT units with omics data suggested sicker patients required more units and partially overlap with the population requiring transfusion of packed red blood cell products. Furthermore, platelet activation was likely increased in the most severely injured patients. Fatty acid levels were significantly lower in PLT transfusion recipients (at time of maximal transfusion: Hour 4) compared with non-recipients, while carnitine levels were significantly higher. Fatty acid levels restore later in the time course (e.g., post-PLT transfusion). The present study provides the first multi-omics characterization of platelet transfusion efficacy in a clinically relevant cohort of trauma patients. Physiological alterations following transfusion were detected, highlighting the efficacy of mass spectrometry-based omics techniques to improve personalized transfusion medicine. More specialized clinical research studies focused on PLT transfusion, including organized pre and post transfusion sample collection and limitation to PLT products only, are required to fully understand subsequent metabolomic and proteomic alterations.

Effect of Platelet Concentrates (PCs) Leucodepletion on the Activation and Efficacy of Platelet Transfusion

Platelet concentrates (PCs) are blood components transfused in thrombocytopenic patients, including patients with blood malignancies. PCs contain leukocytes, which can pose potential side effects and activate platelets, reducing the efficacy of platelet transfusion. The leucodepletion process can be carried out by filtration to reduce the leukocyte count. This study aims to determine the difference between the CD62P expression of nonleucodepleted and leucodepleted PCs and to determine the difference between the Corrected Count Increment (CCI) of patients transfused with nonleucodepleted and leucodepleted PCs. This analytic observational study with a cross-sectional design was carried out on PCs obtained from platelet-rich plasma (PRP-PC). PCs were transfused into 48 blood malignancy patients, Yogyakarta, consisting of two groups i.e the group transfused with nonleucodepleted PCs (24 patients) and the group transfused with leucodepleted PCs (24 patients). CD62P expression in PCs was measured by flow cytometry method, and the CCI of the patients was calculated based on the CCI formula. The difference between the median CD62P expression and CCI of the two groups was analyzed using the Mann- Whitney Test with a significance of p<0.05. The median CD62P expression of the nonleucodepleted and leucodepleted groups were 34.4% (16.8–94.4%) and 21.7% (6.2–34.0%), respectively. There was a statistically significant difference between the CD62P expression of the two groups (p = 0.00). The group transfused with nonleucodepleted, and leucodepleted PCs showed respective median CCI of 18.8 x 109/L (2.4–94.8 x 109/L) and 14.7 x 109/L (2.4–124.0 x 109/L). There was no statistically significant difference between the CCI of the two groups (p = 0.42). It can be concluded that the CD62P expression in the PCs of the leucodepleted group was significantly lower than those of the nonleucodepleted group and that there was no significant difference between the CCI of both groups.

Impact of dose and storage duration of platelet concentrates on platelet recovery between ABO identical and ABO non-identical random donor platelet transfusions in hemato-oncology patients

Introduction and objectivesIt is challenging to adopt a policy of ABO identical platelet transfusion in hemato-oncological patients because of the high demand. Moreover, there are no global standards for the management of ABO non-identical platelet transfusions due to limited evidence. The current study compared the impact of dose and storage duration of platelets on percent platelet recovery (PPR) at 1 h and 24 h between ABO identical and ABO non-identical platelet transfusions in hemato-oncological conditions. The other objectives were to assess the clinical efficacy and compare adverse reactions between the two groups. MethodsA total of 130 random donor platelet transfusion episodes (81 ABO identical and 49 ABO non-identical) were evaluated in 60 eligible patients with different malignant, as well as non–malignant, hematological conditions. All analysis was performed using two-sided tests, and p-values <0.05 were considered significant. ResultsThe PPR at 1 h and 24 h was significantly higher in ABO identical platelet transfusion. Platelet recovery and survival were not affected by the gender, dose or storage duration of platelet concentrate. Aplastic anemia and myelodysplastic syndrome (MDS) disease conditions were observed to be independent risk predictors for 1-h post-transfusion refractoriness. ConclusionABO identical platelets have higher platelet recovery and survival. Both ABO identical and ABO non-identical platelet transfusions have similar efficacy in controlling bleeding episodes up to World Health Organization (WHO) grade two. Assessment of other factors, such as platelet functional properties in the donor, anti-HLA and anti-HPA antibodies, may be needed to better understand the platelet efficacy of platelet transfusions.

Related donor platelet transfusion improves platelet transfusion refractoriness in hematological patients.

Transfusion of HLA-matched platelets can reduce the effect of alloimmune responses on platelet transfusion efficacy; however, finding HLA-matched platelets in the population is nearly impossible. Almost all HLA-matched platelets from related are half-matched, but the hemostatic efficacy of related donor platelets is unclear. Our goal was to compare the hemostatic effect of related donated platelets and unrelated donors platelets. In this retrospective cohort study, we included acute leukemia and myelodysplastic syndrome patients with thrombocytopenia after chemotherapy. These patients were all transfused with platelets. This study excluded patients younger than 16 years and older than 65 years, or patients with abnormal coagulation parameters during platelet transfusion. We compared the hemostatic effect of related donated platelets and unrelated donors platelet. The primary outcome was transfusion efficacy after platelet transfusion, and the number of platelet counts and corrected count increments at 24 h after platelet transfusion. We analyzed 31 patients who received platelet transfusions from related donors (Treatment group) and 35 patients who received platelet transfusions from unrelated donors (Comparator group). Except for the relatively small proportion of patients with myelodysplastic syndrome in the treatment group, baseline clinical and laboratory characteristics were similar between the two groups. Hemostasis and prevention of bleeding in the treatment group showed significant superiority; the number of platelets increased 24 h after platelet transfusion in the treatment group was significantly higher than that in the comparator group. After 24 h, the corrected count increments treatment group was also higher than the comparator group; in the treatment group, the transfusion effect was better when the three sites of HLA-A, B, and C were identical, and the different blood types of platelet donors and recipients did not affect the transfusion effect. Related donated platelets have better hemostasis and prevention effects, and no increase in adverse blood transfusion reactions. It may be a better transfusion strategy for platelet refractoriness patients in emergency situations.

Therapeutic Efficacy of Platelet Transfusion and Analysis of Influencing Factors in 364 patients

Introduction: The aims of this study were to observe the therapeutic effect of platelet (PLT) transfusion and to analyze influencing factors for the sake of providing useful clues for improving the efficacy of PLT transfusion. Methods: Included in this study were patients who received PLT transfusion in the affiliated hospital of Nantong University. Patients’ sex, age, height, weight, PLT transfusion status, and 20–24-h PLT count before and after PLT transfusion were collected to calculate the PLT corrected count increment values before and after PLT transfusion. Solid-phase red cell adherence assay was used to determine PLT antibody. Statistical analysis was performed using SPSS25.0 Software. Results: A total of 364 patients received 1,060 PLT transfusions, including 728 successful transfusions and 332 unsuccessful transfusions. When the patients were grouped according to different etiologies, significant differences in PLT transfusion effectiveness were observed between these groups (χ² = 15.070, p < 0.05). Grouping of the 364 patients according to sex, blood type, and PLT transfusion frequency showed no significant difference in PLT transfusion refractoriness (PTR) between different age-groups and sexes (p > 0.05). With the number of PLT transfusions increasing, PTR increased gradually. PLT antibodies were detected of 364 patients, 67 of them were positive. Among them, 63 cases (94.02%) were positive for HLA class I antibody. Conclusion: To reduce PTR, multiple factors should be considered comprehensively when PLT transfusion therapy is to be implemented in clinical practice. PLT antibody is the main immune factor causing PTR.

Expression and Clinical Significance of circRNA Changes in Stored Erythrocytes During Platelet Transfusion in Acute Lymphoblastic Leukemia.

This study was to store the expression and clinical significance of circRNA changes in red blood cells during platelet transfusion in acute lymphoblastic leukemia (ALL). Sixty patients with ALL who underwent platelet transfusion were enrolled. Post-transfusion symptoms, platelet count (PLT), 24-hour corrected platelet increase index (CCI), and 24-hour platelet recovery rate (PPR) were collected, and their correlation with age, gender, bleeding, infection, splenomegaly, antibiotic use and infusion times were analyzed. High-throughput sequencing was used to detect the expression levels of circRNAs in suspended red blood cells of the blood samples. Then, the circRNA expression profiles were constructed, the differentially expressed circRNAs were screened, and the circRNAs related to platelet transfusion in AML were mined. PLT values of 60 ALL patients after platelet transfusion were significantly increased. Thirty-five patients were effective and 25 were ineffective after platelet transfusion, and the total effective rate was 58.33%. Patients with hemorrhage and splenomegaly, or antibiotic use, or increased blood transfusion frequency will show reduced efficacy of platelet transfusion. A total of 2,358 circRNAs were obtained from all samples, most of which were distributed in 200 - 3,000 nt. circRNAs can be divided into exonic circRNAs (58.74%), sense overlapping circRNAs (21.76%), intronic circRNAs (17.60%), antisense circRNAs (0.93%), and intergenic circRNAs (0.98%). A total of 257 differentially expressed circRNAs were obtained by volcano plot analysis, of which 126 were up-regulated and 131 were down-regulated. Differentially up-regulated and down-regulated circRNAs were mainly enriched in dif-ferent cellular processes. ALL is improved after platelet transfusion. By constructing circRNA expression profiles and screening differentially expressed circRNAs, 257 circRNAs that may be related to ALL platelet transfusion were mined.

Efficacy of platelet transfusion in cardiac surgery

Massive diffuse bleeding is still a problem in cardiovascular surgery. The first line treatment is platelet concentrate transfusion, although there is still insufficient information regarding efficacy, quantity, and timing. The objective of this prospective cohort study was to find out whether the amount of 4 apheresis platelet concentrates could reduce intraoperative bleeding and improve viscoelasticity and aggregometry. 10 patients were enrolled intraoperatively because of life-threatening diffuse bleeding after cardiopulmonary bypass and received 4 apheresis platelet concentrates back-to-back. The units were given every 5 minutes. After every unit, thromboelastometry, performed by ROTEM®, and aggregometry, performed by Multiplate®, were done together with Hematocrit, Hemoglobin, and Platelet Count. Hematocrit and Hemoglobin showed a statistically significant decrease of 14%, whereas Platelet Count showed a statistically significant increase of 205%. MCE-EXTEM increased statistically significant: 46%. There was no statistically significant increase in both ADP and COL results. Even a series of 4 platelet concentrates did not comprehensively improve both essential components of an adequate hemostasis: viscoelasticity and aggregation. Just the transfusion of platelet concentrates alone did not build a sufficient strategy improving hemostasis and reducing bleeding. A positive effect of surgical packing on stopping the bleeding could be seen.

Murine Studies to Test the Efficacy of Platelet Transfusions in the Management of Platelet Function Disorders

Background -In platelets, the nucleotide exchange factor CalDAG-GEFI (Cdg1) is critical for efficient integrin-mediated aggregation upon cellular stimulation. Mutations in Cdg1 have recently been shown to cause a novel platelet function disorder, which is characterized by partially impaired platelet aggregation and moderate-to-severe bleeding. Interestingly, platelet transfusions were successful in the treatment of bleeding in some but not all of these patients.Aims -In this study we investigated the hypotheses that (1) the hemostatic efficacy of transfused platelets is diminished by circulating malfunctional platelets, and (2) a certain ratio of “good” to “bad” platelets has to be reached in order to correct the hemostatic defect observed in these patients.Methods - A recently developed adoptive platelet transfer model was utilized to establish defined levels and ratios of wild-type (WT) to Cdg1-/- platelets in thrombocytopenic recipient mice. Additionally, WT platelets were transfused into mice lacking Cdg1, talin-1 or the extracellular domain of GPIbα (IL4α/GPIbα-tg). Hemostatic plug formation was visualized using intravital microscopy following laser ablation injury to the saphenous vein.Results - Our studies demonstrate that WT platelets are less effective in forming hemostatic plugs when co-transfused into thrombocytopenic mice with large numbers of Cdg1-/- platelets. Consistently, transfusion of WT platelets to a final level of 5 x 107 platelets/mL in circulation had only a minimal effect on the markedly prolonged bleeding time observed in Cdg1-/- or talin1-/- mice, while the same number of platelets rescued the hemostasic defect seen in platelet depleted or non-depleted IL4α/GPIbα-tg mice. Full recovery of hemostasis in Cdg1-/- mice required a final concentration of 2.5 x 108 WT platelets/mL or a ratio of not more than three Cdg1-/- platelets for every WT platelet transfused into these mice.Conclusion - Our studies in mouse models suggest limited efficacy of platelet transfusion therapy in the treatment of platelet function disorders due to competition between “good” and “bad” platelets for von Willebrand factor adhesion sites along the damaged endothelium . To correct the bleeding associated with the platelet function disorder, the fraction of transfused WT platelets has to reach ~25% of all platelets in circulation. DisclosuresNo relevant conflicts of interest to declare.

Platelet Reactivity Testing for Aspirin Patients Who Sustain Traumatic Intracranial Hemorrhage

BackgroundPatients who take aspirin and sustain traumatic intracranial hemorrhage (tICH) are often transfused platelets in an effort to prevent bleeding progression. The efficacy of platelet transfusion is questionable, however, and some medical societies recommend that platelet reactivity testing (PRT) should guide transfusion decisions. The study hypothesis was that utilization of PRT to guide platelet transfusion for tICH patients suspected of taking aspirin would safely identify patients who did not require platelet transfusion. MethodsThis was a retrospective study of patients with blunt tICH who received PRT for known or suspected aspirin use between June 2014 and December 2017 at a level I trauma center. Chart abstraction was conducted to determine home aspirin status, and PRT values were used to classify patients as therapeutic or nontherapeutic on aspirin. Differences were assessed with Kruskal-Wallis and chi-square tests. Results157 patients met study inclusion criteria, and 118 (75%) patients had documented prior aspirin use. PRT results were available approximately 1.7 h (IQR: 0.9, 3.2) after arrival. Upon initial PRT, 70% of patients were considered inhibited and 88% of those patients had aspirin documented as a home medication. Conversely, 18% of patients with home aspirin use had normal platelet reactivity. Clinically significant worsening of the tICH did not significantly differ when comparing those who received platelet transfusion with those who did not (8% versus 7%, P = 0.87). ConclusionsPlatelet reactivity testing can detect platelet inhibition related to aspirin and should guide transfusion decisions for head injured patients in the initial hours after trauma.

Efficacy of HLA-compatible Platelet Transfusion for Patients with Acute Myeloid Leukemia Refractory to Platelet Transfusion

Abstract Introduction/Objective Acute myeloid leukemia (AML) patients often require transfusion support during induction chemotherapy. Platelet transfusion refractoriness (PTR) may develop due to HLA alloimmunization. Management of immune-refractory patients with HLA-compatible platelet transfusions is labor intensive and associated with increased costs. The purpose of this study is to evaluate the efficacy of HLA-compatible platelet units in AML patients. Methods Newly diagnosed AML patients undergoing induction chemotherapy in our institute between 2015 and 2018 were identified. Platelet counts and platelet transfusion data from initiation of chemotherapy until platelet recovery (&amp;gt; 20K/µL and increased consistently) were extracted. A 24-hour posttransfusion corrected count increment (CCI) was calculated to evaluate the efficacy of each platelet transfusion. PTR was declared if a patient had a 24-hour CCI &amp;lt; 4K following two consecutive transfusions. Student’s t-test was used for statistical analysis. Results were presented as mean ± SE, * if p &amp;lt; 0.05. Results We identified 39 patients with newly diagnosed AML. PTR developed in 22/39 (56%) patients during induction chemotherapy. The average CCI was higher among those without PTR compared to those with PTR (8,408 ± 585 vs. 2,923 ± 360*), and overall platelet transfusion burden (in number of units) was lower (7.29 ± 1.0 vs. 18.55 ± 1.71*). HLA antibodies were identified in 3/22 (14%) PTR patients, as 6/22 (27%) were tested. The average CCI during HLA matched transfusions for these 3 patients was higher than that with random units (2,059 ± 149 vs. -126 ± 306*). Compared to HLA-negative PTR patients receiving random units, the average CCI for HLA-compatible transfusions was still lower, though not significantly (2,059 ± 149 vs. 3,099 ± 390, p = 0.33), while the number of HLA- compatible units transfused was significantly higher (31.0 ± 3.0 vs. 16.6 ± 1.45*). Conclusion In a cohort of newly diagnosed AML patients undergoing induction chemotherapy whose PTR was associated with detectable HLA antibodies, transfusion support with HLA-matched products did not lead to reduced overall platelet transfusion rates and CCI remains in the refractory range. This suggests that use of HLA matched platelets among newly diagnosed AML patients with PTR, even in the setting of detectable HLA antibodies, does not appear to result in reduced overall product utilization.

Quantitation of phosphatidylserine-exposing platelets and platelet-derived microparticles in platelet products: A new strategy to improve efficacy of platelet transfusion

Platelet transfusion is an effective therapy to prevent or treat bleeding. Considering the different clinical purposes of transfusion, it is necessary to assess the quality of platelet products prepared in transfusion laboratories. So far, there is no solution to the problem of how best to do this. Here, we summarize the quantitation of phosphatidylserine (PS)-exposing platelets and platelet-derived microparticles (PMPs) in platelet products using previously reported data. Because PS promotes the assembly and enhances the activity of coagulation factors, classifying platelet products according to their concentrations of PS-exposing platelets and PMPs will improve the therapeutic treatment of transfusion recipients.

Management of Bleeding Events Associated with Antiplatelet Therapy: Evidence, Uncertainties and Pitfalls

Bleeding complications are common in patients treated with antiplatelet agents (APA), but their management relies on poor evidence. Therefore, practical guidelines and guidance documents are mainly based on expert opinion. The French Working Group on Perioperative Haemostasis provided proposals in 2018 to enhance clinical decisions regarding the management of APA-treated patients with a bleeding event. In light of these proposals, this review discusses the evidence and uncertainties of the management of patients with a bleeding event while on antiplatelet therapy. Platelet transfusion is the main option as an attempt to neutralise the effect of APA on primary haemostasis. Nevertheless, efficacy of platelet transfusion to mitigate clinical consequences of bleeding in patients treated with APA depends on the type of antiplatelet therapy, the time from the last intake, the mechanism (spontaneous versus traumatic) and site of bleeding and the criteria of efficacy (in vitro, in vivo). Specific antidotes for APA neutralisation are needed, especially for ticagrelor, but are not available yet. Despite the amount of information that platelet function tests are expected to give, little data support the clinical benefit of using such tests for the management of bleeding events in patients treated or potentially treated with APA.

Loss of GPVI and GPIbα contributes to trauma-induced platelet dysfunction in severely injured patients

AbstractTrauma-induced coagulopathy (TIC) is a complex, multifactorial failure of hemostasis that occurs in 25% of severely injured patients and results in a fourfold higher mortality. However, the role of platelets in this state remains poorly understood. We set out to identify molecular changes that may underpin platelet dysfunction after major injury and to determine how they relate to coagulopathy and outcome. We performed a range of hemostatic and platelet-specific studies in blood samples obtained from critically injured patients within 2 hours of injury and collected prospective data on patient characteristics and clinical outcomes. We observed that, although platelet counts were preserved above critical levels, circulating platelets sampled from trauma patients exhibited a profoundly reduced response to both collagen and the selective glycoprotein VI (GPVI) agonist collagen-related peptide, compared with those from healthy volunteers. These responses correlated closely with overall clot strength and mortality. Surface expression of the collagen receptors GPIbα and GPVI was reduced on circulating platelets in trauma patients, with increased levels of the shed ectodomain fragment of GPVI detectable in plasma. Levels of shed GPVI were highest in patients with more severe injuries and TIC. Collectively, these observations demonstrate that platelets experience a loss of GPVI and GPIbα after severe injury and translate into a reduction in the responsiveness of platelets during active hemorrhage. In turn, they are associated with reduced hemostatic competence and increased mortality. Targeting proteolytic shedding of platelet receptors is a potential therapeutic strategy for maintaining hemostatic competence in bleeding and improving the efficacy of platelet transfusions.

Development and Validation of a Machine Learning Algorithm for Prediction of Platelet Transfusion Efficiency in Patients with Hematological Diseases

Background: Prophylactic transfusion of platelets provides a good protection for the implementation of invasive procedures and the prevention of bleeding events during chemotherapy and hematopoietic stem cell transplantation in patients who are suffering from hematological diseases. The issues that what is the optimal dose of platelet transfusion and how to monitor platelet transfusion efficiency are important due to the short storage time of platelet products, rising clinical demands, and decreasing donors. It is worthy that there are amount of studies have been conducted in the past to explore factors that may affect the clinical efficacy of platelet transfusion and characteristics of patients under these different transfusion effects. While, previous studies failed to exactly address the problems of clinical needs for platelet transfusion. Methods: The aim of our study is to develop a model to evaluate the efficacy of platelet transfusion and the statistic method of machine learning algorithm (ML) was involved. The differences between this algorithm and traditional methods are that the former one can continuously be learning from the data and form a self-training model, therefore ML is more accurate than traditional artificial models and generally independent of the model and parameters themselves. We further take the multi-layer fully connected layer neural network model (MLNN) into our consideration because it simulates the multi-layer interconnection of human nervous systems, which is suitable for processing inaccurate and fuzzy information. In our study, the establishment of a neural network model was used to make a multiple-dimension analysis between factors affecting platelet transfusion efficacy and platelet count added value correction index (aCCI), and explore the correlation among these influencing factors as well. Results: The study utilized the data relative to 1840 platelet transfusions performed in 460 patients with hematological diseases. The participants ranged in age from 16 to 92, and the median age was 59.5. There were 199 females and 261 men. The whole data was divided to 2 parts, 2/3 of them were analyzed as a training set and the others were used for validating. We selected 30 factors (including patient-related factors and transfusion product-related characteristics) that may affect the efficacy of platelet transfusion except the storage time of platelet (all data &lt; 2 days), and established a model for predicting platelet transfusion efficacy based on the volume of platelet transfusion. After the model was established, it was tested for goodness of fit, and the results showed that the LOSS value tended to be stable. Conclusions: The establishment of this model may not only be used for predicting the platelet count after platelet transfusions in patients and the amount of platelets that need to be transfused, but also provide supports for the solution of related problems. Disclosures No relevant conflicts of interest to declare.