Platelet Dose Research Articles

Platelet Concentration Explains Variability in Outcomes of Platelet-Rich Plasma for Lateral Epicondylitis: A High Dose Is Critical for a Positive Response: A Systematic Review and Meta-analysis With Meta-regression.

Randomized controlled trials (RCTs) evaluating the efficacy of platelet-rich plasma (PRP) for the management of lateral epicondylitis (LE) have been characterized by substantial variability in reported outcomes. The source of this heterogeneity is uncertain. To determine the effect of estimated platelet concentration on the efficacy of PRP for the management of LE. Systematic review and meta-analysis; Level of evidence, 2. All RCTs evaluating the efficacy of PRP in managing LE were identified. RCTs were classified according to whether the study documented a platelet concentration factor of PRP representing a greater than 3-fold increase over whole blood or a supraphysiological platelet dose (high-dose vs low-dose PRP). The primary outcome was the mean difference (MD) in the visual analog scale (VAS) score at latest follow-up. Random-effects and mixed-effects meta-analyses were performed, and meta-regression was used to evaluate whether differences in outcomes after treatment with PRP could be explained by differences in the concentration of PRP used. Overall, 13 RCTs with a total of 791 patients were included in this analysis, with 5 that utilized low-dose PRP and 8 that used high-dose PRP. Meta-analysis of VAS scores reported by studies that used high-dose PRP resulted in an MD of -1.31 (95% CI, -1.87 to -0.75) in favor of PRP over all alternative treatment strategies (P < .001). Meta-analysis of VAS scores reported by studies that used low-dose PRP resulted in an MD of 0.08 (95% CI, -0.51 to 0.68), suggesting no difference in the effect between PRP and all alternative treatment strategies (P = .79). The platelet concentration factor of PRP used in each RCT was found to be strongly predictive of the VAS score at final follow-up in meta-regression (P < .001), with 58.5% of the heterogeneity in the outcomes of PRP between studies explained by the platelet concentration factor alone. The platelet concentration of PRP may play a significant role in the outcomes of patients with LE. A direct linear relationship was observed between the platelet concentration factor of PRP used and the magnitude of patient-reported symptom relief after the management of LE with PRP. Clinicians should ensure a supraphysiological platelet concentration when preparing PRP for the management of LE.

Impact of Platelet Transfusion at Different Doses in Oncohematology Pediatric Inpatients and Outpatients: A Retrospective Study.

Platelet (PLT) transfusion is an essential strategy to prevent bleeding in children with thrombocytopenia associated to cancer treatment. However, data on optimal pediatric dosing and transfusion thresholds are limited. This retrospective study analyzed data from 607 pediatric patients with hematologic malignancies, nonmalignant disorders, and solid tumors who developed hypoproliferative thrombocytopenia during therapy. In the first phase (Objective 1), the effective response to transfusion (ERTR) was assessed following International Collaboration for Transfusion Medicine guidelines (ICTMG), comparing low-dose (1.1×1011PLT/m2 body surface area) transfusions for inpatients and medium dose (2.2×1011) for outpatients. Transfusion thresholds were set at less than 10,000/µL versus 10,000-20,000/µL, and overall PLT concentrate consumption was analyzed. The second phase (Objective 2) examined the total number of transfusions per patient, incidence of major bleeding events, and bleeding-related mortality rates across dosing groups. ERTR ranged from 65% to 82%, with significantly higher rates in outpatients compared to inpatients. In outpatients with PLT less than 10,000/µL, the medium dose showed no significant advantage over the lower inpatient dose. Similar efficacy was observed between low (<10,000/µL) and high (10,000-20,000/µL) transfusion triggers, with no statistically significant difference in the incidence of major bleeding events across groups. The low-dose strategy was significantly associated with a reduction in PLT volume transfused compared to the standard expected dose. These findings support the application of ICTMG in pediatric settings. The lower PLT dose for inpatients is safe and effective, providing benefits in resource utilization, while a higher transfusion trigger (20,000/µL) does not improve outcomes.

Study of Relationship between Heparin and Platelets in Hemodialysis Patients

Platelets are considered one of the most important components of blood that contribute to the coagulation process, and they also play an important role in the blood clotting process. Platelets may be exposed to some types of anticoagulant drugs, such as heparin, which increases the risk of thrombocytopenia, especially in dialysis patients who receive heparin periodically in the extracorporeal circuit in the dialysis unit; thrombocytopenia may develop due to receiving heparin in every dialysis session, which has been confirmed for patients in previous research. This research, aims to find the relationship between heparin and platelets among dialysis patients. Some parameters were carried on for hemodialysis patients of (Al-Jamil - Raqdalin - Zuwara) hemodialysis centers to support the study of the relationship between them, (CBC, PT, PTT, CT, and BT), also a questionnaire has been collected from the patients for further information. The results showed that there is an inverse relationship between the dose of heparin and platelets at α (0.5), meaning that the higher the dose of heparin, the greater the thrombocytopenia. We also found that there is an inverse relationship between the duration of dialysis and platelets, meaning that the longer the duration of dialysis, the lower the platelet count. The results showed also the presence of clots in the dialysis machine in varying proportions. We can conclude that there are no effects on the types of treatment doses on the platelets. Also, heparin dose and Platelets count have an inverse significant relationship. We can conclude also that there are no significant differences between the average platelets due to the types of heparin at the level of significance.

Development and in vitro evaluation of bioprinted plasma-infused biocarriers for mesenchymal stromal cell delivery in musculoskeletal disorder treatment

A meta-analysis revealed no advantage of surgical over non-surgical treatments, emphasizing the need for non-invasive methods, particularly for prevalent osteoarticular diseases like knee osteoarthritis. To enhance therapeutic efficacy, we developed a plasma-infused gelatin methacryloyl (GelMA) biocarrier loaded with bone marrow-derived mesenchymal stromal cells (BMSCs). These constructs were evaluated in vitro for their properties and paracrine interactions in non-inflamed and inflamed environments. GelMA infused with platelet-rich plasma (PRP) and platelet-poor plasma (FFP) were compared. Pristine GelMA was used as a control. Both PRP and FFP enhanced the proliferation and viability of BMSCs in biocarriers, promoting cell survival pathways while inhibiting necrotic and apoptotic events. Proteomic analysis showed no differences in BMSC behavior between PRP and FFP in the absence of inflammation (p = 0.550). However, both plasmas significantly modified cell behavior under inflammatory conditions (p = 0.001). PRP- and FFP-infused biocarriers activated ten key signaling pathways, including HIF-1a, neuroinflammation, and extracellular matrix turnover. PRP-specific pathways included IL-17, IL-6, and several growth factor signaling pathways. No significant differences in angiogenesis were linked to platelet dose (p = 0.079), but both PRP and FFP significantly enhanced angiogenesis compared to GelMA alone (p &lt; 0.001 for PRP, p = 0.002 for FFP). FFP showed stronger angiogenesis than PRP under IL-1&amp;beta; treatment (p = 0.042). Plasma-infused biocarriers altered BMSC behavior in response to inflammatory cytokines compared to GelMA (p = 0.001). PRP specifically activated TGF-b signaling under IL-1b (Z=2.308, p-value 1.02E-35), which was not seen under TNF-a exposure. These findings suggest that PRP and FFP-infused biocarriers may offer promising improvements in regenerative therapies for inflammatory osteoarticular conditions like knee osteoarthritis.

Use of Low-Dose Platelets in Actively Bleeding Patients: A Retrospective Analysis of a Cardiac Surgery Cohort.

During platelet shortages, many hospitals produce low-dose platelets by splitting a standard platelet unit (>3 × 1011 platelets in the United States) in 2, then providing these low-dose units to patients. While low-dose units were previously found to be effective for prophylactic purposes in patients undergoing chemotherapy in the Prophylactic Platelet Dose (PLADO) trial, their use in actively bleeding patients has not yet been assessed. To assess the use and safety of low-dose platelets in actively bleeding patients. We performed a retrospective review of cardiac surgery cases receiving platelet units for 18 months at 1 hospital. Two cohorts, those receiving only whole-dose platelets (37 cases) and those receiving only low-dose platelets (38 cases), were compared during the intraoperative and the 24-hour perioperative period. Mean number of platelet transfusions, dose of other blood products, estimated blood loss, bleeding complications in index cases, and all-cause mortality within 30 days of discharge were compared. There was no significant difference in mean number of intraoperative platelet transfusions between the cohorts (1.61 versus 1.53, P = .57). There was no significant increase in the transfusion of other blood products, estimated blood loss, bleeding complications in index cases, or all-cause mortality within 30 days of discharge in the low-dose platelet cohort, apart from a small increase in requirement for fresh frozen plasma in the perioperative period. These results suggest that low-dose platelets are tentatively equivalent to whole-dose platelets in cardiac surgery during shortages, with similar transfusion requirements and clinical outcomes between groups. Future multicenter studies are needed to confirm these findings.

Increasing PRP Injection Volume to Target Super- Dose of Platelets for Knee Osteoarthritis: Response.

Increasing PRP Injection Volume to Target Super- Dose of Platelets for Knee Osteoarthritis: Response.

Increasing PRP Injection Volume to Target Super-high Dose of Platelets for Knee Osteoarthritis: Letter to the Editor.

Increasing PRP Injection Volume to Target Super-high Dose of Platelets for Knee Osteoarthritis: Letter to the Editor.

Romiplostim for chemotherapy induced thrombocytopenia in solid tumors: A meta-analysis.

e24137 Background: Chemotherapy-induced thrombocytopenia (CIT), defined as platelets &lt; 100,000/mcL persisting for ≥3-4 weeks post-chemotherapy affects 20-25% of cases necessitating platelet transfusions or dose reductions leading to treatment delays and impacting patient outcomes. (1,2) Despite multiple studied agents, there are no established guidelines. Romiplostim, a thrombopoietin receptor agonist approved for immune thrombocytopenic purpura, stands out. NCCN suggests its use, but pooled analyses are lacking. Our meta-analysis addresses this gap, exploring romiplostim's efficacy in CIT management. Methods: We performed a systematic search of PUBMED, EMBASE, and COCHRANE databases for studies that evaluate the use of romiplostim in the setting of CIT for solid tumors. The primary endpoint was the proportion of patients that showed improvement in platelet counts in response to romiplostim. Secondary endpoints were the proportion of patients that continued full dose chemotherapy dose on romiplostim and incidence of thromboembolic events. Pooled proportions were calculated along with 95% confidence intervals (CI) using a random-effects model. I2 statistic was used to depict inter-study heterogeneity. Results: A total of 10 single arm studies - 3 prospective studies, 3 case series, and 4 retrospective studies were included. The pooled outcomes were: significant improvement of platelet count above 100K with response to romiplostim therapy in 80.53% patients [95 % CI 72.47 - 87.48, I2 = 69%], proportion of patients that continued full dose chemotherapy on romiplostim was 70.89% [95% CI 63.40 - 77.84, I2 = 0%], and incidence of thromboembolic events was 6.81% [ 95% CI 3.64 – 10.89, I2 = 35%]. Variables like platelet transfusions, bleeding events, type and stage of cancer were not reported uniformly and hence subgroup analyses could not be performed. Conclusions: Our analysis reveals that romiplostim improved the platelet counts in majority of patients with underlying CIT associated with solid tumors. It also shows that a majority of the patients were able to resume their full dose chemotherapy when maintained on romiplostim. The incidence rate of thromboembolic events with romiplostim believed to be consistent with what expected of this population with majority having advanced/high-risk malignancies. Given its efficacy, romiplostim may be used for routinely managing CIT in solid tumors. This analysis is limited by lack of comparative studies and warrant further randomized trials to confirm the safety and efficacy of romiplostim in this patient population.

Bleeding Risk Factors in Thrombocytopenic Patients with Hematologic Malignancies

Introduction Despite prophylactic platelet transfusions, World Health Organization (WHO) grade ≥ 2 bleeding occurs in 50 to 70% of patients with hematologic malignancies and hypoproliferative thrombocytopenia secondary to therapy and/or underlying disease (Gernsheimer et al, Blood 2022). Anemia (hematocrit, HCT ≤ 25%), coagulopathy (activated partial thromboplastin time ≥ 30s, international normalized ratio ≥ 1.2), and platelet count ≤ 5000/µl were independently associated with increased risk of bleeding in the PLADO (platelet dose) trial of 1272 patients with hypoproliferative thrombocytopenia treated between 2004 to 2007 (Uhl et al, Blood 2017). Updated data on bleeding outcomes and risk of bleeding is lacking. Methods We performed a post-hoc analysis of bleeding outcomes and bleeding risk factors in 330 patients with hematologic malignancy and hypoproliferative thrombocytopenia from therapy and/or underlying disease randomized at 3 institutions to receive either tranexamic acid (TXA) or placebo in the double-blinded, multicenter American Trial to Evaluate Tranexamic Acid Therapy in Thrombocytopenia (A-TREAT) (Gernsheimer et al, Blood 2022). Patients received prophylactic platelet transfusions for a platelet count of ≤ 10,000/µl and WHO grade bleeding was assessed daily for 30 days after a platelet count ≤ 30,000/µl and study drug was started. Study drug was discontinued when platelet count was ≥ 30,000/ul for 46 hours without platelet transfusion support or until a maximum of 30 days after treatment activation, whichever came first. Red blood cell (RBC) transfusion was given according to local standard of care. Cox proportional hazards regression with time-varying covariates was used to assess the association of patient characteristics with the risk of a first major (grade 2+) bleeding event. HCT, platelet count, inpatient vs. outpatient status, steroid treatment, and fever were recorded daily. Patients were censored at the first of time of withdrawal, death, or day 30. Results WHO grade ≥ 2 bleeding occurred in 46% of patients overall with no difference between the TXA and placebo groups (TXA 44% versus placebo 47%, p=0.66). Bleeding rates were highest in allogeneic stem cell transplant patients, followed by chemotherapy, followed by autologous stem cell transplant. Overall bleeding rates by organ system showed oral and nasal (18%), skin (17%), gastrointestinal (11%), and genitourinary (11%) bleeding (Table 1). WHO grade ≥ 2 vaginal bleeding occurred in 28% of patients of childbearing potential despite widespread use of hormonal suppression. In a proportional hazards regression model of time to first bleeding event, undergoing allogeneic stem cell transplant was associated with a non-significant increased hazard of bleeding vs chemotherapy (HR 1.32, 95% CI 0.92-1.89), whereas autologous transplant had significantly lower hazard of bleeding vs chemotherapy (HR 0.39, 95% CI 0.20-0.76) (Table 2). HCT &amp;lt; 21% was associated with increased bleeding risk even after adjusting for severe thrombocytopenia (HR 2.71, 29% CI 1.37, 5.36). Platelet count &amp;lt; 5000/µl was also associated with increased risk (HR 3.33, 95% CI 1.67-6.61). Inpatient status, presence of fever, and age did not significantly impact risk of first bleed. Conclusions The overall rate of WHO grade &amp;gt;2 bleeding was similar to historical literature with lower rates of gastrointestinal bleeding than previously reported (31% in PLADO). Vaginal bleeding was common despite standard use of hormonal suppression in patients of childbearing potential. Platelet count &amp;lt; 5000/µl remains a risk factor for bleeding. Regardless of platelet count, bleeding risk increased with HCT &amp;lt; 21% suggesting a red blood cell transfusion threshold higher than 21% is unlikely to mitigate bleeding. More investigation is needed on strategies to reduce bleeding in this patient population.

Fetal Maternal Hemorrhage As a Trigger for Fetal/Neonatal Alloimmune Thrombocytopenia: Evidence from a Murine Model

Fetal/neonatal alloimmune thrombocytopenia (FNAIT) is a severe bleeding disorder caused by maternal alloantibodies targeting fetal platelet alloantigens. Among the 37 human platelet alloantigens (HPAs) identified, the HPA-1a/HPA-1b polymorphism, involving a Leu33Pro amino acid substitution in the integrin β3 subunit, is the most common cause of severe FNAIT, particularly in Caucasians. Leu33 serves as a key target for alloantibody binding, leading to fetal and neonatal thrombocytopenia and, in severe cases, spontaneous or trauma-induced intracranial hemorrhage. FNAIT shares a pathophysiologic basis with Hemolytic Disease of the Fetus and Newborn (HDFN), which stem from maternal immunization to alloantigens on fetal platelets and red blood cells (RBCs), respectively. While alloimmunization against RBC alloantigens typically occurs in response to fetal maternal hemorrhage (FMH), a clear link between FMH and maternal alloimmunization against HPA-1a on circulating fetal platelets has remained elusive. To assess whether FMH can induce platelet alloimmunization and lead to the development of FNAIT during pregnancy, we utilized recently developed transgenic mice expressing the HPA-1a allogeneic epitope on a murine GPIIIa backbone. To simulate varying degrees of FMH, we transfused different doses of HPA-1a platelets into wild-type (WT), non-pregnant female mice. We found that transfusing as few as 1x10 7 HPA-1a-positive platelets (equivalent to a FMH of approximately 30 ml in humans) resulted in production of high-titer HPA-1a-specific alloantibodies. Since &amp;gt;25% of the cases of FNAIT in humans are thought to occur in what are experienced as first pregnancies, we further investigated whether exposure to HPA-1a in pregnant female mice could still induce FNAIT. We found that when WT female mice pregnant with HPA-1a-positive fetuses were transfused with HPA-1a-positive platelets, they consistently developed HPA-1a-specific antibodies with similar titers as observed in non-pregnant females and delivered thrombocytopenic pups with FNAIT. Taken together, these findings demonstrate that exposure to HPA-1a-positive platelets in the maternal circulation during pregnancy is sufficient to trigger FNAIT, and that maternal tolerance, normally increased during pregnancy, does not play a significantly immunosuppressive role to prevent alloimmunization to the HPA-1a epitope. These findings support the notion that FMH may be a possible cause of alloimmunization in humans, even during a first pregnancy. Finally, the result of this study further validates the usefulness of this HPA-1a alloantigen-specific humanized transgenic mouse model to explore the etiology and pathophysiology of FNAIT. Further studies should significantly advance preventative and therapeutic strategies for this life-threatening immunologic disorder.

Analysis of the reentry status of blood donors with reactive bloodborne pathogen screening markers in Hangzhou City

Objective: To explore the reentry rate of reactive blood donors in the bloodborne pathogen infection screening in Hangzhou City, and analyze the donation behavior of those who successfully returned. Methods: A retrospective analysis of the return data of blood donors with reactive bloodborne pathogen screening markers was conducted at Zhejiang Provincial Blood Center from June 2017 to May 2022. The reentry process for blood donors with reactive bloodborne pathogen screening markers in Hangzhou City is as follows: after the initial screening period of 6 months, donors can voluntarily apply for return to the blood center. Samples are collected and subjected to routine enzyme-linked immunosorbent assay (ELISA) screening for HBsAg, anti-HCV, HIV Ab/Ag, and anti-TP, as well as a single nucleic acid (HIV/HCV/HBV) test. For samples that show non-reactivity in both ELISA and nucleic acid tests, serum biomarker testing for the reasons of exclusion is performed using chemiluminescence immunoassay (CLIA), and those with non-reactivity are allowed to return. Results: A total of 4 583 reactive blood donors who met the criteria for re-entry applied for reentry, out of which 475 applications were received from donors in the Hangzhou area. Among these, 279 donors were successfully readmitted, resulting in a success rate of 58.74% (279/475). By the end of December 2021, out of the 174 donors who successfully returned, 114 donors chose to donate again. They collectively donated 39 530 ml of whole blood and 1 147.2 therapeutic doses of platelets. Among these, 21 donors once again showed reactivity for pathogen infection biomarkers, accounting for 18.42% (21/114). Conclusion: The reentry strategy has somewhat mitigated the attrition of blood donors. Nevertheless, there are instances where donors who were successfully readmitted show reactivity once more in the screening for pathogen infection biomarkers.

P‐BB‐60 | Platelet Dose in LVDS48 Apheresis Platelets, Leukocytes Reduced

P‐BB‐60 | Platelet Dose in LVDS48 Apheresis Platelets, Leukocytes Reduced

Prophylactic platelet transfusion response in critically ill patients: a prospective multicentre observational study

BackgroundResponse to prophylactic platelet transfusion is suspected to be inconsistent in critically ill patients questioning how to optimize transfusion practices. This study aimed to describe prophylactic platelet transfusion response, to identify factors associated with a suboptimal response, to analyse the correlation between corrected count increment and platelet count increment and to determine the association between poor platelet transfusion response and clinical outcomes.MethodsThis prospective multicentre observational study recruited patients who received at least one prophylactic platelet transfusion in one of the nine participating intensive care units for a period up to 16 months. Poor platelet transfusion response was defined as a corrected count increment (CCI) that adjusts for platelet dose and body surface area, less than 7 at 18–24 h after platelet transfusion. Factors associated with poor platelet transfusion response were assessed in a mixed-effect model. Sensitivity analyses were conducted in patients with and without haematology malignancy and chemotherapy.ResultsPoor platelet transfusion response occurred in 349 of the 472 (73.9%) prophylactic platelet transfusions and in 141/181 (77.9%) patients. The mixed-effect model identified haemoglobin at ICU admission (odds ratio (OR): 0.79 [95% confidence interval (CI) 0.7–0.89]) and body mass index (BMI) (OR: 0.93 [0.89–0.98]) being positively and independently associated with platelet transfusion response, while a haematological malignancy (OR 1.93 [1.09–3.43]), sepsis as primary ICU admission diagnosis (OR: 2.81 [1.57–5.03]), SOFA score (OR 1.10 [1.03; 1.17]) and maximum storage duration of platelet (OR: 1.24 [1.02–1.52]) were independently associated with a suboptimal platelet increment. Clinical outcomes did not differ between groups, nor the requirement for red blood cells. Poor platelet transfusion response was found in 93.5% of patients with haematology malignancy and chemotherapy.ConclusionsIn this study of critically ill patients, of whom more than half had bone marrow failure, almost three quarters of prophylactic platelet transfusions led to suboptimal platelet increment measured 18 to 24 h following platelet transfusion. Platelet storage duration was the only factor associated with poor platelet response that may be accessible to intervention.Trial registration in October 2017: ClinicalTrials.gov: NCT03325140.

Factors affecting the features of platelet-rich plasma in patients with knee osteoarthritis.

The aim of this study was to present an analysis of platelet-rich plasma obtained from patients with knee osteoarthritis and reveal the factors affecting its features. A total of 62 patients (mean age: 56.68 ± 7.13 years) with symptomatic knee osteoarthritis were included in this study. Age (years), gender, height (m), weight (kg), body mass index (kg/m2), duration of symptoms, smoking status, smoking index, general health status, and physical activity scores were recorded. Whole blood and platelet-rich plasma cell counts were performed with a hematology analyzer. White blood cell, red blood cell, and platelet counts were recorded. According to the dose of injected platelets, efficiency of the procedure, purity of platelet-rich plasma, and activation classification, dose of platelets, efficiency of the procedure (platelet recovery rate, %), and purity of the obtained platelet-rich plasma product (relative composition in platelets, %) were calculated. Correlation analysis between the features of platelet-rich plasma and the patient-related variables, including age, gender, body mass index, smoking status, smoking index, presence of other health conditions, physical activity scores, duration of symptoms, and pain levels, was performed. Dose of injected platelets, efficiency of the procedure, purity of platelet-rich plasma, and activation analysis showed that the dose of injected platelets was 3.25 billion, the efficiency of the process was 77%, and the purity rate of the platelet-rich plasma was 98.4%. Platelet-rich plasma platelet count was correlated with whole blood platelet count (r = 0.81, P < .001), whole blood white blood cell count (r = 0.39, P = .002), smoking status (r = 0.56, P = .03), smoking index (r = -0.63, P = .002), and the presence of hypertension (r = -0.31, P=.04). Platelet-rich plasma white blood cell and purity of platelet-rich plasma were correlated with the smoking status of the patients (r = 0.52, P = .01; r = 0.64, P = .003, respectively). This study has demonstrated that high dose and very pure platelet-rich plasma with medium efficiency was yielded with this platelet-rich plasma preparation procedure; whole blood platelet count, the presence of hypertension, and the smoking status of patients affect the features of the obtained platelet-rich plasma. Level IV, Diagnostic Study.

Platelet count and dose, but not comorbidities, predict severe neutropenia in cabazitaxel-treated prostate cancer patients: Aretrospective observational study.

To determine the safety of cabazitaxel and predictors of severe neutropenia caused by cabazitaxel in a patient population that includes those with comorbidities. Of 42 prostate cancer patients treated with cabazitaxel at Osaka Medical and Pharmaceutical University Hospital between September 2014 and June 2022, 33 were included in this study, whereas 6 patients who were outpatients and 3 who were discharged early within 7 days upon patient request were excluded. Logistic regression analysis was used to examine predictors of severe neutropenia. Of the 33 eligible patients, 24 had comorbidities, with hypertension being the most common (n=19), followed by dyslipidemia (n=14) and diabetes (n=11). There was no statistically significant difference in the rate of severe neutropenia due to any of the comorbidities, depending on the presence or absence of the comorbidity. However, the rate of severe neutropenia was significantly higher in patients with baseline platelet levels <22.4×104/μL and those receiving cabazitaxel doses >34 mg/body. In the final model adjusted for age, body mass index, C-reactive protein, and monocyte count, lower baseline platelet levels and higher doses of cabazitaxel were also predictors of the development of severe neutropenia. Comorbidities such as hypertension, dyslipidemia, diabetes mellitus, cerebrovascular disease, chronic kidney disease, liver dysfunction, and cardiac disease did not affect the incidence of severe neutropenia in patients receiving cabazitaxel. The baseline platelet count and the dose of cabazitaxel were also suggested to be markers for the development of severe neutropenia.

Angiogenesis and Tissue Repair Depend on Platelet Dosing and Bioformulation Strategies Following Orthobiological Platelet-Rich Plasma Procedures: A Narrative Review.

Angiogenesis is the formation of new blood vessel from existing vessels and is a critical first step in tissue repair following chronic disturbances in healing and degenerative tissues. Chronic pathoanatomic tissues are characterized by a high number of inflammatory cells; an overexpression of inflammatory mediators; such as tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1); the presence of mast cells, T cells, reactive oxygen species, and matrix metalloproteinases; and a decreased angiogenic capacity. Multiple studies have demonstrated that autologous orthobiological cellular preparations (e.g., platelet-rich plasma (PRP)) improve tissue repair and regenerate tissues. There are many PRP devices on the market. Unfortunately, they differ greatly in platelet numbers, cellular composition, and bioformulation. PRP is a platelet concentrate consisting of a high concentration of platelets, with or without certain leukocytes, platelet-derived growth factors (PGFs), cytokines, molecules, and signaling cells. Several PRP products have immunomodulatory capacities that can influence resident cells in a diseased microenvironment, inducing tissue repair or regeneration. Generally, PRP is a blood-derived product, regardless of its platelet number and bioformulation, and the literature indicates both positive and negative patient treatment outcomes. Strangely, the literature does not designate specific PRP preparation qualifications that can potentially contribute to tissue repair. Moreover, the literature scarcely addresses the impact of platelets and leukocytes in PRP on (neo)angiogenesis, other than a general one-size-fits-all statement that "PRP has angiogenic capabilities". Here, we review the cellular composition of all PRP constituents, including leukocytes, and describe the importance of platelet dosing and bioformulation strategies in orthobiological applications to initiate angiogenic pathways that re-establish microvasculature networks, facilitating the supply of oxygen and nutrients to impaired tissues.

Dose-dependent effect of canine lyophilized platelet on an in vitro hemodilution model

The transfusion of stored platelets has emerged as an efficient method for treating dogs with thrombocytopenia. However, the availability of fresh platelets is limited in veterinary medicine due to demanding storage conditions. Lyophilized platelets have long shelf lives and can be easily stored, increasing their accessibility for thrombocytopenic dogs. Due to the lack of research and information on the dose effect, canine lyophilized platelets are used at a clinical dosage without research-based evidence. This study was to evaluate the dose effect of lyophilized canine platelets on blood coagulability. Three different concentrations of lyophilized canine platelets were added to in vitro hemodilution blood model, increasing the platelet count by 25, 50, and 100 × 106/ml and coagulation profiles were analyzed. The coagulability was evaluated via the plasma fibrinogen concentration, coagulation time, thromboelastography (TEG), and platelet function analyzer (PFA). Higher concentrations of lyophilized platelets showed dose-dependent association with decreased aPTT and R-time of TEG and increased alpha angle and MA of TEG. These results showed the potential that the higher dose of canine lyophilized platelets better improve blood coagulability than the standard dose and provided the basis for further safety and clinical studies.

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.

Longitudinal analysis of annual national hemovigilance data to assess pathogen reduced platelet transfusion trends during conversion to routine universal clinical use and 7-day storage.

France converted to universal pathogen reduced (PR; amotosalen/UVA) platelets in 2017 and extended platelet component (PC) shelf-life from 5- to 7-days in 2018and2019. Annual national hemovigilance (HV) reports characterized longitudinal PC utilization and safety over 11 years, including several years prior to PR adoption as the national standard of care. Data were extracted from published annual HV reports. Apheresis and pooled buffy coat [BC] PC use was compared. Transfusion reactions (TRs) were stratified by type, severity, and causality. Trends were assessed for three periods: Baseline (2010-14; ~7% PR), Period 1 ([P1] 2015-17; 8%-21% PR), and Period 2 ([P2] 2018-20; 100% PR). PC use increased by 19.1% between 2010 and 2020. Pooled BC PC production increased from 38.8% to 68.2% of total PCs. Annual changes in PCs issued averaged 2.4% per year at baseline, -0.02% (P1) and 2.8% (P2). The increase in P2 coincided with a reduction in the target platelet dose and extension to 7-day storage. Allergic reactions, alloimmunization, febrile non-hemolytic TRs, immunologic incompatibility, and ineffective transfusions accounted for >90% of TRs. Overall, TR incidence per 100,000 PCs issued declined from 527.9 (2010) to 345.7 (2020). Severe TR rates declined 34.8% between P1-P2. Forty-six transfusion-transmitted bacterial infections (TTBI) were associated with conventional PCs during baseline and P1. No TTBI were associated with amotosalen/UVA PCs. Infections with Hepatitis E (HEV) a non-enveloped virus resistant to PR, were reported in all periods. Longitudinal HV analysis demonstrated stable PC utilization trends with reduced patient risk during conversion to universal 7-day amotosalen/UVA PCs.

Basic Science of Autologous Orthobiologics: Part 1. Platelet-Rich Plasma.

In recent years, autologous biological preparations have emerged as a growing area of medical innovation in interventional orthopedical procedures and surgical interventions. These cellular therapies are often referred to as orthobiologics and are derived from patient's own tissues, such as blood, bone marrow, and adipose tissue to prepare platelet-rich plasma (PRP), bone marrow concentrate, and adipose tissue concentrate, respectively. In this article, we will emphasize and discuss the physiological variability of autologous PRP bioformulations regarding their effectivity in tissue repair. Furthermore, recent developments concerning platelet dosing, potentially effecting immunomodulation, and pain killing will be described.