Prophylactic Platelet Transfusions Research Articles

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.

Changes in platelet transfusion thresholds utilized in the NICU since PlaNeT-2

Abstract Background Use of prophylactic platelet transfusions in the neonatal setting is a common practice due to concerns about bleeding despite evidence of a developmental mismatch with transfusion of adult platelets. The Platelets for Neonatal Transfusion-Study 2 (PlaNeT-2) published in January 2019 showed that using higher platelet thresholds (50 x 109/L) was associated with more adverse outcomes and no improvement in bleeding events compared to lower platelet thresholds (25 x 109/L). Following this trial, implementation of a lower threshold was provider dependent as there were no changes made to the neonatal intensive care unit (NICU) institutional policies. Our goal was to determine if there were any overall changes in individual clinical practice with thresholds used for platelet transfusions in our NICU and number of transfusions per patient. Methods Our center has a 52 bed level IV NICU that specializes in care for critical and/or preterm infants. We performed a retrospective review from 2017 to 2023 of patients admitted in the NICU who received platelet transfusion and had an available platelet count in the 12 hours prior to the transfusion. Results There were 272 platelet transfusions given to 107 unique NICU patients who had platelet counts available. There were 66 transfusions given to 32 patients pre-PlaNeT-2 (2017-2018) and 206 transfusions given to 75 patients post-PlaNeT-2 (2019-2023). The average platelet count pre-PLaNeT-2(2017 to 2018) was 43 x 109/L (SD±24 x 109/L) and post-PLaNeT-2 (2019 to 2023) was 36 x 109/L (SD±21 x 109/L, p=0.03). Prior to PLaNeT-2, 26% of platelet transfusions were for platelet counts ≤ 25 x 109/L and 35% were for platelet counts between 51 to 100x9/L. Post PLaNeT-2 the percentages changed to 35% and 21% respectively. The percentage of transfusions occurring for platelet counts between 26 to ≤50 x 109/L was 38% and 44%, respectively. The number of platelet transfusions per year did not decrease significantly after the PLaNeT-2 trial (average of 33/year versus 41/year, p=0.5). The number of transfusions per patient before and after PLaNeT-2 did not change (2.1 transfusions per patient versus 2.6 transfusions per patient, p=0.3). Conclusion Platelet thresholds utilized in our center decreased after the PLaNeT-2 trial with less transfusions occurring for platelet counts greater than 50 x 109/L. Although thresholds decreased, the number of transfusions per year and the number of transfusions per patient did not significantly change. Further studies are needed to understand changes in patient outcomes and platelet utilization in the NICU.

Analysis of bleeding outcomes in patients with hypoproliferative thrombocytopenia in the A-TREAT clinical trial.

Despite prophylactic platelet transfusions, hypoproliferative thrombocytopenia is associated with bleeding; historical risk factors include hematocrit (HCT) 25%, activated partial thromboplastin time 30 s, international normalized ratio 1.2, and platelets 5000/μL. We performed a post hoc analysis of bleeding outcomes and risk factors in participants with hematologic malignancy and hypoproliferative thrombocytopenia enrolled in the American Trial to Evaluate Tranexamic Acid Therapy in Thrombocytopenia (A-TREAT) and randomized to receive either tranexamic acid (TXA) or placebo. World Health Organization (WHO) grade 2+ bleeding occurred in 46% of 330 participants, with no difference between the TXA (44%) and placebo (47%) groups (p = 0.66). Overall, the most common sites of bleeding were oronasal (18%), skin (17%), gastrointestinal (11%), and genitourinary (11%). Among participants of childbearing potential, 28% experienced vaginal bleeding. Platelets ≤5000/μL and HCT < 21% (after adjusting for severe thrombocytopenia) were independently associated with increased bleeding risk (HR 3.78, 95% CI 2.16-6.61; HR 2.67, 95% CI 1.35-5.27, respectively). Allogeneic stem cell transplant was associated with nonsignificant increased risk of bleeding versus chemotherapy alone (HR 1.34, 95% CI 0.94-1.91). The overall rate of WHO grade 2+ bleeding was similar to previous reports, albeit with lower rates of gastrointestinal bleeding. Vaginal bleeding was common in participants of childbearing potential. Platelets ≤5000/μL remained a risk factor for bleeding. Regardless of platelet count, bleeding risk increased with HCT < 21%, suggesting a red blood cell transfusion threshold above 21% should be considered to mitigate bleeding. More investigation is needed on strategies to reduce bleeding in this population.

Postoperative bleeding after dentoalveolar surgery in patients with thrombocytopenia—are prophylactic platelet transfusions necessary?

PurposeBenefits of prophylactic platelet (PLT) transfusion before dentoalveolar surgery are unclear. This study investigated the effect of prophylactic PLT transfusions on the incidence of postoperative bleeding (POB) in patients with thrombocytopenia and a PLT count ≤ 75*109/L.MethodsThe cohort in this retrospective study comprised 83 patients with thrombocytopenia ≤ 75*109/L who had undergone dentoalveolar surgery. Exclusion criteria were other coagulation deficiencies or medications that would affect hemostasis. In all, 144 teeth had been removed. POB events were extracted and compared between the group that had received prophylactic PLT transfusion before dentoalveolar surgery and the group that had not.ResultsPOB events were observed in 5 of 83 patients (6.0%) who had a median PLT count of 35*109/L before any transfusion. The group with no postoperative bleeding (NPOB) had a median PLT count of 34*109/L. Two (4.2%) of the 48 patients who had received prophylactic PLT transfusions before dentoalveolar surgery developed POB. Three (8.6%) of the 35 patients who had not received a transfusion experienced POB. The difference between these two groups was not significant (p = 0.646). When two or more teeth were removed in the same session, a significantly higher incidence of POB was observed (p = 0.042).ConclusionsOur data indicate that prophylactic PLT transfusions in thrombocytopenic patients with PLT counts ≤ 75*109/L do not reduce the incidence of POB after dentoalveolar surgery. However, caution is warranted when extracting multiple teeth in the same surgical session since we found this to be significantly associated with an increased risk of POB.

Early prediction of platelet recovery with immature platelet fraction in patients receiving hematopoietic stem cell transplantation.

Hematopoietic stem cell transplantation (HSCT) is pivotal in treating hematologic disorders, yet it poses the risk of post-transplantation pancytopenia. Prophylactic platelet transfusions are often administered to mitigate this risk. Utilizing practical markers, such as immature platelet fraction (IPF), to predict hematopoietic recovery in advance could reduce unnecessary prophylactic transfusions. Our prospective study, involving 53 HSCT patients at Taipei Veterans General Hospital between September 2022 and May 2023, utilized the Sysmex XN analyzer to assess peripheral blood cell parameters. We investigated whether IPF could predict platelet recovery early, determined the optimal cut-off value, and compared platelet usage. Neutrophil and platelet engraftment occurred 10 (median; range: 10-12) and 15 (median; range: 15-18) days post-HSCT. Notably, 71.7% of patients exhibited an IPF increase exceeding 2% before platelet recovery. The optimal cut-off IPF on day 10 for predicting platelet recovery within five days was 2.15% (specificity 0.89, sensitivity 0.65). On average, patients received 3.89 units of post-transplantation platelet transfusion. Our results indicate that IPF serves as a predictive marker for platelet engraftment, peaking before the increase in platelet count. This insight aids clinicians in assessing the need for prophylactic platelet transfusions. Integrating reference IPF values alongside platelet counts enhances the accuracy of evaluating a patient's hematopoietic recovery status. Anticipating the timing of platelet recovery optimizes blood product usage and mitigates transfusion reaction risks.

Platelet transfusions in adult ICU patients with thrombocytopenia: A sub-study of the PLOT-ICU inception cohort study.

Platelet transfusions are frequently used in the intensive care unit (ICU), but current practices including used product types, volumes, doses and effects are unknown. Sub-study of the inception cohort study 'Thrombocytopenia and Platelet Transfusions in the ICU (PLOT-ICU)', including acutely admitted, adult ICU patients with thrombocytopenia (platelet count <150 × 109/L). The primary outcome was the number of patients receiving platelet transfusion in ICU by product type. Secondary outcomes included platelet transfusion details, platelet increments, bleeding, other transfusions and mortality. Amongst 504 patients with thrombocytopenia from 43 hospitals in 10 countries in Europe and the United States, 20.8% received 565 platelet transfusions; 61.0% received pooled products, 21.9% received apheresis products and 17.1% received both with a median of 2 (interquartile range 1-4) days from admission to first transfusion. The median volume per transfusion was 253 mL (180-308 mL) and pooled products accounted for 59.1% of transfusions, however, this varied across countries. Most centres (73.8%) used fixed dosing (medians ranging from 2.0 to 3.5 × 1011 platelets/transfusion) whilst some (mainly in France) used weight-based dosing (ranging from 0.5 to 0.7 × 1011 platelets per 10 kg body weight). The median platelet count increment for a single prophylactic platelet transfusion was 2 (-1 to 8) × 109/L. Outcomes of patients with thrombocytopenia who did and did not receive platelet transfusions varied. Among acutely admitted, adult ICU patients with thrombocytopenia, 20.8% received platelet transfusions in ICU of whom most received pooled products, but considerable variation was observed in product type, volumes and doses across countries. Prophylactic platelet transfusions were associated with limited increases in platelet counts.

Why might cord blood be a better source of platelets for transfusion to neonates?

Thrombocytopenia (defined as a platelet count <150×109/L) is a common condition in preterm neonates and may occur in 18-35% of all infants admitted to the Neonatal Intensive Care Unit (NICU). Neonatal platelet functionality in terms of reactivity is often described as reduced compared to adults, even in healthy, term neonates. However, this platelet "hyporeactivity" does not correspond to a global functional impairment of the normal delicately balanced neonatal hemostatic system. The extent to which neonatal thrombocytopenia and platelet hyporeactivity contribute to the bleeding risk in preterm neonates remains unknown. Prophylactic platelet transfusions are often administered to them to reduce the risk of bleeding. However, recent literature indicates that adopting a higher platelet transfusion threshold than a lower one results in significantly higher death rates or major bleeding and can be harmful. Although the mechanism by which this occurs is not entirely clear, a mismatch between adult transfused platelets and the neonatal hemostatic system, as well as volume overload, are speculated to be potentially involved. Therefore, future research should consider novel transfusion products that may be more suitable for premature neonates. Blood products derived from umbilical cord blood (UCB) are promising, as they might perfectly match neonatal blood features. Here, we discuss the current knowledge about UCB-derived products, focusing on UCB-derived platelet concentrates and their potential for future clinical application. We will discuss how they may overcome the potential risks of transfusing adult-derived platelets to premature infants while maintaining efficacy.

Implementing evidence-based restrictive neonatal intensive care unit platelet transfusion guidelines.

Platelet transfusions are life-saving treatments for specific populations of neonates. However, recent evidence indicates that liberal prophylactic platelet transfusion practices cause harm to premature neonates. New efforts to better balance benefits and risks are leading to the adoption of more restrictive platelet transfusion guidelines in neonatal intensive care units (NICU). Although restrictive guidelines have the potential to improve outcomes, implementation barriers exist. We postulate that as neonatologists become more familiar with the data on the harm of liberal platelet transfusions, enthusiasm for restrictive guidelines will increase and barriers to implementation will decrease. Thus, we focused this educational review on; (1) the adverse effects of platelet transfusions to neonates, (2) awareness of platelet transfusion "refractoriness" in thrombocytopenic neonates and its association with poor outcomes, and (3) the impetus to find alternatives to transfusing platelets from adult donors to NICU patients.

Improving platelet function following prophylactic platelet transfusion in patients with hematological malignancies.

Platelet transfusion is a standard treatment to prevent bleeding in patients with hematological malignancies. Although transfusions can improve platelet count, their impact on platelet function remains controversial. We conducted flow cytometry to assess platelet function before and after transfusion and performed subgroup analyses to examine differences based on blood type, corrected count increment (CCI), and platelet microparticles. Overall, 50 patients who received prophylactic platelet transfusion were enrolled. CD42b expression increased, whereas CD41 expression decreased after transfusion. Apheresis platelets exhibited the lowest expression of PAC-1 and P-selectin when exposed to agonist stimulations. PAC-1 expression increased under high adenosine diphosphate (ADP) stimulation, while P-selectin expression increased under both high ADP and thrombin receptor-activating peptide stimulation. In the subgroup analysis, patients with a CCI >4500 and those with the same blood types exhibited a more significant increase in PAC-1 and P-selectin expression under agonist stimulation. When comparing apheresis platelets collected on different days, only the percentage of platelet-derived microparticles showed a significantincrease. Prophylactic transfusion improved platelet function. Platelet function significantly improved in patients with a CCI >4500, those with the same blood types as that of apheresis platelets, or those with platelet-derived microparticle levels <4.7%. No significant improvement in platelet function was noted after the transfusion of different blood types with acceptable compatibility or the transfusion of incompatible blood types. Our results suggest that transfusing platelets with the same blood type remains the optimal choice.

Chronic liver disease-associated severe thrombocytopenia in Spain: Results from a retrospective study using machine learning and natural language processing

BackgroundPatients with chronic liver disease (CLD) often develop thrombocytopenia (TCP) as a complication. Severe TCP (platelet count<50×109/L) can increase morbidity and complicate CLD management, increasing bleeding risk during invasive procedures. ObjectivesTo describe the real-world scenario of CLD-associated severe TCP patients’ clinical characteristics. To evaluate the association between invasive procedures, prophylactic treatments, and bleeding events in this group of patients. To describe their need of medical resource use in Spain. MethodsThis is a retrospective, multicenter study including patients who had confirmed diagnosis of CLD and severe TCP in four hospitals within the Spanish National Healthcare Network from January 2014 to December 2018. We analyzed the free-text information from Electronic Health Records (EHRs) of patients using Natural Language Processing (NLP), machine learning techniques, and SNOMED-CT terminology. Demographics, comorbidities, analytical parameters and characteristics of CLD were extracted at baseline and need for invasive procedures, prophylactic treatments, bleeding events and medical resources used in the follow up period. Frequency tables were generated for categorical variables, whereas continuous variables were described in summary tables as mean (SD) and median (Q1–Q3). ResultsOut of 1,765,675 patients, 1787 had CLD and severe TCP; 65.2% were male with a mean age of 54.7 years old. Cirrhosis was detected in 46% (n=820) of patients and 9.1% (n=163) had hepatocellular carcinoma. Invasive procedures were needed in 85.6% of patients during the follow up period. Patients undergoing procedures compared to those patients without invasive procedures presented higher rates of bleeding events (33% vs 8%, p<0.0001) and higher number of bleedings. While prophylactic platelet transfusions were given to 25.6% of patients undergoing procedures, TPO receptor agonist use was only detected in 3.1% of them. Most patients (60.9%) required at least one hospital admission during the follow up and 14.4% of admissions were due to bleeding events with a hospital length of stay of 6 (3, 9) days. ConclusionsNLP and machine learning are useful tools to describe real-world data in patients with CLD and severe TCP in Spain. Bleeding events are frequent in those patients who need invasive procedures, even receiving platelet transfusions as a prophylactic treatment, increasing the further use of medical resources. Because that, new prophylactic treatments that are not yet generalized, are needed.

Assessment of the importance of platelet transfusion in patients with severe dengue: a systematic review

Introduction: Dengue is one of the most important vector-borne viral diseases in subtropical and tropical regions. The World Health Organization (WHO) 2009 classified dengue into three groups: dengue without alarm signs, dengue with alarm signs, and severe dengue. According to the type of dengue, various managements have been proposed. The authors suggest that a predictive factor to avoid a poor prognosis in this disease is to keep platelet levels stable in the patient to prevent a fatal outcome. The aim of this paper is to analyze the efficacy of transfusion of platelet agents in the outcome of patients with severe dengue and thrombocytopenia. Material and methods: A bibliographic search was carried out in the Medline, OVID, and Scielo databases from January 1, 2008, to April 31, 2023, using the MeSH terms. Results: 7 articles were included in the systematic review. A wide range in age was found (18 to 79 years). A minimal number of studies detail the comorbidities of patients in their enrollment. Regarding platelet transfusion, the average number of platelet units used in the transfusion case was 5 (2 - 14). Transfusions of ABO identical and compatible pooled platelets transfusion were found to be more successful in increasing platelets. Almost all of the patients included in the studies had platelets &lt;20,000 at enrollment. One study found a significant increase in platelets after transfusion, while the rest did not find it compelling. No mortality associated with platelet transfusion was recorded. Conclusions: Prophylactic platelet transfusion is not recommended as a routine measure in patients with severe dengue and thrombocytopenia. The uncertainty highlights need to reach a specific consensus establishing the appropriate indications for platelet transfusion and what type of patients with dengue virus would be beneficial.

Fibrinogen contribution to clot strength in patients with sepsis and hematologic malignancies and thrombocytopenia—a prospective, single-center, analytical, cross-sectional study

BackgroundPatients with hematological malignancies (HM) frequently present thrombocytopenia and higher risk of bleeding. Although transfusion is associated with higher risk of adverse events and poor outcomes, prophylactic transfusion of platelets is a common practice to prevent hemorrhagic complications. Thromboelastometry has been considered a better predictor for bleeding than isolated platelet counts in different settings. In early stages of sepsis, hypercoagulability may occur due to higher fibrinogen levels. ObjectivesTo evaluate the behavior of coagulation in patients with HM who develop sepsis and to verify whether a higher concentration of fibrinogen is associated with a proportional increase in maximum clot firmness (MCF) even in the presence of severe thrombocytopenia. MethodsWe performed a unicentric analytical cross-sectional study with 60 adult patients with HM and severe thrombocytopenia, of whom 30 had sepsis (sepsis group) and 30 had no infections (control group). Coagulation conventional tests and specific coagulation tests, including thromboelastometry, were performed. The main outcome evaluated was MCF. ResultsHigher levels of fibrinogen and MCF were found in sepsis group. Both fibrinogen and platelets contributed to MCF. The relative contribution of fibrin was significantly higher (60.5 ± 12.8% vs 43.6 ± 9.7%; P < .001) and that of platelets was significantly lower (39.5 ± 12.8% vs 56.4 ± 9.7%; P < .001) in the sepsis group compared with the control group. ConclusionPatients with sepsis and HM presented higher concentrations of fibrinogen than uninfected patients, resulting in greater MCF amplitudes even in the presence of thrombocytopenia.

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.

Tranexamic Acid to Prevent Bleeding in Patients with Hematologic Malignancies and Severe Thrombocytopenia (TREATT trial). a Randomized Placebo-Controlled Trial

Conclusions LJE &amp; ZM and EMW &amp; SJS contributed equally Patients undergoing treatment for hematologic malignancies continue to have a high burden of clinically significant bleeding (WHO grade 2 or above) despite receiving prophylactic platelet transfusions (43% in TOPPS trial, NEJM 2013). One potential approach to reduce the burden of bleeding is antifibrinolytic therapy, which has been shown to reduce bleeding and transfusion needs in patients undergoing surgery. The Trial to EvaluAte Tranexamic acid therapy in Thrombocytopenia (TREATT) is a double-blind randomized controlled trial evaluating the safety and efficacy of tranexamic acid (TXA) in patients with hematologic malignancies with severe thrombocytopenia (EudraCT number 2014-001513-35). We enrolled adults with hematologic malignancies having intensive chemotherapy or a hematopoietic stem cell transplant (HSCT) who were expected to have severe thrombocytopenia (platelet count ≤10x10 9/L for ≥5 days) at 16 UK and 11 Australian sites. We stratified randomization by site. We randomized participants to receive TXA (1g iv or 1.5g orally) or placebo (saline or capsule/tablet) 8-hourly from when platelet count ≤30x10 9/L or as soon as possible if the platelet count was already ≤ 30x10 9/L (no later than 72 hours after start of chemotherapy or HSCT). We stopped treatment if the unsupported platelet count reached ≥ 30x10 9/L, thrombosis occurred, or patient had received 30 days treatment. Patients received red cell and platelet transfusions according to national transfusion guidelines. Bleeding assessments were performed by trained research staff (inpatients) or via a patient diary, with significant bleeding reported to clinicians (outpatients), using validated tools. The primary outcome was the proportion of participants who died or had bleeding of WHO Grade 2 or above from study day 1 ([D1], first day of treatment) to D30. We used marginal Cox proportional hazards regression modelling (adjusted for site to account for clustering) to compare the two arms. Secondary outcomes included: safety outcomes (thrombotic events to D120) and use of blood components. Recruitment was affected by the COVID pandemic. We randomized 616 participants between June 2015 and February 2022 and included 597 in the modified intention to treat (mITT) analysis (platelet count ≤ 30x10 9/L for ≥ 1 day and no exclusion criteria). 16 participants were lost to follow-up prior to D120 (8 each arm); we included them in analyses if possible. Participant mean age was 55.6 years (SD12.2), 38.2% (236/616) were women, 42.9% (264/616) had AML, 35.1% (216/626) autograft and 25.4% (156/626) allograft. There was no evidence of a difference in the risk of death or ≥ Grade 2 bleeding between the TXA and placebo arms (HR 0.92; 95% CI: 0.67, 1.27; p-value 0.62). 29.0% (87/300) of participants in the TXA arm and 32.7% (97/297) in the placebo arm experienced ≥ Grade 2 bleeding, 66.0% (198/300) of participants in the TXA arm and 73.4% (218/297) in the placebo arm experienced ≥ Grade 1 bleeding. There was no evidence of a difference in the risk of death to D30 (HR 2.72; 95% CI 0.29, 25.36; p-value 0.38), however there were only 11 deaths overall. No patient died from bleeding (to D30) or thrombosis (to D120). The proportion of participants surviving to D30 without a platelet transfusion was 8.3% in TXA arm (95% CI: 5.4, 11.9), 6.4% placebo arm (95% CI 3.9, 9.7) (HR 0.92; 95% CI: 0.84, 1.02; p-value 0.10). The proportion of participants surviving to D30 without a red cell transfusion was 29.4% in TXA arm (95% CI: 24.1, 34.8), 20.5% placebo arm (95% CI 16.0, 25.4) (HR 0.82; 95% CI: 0.72, 0.93; p-value 0.003). 13 participants developed thrombosis to D120: 2 arterial events (1 each arm), and 11 venous (7 TXA arm, 4 placebo). 5 participants developed veno-occlusive disease (VOD) to D60 (3 TXA arm, 2 placebo). Additional secondary outcomes (Table 1). Prophylactic TXA had no effect on the incidence of WHO Grade ≥2 bleeding or death when given in addition to prophylactic platelet transfusions to severely thrombocytopenic patients undergoing therapy for hematologic malignancies. The results are consistent with those of a similar trial (A-TREAT, Blood 2022). These results indicate no role for TXA to prevent WHO ≥ Grade 2 bleeding in this patient population. There was no evidence that TXA increases the risk of venous or arterial thrombosis, or VOD, despite use for up to 30 days.

Pregnancy and Delivery Outcome Among Ladies with Glanzmann Thrombasthenia: A Report from Glanzmann Thrombasthenia Registry of Al-Madinah, Saudi Arabia

Introduction Glanzmann's thrombasthenia (GT) is an autosomal recessive bleeding disorder due to functional platelet defects impairing platelet aggregation. AlMadinah has reported the highest prevalence of GT globally, with a prevalence of 1:10,000. Pregnancy had been reported among ladies with GT with different outcomes. As a bleeding disorder, Pregnancy among ladies with GT carries a higher risk for bleeding either during pregnancy or intra and postpartum. Neonates have an increased risk for hemorrhage, either due to alloimmunization or they may carry the gene of GT. Many GT ladies got pregnant earlier when GT diagnosis was difficult, and they did not know their diagnosis; even after the diagnosis was possible, ceasing the menstrual cycle was not culturally acceptable. In this study, we are describing the pregnancies among GT ladies and their outcomes. Methods This is a report from the AlMadinah GT registry in the Madinah Hemophilia Comprehensive Care Center. The registry covers a period of 20 years and includes all patients with a confirmed diagnosis of GT. 136 GT patients were identified. 11 patients had no data available. A spreadsheet designed to collect detailed data about pregnancy, delivery, and neonates. Electronic and hard copy medical records have been accessed to collect data. Data was analyzed by the statistical package of social sciences (SPSS) version 23. The research and ethical committee approved the study. Results Twenty-eight pregnancies have been identified. The median age of mothers at the time of pregnancy was 30 ± 5.7 years (20 - 42 years). Mothers' Gravidity was 1-7 (median 2.5 ± 1.6), and parity was 1-6 (median 2 ±1.4). Five miscarriages (18%) identified occurred at the 17 th, 11 th, 13 th and 15 th gestational weeks. In contrast, 5 th one is not on record. Three miscarriages took place after moderate to severe vaginal bleeding. Mild to severe post-abortion bleeding was controlled with platelets transfusion, activated human recombinant factor 7 (rFVIIa), and tranexamic acid. Thirty-two bleeding episodes occurred during 16 pregnancies, with 1-5 bleeding episodes per pregnancy (Median of 2 episodes). Seven (22%) bleeding episodes were vaginal bleeds, while 25 (78%) were GT-related bleeds such as gum bleeding or epistaxis. Two patients must undergo plasma exchange and be on steroids due to alloimmunization development during pregnancy. Delivery occurred at the gestational age of 34-40 weeks (median 38 ± 2 weeks). Sixteen (70%) deliveries were vaginal, and 7(30%) were cesarean sections. The indications for cesarean sections were family request in 4 cases, fetal distress in two instances, and precautional section in one case. Prophylactic platelets transfusion had given pre-delivery on four occasions, rFVIIa on 4, and a combination of rFVIIa and platelets transfusion on six occasions. Tranexamic acid was used in all cases. Ten deliveries were conducted with no prophylaxis. Post-partum hemorrhage (PPH) occurred in 18 (64%) cases, 13 (72%) cases of primary PPH, and 5 (28%) cases of secondary PPH. We could not find a correlation between pre-delivery prophylaxes and PPH (P=0.2). PPH had controlled successfully with platelets transfusion and rFVIIa though red blood cell transfusion was needed on eight occasions. Twenty-eight pregnancies produced 24 babies (13 girls and 11 boys). Four babies had bleeding (2 intracranial hemorrhages, one subdural hematoma, and one gum oozing), and 9 had alloimmunization with mild to severe thrombocytopenia. Of all babies tested for GT, 6 of them were GT. Conclusions Pregnancy among ladies with GT carries a higher risk of bleeding. Management of pregnancy in women with GT has to be in a Multidisciplinary approach. The high rate of PPH among GT ladies makes it essential to treat it promptly. Pregnancy among ladies with GT should be studied in multi-centers sitting to learn more about clinical courses and management.

Updates in the Management of Dengue Shock Syndrome: A Comprehensive Review.

Dengue is a very serious public health problem that can manifest a wide range of symptoms from asymptomatic to fatal conditions, such as dengue shock syndrome (DSS). It is a life-threatening mosquito-borne viral infection widely spread in tropical areas. Dengue virus transmission occurs from an infected Aedes mosquito to humans. Various factors are responsible for the occurrence of the disease, such as viral load, age of the host, immune status of the host, and genetic variability. Dengue infection occurs in three phases: febrile, critical, and recovery. The febrile phase lasts for seven daysand manifests symptoms such as high-grade fever, headache, arthralgia, and backache, andin some cases, the upper respiratory tract and gastrointestinal tract are also involved. Severe dengue is characterized by endothelial dysfunction that causes vascular permeability and plasma leakage. The fundamental mechanisms of these immune pathologies are not yet known. Dengue manifests various complications such as dengue encephalopathy, encephalitis, stroke, ocular involvement, acute transverse myelitis, myalgia, and cerebellar syndrome, but the most commonly seen is liver involvement. Dengue is managed supportively because there are no proven curative treatments. The cornerstone of care during the critical period of dengue is prudent fluid resuscitation. The first fluid of preference is a crystalloid. Prophylactic transfusion of platelets is not advised. The occurrence of four antigenically different dengue virus serotypes, each able to elicit a cross-reactive and disease-enhancing antibody response against the other three serotypes, has made the creation of the dengue vaccine a difficult undertaking. The development of a dengue vaccine has faced significant challenges due to a lack of the best animal models and a variety of immunological conditions in people, particularly in endemic locations. Dengvaxia is a live attenuated vaccine, which was developed by Sanofi. It is made up of four chimeric vaccine viruses produced by Vero cells.

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.

Prophylactic Platelet Transfusion: Is There Evidence of Benefit, Harm, or No Effect?

The optimal use of prophylactic platelet transfusion remains uncertain in a number of clinical scenarios. Platelet count thresholds have been established in patients with hematologic malignancies, yet thresholds backed by scientific data are limited or do not exist for many patient populations. Clinical scenarios involving transfusion thresholds for thrombocytopenic patients with critical illness, need for surgery or invasive procedures, or those involving specials populations like children and neonates, lack clear evidence for discerning favorable outcomes without undue risk related to platelet transfusion. In addition, while prophylactic platelet transfusions are administered with the goal of enhancing hemostasis, increasing evidence supports critical nonhemostatic roles for platelets related to innate and adaptive immunity, inflammation, and angiogenesis, which may impact patient responses and outcomes. Here we review several recent studies conducted in adult or pediatric patients that highlight the limitations in our current understanding of prophylactic platelet transfusion. Together, these studies underscore the need for additional research, especially in the form of robust randomized clinical trials and integrating additional parameters beyond the platelet count. Future research at the basic, translational, and clinical levels will best define the optimal role for prophylactic transfusion across the lifespan and its broader impact on health and disease.

Platelet transfusions and predictors of bleeding in patients with myelodysplastic syndromes.

This study aimed to describe the burden of thrombocytopenia, supportive care practices, bleeding complications and predictors of bleeding in MDS patients within a large Australian hospital network, to better understand the use and effectiveness of platelet transfusions in MDS. A retrospective cohort study of patients aged ≥18 years with MDS, chronic myelomonocytic leukaemia or MDS/myeloproliferative overlap neoplasm admitted from 2016 to 2018 was conducted. Data were obtained from hospital medical records. One hundred seventy-nine patients (median age 78 years, 61.5% male) were identified. The median platelet count at first admission was 90 × 109 /L. Twenty-eight (15.6%) patients had severe thrombocytopenia (platelet count <20 × 109 /L), of whom nine (32.1%) received prophylactic platelet transfusions, five (17.9%) received tranexamic acid (TXA), seven (25%) received both platelet transfusions and TXA, and seven (25%) received no treatment. Bleeding events requiring hospitalisation occurred in 20 (11.2%) patients. Bleeding was not predicted by presenting platelet count, TXA use, platelet transfusion or anticoagulant/antiplatelet therapies. Three patients died of bleeding, at varying platelet counts (18, 38 and 153 × 109 /L). Thrombocytopenia is common in MDS. Although guidelines recommend otherwise, prophylactic platelet transfusions were commonly used for severe thrombocytopenia. Despite the majority of patients receiving platelet transfusions and/or TXA, 11% developed major bleeding occurring at a wide range of platelet counts.

Association between the development of bronchopulmonary dysplasia and platelet transfusion: a protocol for a systematic review and meta-analysis.

There is a lack of consensus on the management of thrombocytopenia in preterm infants, and the threshold for prophylactic platelet transfusion varies widely among clinicians and institutions. Reports in animal models suggested that platelets may play a relevant role in lung alveolarization and regeneration. Bronchopulmonary dysplasia (BPD) is a severe respiratory condition with a multifactorial origin that affects infants born at the early stages of lung development. Recent randomized controlled trials on the platelets count threshold for prophylactic transfusions in preterm infants with thrombocytopenia suggest that a higher exposition to platelet transfusion may increase the risk of BPD. Here, we report a protocol for a systematic review, which aims to assist evidence-based clinical practice and clarify if the administration of platelet products may be associated with the incidence of BPD and/or death in preterm infants. MEDLINE, Embase, Cochrane databases, and sources of gray literature for conference abstracts and trial registrations will be searched with no time or language restrictions. Case-control studies, cohort studies, and nonrandomized or randomized trials that evaluated the risk for BPD and/or death in preterm infants exposed to platelet transfusion will be included. Data from studies that are sufficiently similar will be pooled as appropriate. Data extraction forms will be developed a priori. Observational studies and nonrandomized and randomized clinical trials will be analyzed separately. Odds ratio with 95% confidence interval (CI) for dichotomous outcomes and the mean difference (95% CI) for continuous outcomes will be combined. The expected heterogeneity will be accounted for using a random-effects model. Subgroup analysis will be performed based on a priori-determined covariate of interest. In case of sufficient homogeneity of interventions and outcomes evaluated, results from subgroups of studies will be pooled together in a meta-analysis. This systematic review will investigate the association of BPD/death with platelet components administration in preterm infants, and, consequently, it will provide reliable indications for the evidence-based management of premature patients with thrombocytopenia.