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International Journal of Molecular... Nov 2023There have been relatively few studies revealing a decreased platelet count in chronic kidney disease (CKD). Although this hematological abnormality is not as well...
There have been relatively few studies revealing a decreased platelet count in chronic kidney disease (CKD). Although this hematological abnormality is not as well documented as renal anemia, platelet functions are altered in the uremic environment and there is an increased risk of bleeding. The aim of this study was to assess the effectiveness of the administration of platelet concentrate in CKD based on how patient prognosis was influenced by platelet transfusion therapy. The study monitored 104 patients with CKD and thrombocytopenia who received platelet transfusion during their hospitalization in the period from 2015 to 2021. The complete blood cell count, serum urea and creatinine, and inflammatory status were tested upon admission. The number of transfused platelet units were considered for each patient. A Kruskal-Wallis H test showed that for one transfused platelet unit, the distribution of the number of platelets (×10/µL) was the same across the categories of associated diagnoses, which was seen as possible risk factors for thrombocytopenia, including liver cirrhosis and urosepsis. With a single exception, all patients exceeded the critical threshold of 20 × 10/µL and 14 patients remained under 50 × 10/µL. Even though our patients exceeded the critical threshold of platelet numbers, in patients with multiple comorbidities, severe, uncontrolled hemorrhages could not be prevented in 4.83% of cases.
Topics: Humans; Platelet Transfusion; Thrombocytopenia; Blood Platelets; Platelet Count; Hemorrhage; Renal Insufficiency, Chronic
PubMed: 37958881
DOI: 10.3390/ijms242115895 -
BioRxiv : the Preprint Server For... Nov 2023Platelet transfusions are increasing with advances in medical care. Based on FDA criteria, platelet units are assessed by measures; however, it is not known how...
BACKGROUND
Platelet transfusions are increasing with advances in medical care. Based on FDA criteria, platelet units are assessed by measures; however, it is not known how platelet processing and storage duration affect function . To address this, we developed a novel platelet transfusion model that meets FDA criteria adapted to mice, and transfused fresh and stored platelets are detected in clots .
STUDY DESIGN AND METHODS
Platelet units stored in mouse plasma were prepared using a modified platelet rich plasma collection protocol. Characteristics of fresh and stored units, including pH, cell count, measures of activity, including activation and aggregation, and post-transfusion recovery (PTR), were determined. Lastly, a tail transection assay was conducted using mice transfused with fresh or stored units, and transfused platelets were identified by confocal imaging.
RESULTS
Platelet units had acceptable platelet and white cell counts and were negative for bacterial contamination. Fresh and 1-day stored units had acceptable pH; the platelets were activatable by thrombin and ADP, aggregable with thrombin, had acceptable PTR, and were present in clots of recipients after tail transection. In contrast, 2-day stored units had clinically unacceptable quality.
DISCUSSION
We developed mouse platelets for transfusion analogous to human platelet units using a modified platelet rich plasma collection protocol with maximum storage of 1 day for an "old" unit. This provides a powerful tool to test how process modifications and storage conditions affect transfused platelet function .
PubMed: 38014145
DOI: 10.1101/2023.11.10.566577 -
Immunological platelet transfusion refractoriness: current insights from mechanisms to therapeutics.Platelets Dec 2024Although there have been tremendous improvements in the production and storage of platelets, platelet transfusion refractoriness (PTR) remains a serious clinical issue... (Review)
Review
Although there have been tremendous improvements in the production and storage of platelets, platelet transfusion refractoriness (PTR) remains a serious clinical issue that may lead to various severe adverse events. The burden of supplying platelets is worsened by rising market demand and limited donor pools of compatible platelets. Antibodies against platelet antigens are known to activate platelets through FcγR-dependent or complement-activated channels, thereby rapidly eliminating foreign platelets. Recently, other mechanisms of platelet clearance have been reported. The current treatment strategy for PTR is to select appropriate and compatible platelets; however, this necessitates a sizable donor pool and technical assistance for costly testing. Consolidation of these mechanisms should be of critical significance in providing insight to establish novel therapeutics to target immunological platelet refractoriness. Therefore, the purposes of this review were to explore the modulation of the immune system over the activation and elimination of allogeneic platelets and to summarize the development of alternative approaches for treating and avoiding alloimmunization to human leukocyte antigen or human platelet antigen in PTR.
Topics: Humans; Platelet Transfusion; Blood Platelets; Thrombocytopenia; Antigens, Human Platelet; HLA Antigens
PubMed: 38314765
DOI: 10.1080/09537104.2024.2306983 -
Annals of Laboratory Medicine Jan 2024Rotational thromboelastometry (ROTEM; TEM International GmbH, Munich, Germany) is a global coagulation test that guides evidence-based platelet transfusion in trauma...
BACKGROUND
Rotational thromboelastometry (ROTEM; TEM International GmbH, Munich, Germany) is a global coagulation test that guides evidence-based platelet transfusion in trauma patients. We evaluated ROTEM parameters for predicting mid-term (five days) platelet transfusion in trauma patients.
METHODS
Maximum clot firmness and clot amplitudes after 5, 10, and 15 mins (A5, A10, and A15, respectively) of fibrin-specific ROTEM (FIBTEM) and extrinsically activated ROTEM (EXTEM) were retrospectively collected from 82 hospitalized, stable, non-bleeding trauma patients after successful initial resuscitation. Platelet-specific ROTEM (PLTEM) was calculated by subtracting FIBTEM from EXTEM. Platelet transfusions were reviewed for five days after ROTEM.
RESULTS
The areas under the curve for FIBTEM, EXTEM, and PLTEM predicting platelet concentrate transfusion of >12 U at mid-term were 0.915-0.923, 0.878-0.896, and 0.551-0.735, respectively. FIBTEM and EXTEM parameters were comparable to those of fibrinogen, fibrin/fibrinogen degradation products, D-dimer, and antithrombin III. Strong correlations (>0.7) were noted between platelet count and EXTEM (A5, A10, and A15) or PLTEM (A5), platelet function (per platelet count) and EXTEM (A10 and A15), and fibrinogen levels and all FIBTEM parameters.
CONCLUSIONS
FIBTEM and EXTEM can reliably predict mid-term platelet transfusion in trauma patients. FIBTEM, EXTEM, and PLTEM parameters correlate with conventional coagulation tests (platelets and fibrinogen).
Topics: Humans; Thrombelastography; Platelet Transfusion; Retrospective Studies; Fibrinogen; Fibrin
PubMed: 37665288
DOI: 10.3343/alm.2024.44.1.74 -
Archives of Disease in Childhood. Fetal... Dec 2023To assess the safety and feasibility of platelet transfusion through small-bore long lines used in the neonatal intensive care unit (NICU), including double-lumen...
OBJECTIVE
To assess the safety and feasibility of platelet transfusion through small-bore long lines used in the neonatal intensive care unit (NICU), including double-lumen umbilical venous catheters (UVCs) and 24 G and 28 G peripherally inserted central catheters (PICCs).
DESIGN
Prospective in vitro controlled study.
SETTING
Blood transfusion service laboratory.
METHODS
In vitro platelet transfusions were set up as per NICU practice. Transfusion line pressure was monitored. Post-transfusion swirling, presence of aggregates, pH analysis and automated cell count in vitro activation response by flow cytometry assessing CD62P expression were assessed.
MAIN OUTCOME MEASURES
All transfusions completed successfully. The rate of infusion was reduced in 5 of 16 transfusions through 28 G lines due to 'pressure high' alarms. There was no difference in swirling values or transfusion aggregate formation, CD62P expression levels, platelet count, platelet distribution width, mean platelet volume, plateletcrit or platelet to large cell ratio across transfusions post-transfusion.
CONCLUSIONS
This study showed that in vitro platelet transfusion performed through 24 G and 28 G neonatal PICC lines and double-lumen UVCs is non-inferior to 24 G short cannulas, using outcome measures of platelet clumping, platelet activation and line occlusion. This suggests that where available these lines can be used if necessary for platelet transfusion.
Topics: Infant, Newborn; Humans; Platelet Transfusion; Intensive Care Units, Neonatal; Prospective Studies; Feasibility Studies; Catheters
PubMed: 37433587
DOI: 10.1136/archdischild-2023-325632 -
Seminars in Thrombosis and Hemostasis Sep 2023Heparin-induced thrombocytopenia (HIT) and vaccine-induced immune thrombotic thrombocytopenia (VITT) are highly prothrombotic (thrombosis frequency ≥50%). Both are... (Review)
Review
Heparin-induced thrombocytopenia (HIT) and vaccine-induced immune thrombotic thrombocytopenia (VITT) are highly prothrombotic (thrombosis frequency ≥50%). Both are caused by platelet-activating anti-platelet factor 4 (PF4) antibodies, forming PF4/IgG-containing immune complexes that engage platelet FcγIIa receptors, producing strong platelet activation. In HIT, heparin crosslinks several PF4 molecules, whereas in VITT, anti-PF4 antibodies alone crosslink PF4. Sufficient levels of circulating anti-PF4 antibodies are needed to create the pathogenic immune complexes on platelet surfaces; this explains why certain serum (plasma)-based assays are highly sensitive for detecting HIT/VITT antibodies. Accordingly, HIT and VITT are "clinical-pathological" disorders, that is, positive testing for such antibodies-together with a compatible clinical picture-is integral for diagnosis. Heparin (low concentrations) HIT antibody-induced platelet activation, but platelet activation by VITT sera is usually by heparin. For both HIT and VITT, high sensitivity (>99% and >95%, respectively) characterizes PF4-dependent enzyme immunoassays (EIAs) and PF4-enhanced platelet activation assays; in contrast, certain rapid immunoassays have high sensitivity for HIT (>90-97%) but poor sensitivity (<25%) for VITT. HIT and VITT antibodies are directed at distinct sites on PF4: solid-phase EIAs and platelet activation assays are indifferent to these distinct antigen targets, but rapid immunoassays are not. We discuss a conceptual model where PF4 is viewed as a "globe," with the heparin-binding site the "equator"; in this model, HIT antibodies are primarily directed at antigen site(s) at the north and south "poles" of PF4 (formed when PF4 binds to heparin), whereas VITT antibodies recognize sites on the equator.
Topics: Humans; Antigen-Antibody Complex; Thrombocytopenia; Heparin; Purpura, Thrombocytopenic, Idiopathic; Thrombosis
PubMed: 36455619
DOI: 10.1055/s-0042-1758818 -
Hematology (Amsterdam, Netherlands) Dec 2023In patients with tumors, inflammation, and blood disorders, hyperferritinemia has been associated with the severity of the underlying disease and is frequently...
BACKGROUND
In patients with tumors, inflammation, and blood disorders, hyperferritinemia has been associated with the severity of the underlying disease and is frequently accompanied by a co-occurring low platelet count or thrombocytopenia. Despite this, no established correlation has been identified between hyperferritinemia and platelet count. In this retrospective, double-center study, we sought to describe the prevalence and severity of thrombocytopenia in patients with hyperferritinemia.
STUDY AND DESIGN
A total of 901 samples were enrolled in this study, all of which had significantly high ferritin levels (>2000 μg/L) between January 2019 and June 2021. We analyzed the general distribution, incidence of thrombocytopenia in patients with hyperferritinemia, and the relationship between ferritin level and platelet count. -values < 0.05 were considered statistically significant.
RESULTS
The total incidence of thrombocytopenia in patients with hyperferritinemia was 64.7%. Hematological diseases were the most frequent cause of hyperferritinemia (43.1%), followed by solid tumors (29.5%) and infectious diseases (11.7%). Patients with thrombocytopenia (<150 × 10/L) had significantly higher ferritin levels than those with platelet counts exceeding 150 × 10/L, with median ferritin levels of 4011 and 3221 μg/L, respectively (< 0.001). Additionally, the results showed that the incidence of thrombocytopenia was higher in hematological patients with chronic transfusion than in those without chronic blood transfusions (93% vs 69%).
CONCLUSIONS
In conclusion, our results suggest that hematological diseases are the most common cause of hyperferritinemia and that patients with chronic blood transfusions are more susceptible to thrombocytopenia. Elevated ferritin levels may act as a trigger for thrombocytopenia.
Topics: Humans; Hyperferritinemia; Retrospective Studies; Prevalence; Thrombocytopenia; Anemia; Hematologic Diseases; Neoplasms; Ferritins
PubMed: 36971518
DOI: 10.1080/16078454.2023.2186047 -
Transfusion Oct 2023Mitochondria play a critical role in the production of cell energy and the regulation of cell death. Therefore, mitochondria orchestrate numerous cell effector...
BACKGROUND
Mitochondria play a critical role in the production of cell energy and the regulation of cell death. Therefore, mitochondria orchestrate numerous cell effector functions, including fine-tuning the immune system. While mitochondria are mainly found intracellularly, they can escape the confine of the cell during the process of extracellular vesicle release. Platelets patrol blood vessels to ensure vasculature integrity and to support the immune system. In blood, platelets are the primary source of circulating mitochondria. Activated platelets produce extracellular vesicles, including a subset of mitochondria-containing vesicles.
STUDY DESIGN AND METHODS
We characterized mitochondrial functions in platelet-derived extracellular vesicles, and examined whether they could impact the bioenergetics of cellular immune recipients using an extracellular flux analyzer to measure real-time bioenergetics.
RESULTS
We validated that extracellular vesicles derived from activated platelets contain the necessary mitochondrial machinery to respirate and generate energy. Moreover, neutrophils and monocytes efficiently captured platelet-derived extracellular vesicles, enhancing their mitochondrial fitness. This process required functional mitochondria from donor platelets, as it was abolished by the inactivation of extracellular mitochondria using mitochondrial poison.
DISCUSSION
Together, the data suggest that extracellular mitochondria produced by platelets may support other metabolic functions through transcellular bioenergetics.
Topics: Humans; Blood Platelets; Mitochondria; Energy Metabolism; Extracellular Vesicles; Exercise
PubMed: 37642274
DOI: 10.1111/trf.17524 -
Transfusion Dec 2023In 2018, platelet (PLT) additive solution-E (PAS-E) was introduced. The implementation of PAS-E was expected to diminish the number of allergic reactions in recipients...
INTRODUCTION
In 2018, platelet (PLT) additive solution-E (PAS-E) was introduced. The implementation of PAS-E was expected to diminish the number of allergic reactions in recipients following a PLT transfusion. Here, we evaluated the efficacy and safety of transfusions with PLTs stored in PAS-E.
STUDY DESIGN AND METHODS
After implementation of PAS-E, data were collected from 2 cohorts of patients with hematological disorders as well as oncology patients, receiving PLTs in PAS-E. A similar patient group in a recent RCT, receiving PLTs in plasma, was used as a historical control group for both cohorts. Endpoints were corrected count increments (CCIs), bleeding scores (only reported in cohort 1), and the incidence of adverse reactions.
RESULTS
In cohort 1, the mean 1-h CCI was 14.3 ± 6.9, and the 24-h CCI was 8.7 ± 5.6. In cohort 2, the 1-h CCI was 11.6 ± 7.8 and the 24-h CCI was 7.0 ± 6.1. In the control group, the 1-h CCI was 15.4 ± 5.5 and 24-h CCI 8.7 ± 4.8. Bleeding complications of WHO grade ≥2 occurred in 40% of patients in cohort 1 compared to 44% in plasma PCs. The incidence of adverse reactions was 1.2% in the two PAS-E cohorts, compared to 3.0% in plasma PCs. National hemovigilance data showed a significant reduction in allergic reactions with PAS-E PC transfusions as compared to plasma PCs with an odds ratio of 0.46 (CI 95% 0.37-0.58).
CONCLUSION
The CCIs of PLTs in PAS-E were decreased compared to plasma PCs, but clinically acceptable. Allergic transfusion reactions were decreased in PAS-E PCs compared to plasma PCs.
Topics: Humans; Blood Platelets; Platelet Transfusion; Blood Safety; Transfusion Reaction; Blood Preservation; Hypersensitivity
PubMed: 37909172
DOI: 10.1111/trf.17583 -
Cureus Oct 2023Ceftaroline is a fifth-generation cephalosporin that can be used for the treatment of serious infections caused by methicillin-resistant (MRSA). A rare adverse effect...
Ceftaroline is a fifth-generation cephalosporin that can be used for the treatment of serious infections caused by methicillin-resistant (MRSA). A rare adverse effect of ceftaroline therapy is thrombocytopenia. Our case involves a 45-year-old male with active intravenous drug usage who presented with persistent fever, lower back pain, and left elbow pain. His bloodcultures were found to be positive for MRSA. He was initially started on vancomycin; subsequently, the antibiotic was changed to daptomycin and ceftaroline, as vancomycin failed to clear the bacteremia. Seven days after initiation of ceftaroline, it was unintentionally discontinued by the electronic health record. Following its resumption two days later, the patient started having epistaxis accompanied by an acute drop in his platelet count from 422,000 cells/µL to less than 2,000 cells/µL. The ceftaroline therapy was discontinued, and he received a platelet transfusion. However, daptomycin was continued, resulting in successful resolution of his bacteremia. The patient's platelet count at discharge improved to 582,000 cells/µL. The patient was diagnosed with ceftaroline-induced thrombocytopenia, and it was added to his list of allergies.
PubMed: 38021885
DOI: 10.7759/cureus.47580