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Expert Review of Hematology 2023Immune thrombocytopenia [ITP] is a common bleeding disorder with an isolated platelet count of less than 100 × 10/L. (Review)
Review
INTRODUCTION
Immune thrombocytopenia [ITP] is a common bleeding disorder with an isolated platelet count of less than 100 × 10/L.
AREAS COVERED
Relevant literature from 2003 to 2022 was retrieved and reviewed from the Google Scholar search engine and PubMed database. Antibodies produced by autoreactive B lymphocytes and the phagocytic function of macrophages are considered the most critical factors in platelet destruction. Also, macrophages present the antigen to T lymphocytes and activate them. Follicular helper T-cells [TFH] play a role in stimulating, differentiating, and activating autoreactive B cells, while cluster of differentiation [CD]-8+ T plays a role in platelet destruction through apoptosis. The classical pathway of the complement system also causes platelet destruction. By inhibiting platelet production, low levels of thrombopoietin and an immune response against megakaryocytes in the bone marrow worsen thrombocytopenia.
EXPERT OPINION
T-cell subset changes and an increase in activated autoreactive B cells, in addition to the function of components of the innate immune system [the complement system, dendritic cells, and natural killer cells], play a critical role in the pathogenesis of the ITP. Accurate detection of these changes may lead to developing new therapeutic strategies and identifying better prognostic/diagnostic factors.
Topics: Humans; Purpura, Thrombocytopenic, Idiopathic; Blood Platelets; Thrombocytopenia; Platelet Count; Megakaryocytes
PubMed: 37668243
DOI: 10.1080/17474086.2023.2255750 -
Blood Transfusion = Trasfusione Del... Nov 2023Most public cord blood (CB) banks currently discard more than 80% of umbilical CB units not suitable for hemopoietic stem cell transplant due to low stem cell count....
BACKGROUND
Most public cord blood (CB) banks currently discard more than 80% of umbilical CB units not suitable for hemopoietic stem cell transplant due to low stem cell count. Although CB platelets, plasma, and red blood cells have been used for experimental allogeneic applications in wound healing, corneal ulcer treatment, and neonatal transfusion, no standard procedures for their preparation have been defined internationally.
MATERIALS AND METHODS
A network of 12 public CB banks in Spain, Italy, Greece, the UK, and Singapore developed a protocol to validate a procedure for the routine production of CB platelet concentrate (CB-PC), CB platelet-poor plasma (CB-PPP), and CB leukoreduced red blood cells (CB-LR-RBC) using locally available equipment and the commercial BioNest ABC and EF medical devices. CB units with >50 mL volume (excluding anticoagulant) and ≥150×10/L platelets were double centrifuged to obtain CB-PC, CB-PPP, and CB-RBC. The CB-RBC were diluted with saline-adenine-glucose-mannitol (SAGM), leukoreduced by filtration, stored at 2-6°C, and tested for hemolysis and potassium (K+) release over 15 days, with gamma irradiation performed on day 14. A set of acceptance criteria was pre-defined. This was for CB-PC: volume ≥5 mL and platelet count 800-1,200×10/L; for CB-PPP: platelet count <50×10/L; and for CB-LR-RBC: volume ≥20 mL, hematocrit 55-65%, residual leukocytes <0.2×10/unit, and hemolysis ≤0.8%.
RESULTS
Eight CB banks completed the validation exercise. Compliance with acceptance criteria was 99% for minimum volume and 86.1% for platelet count in CB-PC, and 90% for platelet count in CB-PPP. Compliance in CB-LR-RBC was 85.7% for minimum volume, 98.9% for residual leukocytes, and 90% for hematocrit. Compliance for hemolysis ≤0.8% decreased from 89.0 to 63.2% from day 0 to 15. K+ release increased from 3.0±1.8 to 25.0±7.0 mmol/L from day 0 to 15, respectively.
DISCUSSION
The MultiCord12 protocol was a useful tool to develop preliminary standardization of CB-PC, CB-PPP, and CB-LR-RBC.
Topics: Infant, Newborn; Humans; Hemolysis; Blood Banking; Erythrocytes; Blood Banks; Blood Platelets
PubMed: 37146297
DOI: 10.2450/BloodTransfus.492 -
Anaesthesia, Critical Care & Pain... Aug 2023
Topics: Humans; Platelet Transfusion; Thrombocytopenia; Platelet Count
PubMed: 37356619
DOI: 10.1016/j.accpm.2023.101271 -
Critical Care (London, England) Aug 2023Thrombocytopenia, hemorrhage and platelet transfusion are common in patients supported with venoarterial extracorporeal membrane oxygenation (VA ECMO). However, current... (Observational Study)
Observational Study
BACKGROUND
Thrombocytopenia, hemorrhage and platelet transfusion are common in patients supported with venoarterial extracorporeal membrane oxygenation (VA ECMO). However, current literature is limited to small single-center experiences with high degrees of heterogeneity. Therefore, we aimed to ascertain in a multicenter study the course and occurrence rate of thrombocytopenia, and to assess the association between thrombocytopenia, hemorrhage and platelet transfusion during VA ECMO.
METHODS
This was a sub-study of a multicenter (N = 16) study on transfusion practices in patients on VA ECMO, in which a retrospective cohort (Jan-2018-Jul-2019) focusing on platelets was selected. The primary outcome was thrombocytopenia during VA ECMO, defined as mild (100-150·10/L), moderate (50-100·10/L) and severe (< 50·10/L). Secondary outcomes included the occurrence rate of platelet transfusion, and the association between thrombocytopenia, hemorrhage and platelet transfusion, assessed through mixed-effect models.
RESULTS
Of the 419 patients included, median platelet count at admission was 179·10/L. During VA ECMO, almost all (N = 398, 95%) patients developed a thrombocytopenia, of which a significant part severe (N = 179, 45%). One or more platelet transfusions were administered in 226 patients (54%), whereas 207 patients (49%) suffered a hemorrhagic event during VA ECMO. In non-bleeding patients, still one in three patients received a platelet transfusion. The strongest association to receive a platelet transfusion was found in the presence of severe thrombocytopenia (adjusted OR 31.8, 95% CI 17.9-56.5). After including an interaction term of hemorrhage and thrombocytopenia, this even increased up to an OR of 110 (95% CI 34-360).
CONCLUSIONS
Thrombocytopenia has a higher occurrence than is currently recognized. Severe thrombocytopenia is strongly associated with platelet transfusion. Future studies should focus on the etiology of severe thrombocytopenia during ECMO, as well as identifying indications and platelet thresholds for transfusion in the absence of bleeding.
TRIAL REGISTRATION
This study was registered at the Netherlands Trial Registry at February 26th, 2020 with number NL8413 and can currently be found at https://trialsearch.who.int/Trial2.aspx?TrialID=NL8413.
Topics: Humans; Platelet Transfusion; Extracorporeal Membrane Oxygenation; Retrospective Studies; Hemorrhage; Thrombocytopenia
PubMed: 37605277
DOI: 10.1186/s13054-023-04612-5 -
Critical Care (London, England) Sep 2023Response to prophylactic platelet transfusion is suspected to be inconsistent in critically ill patients questioning how to optimize transfusion practices. This study... (Observational Study)
Observational Study
BACKGROUND
Response 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.
METHODS
This 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.
RESULTS
Poor 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.
CONCLUSIONS
In 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.
Topics: Humans; Hemorrhage; Platelet Transfusion; Thrombocytopenia; Prospective Studies; Critical Illness; Hematologic Neoplasms
PubMed: 37759268
DOI: 10.1186/s13054-023-04650-z -
The New England Journal of Medicine Aug 2023
Topics: Humans; Platelet Transfusion; Thrombocytopenia; Anemia; Leukopenia
PubMed: 37530839
DOI: 10.1056/NEJMc2307377 -
The New England Journal of Medicine Aug 2023
Topics: Humans; Platelet Transfusion; Thrombocytopenia; Anemia; Leukopenia
PubMed: 37530837
DOI: 10.1056/NEJMc2307377 -
The New England Journal of Medicine Aug 2023
Topics: Humans; Platelet Transfusion; Thrombocytopenia; Anemia; Leukopenia
PubMed: 37530838
DOI: 10.1056/NEJMc2307377 -
BMC Pharmacology & Toxicology Dec 2023To evaluate the efficacy and safety of thrombopoietin receptor agonists (TPO-RAs) in solid tumors with chemotherapy-induced thrombocytopenia (CIT). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To evaluate the efficacy and safety of thrombopoietin receptor agonists (TPO-RAs) in solid tumors with chemotherapy-induced thrombocytopenia (CIT).
METHODS
We conducted a comprehensive search of PubMed, FMRS, Cochrane Library, Web of Science, EMBASE, and ClinicalTrials.gov for randomized controlled trials (RCTs) reporting the efficacy and safety of TPO-RAs in solid tumors with CIT. The search was limited to articles published before April 30, 2022. Primary outcomes included chemotherapy dose reduction or delays, platelet transfusion, the incidence of grade 3 or 4 thrombocytopenia, and bleeding events. Secondary outcomes encompassed the incidence of platelet count > 400 × 10/L, adverse events (AEs), serious AEs, thrombosis, and mortality.
RESULTS
Our analysis encompassed six studies: five rigorous RCTs and one unique study comparing romiplostim to an observation group, involving a total of 489 patients. For primary outcomes, TPO-RAs significantly reduced the incidence of grade 3 or 4 thrombocytopenia (RR = 0.69, 95% CI: 0.52-0.91). After applying the Bonferroni correction for multiple comparisons, the significance of the reduction in grade 3 or 4 thrombocytopenia incidence persisted (P = 0.008). TPO-RAs showed no significant impact on chemotherapy dose reduction or delays (RR = 0.81, 95% CI: 0.65-1.01), platelet transfusion (RR = 1.04, 95% CI: 0.48-2.27), or bleeding events (RR = 0.50, 95% CI: 0.23-1.10). In terms of safety, there were no significant difference in the incidence of any AEs (RR = 0.98, 95% CI:0.92-1.04), serious AEs (RR = 0.79, 95% CI:0.45-1.40), thrombotic events (RR = 1.20, 95% CI:0.51-2.84) and mortality (RR = 1.15, 95% CI:0.55-2.41).
CONCLUSIONS
This meta-analysis suggests that TPO-RAs are generally well-tolerated. However, their efficacy in solid tumors with CIT appears limited, as they only demonstrate a reduction in the incidence of grade 3 or 4 thrombocytopenia.
Topics: Humans; Receptors, Thrombopoietin; Benzoates; Hydrazines; Pyrazoles; Neoplasms; Hemorrhage; Thrombocytopenia; Antineoplastic Agents
PubMed: 38041150
DOI: 10.1186/s40360-023-00707-5