Cold-stored platelets for acute bleeding in cardiac surgical patients: a narrative review.

PURPOSE: Cold-stored platelets (CSP) are an increasingly active topic of international research. They are maintained at 1-6 °C, in contrast to standard room-temperature platelets (RTP) kept at 20-24 °C. Recent evidence suggests that CSP have superior hemostatic properties compared with RTP. This narrative review explores the application of CSP in adult cardiac surgery, summarizes the preclinical and clinical evidence for their use, and highlights recent research. SOURCE: A targeted search of MEDLINE and other databases up to 24 February 2022 was conducted. Search terms combined concepts such as cardiac surgery, blood, platelet, and cold-stored. Searches of trial registries ClinicalTrials.gov and WHO International Clinical Trials Registry Platform were included. Articles were included if they described adult surgical patients as their population of interest and an association between CSP and clinical outcomes. References of included articles were hand searched. PRINCIPAL FINDINGS: When platelets are stored at 1-6 °C, their metabolic rate is slowed, preserving hemostatic function for increased storage duration. Cold-stored platelets have superior adhesion characteristics under physiologic shear conditions, and similar or superior aggregation responses to physiologic agonists. Cold-stored platelets undergo structural, metabolic, and molecular changes which appear to "prime" them for hemostatic activity. While preliminary, clinical evidence supports the conduct of trials comparing CSP with RTP for patients with platelet-related bleeding, such as those undergoing cardiac surgery. CONCLUSION: Cold-stored platelets may have several advantages over RTP, including increased hemostatic capacity, extended shelf-life, and reduced risk of bacterial contamination. Large clinical trials are needed to establish their potential role in the treatment of acutely bleeding patients.

RéSUMé: OBJECTIF: Les plaquettes conservées au froid (PCF) sont un sujet de recherche internationale de plus en plus populaire. Ces plaquettes sont maintenues à une température de 1-6 °C, contrairement aux plaquettes standard conservées à température ambiante (PTA), maintenues à 20­24 °C. Des données probantes récentes suggèrent que les PCF ont des propriétés hémostatiques supérieures aux PTA. Ce compte rendu narratif explore l'application de PCF en chirurgie cardiaque chez l'adulte, résume les données probantes précliniques et cliniques de leur utilisation, et met en évidence les recherches récentes. SOURCES: Une recherche ciblée dans MEDLINE et d'autres bases de données jusqu'au 24 février 2022 a été effectuée. Les termes de recherche combinaient des concepts en anglais tels que cardiac surgery, blood, platelet et cold-stored (soit chirurgie cardiaque, plaquette, et entreposage frigorifique). Des recherches dans les registres d'études ClinicalTrials.gov et le système d'enregistrement international des essais cliniques (ICTRP) de l'OMS ont été incluses. Les articles ont été inclus s'ils décrivaient des patient·es adultes de chirurgie en tant que population d'intérêt et une association entre les PCF et les issues cliniques. Les références des articles inclus ont fait l'objet d'une recherche manuelle. CONSTATATIONS PRINCIPALES: Lorsque les plaquettes sont conservées entre 1 et 6 °C, leur taux métabolique est ralenti, préservant la fonction hémostatique pour une durée d'entreposage accrue. Les plaquettes conservées au froid ont des caractéristiques d'adhésion supérieures dans des conditions de cisaillement physiologique et des réponses d'agrégation similaires ou supérieures aux agonistes physiologiques. Les plaquettes conservées au froid subissent des changements structurels, métaboliques et moléculaires qui semblent les « amorcer ¼ pour une activité hémostatique. Bien que préliminaires, les données probantes cliniques appuient la réalisation d'études comparant les PCF aux PTA chez la patientèle présentant des saignements liés aux plaquettes, tels que les personnes bénéficiant d'une chirurgie cardiaque. CONCLUSION: Les plaquettes conservées au froid peuvent présenter plusieurs avantages par rapport aux PTA, notamment une capacité hémostatique accrue, une durée de conservation prolongée et un risque réduit de contamination bactérienne. De grands essais cliniques sont nécessaires pour établir leur rôle potentiel dans le traitement de la patientèle en hémorragie aiguë.

TEG PlateletMapping assay results may be misleading in the presence of cold stored platelets.

BACKGROUND: Viscoelastic tests (VETs) are used widely to monitor hemostasis in settings such as cardiac surgery. There has also been renewed interest in cold stored platelets (CSPs) to manage bleeding in this setting. CSPs are reported to have altered hemostatic properties compared to room temperature platelets (RTPs), including activation of GPIIb/IIIa. We investigated whether the functional differences between CSP and RTP affected the performance of the PlateletMapping VET on the TEG 5000 and 6s analyzer. METHOD: Platelet concentrates were divided equally into CSP (stored at 4°C ± 2°C) and RTP (stored at 22°C ± 2°C) fractions. Whole blood was treated to induce platelet dysfunction (WBIPD) by incubating with anti-platelet drugs (1.0 µM ticagrelor and 10 µM aspirin) or by simulating cardiopulmonary bypass. WBIPD samples were then mixed with 20% by volume of CSPs or RTPs to model platelet transfusion before analysis using the PlateletMapping VET. RESULTS: Addition of CSPs to WBIPD increased the PlateletMapping MAFIBRIN and MAADP parameters with the TEG 5000 analyzer (both p < 0.0001 compared to addition of buffer alone). This effect was not observed with RTPs. The differential effect of CSPs on the MAFIBRIN corrected after pre-incubation with the GPIIb/IIIa antagonist tirofiban and was quantitatively less with the PlateletMapping test for the TEG 6s analyzer which contains the GPIIb/IIa antagonist abciximab. DISCUSSION: The PlateletMapping MAFIBRIN and MAADP test results may be misleadingly high with CSPs, particularly with the TEG 5000 analyzer, most likely due to constitutive activation of GPIIb/IIIa on CSPs during storage. TEG PlateletMapping results should be interpreted with caution following CSP transfusion.

A prospective evaluation of thromboelastometry (ROTEM) to identify acute traumatic coagulopathy and predict massive transfusion in military trauma patients in Afghanistan.

BACKGROUND: Hemorrhage is the leading cause of preventable trauma-related mortality and is frequently aggravated by acute traumatic coagulopathy (ATC). Viscoelastic tests such as rotational thromboelastometry (ROTEM) may improve identification and management of ATC. This study aimed to prospectively evaluate changes in ROTEM among combat casualties during the first 24 hours and compare the capabilities of our conventional clotting assay (international normalized ratio [INR], >1.2) to a proposed integrated ROTEM model (INR >1.2 with the addition of tissue factor pathway activation thromboelastometry [EXTEM] A5 ≤35 mm and/or EXTEM LI30 <97% on admission) to identify ATC and predict massive transfusion (MT). STUDY DESIGN AND METHODS: This was a prospective observational study of trauma patients treated in NATO hospitals in Afghanistan between January 2012 and June 2013. ROTEM (EXTEM, functional fibrinogen thromboelastometry, APTEM, EXTEM with the addition of a fibrinolysis inhibitor) was performed on admission and at 6 and 24 hours by a designated research team. Treatment teams did not have access to the ROTEM results. RESULTS: ROTEM values were available for 40 male casualties. The integrated ROTEM model classified 15% more patients with ATC than with INR alone and increased the detection of those that required MT by 22%. The sensitivity of the integrated ROTEM model to predict MT was higher than with INR greater than 1.2 (86% vs. 64%); however, specificity with both definitions for predicting MT was poor (38% vs. 50%, respectively). CONCLUSION: These observations support the importance of early identification of and intervention in ATC. Integrating ROTEM into the definition of ATC would increase detection of those requiring MT arguing for its use as an adjunct to clinical presentation in the ultimate decision to initiate MT.

Freedom from frozen: the first British military use of lyophilised plasma in forward resuscitation.

Prehospital use of blood products may improve survival. However, transfusion support with frozen blood components is logistically burdensome and constrains the configuration of prehospital medical support. Alternatives to frozen plasma, including lyophilised plasma, offer the potential for advanced resuscitation in the prehospital environment. We describe the successful use of lyophilised plasma by a UK patrol in the prehospital environment during operations in Afghanistan in 2012 and reflect on recent military experience and the need for further developments.

Therapeutic Utility of Cold-Stored Platelets or Cold-Stored Whole Blood for the Bleeding Hematology-Oncology Patient.

Bleeding related to thrombocytopenia is common in hematology-oncology patients. Platelets stored at room temperature (RTPs) are the current standard of care. Platelets stored in the cold (CSPs) have enhanced hemostatic function relative to RTPs. CSPs were reported to reduce bleeding in hematology-oncology patients. Recent studies have confirmed the enhanced hemostatic properties of CSPs. CSPs may be the better therapeutic option for this population. CSPs may also offer a preferable immune profile, reduced thrombotic risk, and reduced transfusion-transmitted infection risk. The logistical advantages of CSPs would improve outcomes for many patients who currently cannot access platelet transfusions.