During extracorporeal membrane oxygenation (ECMO), a delicate balance is required to titrate systemic anticoagulation to prevent thrombotic complications within the circuit and prevent bleeding in ...the patient. Despite focused efforts to achieve this balance, the frequency of both thrombotic and bleeding events remains high. Anticoagulation is complicated to manage in this population due to the complexities of the hemostatic system that are compounded by age-related developmental hemostatic changes, variable effects of the etiology of critical illness on hemostasis, and blood-circuit interaction. Lack of high-quality data to guide anticoagulation management in ECMO patients results in marked practice variability among centers. One aspect of anticoagulation therapy that is particularly challenging is the use of antithrombin (AT) supplementation for heparin resistance. This is especially controversial in the neonatal and pediatric population due to the baseline higher risk of bleeding in this cohort. The indication for AT supplementation is further compounded by the potential inaccuracy of the diagnosis of heparin resistance based on the standard laboratory parameters used to assess heparin effect. With concerns regarding the adverse impact of bleeding and thrombosis, clinicians and institutions are faced with making difficult, real-time decisions aimed at optimizing anticoagulation in this setting. In this clinically focused review, the authors discuss the complexities of anticoagulation monitoring and therapeutic intervention for patients on ECMO and examine the challenges surrounding AT supplementation given both the historical and current perspectives summarized in the literature on these topics.
The objective of this study was to review the history and current literature regarding the benefits and risks of warm fresh whole blood transfusion to include recent U.S. Army research from ...Afghanistan and Iraq. We also discuss current indications for its use as well as potential civilian applications for large-scale disasters.
The use of warm fresh whole blood currently only persists in emergency life-threatening scenarios when tested stored blood components are not available. Recent combat operations in Afghanistan and Iraq have redirected attention on the benefits and risks of warm fresh whole blood for life-threatening injuries in casualties.
Between March 2003 and July 2007, over 6000 units of warm fresh whole blood have been transfused in Afghanistan and Iraq by U.S. medical providers to patients with life-threatening traumatic injuries with hemorrhage. Preliminary results in approximately 500 patients with massive transfusion indicate that the amount of fresh warm whole blood transfused is independently associated with improved 48-hr and 30-day survival and the amount of stored red blood cells is independently associated with decreased 48-hr and 30-day survival for patients with traumatic injuries that require massive transfusion. Risks of warm fresh whole blood transfusion include the transmission of infectious agents and the potential for microchimerism.
For patients with life-threatening hemorrhage at risk for massive transfusion, if complete component therapy is not available or not adequately correcting coagulopathy, the risk:benefit ratio of warm fresh whole blood transfusion favors its use. In addition, recent evidence suggests that there is potential for warm fresh whole blood to be more efficacious than stored component therapy that includes stored red blood cells in critically ill patients requiring massive transfusion. Efforts must continue to improve the safety of warm fresh whole blood transfusion for patients when it is required in emergency situations. U.S. civilian disaster agencies are preparing guidelines for its use in massive casualty scenarios and prospective, randomized trials are about to start to determine whether stored warm fresh (<24 hrs) whole blood improves outcomes compared with standard stored component therapy.
Red blood cell (RBC) transfusion is common in critically ill, postsurgical, and posttrauma patients in whom both systemic inflammation and immune suppression are associated with adverse outcomes. RBC ...products contain a multitude of immunomodulatory mediators that interact with and alter immune cell function. These interactions can lead to both proinflammatory and immunosuppressive effects. Defining clinical outcomes related to immunomodulatory effects of RBCs in transfused patients remains a challenge, likely due to complex interactions between individual blood product characteristics and patient‐specific risk factors. Unpacking these complexities requires an in‐depth understanding of the mechanisms of immunomodulatory effects of RBC products. In this review, we outline and classify potential mediators of RBC transfusion‐related immunomodulation and provide suggestions for future research directions.
Whole blood: back to the future Spinella, Philip C; Cap, Andrew P
Current opinion in hematology,
11/2016, Volume:
23, Issue:
6
Journal Article
We present data comparing whole blood with blood components and summarize the data that support increased availability of whole blood for patients with life-threatening bleeding.
Recent data indicate ...that whole-blood transfusion is associated with improved or comparable survival compared with resuscitation with blood components. These data complement randomized controlled trials indicating that platelet-containing blood products stored at 4 °C have superior hemostatic function, compared with platelet-containing blood products at 22 °C. Whole blood is rarely available in civilian hospitals and, thus, is rarely transfused into patients with hemorrhagic shock. Misconceptions that whole blood must be ABO specific, that whole blood cannot be leukoreduced and maintain platelets, and that cold storage causes loss of platelet function have limited its availability. Understanding that these barriers are not insurmountable will improve the availability of whole blood and facilitate its use. In addition, there are logistical advantages of whole-blood-based resuscitation, as compared with component therapy, for hemorrhagic shock.
Low titer Group O whole blood stored for up to 21 days at 4 °C merits further study to compare its efficacy and safety with current resuscitation approaches for patients with life-threatening bleeding.
To assess the impact of antifibrinolytics in children with life-threatening hemorrhage.
Secondary analysis of the MAssive Transfusion epidemiology and outcomes In Children study dataset, a ...prospective observational study of children with life-threatening bleeding events.
Twenty-four children's hospitals in the United States, Canada, and Italy.
Children 0-17 years old who received greater than 40 mL/kg of total blood products over 6 hours or were transfused under activation of massive transfusion protocol.
Children were compared according to receipt of antifibrinolytic medication (tranexamic acid or aminocaproic acid) during the bleeding event.
Patient characteristics, medications administered, and clinical outcomes were analyzed using Cox proportional hazard and Kaplan-Meier survival analysis. The primary outcome was 24-hour mortality. Of 449 patients analyzed, median age was 7 years (2-15 yr), and 55% were male. The etiology of bleeding was 46% traumatic, 34% operative, and 20% medical. Twelve percent received antifibrinolytic medication during the bleeding event (n = 54 unique subjects; n = 18 epsilon aminocaproic acid, n = 35 tranexamic acid, and n = 1 both). The antifibrinolytic group was comparable with the nonantifibrinolytic group on baseline demographic and physiologic parameters; the antifibrinolytic group had longer massive transfusion protocol duration, received greater volume blood products, and received factor VII more frequently. In the antifibrinolytic group, there was significantly less 6-hour mortality overall (6% vs 17%; p = 0.04) and less 6-hour mortality due to hemorrhage (4% vs 14%; p = 0.04). After adjusting for age, bleeding etiology, Pediatric Risk of Mortality score, and plasma deficit, the antifibrinolytic group had decreased mortality at 6- and 24-hour postbleed (adjusted odds ratio, 0.29 95% CI, 0.09-0.93; p = 0.04 and adjusted odds ratio, 0.45 95% CI, 0.21-0.98; p = 0.04, respectively).
Administration of antifibrinolytic medications during the life-threatening event was independently associated with improved 6- and 24-hour survivals in bleeding children. Consideration should be given to use of antifibrinolytics in pediatric patients with life-threatening hemorrhage.
BACKGROUND
Hemorrhage is the leading cause of preventable death in military and civilian traumatic injury. Blood product resuscitation improves survival. Low‐titer Type O Whole Blood (LTOWB) was ...recently re‐introduced to the combat theater as a universal resuscitation product for hemorrhagic shock. This study assessed the utilization patterns of LTOWB compared to warm fresh whole blood (WFWB) and blood component therapy (CT) in US Military Operations in Iraq/Syria and Afghanistan known as Operation Inherent Resolve (OIR) and Operation Freedom's Sentinel (OFS) respectively. We hypothesized LTOWB utilization would increase over time given its advantages.
STUDY DESIGN AND METHODS
Using the Theater Medical Data Store, patients receiving blood products between January 2016 and December 2017 were identified. Product utilization ratios (PUR) for LTOWB, WFWB, and CT were compared across Area of Operations (AORs), medical treatment facilities (Role 2 vs. Role 3), and time. PUR was defined as number of blood products transfused/(number of blood products transfused + number of blood products wasted).
RESULTS
The overall PUR for all blood products was 17.4%; the LTOWB PUR was 14.3%. Over the study period, the total number of blood products transfused increased 133%. Although the total whole blood (WB) increased from 2.1% to 6.6% of all products transfused, WFWB use remained at 2% while LTOWB transfusions increased from 0.5% to 4%. Transfusion of LTOWB occurred more in austere Role 2 facilities compared to Role 3 hospitals.
CONCLUSIONS
LTOWB transfusion is feasible in austere, far‐forward environments. Further investigation is needed regarding the safety, clinical outcomes, and drivers of LTOWB transfusions.
This pilot trial focused on feasibility and safety to provide preliminary data to evaluate the hemostatic potential of cold-stored platelets (2° to 6°C) compared with standard room temperature-stored ...platelets (20° to 24°C) in adult patients undergoing complex cardiothoracic surgery. This study aimed to assess feasibility and to provide information for future pivotal trials.
A single center two-stage exploratory pilot study was performed on adult patients undergoing elective or semiurgent complex cardiothoracic surgery. In stage I, a two-armed randomized trial, platelets stored up to 7 days in the cold were compared with those stored at room temperature. In the subsequent single-arm stage II, cold storage time was extended to 8 to 14 days. The primary outcome was clinical effect measured by chest drain output. Secondary outcomes were platelet function measured by multiple electrode impedance aggregometry, total blood usage, immediate and long-term (28 days) adverse events, length of stay in intensive care, and mortality.
In stage I, the median chest drain output was 720 ml (quartiles 485 to 1,170, n = 25) in patients transfused with room temperature-stored platelets and 645 ml (quartiles 460 to 800, n = 25) in patients transfused with cold-stored platelets. No significant difference was observed. The difference in medians between the room temperature- and cold-stored up to 7 days arm was 75 ml (95% CI, -220, 425). In stage II, the median chest drain output was 690 ml (500 to 1,880, n = 15). The difference in medians between the room temperature arm and the nonconcurrent cold-stored 8 to 14 days arm was 30 ml (95% CI, -1,040, 355). Platelet aggregation in vitro increased after transfusion in both the room temperature- and cold-stored platelet study arms. Total blood usage, number of adverse events, length of stay in intensive care, and mortality were comparable among patients receiving cold-stored and room temperature-stored platelets.
This pilot trial supports the feasibility of platelets stored cold for up to 14 days and provides critical guidance for future pivotal trials in high-risk cardiothoracic bleeding patients.
Raising the standards on whole blood Yazer, Mark H; Cap, Andrew P; Spinella, Philip C
The journal of trauma and acute care surgery,
06/2018, Volume:
84, Issue:
6S Suppl 1
Journal Article
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