Haemonetics (United States)

The role of the advanced practice provider (APP) in radiation oncology has developed significantly during the past 25 years. The role and responsibilities continue to evolve as the Centers for Medicare and Medicaid Services r.

SummaryBackgroundPatients undergoing major surgery frequently experience major uncontrolled bleeding. The aim of this systematic review and meta‐analysis was to evaluate the clinical efficacy of using viscoelastic haemostatic assays to manage peri‐operative bleeding in elective surgery.MethodsWe searched PubMed/MEDLINE and Embase databases for randomised controlled trials according to pre‐determined criteria. The primary outcomes were blood product requirements; duration of stay in the operating theatre or ICU; and surgical reintervention rate.ResultsWe included 20 randomised controlled trials. The overall risk of bias was low to moderate. Twelve studies used thromboelastography‐based transfusion algorithms, while eight used thromboelastometry. Viscoelastic haemostatic assay‐guided therapy was associated with a statistically significant reduction in transfusion of red blood cells (standardised mean difference (95%CI) 0.16 (‐0.29 to 0.02)), platelets (standardised mean difference (95%CI) ‐0.33 (‐0.56 to ‐0.10)) and fresh frozen plasma (standardised mean difference (95%CI) ‐0.64 (‐1.01 to ‐0.28)). There was no evidence of an effect of viscoelastic haemostatic assay‐guided therapy on surgical reintervention (relative risk (95%CI) 1.09 (0.70–1.69)). Viscoelastic haemostatic assay‐guided therapy was associated with lower blood loss and shorter ICU duration of stay. There was no evidence of any effect on total duration of stay and all‐cause mortality.ConclusionsViscoelastic haemostatic assay‐guided therapy may reduce peri‐operative blood product transfusion requirements and blood loss during major elective surgery, with no discernible effect on patient‐centred outcomes. The overall quality of evidence was modest.

Nursing has articulated a shared commitment to equity in response to inequities in health and health care; however, understandings of how nurses enact equity are needed to uphold this professional mandate. This Foucauldian discourse analysis examined how nurses' equity-promoting practices are shaped by dominant discourses within the emergency department and illustrated that within this institutional context that constrained equity, nurses engaged in equity-promoting practices through subversion of discursive power. This study illustrates the need for embedding equity discourses within health care systems and ensuring meaningful supports for nurses in enacting equity-promoting practices within the emergency department setting.

From the Department of Anesthesiology, Perioperative, and Pain Medicine, Stanford University School of Medicine, Stanford, California. Accepted for publication October 26, 2022. Funding: J.R.A. is a recipient of grant funding from Foundation for Anesthesia Education and Research. A.J.B. has received honoraria for consulting from Octapharma USA, Inc and Haemonetics Corp. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Alexander J. Butwick, MBBS, FRCA, MS, Department of Anesthesiology, Perioperative, and Pain Management, Stanford University School of Medicine, 300 Pasteur Dr, Stanford, CA 94305. Address e-mail to [email protected]

Convalescent plasma (CP) has been used to treat emerging infectious diseases for over a century. It was notably deployed during the 1918 flu pandemic and has been explored during numerous disease outbreaks, including those caused by other coronaviruses—such as in severe acute respiratory syndrome (SARS)1 and Middle East respiratory syndrome (MERS)2—influenza,3 and Ebola.4 The potential efficacy of CP in COVID-19 was first suggested by several observational studies that associated reduced mortality with CP administration.5 Following results of the PLACID randomized controlled trial (RCT) from India that failed to show a benefit of low-titer CP in moderate COVID-19,6 a prospective RCT from Argentina demonstrated that the administration of CP with a high titer of anti-SARS-CoV-2 immunoglobulins within 3 days after the onset of mild COVID-19 symptoms in older patients could significantly reduce the progression of the disease.7 Further, a retrospective analysis of data from the Expanded Access Program implemented in the United States highlighted not only the safety but also provided signs of efficacy (i.e., dose-dependent effect) of high-titer CP in nonventilated patients,8 again supporting early use. Similarly, a large retrospective, health-record-based analysis showed that administration of CP was associated with lower in-hospital mortality as compared with matched controls.9 Multiple studies showed significant benefits of CP in immunocompromised and oncology patients with COVID-19.10-12 On the other hand, there have been a large number of well-executed clinical trials, such as RECOVERY, REMAP-CAP, or CONCOR-1 that did not find CP to be beneficial, albeit in advanced COVID-19. A summary of some of these findings is maintained in the living systematic Cochrane Review, which reports a "high certainty in the evidence that CP for the treatment of individuals with moderate to severe disease does not reduce mortality and has little to no impact on measures of clinical improvement."13-18 While not known at the time of their inception, studies of CP have focused, disproportionately, on populations (i.e., late-stage COVID-19) and interventions (low-titer CP) that are now known to be suboptimal or ineffective for passive antibody-based therapy, whereby early administration of high-titer plasma is critical.19 As an example, a subgroup analysis of the RECOVERY data for patients without use of corticosteroids (indicative of earlier disease stage) showed a trend toward fewer deaths at 28 days in the CP versus the control groups (19% vs. 24%, respectively). There was a similar observation in patients that did not receive respiratory support.15 Trials of outpatients afford insight into the efficacy of CP in early COVID-19. In addition to the seminal trial by Libster et al.,7 two large clinical trials have evaluated the use of CP in the outpatient setting. Korley et al. (SIREN-C3PO) conducted a multicenter RCT of 511 patients (50 years of age or older, or one or more risk factors for disease progression) to receive centrally sourced high-titer CP (intervention) or saline infusion (control) within 7 days after symptom onset.14 The study was unable to find a significant difference with respect to its primary endpoint (i.e., a 50% relative risk reduction for a composite measure of hospital admission for any reason, seeking emergency or urgent care, or death without hospitalization). However, a post-hoc analysis by the authors showed that if excluding 25 patients that were hospitalized during their initial visit (it is questionable that the intervention could have been effective in that timeframe), the rates were 22.5% for CP versus 29.5% for the control arm (93% posterior probability of superiority of CP).14 Patients in the CP arm showed significant improvement in two secondary endpoints of the study (dyspnea, symptom worsening), offering signals of benefit of CP in this setting.14 Sullivan et al. conducted the largest (1181 treated patients) multicenter RCT in the outpatient setting to date.20 The trial, which enrolled adult patients 18 years or older, independent of risk factors or vaccination status, showed a significant reduction in the primary outcome of COVID-19-related hospitalization within 28 days of plasma transfusion. The primary endpoint occurred in 37 of 589 (6.3%) patients who received placebo control plasma and in 17 of 592 (2.9%) patients who received CP (relative risk, 0.46; one-sided 95% upper bound confidence interval 0.733; p = .004) corresponding to a 54% risk reduction in those who received CP within 9 days of symptom onset.20 On December 7, 2021, the World Health Organization (WHO) revised its living guideline on treatments for COVID-19, stating that "current evidence shows that CP does not improve survival or reduce the need for mechanical ventilation, while it has significant costs," citing evidence that CP confers no benefit in patients with nonsevere COVID-19 (WHO website, retrieved on January 8, 2022: https://www.who.int/news/item/07-12-2021-who-recommends-against-the-use-of-convalescent-plasma-to-treat-covid-19). Of note, the statement from WHO preceded the announcement of the findings from Sullivan et al.20 On December 28, 2021, "The U.S. Food and Drug Administration (FDA) has issued an Emergency Use Authorization to permit the emergency use of the unapproved product, COVID-19 CP with high titers of anti-SARS-CoV-2 antibodies, for the treatment of COVID-19 in patients with immunosuppressive disease or receiving immunosuppressive treatment, in either the outpatient or inpatient setting." (FDA website, retrieved on January 8, 2022: https://www.fda.gov/media/141478/download). This broadened its use to the outpatient setting yet restricted its use to immunocompromised patients. Further guidance on investigational COVID-19 CP to the industry was provided by FDA on January 7, 2022, including direction for the collection of CP (FDA website, retrieved on January 8, 2022: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/investigational-covid-19-convalescent-plasma). CP is a readily scalable intervention given extant blood collection infrastructure. Importantly, it can be deployed rapidly, well before direct-acting antivirals, vaccines, and immunotherapies (e.g., monoclonal antibodies) becoming available. Time is CP's major advantage where availability is measured in days or weeks rather than months or even years for more refined therapies (e.g., vaccines and antiviral therapies). The other major advantage is versatility, the potential ability to use CP to respond to emerging variants (such as omicron). By their nature, outbreaks of highly contagious infectious diseases are characterized by rapid onset, placing intense strain on health care systems. This impedes the ability to establish the safety and efficacy of CP, given the challenges of high-quality data collection in times of crisis. Prospective RCTs of CP are inherently challenging, requiring careful preparation, funding support, and ultimately an infrastructure to execute the study successfully, from product procurement (i.e., donor qualification and collection) to transfusion and posttransfusion evaluation and follow-up. These challenges are universal but are amplified in low- and middle-income countries.21, 22 This explains, in part, the dearth of rigorous data on CP prior to COVID-19, despite its repeated deployment. Before COVID-19, well-designed RCTs of CP were the exception and showed mixed results, from highly effective in the setting of Argentine hemorrhagic fever23 to nonsignificant in the case of severe flu.24 Instead, empirical data supporting use was primarily confined to observational studies, which were potentially flawed by bias, as well as insufficient characterization of the transfused CP and its clinical use, and, thus, confounding. Thanks to the implementation of multiple RCTs, the COVID-19 pandemic has now helped to delineate the clinical utility of CP. This has been achieved despite the myriad of organizational challenges that plagued researchers at the onset of the COVID-19 pandemic. There was insufficient testing capacity to ensure that units of CP were sufficiently characterized to confer the intended effect (i.e., potent passive immunization). As the epidemic shifted to new areas, patients also found themselves in health care facilities with limited access to clinical trials. As experience with CP use grew, it became apparent that CP efficacy was greatest when locally collected from donors with high-titers of neutralizing antibodies and administration proximal to symptom onset or early during hospitalization. So, it took a pandemic of epic proportions, the focus of the global research community, and unprecedented funding to forge an environment in which CP could be tested rigorously, garnering insight into its optimal clinical use. Looking back and drawing on the accumulated experience, CP could have potentially had a more dominant role during the respective SARS (2003), MERS (2012), and most notably the West African Ebola (2013–2016) outbreaks if applied differently. Blood transfusion services might have adapted rapidly to focus on transitioning recovered patients with high-titer antibodies, to become donors early in the disease course. However, this approach requires advanced preparation by the local collection services to respond in a manner that is sufficiently timely to contend with the epidemic surge of clinical cases. This remains an enduring challenge in resource-limited settings. So, where does CP go next? Undoubtedly, the experience from this pandemic will need to be applied for the good of patients globally. Specifically, the high-quality evidence gleaned from rigorous clinical trials can be applied broadly in a way that previous underpowered, small-scale research efforts could not. Looking ahead, another pandemic or more variants of COVID-19 are certain to occur. When that happens, we now are better positioned to apply passive immunotherapy using CP transfusion to confer favorable outcomes. The hard-won knowledge from this pandemic should serve to expedite clinical trials, ethical approval, reliable testing infrastructure to identify safe and efficacious CP, and donation pipelines during similar future crises.25 Recently, the Association for the Advancement of Blood & Biotherapies (AABB) has formed the Passive Antibody Therapies Forum Advisory Group with that goal in mind. The lessons learned from long ago—that plasma with high antibody titers should be safely administered as early as possible for maximum benefit— should be heeded as a guiding principle in the design of clinical trials and associated practices for emergent CP use against future pandemics. All authors are inaugural members of the AABB Passive Antibody Therapies Forum Advisory Group. JH is an employee of Haemonetics Corporation, a manufacturer of plasma collection devices; EMB reports personal fees and nonfinancial support from Terumo BCT, Grifols Diagnostics Solutions, and Abbott Laboratories outside of the submitted work; EMB is a member of the FDA Blood Products Advisory Committee. Any views or opinions that are expressed in this manuscript are that of the author's, based on his own scientific expertise and professional judgment; they do not necessarily represent the views of either the Blood Products Advisory Committee or the formal position of FDA and also do not bind or otherwise obligate or commit either Advisory Committee or the Agency to the views expressed. TB's laboratory at Taipei Medical University has received research grants from plasma industry suppliers (Asahi-Kasei Medical; Merck-Millipore), and TB has served on the scientific advisory board of Haemonetics Corporation.

Modern approaches to resuscitation seek to bring patient interventions as close as possible to the initial trauma. In recent decades, fresh or cold-stored whole blood has gained widespread support in multiple settings as the best first agent in resuscitation after massive blood loss. However, whole blood is not a panacea, and while current guidelines promote continued resuscitation with fixed ratios of blood products, the debate about the optimal resuscitation strategy—especially in austere or challenging environments—is by no means settled. In this narrative review, we give a brief history of military resuscitation and how whole blood became the mainstay of initial resuscitation. We then outline the principles of viscoelastic hemostatic assays as well as their adoption for providing goal-directed blood-component therapy in trauma centers. After summarizing the nascent research on the strengths and limitations of viscoelastic platforms in challenging environmental conditions, we conclude with our vision of how these platforms can be deployed in far-forward combat and austere civilian environments to maximize survival.

MEDLINE, PubMed Central, Embase, and CENTRAL. Clinical studies of adult patients with traumatic brain injury (isolated or polytrauma) who were assessed by either standard thromboelastography or thromboelastography with platelet mapping plus either conventional coagulation assays or platelet function assays from January 1999 to June 2021. Demographics, injury mechanism and severity, diagnostic, laboratory data, therapies, and outcome data were extracted for analysis and comparison. Database search revealed 1,169 sources; eight additional articles were identified by the authors. After review, 31 publications were used for qualitative analysis, and of these, 16 were used for quantitative analysis. Qualitative and quantitative analysis found unique patterns of thromboelastography and thromboelastography with platelet mapping parameters in traumatic brain injury patients. Patterns were distinct compared with healthy controls, nontraumatic brain injury trauma patients, and traumatic brain injury subpopulations including those with severe traumatic brain injury or penetrating traumatic brain injury. Abnormal thromboelastography K-time and adenosine diphosphate % inhibition on thromboelastography with platelet mapping are associated with decreased survival after traumatic brain injury. Subgroup meta-analysis of severe traumatic brain injury patients from two randomized controlled trials demonstrated improved survival when using a viscoelastic hemostatic assay-guided resuscitation strategy (odds ratio, 0.39; 95% CI, 0.17-0.91; p = 0.030). Thromboelastography and thromboelastography with platelet mapping characterize coagulopathy patterns in traumatic brain injury patients. Abnormal thromboelastography profiles are associated with poor outcomes. Conversely, treatment protocols designed to normalize abnormal parameters may be associated with improved traumatic brain injury patient outcomes. Current quality of evidence in this population is low; so future efforts should evaluate viscoelastic hemostatic assay-guided hemostatic resuscitation in larger numbers of traumatic brain injury patients with specific focus on those with traumatic brain injury-associated coagulopathy.

The quantification of the coagulopathic state associated with oncologic and hematologic diseases is imperfectly assessed by common coagulation tests such as prothrombin time, activated partial thromboplastin time, fibrinogen levels, and platelet count. These tests provide a static representation of a component of hemostatic integrity, presenting an incomplete picture of coagulation in these patients. Viscoelastic tests (VETs), such as rotational thromboelastometry (ROTEM) and thromboelastography (TEG), as whole blood analyses, provide data related to the cumulative effects of blood components and all stages of the coagulation and fibrinolytic processes. The utility of VETs has been demonstrated since the late 1960s in guiding blood component therapy for patients undergoing liver transplantation. Since then, the scope of viscoelastic testing has expanded to become routinely used for cardiac surgery, obstetrics, and trauma. In the past decade, VETs' expanded usage has been most significant in trauma resuscitation. However, use of VETs for patients with malignancy-associated coagulopathy (MAC) and hematologic malignancies is increasing. For the purposes of this narrative review, we discuss the similarities between trauma-induced coagulopathy (TIC) and MAC. These similarities center on the thrombomodulin-thrombin complex as it switches between the thrombin-activatable fibrinolysis inhibitor coagulation pathway and activating the protein C anticoagulation pathway. This produces a spectrum of coagulopathy and fibrinolytic alterations ranging from shutdown to hyperfibrinolysis that are common to TIC, MAC, and hematologic malignancies. There is expanding literature regarding the utility of TEG and ROTEM to describe the hemostatic integrity of patients with oncologic and hematologic conditions, which we review here.

Knowledge of platelet count and function is key to ensuring appropriate hemostatic management. We hypothesized that the novel, portable TEG®6s coagulation assessment system could evaluate the contribution of both platelet count and function to clot formation. Whole-blood samples with variable platelet counts were prepared from healthy volunteers. Platelet function was adjusted using seven concentrations of abciximab and evaluated by light transmission aggregometry (LTA) with TRAP agonist. Maximum amplitude (MA), reaction time (R) and activated clotting time (ACT) were assessed in citrated kaolin (CK), CK with heparinase (CKH), citrated RapidTEG® (CRT), and citrated functional fibrinogen (CFF) assays. Positive correlations were observed between platelet count and CK.MA, CKH.MA, and CRT.MA (p < .0001), and CK.R, CKH.R, and CRT.ACT (p < .05). Platelet count could be accurately quantified in the range 28–91 k/μL, 28–86 k/μL and 28–74 k/μL for CK.MA, CKH.MA, and CRT.MA, respectively. CK.MA, CKH.MA, and CRT.MA showed significant negative relationships with abciximab concentration (p < .001). Platelet function inhibition was detected by all three assays at >68% measured by LTA and quantified in the range 68.4–82% (CK), 69.4–88% (CKH), and 69.7–76% (CRT). This demonstrates the TEG®6s analyzer can accurately evaluate platelet count and function at the site-of-care.