Publications

OBJECTIVES: Trauma-induced coagulopathy biomarkers may be influenced by injury mechanism. We sought to identify differences in patterns of coagulopathy with and without severe traumatic brain injury (TBI).

DESIGN: Retrospective cohort study.

SETTING: Harmonized database composed of six major hemorrhagic shock trials: Control of Major Bleeding After Trauma (COMBAT), Cold-stored Platelet Early Intervention in Hemorrhagic Shock (CriSP-HS), Prehospital Air Medical Plasma (PAMPer), Prehospital Whole Blood in Emergency Resuscitation (PPOWER), Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR), and Study of Tranexamic Acid During Air Medical and Ground Prehospital Transport (STAAMP).

PATIENTS: All subjects randomized to placebo or standard-of-care groups with complete data for international normalized ratio (INR), thromboelastography values (alpha angle [AA], K time, maximum amplitude [MA], and lysis in 30 min), and Abbreviated Injury Scores (AISs). Subjects from COMBAT and CriSP-HS were screened and ultimately excluded from the final analysis as they did not meet eligibility criteria.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Stratified principal component (PC) analysis was performed for INR and thromboelastography values. Strata were defined based on AIS scores as: 1) isolated severe TBI (iTBI); 2) severe polytrauma (POLY), those with both major head injury and torso/extremity trauma; and 3) isolated severe torso/extremity trauma (iTRUNK). We identified 506 subjects with complete data: 51 iTBI, 115 POLY, and 340 iTRUNK. For each stratum, two PCs were identified that accounted for more than 65% of the variance. Associations between PC scores and outcomes, including need for blood product transfusion within 24 hours as a surrogate marker for early coagulopathy and bleeding, were examined with logistic regression. For both iTBI and POLY, PC1 included INR, AA, K time, and MA, and was associated with greater odds of early transfusion (odds ratio [OR], 3.57; 95% CI, 1.50-8.45; p = 0.004 for iTBI and OR, 2.29; 95% CI, 1.11-4.75; p = 0.026 for POLY). For iTRUNK, PC1 included INR, AA, and MA and was protective with reduced odds of early transfusion (OR, 0.51; 95% CI, 0.37-0.70; p < 0.001).

CONCLUSIONS: PC analysis demonstrated a unique pattern of coagulation biomarkers common to patients with severe TBI, irrespective of other injuries.

Hemorrhage is the leading cause of preventable death on the battlefield, yet combat medics lack clinical decision support systems to help stratify hemorrhage risk in trauma casualties. We previously trained the Automated Processing of the Physiological Registry for Assessment of Injury Severity - Hemorrhage Risk Index (APPRAISE-HRI) software to associate patterns in vital signs (heart rate and blood pressure) collected from trauma patients with three HRI levels: I (low), II (average), or III (high). To independently validate APPRAISE-HRI and obtain U.S. Food and Drug Administration (FDA) clearance, we collected trauma registry and continuous vital sign data from 5895 trauma patients (543 with hemorrhagic injuries and 5352 controls) in an emergency department or during prehospital transport to one of eight medical centers. The study outcome was hemorrhagic injury, defined by documented injuries and blood transfusion. Using the likelihood ratio to assess the ability of APPRAISE-HRI to stratify hemorrhage risk, we found that hemorrhagic patients were 6.88 times as likely as controls to be at level III, strongly suggesting the presence of hemorrhage at this level. Similarly, hemorrhagic patients were 0.18 times as likely as controls to be at level I, suggesting the absence of hemorrhage at this level. Hemorrhagic patients were almost as likely as controls to be at level II (0.70 times as likely). Subsequently, the U.S. Department of Defense obtained FDA 510(k) clearance for the artificial intelligence-enabled APPRAISE-HRI Class II device (K233249), the first software as a medical device approved for assessing hemorrhage risk in trauma patients, allowing for triage and identification of casualties who need immediate attention and evacuation. (Funded by the U.S. Army Medical Materiel Development Activity and the Combat Casualty Care Program Area Directorate (CCCPAD) of the U.S. Army Medical Research and Development Command (USAMRDC), Fort Detrick, MD and others.).

BACKGROUND: Care for massively bleeding patients has seen a return of focus to the use of cold stored whole blood (WB) as the primary resuscitation treatment. Nonhuman primates (NHP) are the ideal trauma animal model for preclinical hemostatic research as they are most physiologically akin to humans, yet study designs use autologous shed WB which does not fully recapitulate what occurs in human medicine. We sought to evaluate effects of prolonged 4°C storage of NHP WB.

METHODS: WB was collected from 10 anesthetized male rhesus macaques and 5 male cynomolgus macaques into 10% CPDA-1 in 300 mL storage bags. WB units were tested at baseline prior to storage at 4°C and aseptically sampled daily for the first 4 days, then weekly at day 7 through day 28 of storage. Biochemical, hematologic, and hemostatic function parameters were assayed. Data were analyzed using a mixed effects analysis with multiple comparisons if significant.

RESULTS: In both species, red cell, hemoglobin and hematocrit counts remained stable through day 28, while lactate and potassium levels significantly increased as sodium and pH decreased significantly. Hemostatic function significantly declined for both species from day 7 onward.

CONCLUSION: This study describes a viable method of manufacture of NHP stored WB and characterizes the storage lesion in both rhesus and cynomolgus macaques. Observationally, no overt differences were seen between species. Future resuscitation studies utilizing NHP models could improve translational relevance using stored allogenic WB.

The current practice of delaying tranexamic acid administration until after cord clamping may blunt its therapeutic potential in obstetric hemorrhage. Although this precaution aims to avoid fetal exposure, pharmacokinetic and available safety data suggest that such exposure poses minimal fetal risk. Data from limited cesarean and placenta previa studies indicate that earlier administration-before surgical incision or onset of bleeding-may reduce blood loss without harming neonates. Given that tranexamic acid is most effective when given early or before the onset of fibrinolysis, obstetric clinical trials and future protocols should reconsider the current default to post-cord clamping dosing. Earlier, targeted tranexamic acid administration may improve maternal outcomes without compromising neonatal safety and should be considered part of a rational approach in obstetric hemorrhage clinical trials.

BACKGROUND: Virtual care accelerated to the forefront of family physician (FP) care following the COVID-19 pandemic and continues to play a significant role in patient care. The choice between virtual and in-person primary care must be sensitive to patients' contexts particularly for those with multi-morbidity.

OBJECTIVES: This study explored how to make the choice between virtual and in-person FP care for persons living with multi-morbidity that is acceptable to patients and FPs.

METHODS: We conducted a constructivist grounded theory study to understand the processes patients and FPs employ when deciding on the mode of primary care delivery. We used individual interviews to understand the perspectives and expectations of patients with multi-morbidity (2+ chronic conditions) and FPs.

RESULTS: There were two main themes revealed in data analysis: Considerations in choosing mode of delivery (including reason for visit, impact on access, technological logistics, and reimbursement for virtual care) and Process for choosing mode of delivery (including endorsing the patient choice when possible and scheduling visits).

CONCLUSION: This paper integrated the experience of both patients and FPs to understand how to make the choice between virtual and in-person care. This understanding can support the future of FP care where diverse modes of delivery are employed, but currently technological barriers remain. Clinical scheduling systems that depend on telephone interactions between clinic staff and patients do not always support the process patients and FPs indicated they prefer; that is, one that respects patient preference and FP clinical expertise.

Purposes: We explored the experience of older adults living with multimorbidity during the COVID-19 pandemic. Methods: Using a phenomenological approach, we conducted semi-structured interviews with 17 participants aged 50 years and older living with multimorbidity. Data collection and analysis were iterative using a thematic approach. We explored participants' overall pandemic experience as well as querying specifically about pandemic experiences of social isolation, coping and resilience. Results: We describe our findings according to four main themes: (1) Lives disrupted; (2) Diverse social isolation experiences; (3) Coping through seeking solitary and group activities; and (4) Individual ways of enacting resilience and the role of health care to build resilience. Conclusion: We found the experiences of older adults living with multimorbidity during the COVID-19 pandemic were characterized by disruption. When queried social isolation was shared as a prominent concern. We identified the creativity with which participants coped with social isolation and the resilience they marshaled. This study will be used to inform interventions to mitigate social isolation and its effects in a post-pandemic world.

BACKGROUND: Platelet count or function defects can result in hemostatic impairment, leading to life-threatening bleeding complications. While platelet transfusions are used to treat such complications, current clinical practice utilizes only platelet count thresholds to guide transfusion. This is because a single precision diagnostic system that can directly correlate both platelet count and function defects to hemostatic deficits is unavailable.

OBJECTIVES: We developed PlateChek, a whole blood-based dielectric coagulometry microsensor that uses a gold electrode surface-coated with a platelet-specific agonist, and tested the hypothesis that PlateChek can detect hemostatic impairment due to both platelet count and function defects.

METHODS: PlateChek incorporates a gold electrode coated with thrombin receptor-activating peptide-6 (TRAP-6) to render clotting in a platelet-specific manner. Healthy blood was manipulated in vitro to recapitulate platelet count or function defects and tested in PlateChek to assess platelet-specific readout signatures. Finally, blood samples from patients with thrombocytopenia or platelet aggregation dysfunctions were used to validate PlateChek's ability to detect clinically relevant hemostatic impairment.

RESULTS: In PlateChek, clotting kinetics were delayed in samples with platelet counts of <50 k/μL compared to healthy controls and clot firmness was reduced with platelet counts of <100 k/μL. PlateChek was sensitive to prolonged clotting time induced by vorapaxar inhibition and reduced clot firmness induced by tirofiban inhibition. PlateChek was sensitive to platelet counts of <70 k/μL and platelet aggregation dysfunctions in clinical blood samples.

CONCLUSIONS: PlateChek is a novel whole blood-based coagulometer with translational potential that directly correlates both platelet count and function defects to hemostatic impairment.

OBJECTIVES: To evaluate the feasibility of randomizing children on extracorporeal membrane oxygenation (ECMO) to one of two prophylactic platelet transfusion thresholds.

DESIGN: Randomized controlled trial.

SETTING: Ten ECMO centers (nine in United States, one in Israel).

PATIENTS: Critically ill children (0 to younger than 18 yr), supported on ECMO, with no or minimal bleeding within 24 hours of cannulation.

INTERVENTIONS: Children were randomized to a higher platelet threshold (transfused when platelet count < 90 × 109/L) or a lower platelet threshold (transfused when platelet count < 50 × 109/L). Primary feasibility outcome was pre-transfusion platelet count to test for a difference between strategies. Primary safety outcome was progression to severe bleeding, severe clotting, and/or all-cause mortality.

MEASUREMENTS AND MAIN RESULTS: Of 159 patients screened for eligibility, 77% (123/159) met eligibility criteria. Sixty-five percent (80/123) of caregivers were approached for consent. Consent was obtained in 63% (50/80). Enrolled children had a median age of 0.2 years (interquartile range 0.0; 1.7) and 88% (44/50) were supported by veno-arterial (V-A) ECMO. The model-adjusted mean difference in pre-transfusion platelet count between the groups was 32 × 109/L (p < 0.001). Compliance with assigned transfusion threshold was 99.2%. Eleven (22%) children experienced the primary safety outcome. Progression to severe bleeding occurred in 14% (7/50) of patients, whereas progression to severe clotting was observed in 4% (2/50).

CONCLUSIONS: Non-bleeding children on ECMO can be screened, enrolled and randomized to different platelet transfusion strategies within 24 hours of cannulation. Compliance with the protocol was excellent with significant separation in pre-transfusion platelet counts between the arms. Severe bleeding and severe clotting occurred at similar rates in both thresholds. A larger, definitive trial is feasible and needed.

INTRODUCTION: Children living in conflict or post-conflict zones are frequently exposed to explosive injuries, with thousands killed and injured every year. The clinical practice guideline from the Explosive Weapons Trauma Care Collective (EXTRACCT) group provides a review of current best practice for the resuscitation of a child who has sustained a blast injury in low-resource settings.

METHODS: An expert literature review of current practice was undertaken.

RESULTS: The guideline relates to the specific considerations of pediatric resuscitation of a child with a blast injury in low-resource settings. It aims to provide guidance to all health care professionals working in resource-constrained, secondary-level healthcare contexts. It takes into consideration clinical decision-making and treatment algorithms where resource availability is limited with respect to equipment and materials, subspecialist expertise, and critical care capabilities.

CONCLUSION: The strength of the CPG recommendations is limited by a lack of data on pediatric blast victims. Future work is required, including establishing a blast injury victim registry and clinical trials on blast injury management strategies.