U.S. cities will not meet blood product resuscitation standards during major mass casualty incidents: Results of a THOR-AABB working party prospective analysis.

BACKGROUND: Mass casualty incidents (MCIs) create an immediate surge in blood product demand. We hypothesize local inventories in major U.S. cities would not meet this demand. STUDY DESIGN AND METHODS: A simulated blast in a large crowd estimated casualty numbers. Ideal resuscitation was defined as equal amounts of red blood cells (RBCs), plasma, platelets, and cryoprecipitate. Inventory was prospectively collected from six major U.S. cities at six time points between January and July 2019. City-wide blood inventories were classified as READY (>1 U/injured survivor), DEFICIENT (<10 U/severely injured survivor), or RISK (between READY and DEFICIENT), before and after resupply from local distribution centers (DC), and features of DEFICIENT cities were identified. RESULTS: The simulated blast resulted in 2218 injured survivors including 95 with severe injuries. Balanced resuscitation would require between 950 and 2218 units each RBC, plasma, platelets and cryoprecipitate. Inventories in 88 hospitals/health systems and 10 DCs were assessed. Of 36 city-wide surveys, RISK inventories included RBCs (n = 16; 44%), plasma (n = 24; 67%), platelets (n = 6; 17%), and cryoprecipitate (n = 22; 61%) while DEFICIENT inventories included platelets (n = 30; 83%) and cryoprecipitate (n = 12; 33%). Resupply shifted most RBC and plasma inventories to READY, but some platelet and cryoprecipitate inventories remained at RISK (n = 24; 67% and n = 12; 33%, respectively) or even DEFICIENT (n = 11; 31% and n = 6; 17%, respectively). Cities with DEFICIENT inventories were smaller (p <.001) with fewer blood products per trauma bed (p <.001). DISCUSSION: In this simulated blast event, blood product demand exceeded local supply in some major U.S. cities. Options for closing this gap should be explored to optimize resuscitation during MCIs.

Does Gender Matter: A Multi-Institutional Analysis of Viscoelastic Profiles for 1565 Trauma Patients With Severe Hemorrhage.

BACKGROUND: Viscoelastic tests including thromboelastography (TEG) and rotational thromboelastometry (ROTEM) are being used in patients with severe hemorrhage at trauma centers to guide resuscitation. Several recent studies demonstrated hypercoagulability in female trauma patients that was associated with a survival advantage. The objective of our study was to elucidate the effects of gender differences in TEG/ROTEM values on survival in trauma patients with severe hemorrhage. METHODS: A retrospective review of consecutive adult patients receiving massive transfusion protocol (MTP) at 7 Level I trauma centers was performed from 2013 to 2018. Data were stratified by gender and then further examined by TEG or ROTEM parameters. Results were analyzed using univariate and multi-variate analyses. RESULTS: A total of 1565 patients were included with 70.9% male gender (n = 1110/1565). Female trauma patients were older than male patients (43.5 ± .9 vs 41.1 ± .6 years, P = .01). On TEG, females had longer reaction times (6.1 ± .9 min vs 4.8 ± .2 min, P = .03), increased alpha angle (68.6 ± .8 vs 65.7 ± .4, P < .001), and higher maximum amplitude (59.8 ± .8 vs 56.3 ± .4, P < .001). On ROTEM, females had significantly longer clot time (99.2 ± 13.7 vs 75.1 ± 2.6 sec, P = .09) and clot formation time (153.6 ± 10.6 sec vs 106.9 ± 3.8 sec, P < .001). When comparing by gender, no difference for in-hospital mortality was found for patients in the TEG or ROTEM group (P > .05). Multivariate analysis showed no survival difference for female patients (OR 1.11, 95% CI .83-1.50, P = .48). CONCLUSIONS: Although a difference between male and females was found on TEG/ROTEM for certain clotting parameters, no difference in mortality was observed. Prospective multi-institutional studies are needed.

Cold-stored whole blood: A better method of trauma resuscitation?

BACKGROUND: Cold-stored whole blood (CWB) provides a balance of red blood cells, plasma, and platelets in less anticoagulant volume than standard blood component therapy (BCT). We hypothesize that patients receiving CWB along with BCT have improved survival compared with patients receiving only BCT. METHODS: We performed a dual-center case-match study of trauma patients who received CWB and BCT at two urban, Level-I Trauma Centers. Criteria to receive CWB included boys 16 years of older, women older than 50 years, SBP less than 90 mm Hg, and identifiable source of hemorrhage. We performed a 2:1 propensity match against any trauma patient who received 1 unit or greater of packed red cells during their initial trauma bay resuscitation. Endpoints included trauma bay mortality, 30-day mortality, laboratory values at 4 hours and 24 hours, and overall blood product utilization. Comparisons were made with Wilcoxon-ranked sum and Fisher's exact test, p less than 0.05 was significant. RESULTS: Between both institutions, a total of 107 patients received CWB during the study period with 91 being matched to 182 BCT patients for analysis. Hemodynamic parameters of the patients in both groups at the time of presentation were similar. The CWB patients had higher mean hemoglobin (10 ± 2 g/dL vs. 11 ± 2 g/dL; p < 0.001) and hematocrit (29.2 ± 6.1% vs. 32.1 ± 5.8%; p < 0.001) at 24 hours. Importantly, trauma bay mortality was less in CWB patients (8.8% vs. 2.2%;p = 0.039). Thirty-day mortality was not different in CWB patients, and there were no differences in the total amount of blood products transfused at the 4-hour and 24-hour periods. CONCLUSION: Cold-stored whole blood offers the benefit of a balanced resuscitation with improved trauma bay survival and higher mean hemoglobin at 24 hours. A larger, prospective study is needed to determine whether it has a longer-term survival benefit for severely injured patients. LEVEL OF EVIDENCE: Therapeutic, level III.

Loss of PIKfyve in platelets causes a lysosomal disease leading to inflammation and thrombosis in mice.

PIKfyve is essential for the synthesis of phosphatidylinositol-3,5-bisphosphate [PtdIns(3,5)P2] and for the regulation of endolysosomal membrane dynamics in mammals. PtdIns(3,5)P2 deficiency causes neurodegeneration in mice and humans, but the role of PtdIns(3,5)P2 in non-neural tissues is poorly understood. Here we show that platelet-specific ablation of PIKfyve in mice leads to accelerated arterial thrombosis, and, unexpectedly, also to inappropriate inflammatory responses characterized by macrophage accumulation in multiple tissues. These multiorgan defects are attenuated by platelet depletion in vivo, confirming that they reflect a platelet-specific process. PIKfyve ablation in platelets induces defective maturation and excessive storage of lysosomal enzymes that are released upon platelet activation. Impairing lysosome secretion from PIKfyve-null platelets in vivo markedly attenuates the multiorgan defects, suggesting that platelet lysosome secretion contributes to pathogenesis. Our findings identify PIKfyve as an essential regulator for platelet lysosome homeostasis, and demonstrate the contributions of platelet lysosomes to inflammation, arterial thrombosis and macrophage biology.