Jeremy G. Perkins

Increased plasma and platelet to red blood cell ratios improves outcome in 466 massively transfused civilian trauma patients

Objective:To determine the effect of blood component ratios in massive transfusion (MT), we hypothesized that increased use of plasma and platelet to red blood cell (RBC) ratios would result in decreased early hemorrhagic death and this benefit would be sustained over the ensuing hospitalization. Summary Background Data:Civilian guidelines for massive transfusion (MT ≥10 units of RBC in 24 hours) have typically recommend a 1:3 ratio of plasma:RBC, whereas optimal platelet:RBC ratios are unknown. Conversely, military data shows that a plasma:RBC ratio approaching 1:1 improves long term outcomes in MT combat casualties. There is little consensus on optimal platelet transfusions in either civilian or military practice. At present, the optimal combinations of plasma, platelet, and RBCs for MT in civilian patients is unclear. Methods:Records of 467 MT trauma patients transported from the scene to 16 level 1 trauma centers between July 2005 and June 2006 were reviewed. One patient who died within 30 minutes of admission was excluded. Based on high and low plasma and platelet to RBC ratios, 4 groups were analyzed. Results:Among 466 MT patients, survival varied by center from 41% to 74%. Mean injury severity score varied by center from 22 to 40; the average of the center means was 33. The plasma:RBC ratio ranged from 0 to 2.89 (mean ± SD: 0.56 ± 0.35) and the platelets:RBC ratio ranged from 0 to 2.5 (0.55 ± 0.50). Plasma and platelet to RBC ratios and injury severity score were predictors of death at 6 hours, 24 hours, and 30 days in multivariate logistic models. Thirty-day survival was increased in patients with high plasma:RBC ratio (≥1:2) relative to those with low plasma:RBC ratio (<1:2) (low: 40.4% vs. high: 59.6%, P < 0.01). Similarly, 30-day survival was increased in patients with high platelet:RBC ratio (≥1:2) relative to those with low platelet:RBC ratio (<1:2) (low: 40.1% vs. high: 59.9%, P < 0.01). The combination of high plasma and high platelet to RBC ratios were associated with decreased truncal hemorrhage, increased 6-hour, 24-hour, and 30-day survival, and increased intensive care unit, ventilator, and hospital-free days (P < 0.05), with no change in multiple organ failure deaths. Statistical modeling indicated that a clinical guideline with mean plasma:RBC ratio equal to 1:1 would encompass 98% of patients within the optimal 1:2 ratio. Conclusions:Current transfusion practices and survival rates of MT patients vary widely among trauma centers. Conventional MT guidelines may underestimate the optimal plasma and platelet to RBC ratios. Survival in civilian MT patients is associated with increased plasma and platelet ratios. Massive transfusion practice guidelines should aim for a 1:1:1 ratio of plasma:platelets:RBCs.

The ratio of fibrinogen to red cells transfused affects survival in casualties receiving massive transfusions at an army combat support hospital.

BACKGROUND To treat the coagulopathy of trauma, some have suggested early and aggressive use of cryoprecipitate as a source of fibrinogen. Our objective was to determine whether increased ratios of fibrinogen to red blood cells (RBCs) decreased mortality in combat casualties requiring massive transfusion. METHODS We performed a retrospective chart review of 252 patients at a U.S. Army combat support hospital who received a massive transfusion (>or=10 units of RBCs in 24 hours). The typical amount of fibrinogen within each blood product was used to calculate the fibrinogen-to-RBC (F:R) ratio transfused for each patient. Two groups of patients who received either a low (<0.2 g fibrinogen/RBC Unit) or high (>or=0.2 g fibrinogen/RBC Unit) F:R ratio were identified. Mortality rates and the cause of death were compared between these groups, and logistic regression was used to determine if the F:R ratio was independently associated with survival. RESULTS Two-hundred and fifty-two patients who received a massive transfusion with a mean (SD) ISS of 21 (+/-10) and an overall mortality of 75 of 252 (30%) were included. The mean (SD) F:R ratios transfused for the low and high groups were 0.1 grams/Unit (+/-0.06), and 0.48 grams/Unit (+/-0.2), respectively (p < 0.001). Mortality was 27 of 52 (52%) and 48 of 200 (24%) in the low and high F:R ratio groups respectively (p < 0.001). Additional variables associated with survival were admission temperature, systolic blood pressure, hemoglobin, International Normalized Ratio (INR), base deficit, platelet concentration and Combined Injury Severity Score (ISS). Upon logistic regression, the F:R ratio was independently associated with mortality (odds ratio 0.37, 95% confidence interval 0.171-0.812, p = 0.013). The incidence of death from hemorrhage was higher in the low F:R group, 23/27 (85%), compared to the high F:R group, 21/48 (44%) (p < 0.001). CONCLUSIONS In patients with combat-related trauma requiring massive transfusion, the transfusion of an increased fibrinogen: RBC ratio was independently associated with improved survival to hospital discharge, primarily by decreasing death from hemorrhage. Prospective studies are needed to evaluate the best source of fibrinogen and the optimal empiric ratio of fibrinogen to RBCs in patients requiring massive transfusion.

Increased Mortality Associated With the Early Coagulopathy of Trauma in Combat Casualties

BACKGROUND Recent civilian studies have documented a relationship between increased mortality and the presence of an early coagulopathy of trauma diagnosed in the emergency department (ED). We hypothesized that acute coagulopathy (international normalized ratio >/=1.5) in combat casualties was associated with increased injury severity and mortality as is seen in civilian trauma patients. METHODS A retrospective study of combat casualties who received a blood transfusion at a single combat support hospital between September 2003 and December 2004 was performed. Coagulation status, pH, base deficit, and temperature were recorded at arrival to the ED. These were analyzed by Injury Severity Score (ISS), associated injury patterns, and mortality. RESULTS A total of 3,287 patients were treated at the combat support hospital during the study period. Of these, 391 patients were transfused and primarily admitted, thus meeting the study criteria, 347 had coagulation data, and 92% had a penetrating mechanism. The prevalence of acute coagulopathy in transfused casualties measured with point-of-care devices at arrival in the ED was 38%. Mortality in those who were coagulopathic at arrival to the ED was 24% (32/133) versus 4% (8/214) in those not presenting with coagulopathy (p < 0.001). The prevalence of mortality by coagulopathy increased as ISS increased. Coagulopathy and acidosis were associated with mortality, odds ratio (OR), 5.38 [95% confidence interval (CI), 1.55-11.37] and 6.9 (95% CI, 2.1-19.5), respectively. Temperature did not affect outcomes (OR, 1.1; 95% CI, 0.4-2.6). CONCLUSIONS The early coagulopathy of trauma was rapidly diagnosed in the ED and present in more than one-third of combat casualties who received a transfusion, similar to the incidence found in civilian trauma patients. Coagulopathy, independent of hypothermia but strongly correlated with acidosis and ISS, was associated with mortality in combat casualties, similar to that found in civilian trauma patients. Early diagnosis and treatment of acute traumatic coagulopathy with new resuscitation paradigms may improve outcomes.

Warm Fresh Whole Blood Is Independently Associated With Improved Survival for Patients With Combat-Related Traumatic Injuries

BACKGROUND Increased understanding of the pathophysiology of the acute coagulopathy of trauma has lead many to question the current transfusion approach to hemorrhagic shock. We hypothesized that warm fresh whole blood (WFWB) transfusion would be associated with improved survival in patients with trauma compared with those transfused only stored component therapy (CT). METHODS We retrospectively studied US Military combat casualty patients transfused >or=1 unit of red blood cells (RBCs). The following two groups of patients were compared: (1) WFWB, who were transfused WFWB, RBCs, and plasma but not apheresis platelets and (2) CT, who were transfused RBC, plasma, and apheresis platelets but not WFWB. The primary outcomes were 24-hour and 30-day survival. RESULTS Of 354 patients analyzed there were 100 in the WFWB and 254 in the CT group. Patients in both groups had similar severity of injury determined by admission eye, verbal, and motor Glasgow Coma Score, base deficit, international normalized ratio, hemoglobin, systolic blood pressure, and injury severity score. Both 24-hour and 30-day survival were higher in the WFWB cohort compared with CT patients, 96 of 100 (96%) versus 223 of 254 (88%), (p = 0.018) and 95% to 82%, (p = 0.002), respectively. An increased amount (825 mL) of additives and anticoagulants were administered to the CT compared with the WFWB group, (p < 0.001). Upon multivariate logistic regression the use of WFWB and the volume of WFWB transfused was independently associated with improved 30-day survival. CONCLUSIONS In patients with trauma with hemorrhagic shock, resuscitation strategies that include WFWB may improve 30-day survival, and may be a result of less anticoagulants and additives with WFWB use in this population.

A predictive model for massive transfusion in combat casualty patients.

BACKGROUND Massive transfusion (MT) is associated with increased morbidity and mortality in severely injured patients. Early and aggressive use of blood products in these patients may correct coagulopathy, control bleeding, and improve outcomes. However, rapid identification of patients at risk for MT has been difficult. We postulated that evaluation of clinical variables routinely assessed upon admission would allow identification of these patients for earlier, more effective intervention. METHODS A retrospective cohort study was conducted at a single combat support hospital to identify risk factors for MT in patients with traumatic injuries. Demographic, diagnostic, and laboratory variables obtained upon admission were evaluated. Univariate and multivariate analyses were performed. An algorithm was formulated, validated with an independent dataset and a simple scoring system was devised. RESULTS Three thousand four hundred forty-two patient records were reviewed. At least one unit of blood was transfused to 680 patients at the combat support hospital. Exclusion criteria included age less than 18 years, transfer from another medical facility, designation as a security internee, or incomplete data fields. The final number of patients was 302, of whom 26.5% (80 of 302) received a MT. Patients with MT had higher mortality (29 vs. 7% [p < 0.001]), and an increased Injury Severity Score (25 +/- 11.1 vs. 18 +/- 16.2 [p < 0.001]). Four independent risk factors for MT were identified: heart rate >105 bpm, systolic blood pressure <110 mm Hg, pH <7.25, and hematocrit <32.0%. An algorithm was created to analyze the risk of MT (area under the curve [AUC] = 0.839). In an independent data set of 396 patients the ability to accurately identify those requiring MT was 66% (AUC = 0.747). CONCLUSIONS Independent predictors for MT were identified in a cohort of severely injured patients requiring transfusions. Patients requiring a MT can be identified with variables commonly obtained upon hospital admission.

A Reduction in Clot Formation Rate and Strength Assessed by Thrombelastography Is Indicative of Transfusion Requirements in Patients With Penetrating Injuries

BACKGROUND Bleeding is a major cause of death in patients with traumatic injuries. Recently, thrombelastography (TEG) has been suggested as an additional means of evaluating coagulation in trauma patients. We hypothesized that TEG data would aid in defining the coagulopathy of trauma in patients with penetrating traumatic injuries. METHODS A retrospective study was performed of patients (n = 44) with penetrating injuries admitted to a combat support hospital during a 2-month period in 2004. Recorded data included standard laboratory data, TEG parameters, and blood product use in the first 24 hours after admission. Values were compared with clinically accepted ranges and those obtained from the Haemoscope Corporation. RESULTS At admission, International Normalization Ratio, prothrombin time, and partial thromboplastin time were increased in 39% (>or=1.5), 31% (>16 seconds), and 37% (>40 seconds) of patients, respectively, suggesting hypocoagulation, but these variables did not correlate with the use of blood products (p > 0.05). TEG values obtained within 24 hours of admission (6 hours +/- 5.7 hours; median of 4.5 hours) demonstrated hypocoagulation based on delayed propagation of the clot (increased K time and reduced alpha-angle) and decreased clot strength (reduced maximal amplitude [MA]). MA correlated (r = 0.57, p < 0.01) with blood product use as well as platelet count (r = 0.61, p < 0.01). Patients with reduced MA (n = 23) used more blood products and had reduced platelet counts and hematocrit. CONCLUSION Thrombelastography was a more accurate indicator of blood product requirements in our patient population than prothrombin time, partial thromboplastin time, and International Normalization Ratio. Thrombelastography enhanced by platelet count and hematocrit can guide blood transfusion requirements.

Evidence-based practice guidelines for plasma transfusion

BACKGROUND: There is little systematically derived evidence‐based guidance to inform plasma transfusion decisions. To address this issue, the AABB commissioned the development of clinical practice guidelines to help direct appropriate transfusion of plasma.

Effect of plasma and red blood cell transfusions on survival in patients with combat related traumatic injuries.

BACKGROUND The amount and age of stored red blood cells (RBCs) are independent predictors of multiorgan failure and death in transfused critically ill patients. The independent effect of plasma transfusion on survival has not been evaluated. Our objective was to determine the independent effects of plasma and RBC transfusion on survival for patients with combat-related traumatic injuries receiving any blood products. METHODS We performed a retrospective review of 708 patients transfused at least one unit of a blood product at one combat support hospital between November 2003 and December 2004. Admission vital signs, laboratory values, amount of blood products transfused in a 24-hour period, and Injury Severity Score (ISS) were analyzed by multivariate logistic regression to determine independent associations with in-hospital mortality. RESULTS Seven hundred and eight of 3,287 (22%) patients admitted for traumatic injuries were transfused a blood product. Median ISS was 14 (range, 9-25). In-hospital mortality was 12%. Survival was associated with admission Glasgow Coma Scale score, SBP, temperature, hematocrit, base deficit, INR, amount of RBCs transfused, and massive transfusion. Each transfused FFP unit was independently associated with increased survival (OR: 1.17; 95% CI: [1.06-1.29]; p = 0.002); each transfused RBC unit was independently associated with decreased survival (OR: 0.86; [0.8-0.92]; p = 0.001). A subset analysis of patients (n = 567) without massive transfusion (1-9 RBC/FWB units) also revealed an independent association between each FFP unit and improved survival (OR: 1.22; 95% CI: [1.0-1.48]; p = 0.05) and between each RBC unit and decreased survival (OR: 0.77; [0.64-0.92]; p = 0.004). CONCLUSION For trauma patients transfused at least one unit of a blood product, FFP and RBC amounts were independently associated with increased survival and decreased survival, respectively. Prospective studies are needed to determine whether the early and increased use of plasma and decreased use of RBCs affect mortality for patients with traumatic injuries requiring transfusion.

Increased platelet:RBC ratios are associated with improved survival after massive transfusion.

BACKGROUND Several recent military and civilian trauma studies demonstrate that improved outcomes are associated with early and increased use of plasma-based resuscitation strategies. However, outcomes associated with platelet transfusions are poorly characterized. We hypothesized that increased platelet:red blood cells (RBC) ratios would decrease hemorrhagic death and improve survival after massive transfusion (MT). METHODS A transfusion database of patients transported from the scene to 22 Level I Trauma Centers over 12 months in 2005 to 2006 was reviewed. MT was defined as receiving ≥ 10 RBC units within 24 hours of admission. To mitigate survival bias, 25 patients who died within 60 minutes of arrival were excluded from analysis. Six random donor platelet units were considered equal to a single apheresis platelet unit. Admission and outcome data associated with the low (>1:20), medium (1:2), and high (1:1) platelet:RBC ratios were examined. These groups were based on the median value of the tertiles for the ratio of platelets:RBC units. RESULTS Two thousand three hundred twelve patients received at least one unit of blood and 643 received an MT. Admission vital signs, INR, temperature, pH, Glasgow Coma Scale, Injury Severity Score, and age were similar between platelet ratio groups. The average admission platelet counts were lower in the patients who received the high platelet:RBC ratio versus the low ratio (192 vs. 216, p = 0.03). Patients who received MT were severely injured, with a mean (± standard deviation) Injury Severity Score of 33 ± 16 and received 22 ± 15 RBCs and 11 ± 14 platelets within 24 hours of injury. Increased platelet ratios were associated with improved survival at 24 hours and 30 days (p < 0.001 for both). Truncal hemorrhage as a cause of death was decreased (low: 67%, medium: 60%, high: 47%, p = 0.04). Multiple organ failure mortality was increased (low: 7%, medium: 16%, high: 27%, p = 0.003), but overall 30-day survival was improved (low: 52%, medium: 57%, high: 70%) in the high ratio group (medium vs. high: p = 0.008; low vs. high: p = 0.007). CONCLUSION Similar to recently published military data, transfusion of platelet:RBC ratios of 1:1 was associated with improved early and late survival, decreased hemorrhagic death and a concomitant increase in multiple organ failure-related mortality. Based on this large retrospective study, increased and early use of platelets may be justified, pending the results of prospective randomized transfusion data.

An Evaluation of the Impact of Apheresis Platelets Used in the Setting of Massively Transfused Trauma Patients

INTRODUCTION Trauma is a major cause of morbidity and mortality worldwide. Of patients arriving to trauma centers, patients requiring massive transfusion (MT, >or=10 units in 24 hours) are a small patient subset but are at the highest risk of mortality. Transfusion of appropriate ratios of blood products to such patients has recently been an area of interest to both the civilian and military medical community. Plasma is increasingly recognized as a critical component, though less is known about appropriate ratios of platelets. Combat casualties managed at the busiest combat hospital in Iraq provided an opportunity to examine this question. METHODS In-patient records for 8,618 trauma casualties treated at the military hospital in Baghdad more than a 3-year interval between January 2004 and December 2006 were retrospectively reviewed and patients requiring MT (n = 694) were identified. Patients who required MT in the first 24 hours and did not receive fresh whole blood were divided into study groups defined by source of platelets: (1) patient receiving a low ratio of platelets (<1:16 apheresis platelets per stored red cell unit, aPLT:RBC) (n = 214), (2) patients receiving a medium ratio of platelets (1:16 to <1:8 aPLT:RBC) (n = 154), and (3) patients receiving a high ratio of platelets (>or=1:8 aPLT:RBC) (n = 96). The primary endpoint was survival at 24 hours and at 30 days. RESULTS At 24 hours, patients receiving a high ratio of platelets had higher survival (95%) as compared with patients receiving a medium ratio (87%) and patients receiving the lowest ratio of platelets (64%) (log-rank p = 0.04 and p < 0.001, respectively). The survival benefit for the high and medium ratio groups remained at 30 days as compared with those receiving the lowest ratio of platelets (75% and 60% vs. 43%, p < 0.001 for both comparisons). On multivariate regression, plasma:RBC ratios and aPLT:RBC were both independently associated with improved survival at 24 hours and at 30 days. CONCLUSION Transfusion of a ratio of >or=1:8 aPLT:RBC is associated with improved survival at 24 hours and at 30 days in combat casualties requiring a MT within 24 hours of injury. Although prospective study is needed to confirm this finding, MT protocols outside of investigational research should consider incorporation of appropriate ratios of both plasma and platelets.