Philip C. Spinella

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.

Duration of red blood cell storage is associated with increased incidence of deep vein thrombosis and in hospital mortality in patients with traumatic injuries

IntroductionIn critically ill patients the relationship between the storage age of red blood cells (RBCs) transfused and outcomes are controversial. To determine if duration of RBC storage is associated with adverse outcomes we studied critically ill trauma patients requiring transfusion.MethodsThis retrospective cohort study included patients with traumatic injuries transfused ≥5 RBC units. Patients transfused ≥ 1 unit of RBCs with a maximum storage age of up to 27 days were compared with those transfused 1 or more RBC units with a maximum storage age of ≥ 28 days. These study groups were also matched by RBC amount (+/- 1 unit) transfused. Primary outcomes were deep vein thrombosis and in-hospital mortality.ResultsTwo hundred and two patients were studied with 101 in both decreased and increased RBC age groups. No differences in admission vital signs, laboratory values, use of DVT prophylaxis, blood products or Injury Severity Scores were measured between study groups. In the decreased compared with increased RBC storage age groups, deep vein thrombosis occurred in 16.7% vs 34.5%, (P = 0.006), and mortality was 13.9% vs 26.7%, (P = 0.02), respectively. Patients transfused RBCs of increased storage age had an independent association with mortality, OR (95% CI), 4.0 (1.34 - 11.61), (P = 0.01), and had an increased incidence of death from multi-organ failure compared with the decreased RBC age group, 16% vs 7%, respectively, (P = 0.037).ConclusionsIn trauma patients transfused ≥5 units of RBCs, transfusion of RBCs ≥ 28 days of storage may be associated with deep vein thrombosis and death from multi-organ failure.

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.

Warm fresh whole blood transfusion for severe hemorrhage: U.S. military and potential civilian applications.

Objective: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. Background: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. Main Results: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. Conclusions: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.

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.

The effect of recombinant activated factor VII on mortality in combat-related casualties with severe trauma and massive transfusion

BACKGROUND The majority of patients with potentially survivable combat-related injuries die from hemorrhage. Our objective was to determine whether the use of recombinant activated factor VII (rFVIIa) decreased mortality in combat casualties with severe trauma who received massive transfusions and if its use was associated with increased severe thrombotic events. METHODS We retrospectively reviewed a database of combat casualty patients with severe trauma (Injury Severity Score [ISS] >15) and massive transfusion (red blood cell [RBCs] >/=10 units/24 hours) admitted to one combat support hospital in Baghdad, Iraq, between December 2003 and October 2005. Admission vital signs and laboratory data, blood products, ISS, 24-hour and 30-day mortality, and severe thrombotic events were compared between patients who received rFVIIa (rFVIIa) and did not receive rFVIIa (rFVIIa). RESULTS Of 124 patients in this study, 49 patients received rFVIIa and 75 did not. ISS, laboratory values, and admission vitals did not differ between rFVIIa and rFVIIa groups, except for systolic blood pressure (mm Hg) 105 +/- 33 and 92 +/- 28, p = 0.02 and temperature ( degrees F) 96.3 +/- 2.1 and 95.2 +/- 2.4, p = 0.03, respectively. Interactions between all vital signs and laboratory values measured upon admission, to include systolic blood pressure and temperature, were not significant when measured between rFVIIa use and 30-day mortality. Twenty-four-hour mortality was 7 of 49 (14%) in rFVIIa and 26 of 75 (35%) in rFVIIa, (p = 0.01); 30-day mortality was 15 of 49 (31%) and 38 of 75 (51%), (p = 0.03). Death from hemorrhage was 8 of 14 (57%) for rFVIIa patients compared with 29 of 37 (78%) for rFVIIa patients, (p = 0.12). The incidence of severe thrombotic events was similar in both groups. CONCLUSIONS The early use of rFVIIa was associated with decreased 30-day mortality in severely injured combat casualties requiring massive transfusion, but was not associated with increased risk of severe thrombotic events.

Ten-year analysis of transfusion in Operation Iraqi Freedom and Operation Enduring Freedom: increased plasma and platelet use correlates with improved survival.

BACKGROUND The Joint Theater Trauma Registry database, begun early in Operation Iraqi Freedom and Operation Enduring Freedom, created a comprehensive repository of information that facilitated research efforts and produced rapid changes in clinical care. New clinical practice guidelines were adopted throughout the last decade. The damage-control resuscitation clinical practice guideline sought to provide high-quality blood products in support of tissue perfusion and hemostasis. The goal was to reduce death from hemorrhagic shock in patients with severe traumatic bleeding. This 10-year review of the Joint Theater Trauma Registry database reports the military’s experience with resuscitation and coagulopathy, evaluates the effect of increased plasma and platelet (PLT)–to–red blood cell ratios, and analyzes other recent changes in practice. METHODS Records of US active duty service members at least 18 years of age who were admitted to a military hospital from March 2003 to February 2012 were entered into a database. Those who received at least one blood product (n = 3,632) were included in the analysis. Data were analyzed with respect to interactions within and between categories (demographics, admission characteristics, hospital course, and outcome). Transfusions were analyzed with respect to time, survival, and effect of increasing transfusion ratios. RESULTS Coagulopathy was prevalent upon presentation (33% with international normalized ratio ≥ 1.5), correlated with increased mortality (fivefold higher), and was associated with the need for massive transfusion. High transfusion ratios of fresh frozen plasma and PLT to red blood cells were correlated with higher survival but not decreased blood requirement. Survival was most correlated with PLT ratio, but high fresh frozen plasma ratio had an additive effect (PLT odds ratio, 0.22). CONCLUSION This 10-year evaluation supports earlier studies reporting the benefits of damage-control resuscitation strategies in military casualties requiring massive transfusion. The current analysis suggests that defects in PLT function may contribute to coagulopathy of trauma. LEVEL OF EVIDENCE Epidemiologic study, level IV.

Association between length of storage of transfused red blood cells and multiple organ dysfunction syndrome in pediatric intensive care patients

BACKGROUND: The objective was to determine if there is an association between red blood cell (RBC) storage time and development of new or progressive multiple organ dysfunction syndrome (MODS) in critically ill children.