Analysis of breast cancer in young women in the Department of Defense (DOD) database.

PURPOSE: Breast tumors from young women under the age of 40 account for approximately 7% of cases and have a poor prognosis independent of established prognostic factors. We evaluated the patient population served by the Military Health System, where a disproportionate number of breast cancer cases in young women are seen and treated in a single universal coverage healthcare system. METHODS: The Military Health System Repository and the DoD Central Registration databases were used to identify female breast cancer patients diagnosed or treated at military treatment facilities from 1998 to 2007. RESULTS: 10,066 women were diagnosed with invasive breast cancer at DoD facilities from 1998 to 2007, of which 11.3% (1139), 23.4% (2355) and 65.2% (6572) were < 40, 40-49 and > 50 years old (yo), respectively, at diagnosis. 53% in the < 40 yo cohort were white, 25% were African American (AA) and 8% were Hispanic, with 14% undisclosed. Breast cancer in women diagnosed < 40 yo was more high grade (p < 0.0001), Stage II (p < 0.0001) and ER negative (p < 0.0001). There was a higher rate of bilateral mastectomies among the women < 40 compared to those 40-49 and > 50 (18.4% vs. 9.1% and 5.0%, respectively). Independent of disease stage, chemotherapy was given more frequently to < 40 yo (90.43%) and 40-49 yo (81.44%) than ≥ 50 yo (53.71%). The 10-year overall survival of younger women was similar to the ≥ 50 yo cohort. Outcomes in the African American and Hispanic subpopulations were comparable to the overall cohort. CONCLUSION: Younger women had a similar overall survival rate to older women despite receiving more aggressive treatment.

Comparison of platelet transfusion as fresh whole blood versus apheresis platelets for massively transfused combat trauma patients (CME).

BACKGROUND: At major combat hospitals, the military is able to provide blood products to include apheresis platelets (aPLT), but also has extensive experience using fresh whole blood (FWB). In massively transfused trauma patients, we compared outcomes of patients receiving FWB to those receiving aPLT. STUDY DESIGN AND METHODS: This study was a retrospective review of casualties at the military hospital in Baghdad, Iraq, between January 2004 and December 2006. Patients requiring massive transfusion (≥10 units in 24 hr) were divided into two groups: those receiving FWB (n = 85) or aPLT (n = 284) during their resuscitation. Admission characteristics, resuscitation, and survival were compared between groups. Multivariate regression analyses were performed comparing survival of patients at 24 hours and at 30 days. Secondary outcomes including adverse events and causes of death were analyzed. RESULTS: Unadjusted survival between groups receiving aPLT and FWB was similar at 24 hours (84% vs. 81%, respectively; p = 0.52) and at 30 days (60% versus 57%, respectively; p = 0.72). Multivariate regression failed to identify differences in survival between patients receiving PLT transfusions either as FWB or as aPLT at 24 hours or at 30 days. CONCLUSIONS: Survival for massively transfused trauma patients receiving FWB appears to be similar to patients resuscitated with aPLT. Prospective trials will be necessary before consideration of FWB in the routine management of civilian trauma. However, in austere environments where standard blood products are unavailable, FWB is a feasible alternative.

Impact of improved combat casualty care on combat wounded undergoing exploratory laparotomy and massive transfusion.

BACKGROUND: Studies have shown decreased mortality after improvements in combat casualty care, including increased fresh frozen plasma (FFP):red blood cell (RBC) ratios. The objective was to evaluate the evolution and impact of improved combat casualty care at different time periods of combat operations. METHODS: A retrospective review was performed at one combat support hospital in Iraq of patients requiring both massive transfusion (≥ 10 units RBC in 24 hours) and exploratory laparotomy. Patients were divided into two cohorts based on year wounded: C1 between December 2003 and June 2004, and C2 between September 2007 and May 2008. Admission data, amount of blood products and fluid transfused, and 48 hour mortality were compared. Statistical significance was set at p < 0.05. RESULTS: There was decreased mortality in C2 (47% vs. 20%). Patients arrived warmer with higher hemoglobin. They were transfused more RBC and FFP in the emergency department (5 units ± 3 units vs. 2 units ± 2 units; 3 units ± 2 units vs. 0 units ± 1 units, respectively) and received less crystalloid in operating room (3.3 L ± 2.2 L vs. 8.5 L ± 4.9 L). The FFP:RBC ratio was also closer to 1:1 in C2 (0.775 ± 0.32 vs. 0.511 ± 0.21). CONCLUSIONS: The combination of improved prehospital care, trauma systems approach, performance improvement projects, and improved transfusion or resuscitation practices have led to a 50% decrease in mortality for this critically injured population. We are now transfusing blood products in a ratio more consistent with 1 FFP to 1 RBC. Simultaneously, crystalloid use has decreased by 61%, all of which is consistent with hemostatic resuscitation principles.

The association of blood component use ratios with the survival of massively transfused trauma patients with and without severe brain injury.

BACKGROUND: The effect of blood component ratios on the survival of patients with traumatic brain injury (TBI) has not been studied. METHODS: A database of patients transfused in the first 24 hours after admission for injury from 22 Level I trauma centers over an 18-month period was queried to find patients who (1) met different definitions of massive transfusion (5 units red blood cell [RBC] in 6 hours vs. 10 units RBC in 24 hours), (2) received high or low ratios of platelets or plasma to RBC units (<1:2 vs. ≥ 1:2), and (3) had severe TBI (head abbreviated injury score ≥ 3) (TBI+). RESULTS: Of 2,312 total patients, 850 patients were transfused with ≥ 5 RBC units in 6 hours and 807 could be classified into TBI+ (n = 281) or TBI- (n = 526). Six hundred forty-three patients were transfused with ≥ 10 RBC units in 24 hours with 622 classified into TBI+ (n = 220) and TBI- (n = 402). For both high-risk populations, a high ratio of platelets:RBCs (not plasma) was independently associated with improved 30-day survival for patients with TBI+ and a high ratio of plasma:RBCs (not platelets) was independently associated with improved 30-day survival in TBI- patients. CONCLUSIONS: High platelet ratio was associated with improved survival in TBI+ patients while a high plasma ratio was associated with improved survival in TBI- patients. Prospective studies of blood product ratios should include TBI in the analysis for determination of optimal use of ratios on outcome in injured patients.

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.

Role of natural killer cells in innate protection against lethal ebola virus infection.

Ebola virus is a highly lethal human pathogen and is rapidly driving many wild primate populations toward extinction. Several lines of evidence suggest that innate, nonspecific host factors are potentially critical for survival after Ebola virus infection. Here, we show that nonreplicating Ebola virus-like particles (VLPs), containing the glycoprotein (GP) and matrix protein virus protein (VP)40, administered 1-3 d before Ebola virus infection rapidly induced protective immunity. VLP injection enhanced the numbers of natural killer (NK) cells in lymphoid tissues. In contrast to live Ebola virus, VLP treatment of NK cells enhanced cytokine secretion and cytolytic activity against NK-sensitive targets. Unlike wild-type mice, treatment of NK-deficient or -depleted mice with VLPs had no protective effect against Ebola virus infection and NK cells treated with VLPs protected against Ebola virus infection when adoptively transferred to naive mice. The mechanism of NK cell-mediated protection clearly depended on perforin, but not interferon-gamma secretion. Particles containing only VP40 were sufficient to induce NK cell responses and provide protection from infection in the absence of the viral GP. These findings revealed a decisive role for NK cells during lethal Ebola virus infection. This work should open new doors for better understanding of Ebola virus pathogenesis and direct the development of immunotherapeutics, which target the innate immune system, for treatment of Ebola virus infection.

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. STUDY DESIGN AND METHODS: A systematic review (SR) and meta-analysis of randomized and observational studies was performed to quantify known benefits and harms of plasma transfusion in common clinical scenarios (see accompanying article). A multidisciplinary guidelines panel then used the SR and the GRADE methodology to develop evidence-based plasma transfusion guidelines as well as identify areas for future investigation. RESULTS: Based on evidence ranging primarily from moderate to very low in quality, the panel developed the following guidelines: 1) The panel suggested that plasma be transfused to patients requiring massive transfusion. However, 2) the panel could not recommend for or against transfusion of plasma at a plasma : red blood cell ratio of 1:3 or more during massive transfusion, 3) nor could the panel recommend for or against transfusion of plasma to patients undergoing surgery in the absence of massive transfusion. 4) The panel suggested that plasma be transfused in patients with warfarin therapy-related intracranial hemorrhage, 5) but could not recommend for or against transfusion of plasma to reverse warfarin anticoagulation in patients without intracranial hemorrhage. 6) The panel suggested against plasma transfusion for other selected groups of patients. CONCLUSION: We have systematically developed evidence-based guidance to inform plasma transfusion decisions in common clinical scenarios. Data from additional randomized studies will be required to establish more comprehensive and definitive guidelines for plasma transfusion.

Popliteal artery repair in massively transfused military trauma casualties: a pursuit to save life and limb.

BACKGROUND: Popliteal artery war wounds can bleed severely and historically have high rates of amputation associated with ligation (72%) and repair (32%). More than before, casualties are now surviving the initial medical evacuation and presenting with severely injured limbs that prompt immediate limb salvage decisions in the midst of life-saving maneuvers. A modern analysis of current results may show important changes because previous limb salvage strategies were limited by the resuscitation and surgical techniques of their eras. Because exact comparisons between wars are difficult, the objective of this study was to calculate a worst-case (a pulseless, fractured limb with massive hemorrhage from popliteal artery injury) amputation-free survival rate for the most severely wounded soldiers undergoing immediate reconstruction to save both life and limb. METHODS: We performed a retrospective study of trauma casualties admitted to the combat support hospital at Ibn Sina Hospital in Baghdad, Iraq, between 2003 and 2007. US military casualties requiring a massive transfusion (> or = 10 blood units transfused within 24 hours of injury) were identified. We extracted data on the subset of casualties with a penetrating supra or infrageniculate popliteal arterial vascular injury. Demographics, injury mechanism, Injury Severity Score, tourniquet use, physiologic parameters, damage control adjuncts, surgical repair techniques, operative time, and outcomes (all-cause 30-day mortality, amputation rates, limb salvage failure, and graft patency) were investigated. RESULTS: Forty-six massively transfused male casualties, median age 24 years (range, 19-54 years; mean Injury Severity Score, 19 +/- 8.0), underwent immediate orthopedic stabilization and vascular reconstruction. There was one early death. The median operative time for the vascular repairs was 217 minutes (range, 94-630 minutes) and included all damage control procedures. Combined arterial and venous injuries occurred in 17 (37%). Ligation was performed for no arterial and 9 venous injuries. Amputations (transtibial or transfemoral) were considered limb salvage failures (14 of 48, 29.2%) and were grouped as immediate (< or = 48 hours, 5), early (>48 hours and < or = 30 days, 6), or late (>30 days, 3). Limb losses were from graft thrombosis, infection, or chronic pain. Combined arterial and venous injuries occurred in 17 (37%). Ligation was performed for no arterial and nine venous injuries. For a median follow-up (excluding death) of 48 months (range, 23-75 months), the amputation-free survival rate was 67%. CONCLUSIONS: This study, a worst-case study, showed comparable results to historical controls regarding limb salvage rates (71% for Iraq vs. 56-69% for the Vietnam War). Thirty-day survival (98%), 4-year amputation-free survival (67%), and complication-free rates (35%) fill knowledge gaps. Guidelines for managing popliteal artery injuries show promising results because current resuscitation practices and surgical care yielded similar amputation rates to prior conflicts despite more severe injuries. Significant transfusion requirements and injury severity may not indicate a life-over-limb strategy for popliteal arterial repairs. Future studies of limb salvage failures may help improve casualty care by reducing the complications that directly impact amputation-free survival.

Use of recombinant factor VIIa in US military casualties for a five-year period.

BACKGROUND: Two prospective randomized trauma trials have shown recombinant factor VIIa (rFVIIa) to be safe and to decrease transfusion requirements. rFVIIa is presently used in 22% of massively transfused civilian trauma patients. The US Military has used rFVIIa in combat trauma patients for five years, and two small studies of massively transfused patients described an association with improved outcomes. This study was undertaken to assess how deployed physicians are using rFVIIa and its impact on casualty outcomes. METHODS: US combat casualties (n = 2,050) receiving any blood transfusion from 2003 to 2009 were reviewed to compare patients receiving rFVIIa (n = 506) with those who did not (n = 1,544). Propensity-score matching (primary analysis) and multivariable logistic regression were used to compare outcomes. Differences were determined at p < 0.05. RESULTS: Twenty-five percent of patients received rFVIIa. Significant differences were noted between groups in indices of injury severity (Injury Severity Score, Abbreviated Injury Scale score, and Glasgow Coma Scale score), admission physiology (systolic blood pressure, diastolic blood pressure, heart rate, temperature, base deficit, hemoglobin, and international normalization ratio), and use of blood products, indicating that patients treated with rFVIIa were more severely injured, in shock, and coagulopathic. For propensity-score matching, factors associated with death were used: Injury Severity Score, Glasgow Coma Scale score, heart rate, systolic blood pressure, diastolic blood pressure, Hgb, and total packed red blood cell. A total of 266 patients per group were matched; 52% of the rFVIIa group. After pairing, there were no significant differences in any of the demographics, including incidence of massive transfusion (53% vs. 51%). There was no difference in the rate of complications (21% vs. 21%) or mortality (14% vs. 20%) for patients not treated or receiving rFVIIa, respectively. CONCLUSION: In military casualties, rFVIIa is used in the most severely injured patients based on physician selection rather than on guideline criteria. Use of rFVIIa is not associated with an improvement in survival or an increase in complications. The undetected bias of physician selection of patients for treatment with rFVIIa, likely, has an impact on case matching to achieve equivalence similar to that of randomized control studies. This inability to match populations, thus, prevents definitive interpretation of this study and others studies of similar design. This problem emphasizes the need to develop entry criteria to identify patients who could potentially benefit from use of rFVIIa and the need to subsequently perform efficacy studies.

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.

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.

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 > or =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 (> or =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 (> or =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.

Massive transfusion and nonsurgical hemostatic agents.

BACKGROUND: Hemorrhage in trauma is a significant challenge, accounting for 30% to 40% of all fatalities, second only to central nervous system injury as a cause of death. However, hemorrhagic death is the leading preventable cause of mortality in combat casualties and typically occurs within 6 to 24 hrs of injury. In cases of severe hemorrhage, massive transfusion may be required to replace more than the entire blood volume. Early prediction of massive transfusion requirements, using clinical and laboratory parameters, combined with aggressive management of hemorrhage by surgical and nonsurgical means, has significant potential to reduce early mortality. DISCUSSION: Although the classification of massive transfusion varies, the most frequently used definition is ten or more units of blood in 24 hrs. Transfusion of red blood cells is intended to restore blood volume, tissue perfusion, and oxygen-carrying capacity; platelets, plasma, and cryoprecipitate are intended to facilitate hemostasis through prevention or treatment of coagulopathy. Massive transfusion is uncommon in civilian trauma, occurring in only 1% to 3% of trauma admissions. As a result of a higher proportion of penetrating injury in combat casualties, it has occurred in approximately 8% of Operation Iraqi Freedom admissions and in as many as 16% during the Vietnam conflict. Despite its potential to reduce early mortality, massive transfusion is not without risk. It requires extensive blood-banking resources and is associated with high mortality. SUMMARY: This review describes the clinical problems associated with massive transfusion and surveys the nonsurgical management of hemorrhage, including transfusion of blood products, use of hemostatic bandages/agents, and treatment with hemostatic medications.

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.

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.

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.

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.

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.

Successful perioperative management in a patient with factor XI deficiency.

Factor XI (FXI) deficiency is an autosomal disorder which manifests as bleeding of varying severity. While homozygotes typically experience more dramatic bleeding symptoms, heterozygotes may experience clinically significant bleeding following surgical procedures or trauma, and therefore the condition is not purely recessive. The clinical significance of FXI deficiency is complicated in that FXI levels do not correlate well with bleeding severity, and in fact the bleeding risk is variable even for an individual in response to different haemostatic challenges. We present the case of a 74-year-old man of Ashkenazi Jewish heritage with a family and personal history of bleeding during surgical procedures, who presented with excessive bleeding following total thyroidectomy. He was found to have a FXI level of 52% (low normal). Genetic testing revealed that he was heterozygous for the c.403G>T mutation. This case demonstrates successful work-up and perioperative management of a patient with FXI deficiency.