Massive Transfusion Patients Research Articles

Mechanism of Injury Affects Acute Coagulopathy of Trauma in Combat Casualties

Recent evidence suggests trauma involving total body tissue damage increases the acute coagulopathy of trauma (ACOT) by various mechanisms, especially in massive transfusion (MT). Our hypothesis was that MT patients injured by explosion will have a higher international normalization ratio (INR) at admission than MT patients injured by gunshot wound (GSW). A retrospective review was performed on US military injured in Operation Iraqi Freedom/Operation Enduring Freedom from March 2003 to September 2008, who received MT (≥ 10 red blood cells in 24 hours) and had an INR on admission. Two cohorts were created based on mechanism. Admission vital signs, labs, transfusion, and mortality data were compared. Seven hundred fifty-one MT patients were identified. Four hundred fifty patients had admission INR and were injured by either GSW or explosion. Patients demonstrated similar injury severity scale and Glasgow Coma Scale. Patients injured by explosion presented with higher INR, greater base deficit, and more tachycardic than patients injured by GSW. Transfusion of blood products was similar between both groups. The primary finding of this study is that patients injured by explosion presented with a higher INR than those injured by GSW, even with similar injury severity scale. In addition, patients injured by explosion presented more tachycardic and with a greater base deficit. These findings support the theory that ACOT is affected by the amount of tissue injured. Further research is needed into the pathophysiology of ACOT because this may impact care of patients with total body tissue damage/hypoxia and improve the treatment of their coagulopathy while minimizing the attendant complications.

Fibrinogen concentrate for management of bleeding

Fibrinogen concentrate for management of bleeding

Clinical Observation Study of Massive Blood Transfusion in a Tertiary Care Hospital in Korea

PurposeMassive blood transfusios are uncommon. The goal of this study was to propose an ideal ratio for the blood component of massive hemorrhage treatment after review of five years of massive transfusion practice, in order to have the best possible clinical outcomes.Materials and MethodsWe defined a 'massive transfusion' as receiving 10 or more units of red blood cells in one day. A list of patients receiving a massive transfusion from 2004 to 2008 was generated using the electronic medical records. For each case, we calculated the ratio of blood components and examined its relationship to their survival.ResultsThree hundred thirty four patients underwent massive transfusion during the five years of the study. The overall seven-day hospital mortality for massive transfusion patients was 26.1%. Factors independently predictive of survival were a fresh-frozen plasma (FFP)/packed red blood cell (pRBC) ratio≥1.1 with an odds ratio (OR) of 1.96 (1.03-3.70), and elective admission with an OR of 2.6 (1.52-4.40). The receiver operation characteristic (ROC) curve suggest that a 1 : 1 : 1 ratio of pRBCs to FFP to platelets is the best ratio for survival.ConclusionFixing blood-component ratios during active hemorrhage shows improved outcomes. Thus, the hospital blood bank and physician hypothesized that a fixed blood component ratio would help to reduce mortality and decrease utilization of the overall blood component.

Resuscitation beyond the abdominal compartment syndrome

In the 1980s, we witnessed tremendous advances in trauma care including trauma system development, advanced trauma life support, damage control surgery and ICU resuscitation. As a result, patients who used to bleed to death in the operating room survived. However, many went on to develop multiple organ failure (MOF) and in the mid-1990s, an epidemic of abdominal compartment syndrome (ACS) that emerged in these MOF survivors stimulated fundamental changes in early management of patients arriving in shock with severe bleeding. In the early 2000s, a massive transfusion protocol (emphasizing aggressive use of fresh frozen plasma) coupled with hypotensive resuscitation and rapid hemorrhage control were implemented and refined at a busy level I trauma center in Houston, Texas, USA. These changes were associated with a 50% reduction in mortality in massive transfusion patients, and ACS virtually disappeared. ACS is a modifiable link in the MOF cascade to death after severe shock. However, as ACS disappears, MOF is still occurring. Although fewer patients are dying of MOF, it remains the leading cause of prolonged ICU stays and long-term disability. This experience underscores the importance of ongoing epidemiologic characterization of postinjury MOF.

The Role of Rotation Thromboelastometry in Early Prediction of Massive Transfusion

Early prediction of massive transfusion (MT) is critical in the management of severely injured trauma patients. Variables available early after injury including physiologic, laboratory, and rotation thromboelastometric (ROTEM) parameters were evaluated as predictors for the need of MT. After Institutional Review Board approval, we retrospectively reviewed a cohort of severely injured trauma patients (Injury Severity Score ≥ 16) admitted to a Level I trauma center with available ROTEM measurements on hospital admission during a 1-year study period. Patients with isolated head injury (Abbreviated Injury Scale head ≥ 3 and Abbreviated Injury Scale chest, abdomen, and extremity < 3) and patients with a penetrating mechanism of injury were excluded. Patients who received a MT (≥ 10 units packed red blood cell within 24 hours of admission) were compared with patients who did not. Variables independently associated with MT were identified using stepwise logistic regression. A total of 53 patients met inclusion criteria. Of these, 18 patients (34.0%) received a MT and 35 patients (66.0%) did not. Massively transfused patients had significantly lower baseline hemoglobin values (7.9 g/dL ± 0.4 g/dL vs. 11.4 g/dL ± 0.4 g/dL; p < 0.001) and a trend toward higher lactate (4.8 mmol/L ± 0.8 mmol/L vs. 3.0 mmol/L ± 0.3 mmol/L; p = 0.056) and base deficit values (5.9 mmol/L ± 1.1 mmol/L vs. 3.6 mmol/L ± 0.6 mmol/L; p = 0.052). Mean international normalized ratio (1.46 ± 0.07 vs. 1.22 ± 0.05; p = 0.001) and partial thromboplastin times (42.4 seconds ± 5.0 seconds vs. 29.7 seconds ± 1.8 seconds; p < 0.001) were significantly higher in MT patients. Patients receiving a MT had significantly altered ROTEM values on admission compared with non-MT patients. An increase in the clot formation time (471.3 seconds ± 169.9 seconds vs. 178.1 seconds ± 19.9 seconds; p = 0.001), a shortening of the maximum clot firmness (37.5 mm ± 2.9 mm vs. 50.7 mm ± 1.4 mm; p < 0.001), and a shortening of the clot amplitude at all time points (10/20/30 minutes) were observed in massively transfused trauma patients. Variables independently associated with MT included a hemoglobin level ≤ 10 g/dL and an abnormal maximum clot firmness value (area under the receiver operator characteristic curve: 0.831 [95% confidence interval: 0.719-0.942; p < 0.001]). Hemoglobin ≤ 10 g/dL and an abnormal maximum cloth firmness measured by rotation thromboelastometry on admission reliably predict the need for MT. Prospective validation of the effectiveness of thromboelastometry to guide the transfusion practice after trauma is warranted.

High Transfusion Ratios Are Not Associated With Increased Complication Rates in Patients With Severe Extremity Injuries

High transfusion ratios of plasma to packed red blood cells (>1:2) have been associated with increased survival and increased complications in patients receiving massive transfusion (MT). We hypothesized that high ratio transfusion would be associated with no survival benefit and increased complications in combat victims with compressible hemorrhage. A retrospective analysis of soldiers injured in the current conflict during 5 years (n = 2,105) who received blood was performed on those with isolated extremity (abbreviated injury scale extremity score > or = 3 and abbreviated injury scale score 0-2 in all other regions) injury comparing those who received a MT with those who did not. Transfusion ratios in the first 24 hours were correlated with outcomes. Injury severity score (14.6 vs. 12.1; p < 0.05), international normalized ratio (1.65 vs. 1.28; p < 0.05), and base deficit (8.0 vs. 3.7; p < 0.05) were higher in the MT group. High transfusion ratios were associated with a trend toward decreased mortality (17.2% vs. 6.9%; p = 0.07) in MT patients and no increased complications (20.7% vs. 26.4%; p > 0.05). In those receiving a non-MT, high ratios were associated with similar mortality (4.8% vs. 3.9%; p > 0.05) and complications (12.4% vs. 9.2%; p > 0.05). Extremity injured patients receiving MT may benefit from high transfusion ratios and do not experience increased complications. No change in mortality or complications was observed in non-MT patients across transfusions ratios. High transfusion ratios are not associated with increased complications in patients with isolated extremity injury regardless of whether a MT is required.

Increased number of coagulation products in relationship to red blood cell products transfused improves mortality in trauma patients

Recent data from military and civilian centers suggest that mortality is decreased in massive transfusion patients by increasing the transfusion ratio of plasma and platelet (PLT) products, and fibrinogen in relationship to red blood cell (RBC) products during damage control resuscitation and surgery. This study investigates the relationship of plasma:RBC, PLT:RBC, and cryoprecipitate:RBC transfusion ratios to mortality in massively transfused patients at a civilian Level 1 trauma center. Demographic, laboratory, transfusion, and outcome data were collected prospectively from February 1, 2007, to January 31, 2009, and retrospectively from February 1, 2005, to January 31, 2007, on all injured patients who underwent massive transfusion (defined as >or=10 RBC products within 24 hr). Mortality was analyzed in relation to the plasma:RBC, PLT:RBC, and cryoprecipitate:RBC transfusion ratios using both univariate and multivariate analyses. A total of 214 patients received massive transfusion secondary to traumatic injury. High versus low transfusion ratios were associated with improved 30-day survival: plasma:RBC 59% versus 44%, p = 0.03; PLT:RBC 63% versus 33%, p < 0.01; and cryoprecipitate:RBC 66% versus 41%, p < 0.01. By multivariable stepwise logistic regression analysis, increased plasma:RBC (p = 0.02) and PLT:RBC (p = 0.02), and decreased age (p = 0.02), ISS (p < 0.01) and total RBCs (p = 0.03) were statistically associated with improved 30-day survival. In the civilian setting, plasma, PLT, and cryoprecipitate products significantly increased 30-day survival in trauma patients. Future prospective randomized clinical trials are required to determine the optimal transfusion ratios.

Early Predictors of Massive Transfusion in Patients Sustaining Torso Gunshot Wounds in a Civilian Level I Trauma Center

Early prediction of the need for massive transfusion (MT) remains difficult. We hypothesized that MT protocol (MTP) utilization would improve by identifying markers for MT (>10 units packed red blood cell [PRBC] in 24 hours) in torso gunshot wounds (GSW) requiring early transfusion and operation. Data from all MTPs were collected prospectively from February 1, 2007, to January 31, 2009. Demographic, transfusion, anatomic, and operative data were analyzed for MT predictors. Of the 216 MTP activations, 78 (36%) patients sustained torso GSW requiring early transfusion and operation. Five were moribund and died before receiving MT. Of 73 early survivors, 56 received MT (76%, mean 19 units PRBC) and 17 had early bleeding control (EBC), (24%, mean 5 units PRBC). Twelve transpelvic and 13 multicavitary wounds all received MT regardless of initial hemodynamic status (mean systolic blood pressure: 96 mm Hg; range, 50-169). Of 31 MT patients with low-risk trajectories (LRT), 18 (58%) had a systolic blood pressure <90 mm Hg compared with 3 of 17 (17%) in the EBC group (p < 0.01). In these same groups, a base deficit of <-10 was present in 27 of 31 (92%) MT patients versus 4 of 17 (23%) EBC patients (p < 0.01). The presence of both markers identified 97% of patients with LRT who requiring MT and their absence would have potentially eliminated 16 of 17 EBC patients from MTP activation. In patients requiring early operation and transfusion after torso GSW: (1) early initiation of MTP is reasonable for transpelvic and multicavitary trajectories regardless of initial hemodynamic status as multiple or difficult to control bleeding sources are likely and (2) early initiation of MTP in patients with LRT may be guided by a combination of hypotension and acidosis, indicating massive blood loss.

Increased Plasma and Platelet to Red Blood Cell Ratios Improves Outcome in 466 Massively Transfused Civilian Trauma Patients

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. 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. 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. 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. 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 in Trauma Patients: Tissue Hemoglobin Oxygen Saturation Predicts Poor Outcome

Severely bleeding trauma patients requiring massive transfusion (MT) often experience poor outcomes. Our purpose was to determine the potential role of near infrared spectrometry derived tissue hemoglobin oxygen saturation (StO2) monitoring in early prediction of MT, and in the identification of those MT patients who will have poor outcomes. Data from a prospective multi-institution StO2 monitoring study were analyzed to determine the current epidemiology of MT (defined as transfusion volume >/=10 units packed red blood cells in 24 hours of hospitalization). Multivariate logistic regression was used to develop prediction models. Seven US level I trauma centers (TC) enrolled 383 patients. 114 (30%) required MT. MT progressed rapidly (40% exceeded MT threshold 2 hours after TC arrival, 80% after 6 hours). One third of MT patients died. Two thirds of deaths were due to early exsanguination and two thirds of early exsanguination patients died within 6 hours. One third of the early MT survivors developed multiple organ dysfunction syndrome. MT could be predicted with standard, readily available clinical data within 30 minutes and 60 minutes of TC arrival (area under the receiver operating characteristic curve = 0.78 and 0.80). In patients who required MT, StO2 was the only consistent predictor of poor outcome (multiple organ dysfunction syndrome or death). MT progresses rapidly to significant morbidity and mortality despite level I TC care. Patients who require MT can be predicted early, and persistent low StO2 identifies those MT patients destined to have poor outcome. The ultimate goal is to identify these high risk patients as early as possible to test new strategies to improve outcome. Further validation studies are needed to analyze appropriate allocation and study appropriate use of damage control interventions.

Early Versus Late Recombinant Factor VIIa in Combat Trauma Patients Requiring Massive Transfusion

Coagulopathy is a consequence of severe trauma, especially in massively transfused patients (>or=10 units of red blood cells in 24 hours), and is associated with increased mortality. We hypothesized that recombinant factor VIIa (rFVIIa) administered to massive transfusion patients before transfusion of 8 units of blood (early) would reduce transfusion requirements compared with rFVIIa after 8 units (late). We retrospectively reviewed records for trauma admissions to combat support hospitals in Iraq between January 2004 and October 2005. Patients requiring a massive transfusion and receiving rFVIIa were identified. Groups were divided into those who received rFVIIa early or late. Of 5,334 trauma patients (civilian and military), 365 (6.8%) required massive transfusion. Of these, 117 (32%) received rFVIIa. Complete records for blood transfusions were available for 61 patients: 90% had penetrating trauma, 17 received rFVIIa early, and 44 received it late. At admission, temperature, heart rate, blood pressure, Glasgow Coma Scale score, base deficit, hemoglobin, platelets, prothrombin time/International Normalized Ratio, and Injury Severity Score were similar in both groups as were administered units of fresh frozen plasma, fresh whole blood, cryoprecipitate (cryo), and crystalloid. The early rFVIIa group required fewer units of blood during the first 24-hour period (mean 20.6 vs. 25.7, p=0.048) and fewer units of stored red blood cells (mean 16.7 vs. 21.7, p=0.049). Early and late mortality (33.3% vs. 34.2%, p=NS), acute respiratory distress syndrome (5.9 vs. 6.8%, p=NS), infection (5.9% vs. 9.1%, p=NS), and thrombotic events (0% vs. 2.3%, p=NS) were similar. Early administration of rFVIIa decreased red blood cell use by 20% in trauma patients requiring massive transfusion.

C3a and adult respiratory distress syndrome after massive transfusion.

We compared the degree of complement activation in 15 patients receiving massive blood transfusions and 21 patients with the septic syndrome and examined its association with other risk factors for adult respiratory distress syndrome (ARDS). Patients with massive transfusion (n = 8) as their only risk factor for ARDS had lower C3a levels (250 +/- 80 ng/ml) and a lower incidence of ARDS (0%) than patients with massive transfusion plus other risk factors (n = 7; C3a, 600 +/- 120 ng/ml; ARDS, 55%) or patients with the septic syndrome (n = 21; C3a, 540 +/- 80 ng/ml; ARDS, 19%). In our patients, the degree of complement activation appeared to reflect the presence of complicating clinical conditions.