Janice M. Nelson

Impact of Plasma Transfusion in Trauma Patients Who Do Not Require Massive Transfusion

BACKGROUND For trauma patients requiring massive blood transfusion, aggressive plasma usage has been demonstrated to confer a survival advantage. The aim of this study was to evaluate the impact of plasma administration in nonmassively transfused patients. STUDY DESIGN Trauma patients admitted to a Level I trauma center (2000-2005) requiring a nonmassive transfusion (<10 U packed RBC [PRBC] within 12 hours of admission) were identified retrospectively. Propensity scores were calculated to match and compare patients receiving plasma in the first 12 hours with those who did not. RESULTS The 1,716 patients (86.1% of 1,933 who received PRBC transfusion) received a nonmassive transfusion. After exclusion of 31 (1.8%) early deaths, 284 patients receiving plasma were matched to patients who did not. There was no improvement in survival with plasma transfusion (17.3% versus 14.1%; p = 0.30) irrespective of the plasma-to-PRBC ratio achieved. However, the overall complication rate was significantly higher for patients receiving plasma (26.8% versus 18.3%, odds ratio [OR] = 1.7; 95% CI, 1.1-2.4; p = 0.016). As the volume of plasma increased, an increase in complications was seen, reaching 37.5% for patients receiving >6 U. The ARDS rate specifically was also significantly higher in patients receiving plasma (9.9% versus 3.5%, OR = 3.0; 95% CI, 1.4-6.2; p = 0.004]. Patients receiving >6 U plasma had a 12-fold increase in ARDS, a 6-fold increase in multiple organ dysfunction syndrome, and a 4-fold increase in pneumonia and sepsis. CONCLUSIONS For nonmassively transfused trauma patients, plasma administration was associated with a substantial increase in complications, in particular ARDS, with no improvement in survival. An increase in multiple organ dysfunction, pneumonia, and sepsis was likewise seen as increasing volumes of plasma were transfused. The optimal trigger for initiation of a protocol for aggressive plasma infusion warrants prospective evaluation.

Hyperfibrinolysis Elicited via Thromboelastography Predicts Mortality in Trauma

BACKGROUND The acute coagulopathy of trauma has been identified as a critical determinant of outcomes. Antifibrinolytic agents have recently been demonstrated to improve outcomes. This prospective study was designed to assess coagulopathy in trauma patients using thromboelastography. STUDY DESIGN Trauma patients meeting our institutions highest tier of trauma team activation criteria were prospectively enrolled during a 5-month period ending April 1, 2011. Thromboelastography was performed at admission, +1 hour, +2 hours, and +6 hours using citrated blood. Hyperfibrinolysis was defined as estimated percent lysis ≥15%. Patients were followed throughout their hospital course to collect clinical data and outcomes. RESULTS One hundred and eighteen patients were enrolled (77.1% were male, 51.7% had penetrating trauma, 7.6% had systolic blood pressure <90 mmHg, 47.5% had Injury Severity Score >16, and 23.7% had Glasgow Coma Scale score ≤8). Hyperfibrinolysis was present in 13 patients (11.0%), with a mean time to detection of 13 minutes (range 2 to 60 minutes). By the 6-hour sampling, 8 (61.5%) of the hyperfibrinolytic patients had expired from hemorrhage. Survivors at this point demonstrated correction of coagulopathy, however, 12 patients (92.3%) ultimately expired (75% hemorrhage, 25% head injury). On stepwise logistic regression, hyperfibrinolysis was a strong predictor of early (24 hours) mortality (odds ratio = 25.0; 95% CI, 2.8-221.4; p = 0.004), predicting 53% of early deaths. Compared with patients without hyperfibrinolysis, patients with hyperfibrinolysis had a greater need for massive transfusion (76.9% vs 8.7%; adjusted odds ratio = 19.1; 95% CI, 3.6-101.3; p < 0.001) and had a greater early mortality (69.2% vs 1.9%; adjusted odds ratio = 55.8; 95% CI, 7.2-432.3; p < 0.001) and in-hospital mortality (92.3% vs 9.5%; adjusted odds ratio = 55.5; 95% CI, 4.8-649.7; p = 0.001). CONCLUSIONS In this prospective analysis, hyperfibrinolysis on thromboelastography developed in approximately 10% of patients and was considerably more likely to require massive transfusion. Hyperfibrinolysis was a strong independent predictor of mortality. Additional evaluation of the role of thromboelastography-directed antifibrinolytic therapies is warranted.

The Impact of Platelet Transfusion in Massively Transfused Trauma Patients

BACKGROUND The impact of platelet transfusion in trauma patients undergoing a massive transfusion (MT) was evaluated. STUDY DESIGN The Institutional Trauma Registry and Blood Bank Database at a Level I trauma center was used to identify all patients requiring an MT (≥10 packed red blood cells [PRBC] within 24 hours of admission). Mortality was evaluated according to 4 apheresis platelet (aPLT):PRBC ratios: Low ratio (<1:18), medium ratio (≥1:18 and <1:12), high ratio (≥1:12 and <1:6), and highest ratio (≥1:6). RESULTS Of 32,289 trauma patients, a total of 657 (2.0%) required an MT. At 24 hours, 171 patients (26.0%) received a low ratio, 77 (11.7%) a medium ratio, 249 (37.9%) a high ratio, and 160 (24.4%) the highest ratio of aPLT:PRBC. After correcting for differences between groups, the mortality at 24 hours increased in a stepwise fashion with decreasing aPLT:PRBC ratio. Using the highest ratio group as a reference, the adjusted relative risk of death was 1.67 (adjusted p = 0.054) for the high ratio group, 2.28 (adjusted p = 0.013) for the medium ratio group, and 5.51 (adjusted p < 0.001) for the low ratio group. A similar stepwise increase in mortality with decreasing platelet ratio was observed at 12 hours after admission and for overall survival to discharge. After stepwise logistic regression, a high aPLT:PRBC ratio (adjusted p < 0.001) was independently associated with improved survival at 24 hours. CONCLUSIONS For injured patients requiring a massive transfusion, as the apheresis platelet-to-red cell ratio increased, a stepwise improvement in survival was seen. Prospective evaluation of the role of platelet transfusion in massively transfused patients is warranted.

Impact of fibrinogen levels on outcomes after acute injury in patients requiring a massive transfusion.

BACKGROUND For critically injured patients requiring a massive transfusion, the optimal plasma fibrinogen level is unknown. The purpose of this study was to examine the impact of the fibrinogen level on mortality. We hypothesized that decreasing fibrinogen levels are associated with worse outcomes. STUDY DESIGN All patients undergoing a massive transfusion from January 2000 through December 2011 were retrospectively identified. Those with a fibrinogen level measured on admission to the surgical ICU were analyzed according to their fibrinogen level (normal [≥180 mg/dL], abnormal [≥101 to <180 mg/dL], and critical [≤100 mg/dL]). Primary outcome was death. Multivariate analysis evaluated the impact of fibrinogen on survival. RESULTS There were 260 patients who met inclusion criteria. Ninety-two patients had normal admission fibrinogen levels, 114 had abnormal levels, and 54 patients had critical levels. Patients with a critical fibrinogen level had significantly higher mortality at 24 hours compared with patients with abnormal (31.5% vs 5.3%; adj. p < 0.001) and normal fibrinogen levels (31.5% vs 4.3%; adjusted p < 0.001). Patients with a critical fibrinogen level had significantly higher in-hospital mortality compared with patients with abnormal (51.9% vs 25.4%; adjusted p = 0.013) and normal fibrinogen levels (51.9% vs 18.5%; adjusted p < 0.001). A critical fibrinogen level was the most important independent predictor of mortality (p = 0.012). CONCLUSIONS For patients undergoing a massive transfusion after injury, as the fibrinogen level increased, a stepwise improvement in survival was noted. A fibrinogen level ≤100 mg/dL was a strong independent risk factor for death. The impact of an aggressive fibrinogen replacement strategy using readily available products warrants further prospective evaluation.

Making thawed universal donor plasma available rapidly for massively bleeding trauma patients: experience from the Pragmatic, Randomized Optimal Platelets and Plasma Ratios (PROPPR) trial

The Pragmatic, Randomized Optimal Platelets and Plasma Ratios (PROPPR) trial was a randomized clinical trial comparing survival after transfusion of two different blood component ratios for emergency resuscitation of traumatic massive hemorrhage. Transfusion services supporting the study were expected to provide thawed plasma, platelets, and red blood cells within 10 minutes of request.

Impact of the duration of platelet storage in critically ill trauma patients

BACKGROUND There is increasing evidence that the duration of red blood cell (RBC) storage negatively impacts outcomes. Data regarding prolonged storage of other blood components, however, are lacking. The aim of this study was to evaluate how the duration of platelet storage affects trauma patient outcomes. METHODS Trauma patients admitted to a Level I trauma center requiring platelet transfusion (2006-2009) were retrospectively identified. Apheresis platelets (aPLT) containing ≥3 × 10(11) platelets/unit were used exclusively. Patients were analyzed in three groups: those who received only aPLT stored for ≤3 days, 4 days, and 5 days. The outcomes included mortality and complications (sepsis, acute respiratory distress syndrome, renal, and liver failure). RESULTS Three hundred eighty-one patients were available for analysis (128 received aPLT ≤3 days old; 109 = 4 days old; and 144 = 5 days old). There were no significant demographic differences between groups. Patients receiving aPLT aged = 4 days had significantly higher Injury Severity Score (p = 0.022) and were more likely to have a head Abbreviated Injury Scale ≥3 (p = 0.014). There were no differences in volumes transfused or age of RBC, plasma, cryoprecipitate, or factor VIIa. After adjusting for confounders, exposure to older aPLT did not impact mortality; however, with increasing age, complications were significantly higher. The rate of sepsis, in particular, was significantly increased (5.5% for aPLT ≤3 days vs. 9.2% for aPLT = 4 days vs. 16.7% for aPLT = 5 days, adjusted p = 0.033). For acute respiratory distress syndrome and renal and liver failure, similar trends were observed. CONCLUSIONS In critically ill trauma patients, there was a stepwise increase in complications, in particular sepsis, with exposure to progressively older platelets. Further evaluation of the underlying mechanism and methods for minimizing exposure to older platelets is warranted.

The impact of uncross-matched blood transfusion on the need for massive transfusion and mortality: analysis of 5,166 uncross-matched units.

BACKGROUND The objective of this study was to analyze the outcomes associated with uncross-matched blood transfusion during trauma resuscitation. Our hypothesis was that uncross-matched blood transfusion is a predictor of the need for massive transfusion and mortality. METHODS All injured patients receiving packed red blood cell (PRBC) transfusion during a 6-year period ending December 2005 were identified from the blood bank database at a level I trauma center. Uncross-matched red blood cell (URBC) and cross-matched red blood cells, plasma and platelet utilization, and injury demographics were abstracted for each patient. RESULTS Of 25,599 trauma patients, 4,241 (16.6%) patients received 29,375 units of PRBC and 1,236 (29.1%) of the transfused patients received 5,166 units of URBC during their resuscitation. Patients requiring URBC had a higher mortality (39.6% vs. 11.9%, p < 0.001) and were more likely to require massive (> or = 10 PRBC during 12 hours) transfusion (29.3% vs. 1.8%, p < 0.001). There was a stepwise increase in mortality with increasing URBC transfusion. After adjusting for age, gender, mechanism, hypotension at admission, emergency department intubation, initial hemoglobin, Glasgow Coma Scale, Abbreviated Injury Scale, Injury Severity Score, and amount of blood products received; URBC remained an independent predictor of mortality (adjusted odds ratio 2.15; 95% confidence interval 1.58-2.94; p < 0.001) and massive transfusion (adjusted odds ratio, 11.87; 95% confidence interval, 8.43-16.7; p < 0.001). Patients receiving URBC also utilized more blood components (11.9 +/- 12.7 vs. 4.9 +/- 5.8 units of PRBC, p < 0.001; 5.1 +/- 8.9 vs. 2.0 +/- 4.8 units of plasma, p < 0.001; and 1.1 +/- 2.5 vs. 0.4 +/- 1.6 units of platelets, p < 0.001). CONCLUSION The requirement for uncross-matched blood during the acute resuscitation of trauma patients is an independent predictor of mortality and the need for massive transfusion. A URBC request during resuscitation should be considered by the blood bank as a potential trigger to prepare for massive transfusion.

The increasing burden of phlebotomy in the development of anaemia and need for blood transfusion amongst trauma patients

BACKGROUND Diagnostic laboratory tests are an integral part of the management of trauma patients, however, may be responsible for significant iatrogenic blood loss. The purpose of this study was to examine how phlebotomy practises have changed over time, and to assess the impact of these practises on patient outcomes. METHODS A continuous series of injured patients admitted to a level I trauma centre (March-April 2004) was compared to the same period in 2009. All diagnostic tests and blood volumes withdrawn for each patient were tabulated. Primary outcomes were in-hospital mortality and length of stay (LOS); secondary outcomes were development of anaemia (Hgb<9 g/dl) and need for blood transfusion. A cost analysis was performed to determine the financial impact of the blood tests ordered. RESULTS The 360 patients in 2009 and 384 patients in 2004 demonstrated no significant differences in demographics or clinical data. When outcomes were compared, there were no significant differences in hospital LOS, ICU LOS or mortality. From 2004 to 2009, the mean number of laboratory tests per patient increased significantly (21.2±32.5 to 28.5±44.4, p=0.003). The total blood volumes drawn during the hospital stay also increased significantly (144.4±191.2 ml to 187.3±265.1 ml, p=0.025). For ICU patients (329.7±351.0 ml to 435.9±346.3 ml, p=0.048). There was a 25% increase in costs due to laboratory blood tests over the study period. For ICU patients, a 36% increase in costs was observed. CONCLUSIONS From 2004 to 2009, there was a significant increase in the utilisation of diagnostic laboratory tests in the management of the injured patient with no demonstrable improvements in mortality or LOS. Further prospective evaluation of these results is warranted.

Autoanti-Ge associated with severe autoimmune hemolytic anemia

Severe autoimmune hemolytic anemia due to anti‐Ge is described. The patients red cells had a positive direct antiglobulin test, and they typed as Ge+ using saline reactive reagents. Anti‐Ge was eluted from her RBCs, and her serum had an IgG and IgM anti‐Ge2,3.

Compatibility of ADSOL-stored red cells with intravenous solutions

Five percent dextrose in water (D5W) and lactated Ringers (RL) are two intravenous solutions that are incompatible with citrate phosphate dextrose (CPD) anticoagulated RBCs. Hemolysis, agglutination, and clotting can occur when RBCs are mixed with, infused together with, or transfused in the same line following administration of these fluids. Although minimal plasma remains in units of RBCs containing adenine-saline-dextrose solution (ADSOL; Fenwal Laboratories, Deerfield, IL), clots are seen immediately after contact is made with RL. Clumping and hemolysis are seen when ADSOL-stored RBCs or saline-washed RBCs are mixed with D5W. This study reinforces the unsafe practice of mixing RBCs with certain intravenous solutions.