Ira A. Shulman

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.

Impact of plasma transfusion in massively transfused trauma patients.

OBJECTIVE The objective of this study was to determine the optimal use of fresh-frozen plasma (FFP) in trauma. Our hypothesis was that a higher FFP: packed red blood cells (PRBC) ratio is associated with improved survival. METHODS This is a 6-year retrospective trauma registry and blood bank database study in a level I trauma center. All massively transfused patients (> or =10 PRBC during 24 hours) were analyzed. Patients with severe head trauma (head Abbreviated Injury Severity score > or =3) were excluded from the analysis. Patients were classified into four groups according to the FFP:PRBC ratio received: low ratio (< or =1:8), medium ratio (>1:8 and < or =1:3), high ratio (>1:3 and < or =1:2), and highest ratio (>1:2). RESULTS Of 25,599 trauma patients, 4,241 (16.6%) received blood transfusion. Massive transfusion occurred in 484 (11.4%) of the transfused. After exclusion of 101 patients with severe head injury 383 patients were available for analysis. The mortality rate decreased significantly with increased FFP transfusion. However, there does not seem to be a survival advantage after a 1:3 FFP:PRBC ratio has been reached. Using the highest ratio group as a reference, the relative risk of death was 0.97 (p = 0.97) for the high ratio group, 1.90 (p < 0.01) for the medium ratio group, and 3.46 (p < 0.01) for the low ratio group. There was an increasing trend toward more FFP use during time with the mean units per patient increasing 83% from 6.3 +/- 4.6 in 2000 to 11.5 +/- 9.7 in 2005. CONCLUSION Higher FFP:PRBC ratio is an independent predictor of survival in massively transfused patients. Aggressive early use of FFP may improve outcome in massively transfused trauma patients.

The sickle cell hemolytic transfusion reaction syndrome

BACKGROUND: Patients with sickle cell anemia may develop serious, life‐ threatening hemolytic transfusion reactions (HTRs). More severe anemia may develop after the HTR than was present before transfusion, which suggests the possibility of an increased rate of hemolysis of autologous red cells. STUDY DESIGN AND METHODS: The signs and symptoms occurring during eight severe HTRs that occurred in five patients with sickle cell anemia were reviewed, as were published reports by other investigators. Calculations of red cell production and destruction incorporating known correction factors for reticulocyte maturation were performed to determine the most probable mechanism for the striking drop in hematocrit observed in several instances. RESULTS: A characteristic constellation of findings was recognized in some severe HTRs in patients with sickle cell anemia. Calculations of daily red cell production and senescence indicated that a marked drop in hematocrit occurs when erythropoiesis is suppressed in a patient with a short red cell life span and that this could account for severe posttransfusion anemia when donor red cells are hemolyzed during an HTR. CONCLUSION: A sickle cell HTR syndrome was defined. A rapid increase in the severity of anemia occurs in patients with sickle cell anemia when all donor red cells are hemolyzed during an HTR and when there is suppression of erythropoiesis, as commonly occurs as a result of transfusion or concomitant illness. Although an increased rate of hemolysis of autologous red cells may also occur, more definitive data are required to document that in these patients.

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.

Patient safety and blood transfusion: new solutions

Current risk from transfusion is largely because of noninfectious hazards and defects in the overall process of delivering safe transfusion therapy. Safe transfusion therapy depends on a complex process that requires integration and coordination among multiple hospital services including laboratory medicine, nursing, anesthesia, surgery, clerical support, and transportation. The multidisciplinary hospital transfusion committee has been traditionally charged with oversight of transfusion safety. However, in recent years, this committee may have been neglected in many institutions. Resurgence in hospital oversight of patient safety and transfusion efficacy is an important strategy for change. A new position, the transfusion safety officer (TSO), has been developed in some nations to specifically identify, resolve, and monitor organizational weakness leading to unsafe transfusion practice. New technology is becoming increasingly available to improve the performance of sample labeling and the bedside clerical check. Several technology solutions are in various stages of development and include wireless handheld portable digital assistants, advanced bar coding, radiofrequency identification, and imbedded chip technology. Technology-based solutions for transfusion safety will depend on the larger issue of the technology for patient identification. Devices for transfusion safety hold exciting promise but need to undergo clinical trials to show effectiveness and ease of use. Technology solutions will likely require integration with delivery of pharmaceuticals to be financially acceptable to hospitals.

Phenotype Matching of Donor Red Blood Cell Units for Nonalloimmunized Sickle Cell Disease Patients: A Survey of 1182 North American Laboratories

CONTEXT The transfusion of donor red blood cell units (RBCs) that lack certain red cell antigens (such as C, E, and K) when the corresponding antigens are absent from the recipients red cells has been shown to reduce the risk of red cell alloimmunization in sickle cell disease patients. However, data are limited regarding the extent to which transfusion services routinely perform red cell antigen phenotype testing of nonalloimmunized sickle cell disease patients, and then use that information to select donor RBCs lacking 1 or more of the red cell antigens that the patients red cells do not express. OBJECTIVE To determine the extent to which transfusion services routinely perform red cell antigen phenotype testing of nonalloimmunized sickle cell disease patients, and then use that information to select donor RBCs lacking 1 or more of the red cell antigens that the patients red cells do not express. DESIGN An educational subsection of a College of American Pathologists Proficiency Testing Survey (J-C 2003) assessed transfusion service practices regarding performance of red cell antigen phenotype testing of nonalloimmunized sickle cell disease patients and how transfusion services use this information for the selection of donor RBCs. The data analysis of the survey included 1182 North American laboratories. RESULTS Data from 1182 laboratories were included in the survey analysis, of which the majority (n = 743) reported that they did not routinely perform phenotype testing of sickle cell disease patients for antigens other than ABO and D. The other 439 laboratories reported that they did routinely perform phenotype testing of sickle cell disease patients for antigens in addition to ABO and D. The majority of these 439 laboratories (three fourths; n = 330) reported that they used these patient data for prophylactic matching with donor RBCs when sickle cell disease patients required transfusion. When phenotype-matched donor RBCs were used, the antigens most commonly matched (85% of the time) were C, E, and K. CONCLUSIONS The majority of North American hospital transfusion service laboratories do not determine the red cell antigen phenotype of nonalloimmunized sickle cell disease patients beyond ABO and D. Those laboratories that do determine the red cell phenotype of nonalloimmunized sickle cell disease patients beyond ABO and D most commonly match for C, E, and K antigens when phenotype-matched donor RBCs are used.

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.