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Platelet adenosine diphosphate receptor inhibition provides no advantage in predicting need for platelet transfusion or massive transfusion

Stettler, Gregory R; Moore, Ernest E; Moore, Hunter B; Nunns, Geoffrey R; Huebner, Benjamin R; Einersen, Peter; Ghasabyan, Arsen; Silliman, Christopher C; Banerjee, Anirban; Sauaia, Angela
BACKGROUND:Thrombelastography platelet mapping is a useful assay to assess antiplatelet therapy. Inhibited response to the adenosine diphosphate receptor on platelets occurs early after injury, but recent work suggests this alteration occurs even with minor trauma. However, the utility of thrombelastography platelet mapping, specifically the percent of adenosine diphosphate receptor inhibition, in predicting outcomes and guiding platelet transfusion in trauma-induced coagulopathy remains unknown We assessed the role of percent of adenosine diphosphate-inhibition in predicting survival, requirement for massive transfusion or platelet transfusion in patients at risk for trauma-induced coagulopathy. METHODS:Thrombelastography platelet mapping was assessed in 303 trauma activation patients from 2014-2016 and in 89 healthy volunteers. Percent of adenosine diphosphate-inhibition is presented as median and interquartile range. We compared the area under the receiver operating characteristic curve of percent of adenosine diphosphate-inhibition, platelet count, and rapid thrombelastography maximum amplitude for in-hospital mortality, massive transfusion (>10 red blood cells or death/6 hours), and platelet transfusion (>0 platelet units or death/6 hour). RESULTS:Overall, 35 (11.5%) patient died, 27 (8.9%) required massive transfusion and 46, platelet transfusions (15.2%). Median percent of adenosine diphosphate-inhibition was 42.5% (interquartile range: 22.4-69.1%), compared with 4.3 % (interquartile range: 0-13.5%) in healthy volunteers (P < .0001). Patients that died, had a massive transfusion, or platelet transfusion had higher percent of adenosine diphosphate-inhibition than those that did not (P < .05 for all). However, percent of adenosine diphosphate-inhibition did not add significantly to the predictive performance of maximum amplitude or platelet count for any of the 3 outcomes, after adjustment for confounders. Subgroup analyses by severe traumatic brain injury, severe injury and requirement of red blood cells showed similar results. CONCLUSION:Adenosine diphosphate receptor inhibition did not add predictive value to predicting mortality, massive transfusion, or platelet transfusion. Thus, the role of thrombelastography platelet mapping as a solitary tool to guide platelet transfusions in trauma requires continued refinement.
PMID: 28964508
ISSN: 1532-7361
CID: 5012922

Tranexamic acid is associated with increased mortality in patients with physiological fibrinolysis

Moore, Hunter B; Moore, Ernest E; Huebner, Benjamin R; Stettler, Gregory R; Nunns, Geoffrey R; Einersen, Peter M; Silliman, Christopher C; Sauaia, Angela
BACKGROUND:Tranexamic acid (TXA) administration after trauma has not been proven to improve survival in the United States. Trauma patients were presented to the hospital with a spectrum of fibrinolytic activity, in which physiological levels of fibrinolysis are associated with the lowest mortality. We hypothesize that trauma patients who present to the hospital with physiological levels of fibrinolysis will have increased mortality if they receive TXA. MATERIALS AND METHODS:Severely injured trauma patients, followed prospectively from 2014 to 2016, were included in the analysis. The patient's first thrombelastography was used to stratify patients into fibrinolysis phenotypes which included fibrinolysis shutdown, physiological fibrinolysis, and systemic hyperfibrinolysis. The primary outcome was in-hospital mortality. RESULTS:A total of 232 patients were analyzed (11% received TXA) with an overall mortality rate of 20%. TXA administration was associated with a higher new injury severity score (49 versus 28; P = 0.001), massive transfusion rate (69% versus 12%; P < 0.001), and mortality (52% versus 17%; P < 0.001). Hyperfibrinolysis and shutdown had higher mortality rates than physiological group (24% versus 30% versus 14%; P = 0.050). The effect of TXA within phenotypes was not significant for shutdown (28% versus 38%; P = 0.604) but was significant in the physiological group (11% versus 63%; P < 0.001) and systemic hyperfibrinolysis (19% versus 55%; P = 0.023). After adjusting for new injury severity score, TXA remained a significant predictor of mortality for patients with physiological fibrinolysis (P = 0.018). CONCLUSIONS:There was no clear benefit of receiving TXA in this study, and patients who present to the hospital with physiologic levels of fibrinolysis, who received TXA, had the highest mortality. The role of TXA in mature trauma systems remains unclear, and emerging data supports it may have adverse effects.
PMID: 28755903
ISSN: 1095-8673
CID: 5012912

Viscoelastic Tissue Plasminogen Activator Challenge Predicts Massive Transfusion in 15 Minutes

Moore, Hunter B; Moore, Ernest E; Chapman, Michael P; Huebner, Benjamin R; Einersen, Peter M; Oushy, Solimon; Silliman, Christopher C; Banerjee, Anirban; Sauaia, Angela
BACKGROUND:Coagulopathy is associated with massive transfusion in trauma, yet most clinical scores to predict this end point do not incorporate coagulation assays. Previous work has identified that shock increases circulating tissue plasminogen activator (tPA). When tPA levels saturate endogenous inhibitors, systemic hyperfibrinolysis can occur. Therefore, the addition of tPA to a patient's blood sample could stratify a patients underlying degree of shock and early coagulation changes to predict progression to massive transfusion. We hypothesized that a modified thrombelastography (TEG) assay with exogenous tPA would unmask patients' impending risk for massive transfusion. STUDY DESIGN/METHODS:Trauma activations were analyzed using rapid TEG and a modified TEG assay with a low and high dose of tPA. Clinical scores (shock index, assessment of blood consumption, and trauma-associated severe hemorrhage) were compared with TEG measurements to predict the need for massive transfusion using areas under the receiver operating characteristic curves. RESULTS:Three hundred and twenty-four patients were analyzed, 17% required massive transfusion. Massive transfusion patients had a median shock index of 1.2, assessment of blood consumption score of 1, and trauma-associated severe hemorrhage score of 12. Rapid TEG and tPA TEG parameters were significantly different in all massive transfusion patients compared with non-massive transfusion patients (all p < 0.02). The low-dose tPA lysis at 30 minutes had the largest the area under the receiver operating characteristic curve (0.86; 95% CI 0.79 to 0.93) for prediction of massive transfusion, similar to international normalized ratio of prothrombin time of 0.86 (95% CI 0.81 to 0.91), followed by trauma-associated severe hemorrhage score (0.83; 95% CI 0.77 to 0.89). Combing trauma-associated severe hemorrhage and tPA-TEG variables results in a positive prediction of massive transfusion in 49% of patients with a 98% negative predictive value. CONCLUSIONS:The tPA-TEG identifies trauma patients who require massive transfusion efficiently in a single assay that can be completed in a shorter time than other scoring systems, which has improved performance when combined with international normalized ratio. This new method is consistent with our understanding of the molecular events responsible for trauma-induced coagulopathy.
PMID: 28522144
ISSN: 1879-1190
CID: 5012902

Rapid thrombelastography thresholds for goal-directed resuscitation of patients at risk for massive transfusion

Einersen, Peter M; Moore, Ernest E; Chapman, Michael P; Moore, Hunter B; Gonzalez, Eduardo; Silliman, Christopher C; Banerjee, Anirban; Sauaia, Angela
BACKGROUND:Uncontrolled hemorrhage is a leading cause of mortality after trauma accounting for up to 40% of deaths. Massive transfusion protocols offer a proven benefit in resuscitation of these patients. Recently, the superiority of thrombelastography (TEG)-guided resuscitation over strategies guided by conventional clotting assays has been established. We seek to determine optimal thresholds for rapid (r)-TEG driven resuscitation. METHODS:The r-TEG data were reviewed for 190 patients presenting to our level 1 trauma center from 2010 to 2015. Criteria for inclusion were highest level trauma activation in patients 18 years or older with hypotension presumed due to acute blood loss. Exclusion criteria included isolated gunshot wound to the head, pregnancy, and chronic liver disease. Receiver operating characteristic (ROC) analysis was performed to test the predictive performance of r-TEG for massive transfusion requirement defined by need for (1) >10 units of RBCs total or death in the first 6 hours or (2) >4 units of RBCs in any hour within the first 6 hours. Cutpoint analysis was then performed to determine optimal thresholds for TEG-based resuscitation. RESULTS:The ROC analysis of r-TEG yielded areas under the curve (AUC) greater than 70% for all outputs with respect to both transfusion thresholds considered, with exception of activated clotting time and lysis at 30 minutes for greater than 4 U RBC in any hour in the first 6 hours. Optimal cutpoint analysis of the resultant ROC curves was performed and for each value, the most sensitive cutpoint was identified, respectively activated clotting time of 128 seconds or longer, angle (α) of 65 degrees or less, maximum amplitude of 55 mm or less, and lysis at 30 minutes of 5% or greater. CONCLUSIONS:Through ROC analysis of prospective TEG data, we have identified optimal thresholds to guide hemostatic resuscitation. These thresholds should be validated in a prospective multicenter trial. LEVEL OF EVIDENCE:Therapeutic study, level V.
PMID: 27805995
ISSN: 2163-0763
CID: 5012892

Positron emission tomography (PET) has limited utility in the staging of pancreatic adenocarcinoma

Einersen, Peter; Epelboym, Irene; Winner, Megan D; Leung, David; Chabot, John A; Allendorf, John D
BACKGROUND:Positron emission tomography (PET) as an adjunct to conventional imaging in the staging of pancreatic adenocarcinoma is controversial. Herein, we assess the utility of PET in identifying metastatic disease and evaluate the prognostic potential of standard uptake value (SUV). METHODS:Imaging and follow-up data for patients diagnosed with pancreatic adenocarcinoma were reviewed retrospectively. Resectability was assessed based on established criteria, and sensitivity, specificity, and accuracy of PET were compared to those of conventional imaging modalities. RESULTS:For 123 patients evaluated 2005-2011, PET and CT/MRI were concordant in 108 (88 %) cases; however, PET identified occult metastatic lesions in seven (5.6 %). False-positive PETs delayed surgery for three (8.3 %) patients. In a cohort free of metastatic disease in 78.9 % of cases, the sensitivity and specificity of PET for metastases were 89.3 and 85.1 %, respectively, compared with 62.5 and 93.5 % for CT and 61.5 and 100.0 % for MRI. Positive predictive value and negative predictive value of PET were 64.1 and 96.4 %, respectively, compared with 75.0 and 88.9 % for CT and 100.0 and 91.9 % for MRI. Average difference in maximum SUV of resectable and unresectable lesions was not statistically significant (5.65 vs. 6.5, p = 0.224) nor was maximum SUV a statistically significant predictor of survival (p = 0.18). CONCLUSION/CONCLUSIONS:PET is more sensitive in identifying metastatic lesions than CT or MRI; however, it has a lower specificity, lower positive predictive value, and in some cases, can delay definitive surgical management. Therefore, PET has limited utility as an adjunctive modality in staging of pancreatic adenocarcinoma.
PMID: 24928186
ISSN: 1873-4626
CID: 3486742

Positron Emission Tomography (PET) Has Limited Utility in Preoperative Staging of Pancreatic Adenocarcinoma [Meeting Abstract]

Einersen, Peter; Epelboym, Irene; Winner, Megan; Leung, David; Chabot, John A.; Allendorf, John D.
ISSN: 0016-5085
CID: 3509892