Comparison of dosing errors between tenecteplase and alteplase for management of acute ischemic stroke.

BACKGROUND: Acute ischemic stroke (AIS) is a medical emergency leading to morbidity and mortality. Thrombolytic therapy is currently the mainstay for the management of AIS owing to its improvement in neurologic function at 3 months. OBJECTIVES: The objective of this study was to compare the frequency of dosing errors made with tenecteplase versus alteplase administration in management of AIS. The secondary objectives evaluated efficacy outcomes of intensive care unit length of stay (LOS), hospital LOS, and time from door to needle and safety outcomes of bleeding and all-cause mortality between groups. METHODS: This multicenter retrospective cohort study included patients with AIS treated with thrombolytics (tenecteplase or alteplase). The study evaluated patients at 9 different hospitals in a Texas Network between August 2018 and August 2020. RESULTS: There were 3808 patients evaluated for inclusion and 359 were included: 171 in the tenecteplase group and 188 in the alteplase group. There were no differences found in dosing errors between tenecteplase and alteplase (25.7% vs. 32.4%, P = 0.16). There was no difference in all-cause mortality (tenecteplase 1.8% vs. alteplase 5.3%, P = 0.09) or bleeding events (tenecteplase 8.8% vs. alteplase 7.4%, P = 0.64). Patients who received tenecteplase had improved door to needle time < 60 minutes (tenecteplase 60% vs. alteplase 49%, P = 0.04). CONCLUSION: There was no difference in dosing errors between tenecteplase and alteplase for the management of AIS. Tenecteplase was associated with shorter door to needle times, which may be caused by simpler administration times. Institutions could consider strategies to mitigate dosing errors for thrombolytic therapies.

The AAST prospective observational multicenter study of the initial experience with reversal of direct oral anticoagulants in trauma patients.

BACKGROUND: Drug-specific agents for the reversal of direct oral anticoagulants (DOACs) were recently approved. We hypothesized that the approval of these reversal agents would lead improved outcomes for trauma patients taking DOACs. METHODS: A multicenter, prospective (2015-2018), observational study of all adult trauma patients taking DOACs who were admitted to one of fifteen participating trauma centers was performed. The primary outcome was mortality. RESULTS: For 606 trauma patients on DOACs, those reversed were older (78 vs. 74, p = 0.007), more severely injured (ISS: 16 vs. 5, p < 0.0001), had more severe head injuries (Head AIS: 2.9 vs. 1.3, p < 0.0001), and higher mortality (11% vs. 3%, p = 0.001). Patients who received drug-specific agents (idarucizumab, andexanet alfa) had higher mortality (30% vs. 8%, p = 0.04) than those reversed with factor concentrates. However, the low usage of drug-specific reversal agents limits our ability to assess their efficacy and safety. CONCLUSIONS: DOAC reversal was not independently associated with mortality. At present, the overall usage of drug-specific reversal agents is too sparing to meaningfully assess outcomes in trauma.

Desmopressin is a transfusion sparing option to reverse platelet dysfunction in patients with severe traumatic brain injury.

BACKGROUND: Platelet dysfunction (PD) is an independent predictor of mortality in patients with severe traumatic brain injury (sTBI). Platelet transfusions (PLTs) have been shown to be an effective treatment strategy to reverse platelet inhibition. Their use is contingent on availability and may be associated with increased cost and transfusion-related complications, making desmopressin (DDAVP) attractive. We hypothesized that DDAVP would correct PD similarly to PLTs in patients with sTBI. METHODS: This retrospective study evaluated all blunt trauma patients admitted to an urban, level 1 trauma center from July 2015 to October 2016 with sTBI (defined as head abbreviated injury scale [AIS] ≥3) and PD (defined as adenosine diphosphate [ADP] inhibition ≥60% on thromboelastography) and subsequently received treatment. Per our institutional practice, patients with sTBI and PD are transfused one unit of apheresis platelets to reverse inhibition. During a platelet shortage, we interchanged DDAVP for the initial treatment. Patients were classified as receiving DDAVP or PLT based on the initial treatment. RESULTS: A total of 57 patients were included (DDAVP, n = 23; PLT, n = 34). Patients who received DDAVP were more severely injured (injury severity score, 29 vs. 23; p = 0.045), but there was no difference in head AIS (4 vs. 4, p = 0.16). There was no difference between the two groups in admission platelet count (244 ± 68 × 10/µL vs. 265 ± 66 × 10/µL, p = 0.24) or other coagulation parameters such as prothrombin time, partial thromboplastin time, or international normalized ratio. Before treatment, both groups had similar ADP inhibition as measured by thromboelastography (ADP, 86% vs. 89%, p = 0.34). After treatment, both the DDAVP and PLT groups had similar correction of platelet ADP inhibition (p = 0.28). CONCLUSION: In patients with severe traumatic brain injury and PD, DDAVP may be an alternative to PLTs to correct PD. LEVEL OF EVIDENCE: Therapeutic, level IV.

Goal-directed platelet transfusions correct platelet dysfunction and may improve survival in patients with severe traumatic brain injury.

BACKGROUND: Platelet dysfunction, defined as adenosine diphosphate inhibition greater than 60% on thromboelastogram, is an independent predictor of increased mortality in patients with severe traumatic brain injury (TBI). We changed our practice to transfuse platelets for all patients with severe TBI and platelet dysfunction. We hypothesized that platelet transfusions would correct platelet dysfunction and improve mortality in patients with severe TBI. METHODS: This retrospective review included adult trauma patients admitted to our Level I trauma center from July 2015 to October 2016 with severe TBI (head Abbreviated Injury Scale score ≥ 3) who presented with platelet dysfunction and subsequently received a platelet transfusion. Serial thromboelastograms were obtained to characterize the impact of platelet transfusion on clot strength. Subsequently, the platelet transfusion group was compared to a group of historical controls with severe TBI patients and platelet dysfunction who did not receive platelet transfusion. RESULTS: A total of 35 patients with severe TBI presented with platelet dysfunction. Following platelet transfusion clot strength improved as represented by decreased K time, increased α angle, maximum amplitude, and G-value, as well as correction of adenosine diphosphate inhibition. When comparing to 51 historic controls with severe TBI and platelet dysfunction, the 35 study patients who received a platelet transfusion had a lower mortality (9% vs. 35%; p = 0.005). In stepwise logistic regression, platelet transfusion was independently associated with decreased mortality (odds ratio, 0.23; 95% confidence interval, 0.06-0.92; p = 0.038). CONCLUSION: In patients with severe TBI and platelet dysfunction, platelet transfusions correct platelet inhibition and may be associated with decreased mortality. LEVEL OF EVIDENCE: Therapeutic, level II.