Platelet Transfusion Does Not Improve Outcomes in Brain Injured Patients on Antiplatelet Therapy

Platelet Transfusion Does Not Improve Outcomes in Brain Injured Patients on Antiplatelet Therapy_ P. Maluso1 , C.L. Reynolds3 , M. Patel4 , S. Holland5 , N. Gamsky1 , H. Moore2 , E. Acquista6 , M. Carrick7 , R.L. Amdur1 , H. Hancock5 , J. Dunn9 , B. Sarani1 ; 1George Washington University School Of Medicine And Health Sciences, Surgery, Washington, DC, USA; 2Carle Foundation Hospital, Surgery, Urbana, IL, USA; 3East Carolina University Brody School Of Medicine, Surgery, Greenville, NC, USA; 4Vanderbilt University Medical Center, Surgery, Nashville, TN, USA; 5San Antonio Military Medical Center, Surgery, Fort Sam Houston, TX, USA; 6University Of North Carolina At Chapel Hill, Surgery, Chapel Hill, NC, USA; 7Medical Center At Plano, Surgery, Plano, TX, USA; 8Columbia University College Of Physicians And Surgeons, Surgery, New York, NY, USA; 9Medical Center Of The Rockies, Surgery, Loveland, CO, USA_x000D_ Introduction: Brain injury is the most common cause of death following trauma. Platelet dysfunction is associated with worsening hemorrhage following brain injury (TBI). Use of antiplatelet medications (APM) is common, especially in elderly patients but the efficacy of platelet transfusion remains unknown. Thrombelastography platelet mapping (TEG-PM) assesses platelet function. We hypothesize that platelet transfusion can reverse the effects of APM but does not improve clinical outcomes in TBI patients on APM. Methods: A 2 year prospective, observational study at 6 US trauma centers was performed. Patients over 17 years old on APM with CT evident TBI after blunt injury were enrolled. Patients underwent TEG-PM and brain CT on arrival and repeat imaging within 24 hours. Platelets were transfused and repeat TEG-PM was ordered at physician discretion. Demographics, platelet transfusion, brain CT and TEG-PM results, length of stay (LOS), and injury severity score (AIS) were abstracted. Groups were compared using student t-test. Results: 66 patients were enrolled (89% aspirin, 34% clopidogrel, 2% ticagrelor). 23 patients underwent platelet transfusion (table). The transfused group had significantly higher AIS and CT brain injury scores. TEG variables were not significantly associated with the decision to transfuse platelets(table 2). MA(AA) increased and %inhibition(AA) decreased significantly following transfusion but other parameters were unchanged. CT brain injury scores did not change after transfusion (mean change 0.10 ± 0.41, p=0.1). Among non-transfused patients with repeat CT scores available (n=29), the change in mean Marshall CT score was 0. Among transfused patients (n=23), mean CT score change before/after transfusion was 0.22 ± 0.60 (p=0.1). Transfusion was associated with longer LOS (7.8 v 3.5 days, p\u3c0.01), but this was not significant after controlling for AIS. There was no difference in mortality. Conclusion:Platelet transfusion significantly decreases degree of platelet inhibition in the arachidonic acid pathway in TBI patients but is not associated with change in CT brain injury scores or clinical outcomes

Polygenic Dissection of Diagnosis and Clinical Dimensions of Bipolar Disorder and Schizophrenia

Bipolar disorder and schizophrenia are two often severe disorders with high heritabilities. Recent studies have demonstrated a large overlap of genetic risk loci between these disorders but diagnostic and molecular distinctions still remain. Here, we perform a combined genome-wide association study (GWAS) of 19 779 bipolar disorder (BP) and schizophrenia (SCZ) cases versus 19 423 controls, in addition to a direct comparison GWAS of 7129 SCZ cases versus 9252 BP cases. In our case–control analysis, we identify five previously identified regions reaching genome-wide significance (CACNA1C, IFI44L, MHC, TRANK1 and MAD1L1) and a novel locus near PIK3C2A. We create a polygenic risk score that is significantly different between BP and SCZ and show a significant correlation between a BP polygenic risk score and the clinical dimension of mania in SCZ patients. Our results indicate that first, combining diseases with similar genetic risk profiles improves power to detect shared risk loci and second, that future direct comparisons of BP and SCZ are likely to identify loci with significant differential effects. Identifying these loci should aid in the fundamental understanding of how these diseases differ biologically. These findings also indicate that combining clinical symptom dimensions and polygenic signatures could provide additional information that may someday be used clinically

Genome-wide association study identifies five new schizophrenia loci

We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded genome-wide significant associations with schizophrenia for seven loci, five of which are new (1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33) and two of which have been previously implicated (6p21.32-p22.1 and 18q21.2). The strongest new finding (P = 1.6 × 10 -11) was with rs1625579 within an intron of a putative primary transcript for MIR137 (microRNA 137), a known regulator of neuronal development. Four other schizophrenia loci achieving genome-wide significance contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a previously unknown etiologic mechanism in schizophrenia. In a joint analysis with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 × 10 -9), ANK3 (rs10994359, P = 2.5 × 10 -8) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 × 10 -9). © 2011 Nature America, Inc. All rights reserved