Thromboelastogram-Guided Resuscitation for Patients with Traumatic Brain Injury on Novel Anticoagulants.

Traumatic brain injuries in patients on antithrombotic agents carry significant morbidity. Initial therapy is centered around reversal of these agents. The thromboelastogram (TEG) maps the clotting cascade to guide reversal. A retrospective chart review was conducted for 118 patients presenting with a traumatic brain injury while on antithrombotics. Patients were divided between those who received a TEG on arrival and those who did not. The primary endpoint was overall mortality. Secondary endpoints included blood product utilization, and outcomes associated with specific novel anticoagulants. Mortality in the control group was 20.3 per cent compared with 18.5 per cent in the TEG group (P = 0.81). For less severe injuries, the control group mortality was 3.8 per cent and the TEG group mortality was 8.7 per cent (P = 0.64). For more severe injuries, mortality in the control versus TEG groups were 31.6 per cent and 25.8 per cent, respectively (P = 0.73). Blood product utilization was significantly lower in the TEG group (P = 0.002). Overall mortality was not significantly different between the groups. However, when stratified by severity of injury, mortality was reduced in the TEG-guided group in severely injured patients. Blood product utilization was significantly reduced with TEG-guided reversal. Trauma centers can improve the utilization of blood products in reversal of antithrombotics with the use of TEG.

Brief Report: Seroprevalence of Pertussis Infection in HIV-Infected Adults in the United States.

Pertussis is a resurgent infection that can cause significant morbidity among adults. CD4 T cells are necessary for its clearance, but pertussis studies in HIV-infected adults are limited to case reports. We analyzed stored serum samples from 299 HIV-infected adults to determine the seroprevalence of pertussis among this population. We found that 4.3% of subjects had serologic evidence of recent pertussis infection, and annual incidence of pertussis infection among subjects not vaccinated against pertussis in the last 5 years was 10.5%-17.5%. Prospective studies are needed to define the clinical presentation of pertussis in HIV-infected adults and to optimize vaccination strategies.

A Novel ERAP2 Haplotype Structure in a Chilean Population: Implications for ERAP2 Protein Expression and Preeclampsia Risk.

Single nucleotide polymorphisms (SNPs) in the endoplasmic reticulum aminopeptidase 2 (ERAP2) gene are associated with preeclampsia (PE) in different populations. rs2549782, a coding variant (N392K) that significantly affects substrate specificity, is in linkage disequilibrium (LD) with rs2248374, a marker SNP associated with ERAP2 protein expression in previously studied populations. As a result of non-sense mediated RNA decay, ERAP2 protein is not expressed from the rs2248374 G allele. We previously reported that the fetal rs2549782 minor G allele is associated with PE in African-Americans, but not Chileans. In this study, we found that rs2549782 was in LD with rs2248374 in African-Americans, but not in Chileans. The unexpected lack of strong LD in Chileans raised the possibility that rs2248374 could be associated with PE in the absence of an association with rs2549782. However, we found no significant association for this allele with PE in Chileans. Chileans homozygous for the rs2248374 G allele did not express 110 kDa ERAP2 protein, consistent with non-sense mediated RNA decay, and carriers of the rs2248374 A allele did. We conclude that the Chilean ERAP2 haplotype structure allows for the expression of the major T allele of rs2549782 encoding 392N, which could impact peptide trimming and antigen presentation. Our discovery of racial differences in genetic structure and association with PE reveal here-to-fore unrecognized complexity of the ERAP2 locus.

Fetal ERAP2 variation is associated with preeclampsia in African Americans in a case-control study.

BACKGROUND: Preeclampsia affects 3-8% of pregnancies and is a major cause of maternal and perinatal morbidity and mortality worldwide. This complex disorder is characterized by alterations in the immune and vascular systems and involves multiple organs. There is strong evidence for a genetic contribution to preeclampsia. Two different single nucleotide polymorphisms (SNPs) in the endoplasmic reticulum aminopeptidase 2 (ERAP2) gene were recently reported to be associated with increased risk for preeclampsia in two different populations. ERAP2 is expressed in placental tissue and it is involved in immune responses, inflammation, and blood pressure regulation; making it is an attractive preeclampsia candidate gene. Furthermore, ERAP2 expression is altered in first trimester placentas of women destined to develop preeclampsia. METHODS: A case-control design was used to test for associations between two SNPs in ERAP2, rs2549782 and rs17408150, and preeclampsia status in 1103 Chilean maternal-fetal dyads and 1637 unpaired African American samples (836 maternal, 837 fetal). RESULTS: We found that the fetal minor allele (G) of rs2549782 was associated with an increased risk for preeclampsia in the African American population (P = 0.009), but not in the Chilean population. We found no association between rs17408150 and risk for preeclampsia in the Chilean population. Association between rs17408150 and risk for preeclampsia was not tested in the African American population due to the absence of the minor allele in this population. CONCLUSIONS: We report an association between fetal ERAP2 and preeclampsia in an African American population. In conjunction with previous studies, which have found maternal associations with this gene in an Australian/New Zealand population and a Norwegian population, ERAP2 has now been associated with preeclampsia in three populations. This provides strong evidence that ERAP2 plays a role in the development of preeclampsia.