Introduction Massive transfusion (MT) is frequently required during liver transplantation. Risk stratification of transplant patients at risk for MT is an appealing concept, but remains poorly developed. Thrombelastography (TEG) has recently been shown to reduce mortality when employed for trauma resuscitation. We hypothesize that preoperative TEG can be used to risk stratify patients for massive transfusion. Material and Methods Liver transplant patients had blood drawn prior to surgical incision and assayed via TEG. Pre-operative TEG measurements were collected in addition to standard laboratory coagulation tests. TEG variables including R-time (reaction time), angle, MA (maximum amplitude), and LY30 (clot lysis 30 minutes after MA) were correlated to red blood cell (RBC) units, plasma (FFP), cryoprecipitate (Cryo), and platelets (Plt) during the first 24 hours following surgery, and tested for their performance using a receiver operating characteristic (ROC) curve. Results 28 patients were included in the analysis with a median MELD (Model for End-Stage Liver Disease) score of 17; 36% received a massive transfusion. The TEG variables associated with MT (defined as ≥10 RBC units/24hr) were a low MA (p<0.001) and low angle (p=0.014). A high INR (International Normalized Ratio of prothrombin time) (p=0.003) and low platelet count (p=0.007) were also associated with massive transfusion. MA had the highest area under the curve (0.861) followed by INR (0.803). A MA of less than 47mm has a sensitivity of 90% and specificity of 72% to predict a massive transfusion. MA was the only coagulation variable that correlated strongly to all blood products transfused. Conclusion TEG MA has a high predictability of massive transfusion during liver transplantation. The use of TEG pre-operatively may help guide more cost effective blood bank preparation for this procedure as only a third of patients required a massive transfusion.

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The role of inflammation in oxalate-induced nephrolithiasis is debated. Our gene expression study indicated an increase in interleukin-2 receptor β (IL-2Rβ) mRNA in response to oxalate (Koul S, Khandrika L, Meacham RB, Koul HK. PLoS ONE 7: e43886, 2012). Herein, we evaluated IL-2Rβ expression and its downstream signaling pathway in HK-2 cells in an effort to understand the mechanisms of oxalate nephrotoxicity. HK-2 cells were exposed to oxalate for various time points in the presence or absence of SB203580, a specific p38 MAPK inhibitor. Gene expression data were analyzed by Ingenuity Pathway Analysis software. mRNA expression was quantitated via real-time PCR, and changes in protein expression/kinase activation were analyzed by Western blotting. Exposure of HK-2 cells to oxalate resulted in increased transcription of IL-2Rβ mRNA and increased protein levels. Oxalate treatment also activated the IL-2Rβ signaling pathway (JAK1/STAT5 phosphorylation). Moreover, the increase in IL-2Rβ protein was dependent upon p38 MAPK activity. These results suggest that oxalate-induced activation of the IL-2Rβ pathway may lead to a plethora of cellular changes, the most common of which is the induction of inflammation. These results suggest a central role for the p38 MAPK pathway in mediating the effects of oxalate in renal cells, and additional studies may provide the key to unlocking novel biochemical targets in stone disease.