Preoperative thrombelastography maximum amplitude predicts massive transfusion in liver transplantation.

BACKGROUND: 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 used for trauma resuscitation. We hypothesize that preoperative TEG can be used to risk stratify patients for MT. MATERIAL AND METHODS: Liver transplant patients had blood drawn before surgical incision and assayed via TEG. Preoperative TEG measurements were collected in addition to standard laboratory coagulation tests. TEG variables including R-time (reaction time), angle, maximum amplitude (MA), and LY30 (clot lysis 30 min after MA) were correlated to red blood cell units, plasma (fresh frozen plasma), cryoprecipitate, and platelets during the first 24 h after surgery and tested for their performance using a receiver-operating characteristic curve. RESULTS: Twenty-eight patients were included in the analysis with a median Model for End-Stage Liver Disease score of 17; 36% received a MT. The TEG variables associated with MT (defined as ≥10 red blood cell units/24 h) were a low MA (P < 0.001) and low angle (P = 0.014). A high international normalized ratio of prothrombin time (P = 0.003) and low platelet count (P = 0.007) were also associated with MT. MA had the highest area under the curve (0.861) followed by international normalized ratio of prothrombin time (0.803). An MA of less than 47 mm has a sensitivity of 90% and specificity of 72% to predict a MT. MA was the only coagulation variable that correlated strongly to all blood products transfused. CONCLUSIONS: TEG MA has a high predictability of MT during liver transplantation. The use of TEG preoperatively may help guide more cost effective blood bank preparation for this procedure as only a third of patients required a MT.

Oxalate upregulates expression of IL-2Rß and activates IL-2R signaling in HK-2 cells, a line of human renal epithelial cells.

The role of inflammation in oxalate-induced nephrolithiasis is debated. Our gene expression study indicated an increase in interleukin-2 receptor ß (IL-2Rß) mRNA in response to oxalate (Koul S, Khandrika L, Meacham RB, Koul HK. PLoS ONE 7: e43886, 2012). Herein, we evaluated IL-2Rß 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-2Rß mRNA and increased protein levels. Oxalate treatment also activated the IL-2Rß signaling pathway (JAK1/STAT5 phosphorylation). Moreover, the increase in IL-2Rß protein was dependent upon p38 MAPK activity. These results suggest that oxalate-induced activation of the IL-2Rß 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.